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Revolution Flea Control (active ingredient: Selamectin) - Information About Revolution For Pets.
Important note: I have researched and written this page to provide information on Revolution flea control from a veterinary perspective. I am not paid to promote Revolution for pets, however, I can say that I have used the product in practice and have found it works very well as an effective monthly flea killer, heartworm preventative, mite eradicator and intestinal wormer for cats and dogs (the function for which it was designed). If I had a pet with Sarcoptic mange, in particular, I wouldn't choose anything else. Furthermore, in a review of flea control products selected for use in a shelter situation (lots of dogs and cats and loads of fleas coming in the door every day), Revolution for Dogs and Cats was selected by my team as one of the three flea control products favored for use (nitenpyram and imidacloprid being the other two), a decision that was based on many factors including: efficacy, safety, duration of action, environmental flea control, animal species treated and range of parasites treated. 
Revolution Flea Control (Selamectin) - Contents: 1) What is the active ingredient of Revolution flea control? 2) What does Revolution do to fleas and other target parasites? How does the Selamectin insecticide work? 3) Parasites killed by Revolution for pets: 3a) Revolution kills adult fleas, their larvae and their eggs. 3b) Revolution kills certain mites, certain lice and certain ticks. 3c) Revolution prevents heartworm but does not kill already-established adult heartworms or their first-stage larvae. 3d) Revolution kills various worms all over the body (including bladder, lung and intestinal tract), except the brain. 4) Revolution for dogs and cats - how to use Revolution spot-on parasite control (includes information on storage and dosing). 5) How long does Revolution flea control work for once it has been given? Does it really last the full month? 6) Is Revolution flea treatment waterproof? Can I get my dog or cat wet after using it? 7) What age can dogs and cats start having Revolution for pets? 8) Can Revolution Selamectin be used on pregnant or lactating animals? 9) Selamectin insecticide has been used successfully off-label in many species, not just the dog and cat. 10) Revolution flea medicine safety and side effects - includes info on Revolution safety in collie breeds. 11) How safe is Selamectin for people? Can I touch it? 12) Is Revolution flea treatment useful in dogs and cats suffering Flea Allergy Dermatitis (FAD)? 13) Selamectin insecticide and the environment - things to be aware of.
1) What is the active ingredient of Revolution flea control? The active ingredient in Revolution flea control is a chemical compound called Selamectin. Selamectin belongs to a large family of antiparasitic compounds known as macrocyclic lactones (16-membered macrocyclic lactones). Except for the spinosyn subgroup (not discussed on this page), the macrocyclic lactone chemicals all work in a similar fashion by binding to and activating the glutamate-gated chloride channels on the nerves and muscles of worms and insects, causing an influx of chloride ions to flood into these cell-types. This chloride ion influx, in turn, produces a failure of nerve and muscle excitability (failure of the nerves and muscles to be able to respond to activation commands) resulting in immobility and flaccid paralysis of the insects and worms. The limp worms and insects subsequently fall off the host animal (or are swept out of the intestinal tract by normal bowel motions) and die in the environment (see next section for full details). A similar effect on a related chloride channel (the GABA-gated chloride channel) also occurs in insects (but not worms), with the same paralysis and elimination results. Two to three major families of macrocyclic lactones exist. The first group is the 'avermectins', which includes such commonly-used antiparacidal drugs as abamectin, ivermectin, eprinomectin, doramectin, selamectin and emamectin. The earliest of these (abamectin, ivermectin and eprinomectin) were derived from the anti-parasitic fermentation products of a soil microbe called Streptomyces avermitilis. Later, genetically altered, mutant forms of this microbe were utilized to create Doramectin and then Selamectin (Selamectin is considered to be a 'semi-synthetic' avermectin). The semi-synthetic variants of the avermectin group (including Selamectin) were created to produce improvements in many features of the macrocyclic lactone family including: safety (e.g. Selamectin is not thought to cross the blood-brain barrier as easily, resulting in improved safety for mammals, in particular ivermectin-sensitive breeds like collies); range of parasites killed; specificity of parasites killed and reduced environmental harm (e.g. emamectin is not considered to be as environmentally unfriendly to dung-decomposition insects as some of the other macrocyclic lactones are). Closely related is the second macrocyclic lactone group: the 'milbemycins'. These chemicals are very similar in structure to the avermectins in that they have the all-important 16-carbon lactone structure essential to the chemicals' functionality, however, they lack a sugar (disaccharide) moiety. The earliest milbemycins were derived from the anti-parasitic fermentation products of a soil microbe called Streptomyces hygroscopicus, however, other organisms (S. cyanogriseus, S thermoarchaensis) have also been found to create it. Similar to the situation seen with the avermectins, synthetic forms of milbemycin have also been created. A newer (third) macrocyclic lactone group has also been recently developed, called the 'spinosyn' group. I will not discuss this group further as it shall be covered in my discussion on the flea control pill ingredient: spinosad (Comfortis). The spinosyn group does not work on the same nerve receptors as the other two macrocyclic lactone groups do. The avermectins are commonly used in animal medicine (especially livestock medicine) to kill a broad range of internal and external parasites in livestock animals, horses, poultry and domestic pets including: intestinal worms, lung worms, other nematodes, mites, certain ticks, certain lice, certain other parasitic arthropods, heartworm larvae (to prevent heartworm disease), fleas and a host of unmentioned parasites. The milbemycins have featured more prominently in small animal medicine (dog and cat medicine, mostly) in products designed to eradicate fleas, mites and a range of internal nematode (worm) parasites, including heartworm. Both families of macrocyclic lactone drug have similar chemical properties and their effects on parasites; their tissue distribution inside the treated animal; their side effects; their safety profile with regard to animals, humans and the environment, as well as their reluctance to induce drug resistance and cross-resistance are considered to be quite similar. It should be noted that some variation does exist because of extra traits added to the semi-synthetic avermectin and milbemycin derivatives by genetic engineering and changes to their chemical structure. For example, the selamectin compound now contained in Revolution for pets was designed to be a chemical with 'adequate' internal parasite control properties but exceptional external parasite eradication properties (which is why you mostly see the chemical in mite and flea control products like Revolution flea control and not in all-wormers). It was also designed to be less toxic to ivermectin-sensitive animals like collies. A 2011 article in Current Pharmaceutical Biotechnology examines the different "Pharmacokinetic features of the antiparasitic Macrocyclic Lactones." The article reports that the macrocyclic lactones are all highly lipid soluble (attracted to fat stores in the body) and that this characteristic greatly contributes to the drugs having an extensive body and organ distribution (including the sebaceous glands and intestinal tract). High lipid solubility also affects the drugs' metabolism and helps the macrocyclic lactones to persist and last in the body for longer periods of time (fat sequestration and resultant 'slow-release' enables certain products, including Revolution flea control, to maintain an anti-parasitic effect for a prolonged duration of time without needing re-dosing). The tendency for macrocyclic lactones to accumulate and leach slowly from body fat stores also accounts for why there are differences in the distribution, metabolism and persistence of macrocyclic lactones between different breeds, species, genders and individuals whose levels of body fat may differ. The article abstract also comments on how "subtle structural changes" have been made to various macrocyclic lactone compounds to "reduce distribution to the central nervous system and mammary gland, thus allowing use of some compounds such as selamectin in 'toxicity sensitive' breeds of collie dog ... and the use of eprinomectin (EPM) in dairy cattle with a nil-milk withdrawal period." Author's note - the various macrocyclic lactones (including Selamectin) are sometimes referred to as 'endectocides'. This term merely means that the drug is capable of killing and controlling parasites both internally (inside the animal's body) and externally (on its skin). The drugs are capable of doing this because, once they are absorbed into the treated animal's body (e.g. after topical, injectable or oral dosing) they distribute widely throughout the animal's tissues and skin, killing a wide spectrum of parasite types wherever they hide (except the brain). Revolution for pets: Selamectin as it occurs in Revolution flea control liquid is clear and colorless, tending towards yellow. Revolution pet medicine contains alcohol and therefore gives off a mild alcohol odour that is in no-way noxious. Selamectin, like all the macrocyclic lactones, is lipophilic, meaning that it binds well with fats (lipids, including body fat) and organic solvents (e.g. alcohols), but does not dissolve to form a homogenous solution or suspension with water. Selamectin is chemically stable under normal conditions of storage and it is not dangerously incompatible with other materials or surfaces. The product is not an oxidiser nor is it corrosive. It does not decompose to produce hazardous compounds. Selamectin strongly absorbs UV light at 245nm, which is a characteristic that has been utilised in lab tests designed to detect levels of Selamectin in tissues and other substances. Selamectin does, however, break down and become rapidly inactivated by UV light and should therefore be kept out of direct sunlight. Because it contains alcohol, Revolution flea control is highly flammable and must be kept away from open flames, high heat and sparks and other situations where ignition is possible. The selamectin chemical is capable of boiling (boiling temperature is 84 degrees Celsius) and even igniting (flashpoint is 19 degrees Celsius). The Selamectin in Revolution flea control absorbs into the bloodstream of the host animal when applied topically (other macrocyclic lactones absorb into the bloodstream when given either orally, topically or by injection). Cats and dogs differ in their uptake of topical Selamectin. According to a 2002 article in the Journal of Veterinary Pharmacology and Therapeutics, 4.4% of a topical dose is bioavailable to dogs, whereas a good 74% is bioavailable to cats. Cats reach a peak level of Selamectin in their blood plasma within a day (15hr +/- 12 hrs), whereas it takes a couple of days for dogs to reach their peak plasma levels (72hr +/- 48hr). The peak level seen in cats is also much much higher than that seen in dogs, suggesting a larger and more-rapid effect might be expected in cats than in dogs. From the bloodstream, the Selamectin distributes widely throughout the fats and organs of the body (except for the brain, which excludes it). It sequesters in the lipid-containing sebaceous glands of the entire skin surface, thereby, having a skin-wide effect on surface parasites like fleas, mites and ticks (e.g. selamectin is secreted onto the skin surface when the sebaceous glands secrete their skin oils). The selamectin is also secreted into the intestinal tract, bladder and lung, killing parasites localized in these regions (e.g. lungworms in cats, roundworms in the gut, bladder-worms in rats). The 2002 Journal of Veterinary Pharmacology and Therapeutics article also examined the bioavailability, bodily distribution, peak plasma levels and clearance of Selamectin when given to dogs and cats by oral and intravenous routes. Since Revolution for cats and dogs is not given by these means, I will not comment further on these routes of administration here. One comment I will make is that quite high doses of Selamectin (24mg/kg, which is 4x the normal dose) were given to dogs and cats by both topical and oral routes and no adverse effects were noted in the test subjects. This suggests a good safety profile for the drug. Although the MSDS considers Selamectin (Revolution flea control) to be non-dangerous when used appropriately, it is considered to be irritant to the eyes (especially since it contains alcohol) and sometimes the skin. Eyes need to be flushed thoroughly with water or an eye irrigation solution if the product gets into the eyes and it is recommended that hands are washed thoroughly with soap and water after the product is applied to pets. Revolution for pets is extremely bitter tasting (cats that lick it will often salivate profusely with distaste). There is also potential for the product to be harmful if ingested in large quantities (Revolution flea control is not intended for oral use). The product should therefore be stored out of reach of children in a dark, dry, cool site well away from food and water sources intended for human or animal consumption. Should the product be swallowed or allowed to contaminate the eyes, medical advice should be sought. Revolution for pets has a wide safety margin, however, overdoses could potentially result in signs of toxicity, some of which are severe, particularly in ivermectin-sensitive animals (e.g. collies, young animals). Selamectin toxicity and side effects are discussed in section 10. Overdosing should therefore be avoided. Tests on laboratory animals and cell cultures have determined that the chemical, Selamectin (Revolution flea control) does not cause cancer. Revolution has, at super high doses (and high frequencies), been found to cause a range of reproductive effects, including: fetal toxicity and death, developmental deformities and maternal toxicity (poisoning of the mother). Some of these effects may not be solely related to the Selamectin, but to the alcohol components also contained within the Revolution flea control product. It should be noted that, whilst no 100% guarantee can be made that a pregnant or lactating animal treated with Revolution flea control will not have some form of adverse reaction (e.g. a deformed fetus), the manufacturer has approved the product for use in pregnant and lactating animals (studies done on pregnant dogs and cats have supported this claim). The studies done on rodents, which showed the reproductive side effects mentioned above, were done using massive doses of the product (well beyond that which a pet owner or vet would ever conceive of giving). The product was often given for days at a time (not monthly) and by the oral route (which is not how the product should be used). At normal dose rates, given monthly and topically, Revolution for pets should be safe to use in pregnant animals and animals intended for breeding (see MSDS publications), though no 100% guarantee could ever be given for all individuals. Studies have found that the product is non-hypersensitising (i.e. animals tested didn't start to react to it with repeated use), however, skin sensitivity reactions have been known to occur (see side effects section) in individual animals and humans exposed to Revolution for pets. Selamectin insecticide has not yet been associated with drug resistance (i.e. the fleas and parasites are not yet resistant to its effects), however, parasite drug resistance has popped up from time to time with some of the older 'mectins' such as ivermectin. Although these incidents are not common and are slow to develop, they do highlight the potential for drug resistance to occur in parasites should users of endectocide products not use them wisely. The macrocyclic lactones are some of the safest and most effective antiparasitic drugs ever invented and we are lucky to have them. Smart parasite management plans, smart drenching (e.g. drench rotation), choosing programs that minimize the selection of resistant parasites are all needed if macrocyclic lactones are to last us through future decades. Revolution flea control is considered compatible with a range of drug products, including: many antibiotics, vaccines, non-steroidal anti-inflammatory drugs, corticosteroids, all-wormers, shampoos, dips, lufenuron, permethrin, praziquantel, febantel and pyrantel among others. The potential for toxicity is increased, particularly in sensitive animals, if macrocyclic lactones are administered at the same time as drugs that compete with the macrocyclic lactones for places on p-glycoprotein excretion molecules (e.g. ketoconazole). The Synonym for Selamectin is: UK-124114 and The Chemical Abstracts Service (CAS) registry number is: 220119-17-5 The CBNumber: CB0947411 To see the MSDS of Revolution For Pets: http://www.pfizeranimalhealth.co.nz/sites/pfizeranimalhealth/PAH%20Document%20Library/Pfizer%20MSDS%20-%20REVOLUTION%20for%20Puppies%20%20Kittens.pdf
2) What does Revolution do to fleas and other target parasites? How does the Selamectin insecticide work? Revolution flea control spot-ons are administered to dogs, cats and other animal species topically (directly on the skin). The Selamectin present in the Revolution flea medication absorbs into the animal's body and enters the animal's bloodstream, circulating within the blood plasma. Adult fleas, ticks, sucking lice, hookworms and various parasites that live within the bloodstream ingest the Selamectin medication when they drink the blood of the medicated dog or cat. Mites and chewing lice ingest the chemical when they feed on hair and dander containing the skin-secreted chemical. Certain worms that live in the blood (e.g. filarial nematodes) and gut may also absorb the poison directly through their skin. Cats and dogs differ in their uptake of topical Selamectin. According to a 2002 article in the Journal of Veterinary Pharmacology and Therapeutics, 4.4% of a topical dose is bioavailable to dogs, whereas a good 74% is bioavailable to cats. Cats reach a peak level of Selamectin in their blood plasma within a day (15hr +/- 12 hrs), whereas it takes a couple of days for dogs to reach their peak plasma levels (72hr +/- 48hr). The peak level seen in cats is also much much higher than that seen in dogs. From the bloodstream, the Selamectin distributes widely throughout the animal's body. Some of it sequesters in the fat stores of the body, from where it leaches out slowly into the blood and tissues, creating the long-term, slow release, "monthly" effect Revolution flea control is known for (Revolution flea control persists longer in the bodies of animals with higher levels of body fat). Some of it enters the sebaceous glands of the animal's skin, such that small amounts of the chemical get secreted onto the skin every time the glands secrete their oily sebum. This allows the chemical to be distributed all over the animal's skin for many weeks, resulting in long durations of effective flea control. The fact that the chemical travels in the blood and is secreted continuously by the sebaceous glands deep within the skin also makes Revolution flea control resistant to being washed or shampooed away. Selamectin is also secreted into such organs as the lung, liver, gastrointestinal tract (via excretion through the bile) and even the kidney (exiting via the bladder), where it acts to kill susceptible parasites in these tissues. It is thought that levels of macrocyclic lactones (e.g. Selamectin) can accumulate and persist in such tissues (especially the lungs, skin and intestine) at levels greater than that seen in the plasma for weeks to months, making the drugs highly effective at killing parasites in these organs (for example, Doramectin accumulates in the lungs, making it an excellent killer of the cat lungworm Aelurostrongylus abstrusus). Much of the Selamectin that enters the gastrointestinal tract via biliary excretion is lost to the feces (feces are the main means by which Selamectin is excreted from the body), however, some is reabsorbed back into the body and bloodstream via the intestines (similar to what happens when the drug is given orally), where it gets to have another turn at killing parasites. This cycle of biliary secretion and intestinal reabsorption is termed enterohepatic recycling. Around 20% of each lot of Selamectin entering the intestinal tract is reabsorbed in this way. This enterohepatic recycling is another reason why Revolution maintains its effect for such long periods of time in the body. Selamectin is minimally metabolised (broken-down) by the body and the Selamectin that enters the blood, fat, organs, skin, bile and intestine is largely unchanged from the form that was first applied to the skin. Selamectin and the brain: Being lipid soluble (lipophilic), Selamectin, like all the macrocyclic lactones, can pretty much go where it likes in the body, since most cellular membranes (the walls of cells) are constructed of fats (lipids) that Selamectin can simply pass on through. The chemical can not, however, move easily into the brain or nervous system because special properties of the cells lining the blood vessels of the brain and nervous system prevent this (this is the 'blood-brain barrier' or BBB) just as they prevent all manner of nasty toxins and organisms from moving into the brain tissue. Any macrocyclic lactone that does make it past the BBB and into the central nervous system is rapidly removed by a special transport system called a p-glycoprotein transport system. This transport system binds up the macrocyclic lactones, transports them back past the BBB and returns them to the bloodstream (thereby preventing the chemicals from having a toxic effect on the brain). The p-glycoprotein transport proteins are also present in the liver, kidney and intestinal tract where they help to enhance the body-wide excretion of macrocyclic lactones like Selamectin via the intestine and, to a lesser extent, the kidneys. The p-glycoprotein transport proteins basically snatch up molecules of Selamectin from the blood and fling them into the biliary tract, kidney tubules and gut lumen, where they are excreted from the body (some molecules will be reabsorbed from the intestinal tract to have another turn through the blood circulation due to 'enterohepatic recycling'). In some animals (e.g. certain breeds of dog, including collie breeds and their crosses, Murray Grey cattle), the p-glycoprotein transport proteins are defective. This is due to genetic defects of the gene (the ABCB1 gene) coding for them (in collies the genetic defect in the p-glycoprotein transport protein gene is a 4-base pair deletion mutation). Such animals are more likely to experience toxic neurological side effects from macrocyclic lactones (even at therapeutic levels) because any of the chemical that manages to cross the BBB will not be rapidly eliminated from the nervous system and brain due to the defective p-glycoprotein transport proteins. Additionally, macrocyclic lactones will tend to persist at higher levels and for longer in the bodies of such animals (increasing the risk of bioaccumulation and toxicity) because there are no p-glycoprotein transport proteins available to assist with active excretion of the drug from the body. Note - Selamectin is thought to be one of the less brain-penetrating macrocyclic lactones and therefore pose a reduced risk of causing toxicity in collies and other sensitive breeds (e.g. Australian Coolies). Certain medications (e.g. ketoconazole) alter the function of the p-glycoprotein transport proteins or compete with the macrocyclic lactones for them. This results in the p-glycoprotein transport proteins being less effective at clearing the macrocyclic lactones from the brain or body, resulting in a longer duration of macrocyclic lactone persistence within the body and an increased risk of neurological toxicity (even in animals without the gene defect). How do insect and worm parasites take in Revolution for pets: Revolution flea control is only taken up into the adult flea's body during blood feeding. The flea will not be poisoned by contact with the chemical alone, as is seen with certain other insecticidal compounds like Imidacloprid. In addition to killing adult fleas, Selamectin also renders the flea eggs laid by such fleas infertile and incapable of developing and hatching. Other arthropod parasites like mites, ticks and lice are similarly killed by ingestion of the macrocyclic lactone compound, whether it be through blood consumption or consumption of treated dander. Worms are also killed by ingestion of Selamectin (e.g. hookworms take up Selamectin when they drink the blood of the treated host animal), however, it is thought that certain filarial worms (e.g. heartworm larvae) and certain gastrointestinal nematodes may also be killed via absorption of the macrocyclic lactone through the skin (i.e. without the need for consumption). Flea larvae in the host animal's environment become poisoned when dander (skin flakes) or flea feces (their natural diet) containing Selamectin drop into the environment from the host animal's skin. The flea larva consumes the Selamectin insecticide through consumption of the treated dander (or flea feces). Though Selamectin does have the ability to kill a range of internal parasites, including certain intestinal worms and stage 3 heartworm larvae, the chemical was specifically designed to have exceptional activity against external arthropod parasites. Thus, Revolution for pets is mostly considered to be a "flea control product" and "mite killer" with bonus effects against heartworm and other worms. An article published in Veterinary Parasitology in 2005 looked at the deposition of radio-labeled Selamectin and Ivermectin in the brains of fleas. It found that higher levels of macrocyclic lactones were found in the fleas that ingested larger amounts of treated blood (i.e. a dose effect). It found that the drugs localised in sites of the flea brain which were high in glutamate-gated chloride channels. It also found that the concentration of selamectin in the brains of the fleas was always greater than that of ivermectin, confirming the "higher potency of selamectin against fleas compared to ivermectin." How Revolution for pets works: Nerve and muscle cells spend part of their time 'at rest', meaning that, in the case of nerves, they are not actively transmitting nerve impulses (signals from nerve to nerve) and, in the case of muscles, they are not actively contracting. When in the state of rest, these nerve and muscle cells exist in a state of readiness, prepared to go into 'excitation mode' should a nearby nerve send them a signal (normally a chemical signal via a neurotransmitter - see below explanation) indicating a need for the resting nerve or muscle to activate. Explanatory author's note: Nerves are not continuous. For example, one nerve doesn't go straight from the brain to a toe. When the brain wants to tell a toe to move, it sends electrical nerve signals to the toe along of chain of interlinking nerves. These nerves communicate by relaying signals to one other in order along the chain. When one nerve wants to relay a signal (say, to the next nerve along the chain or to the muscle it wants to activate, like a toe muscle), it must do so by secreting a chemical called a neurotransmitter. This neurotransmitter crosses a small gap between the nerve that secreted it (the nerve 'sending the message') and the next nerve or muscle intended for activation. This gap is called a "synapse". The secreted neurotransmitter binds to a receptor on the nerve or muscle intended for activation, causing activation to occur. Receptors that trigger 'activation' upon binding with a neurotransmitter are called activation receptors. Resting nerves and muscles are 'ready to activate' because of a difference in polarity (or charge) that exists between the inside of the nerve or muscle cell membrane and the outside of the cell membrane (exterior to the nerve or muscle). At rest, the inside of the nerve or muscle cell is negatively charged compared to the outside (around -90 millivolts). This is because the inside of the nerve or muscle cell contains loads of chloride ions, which are negatively charged. When a neurotransmitter makes contact with a nerve or muscle 'activation receptor', the receptor, which runs right through the membrane wall of the nerve or muscle cell, responds by opening up a tunnel between the inside and the outside of the cell (a tunnel right through the cell membrane). Sodium ions, which are positively charged, rush through the tunnel (sodium channel) from the outside of the cell to the inside of the cell (they are attracted to the negative charge), causing the negative charge of the inside of the cell to lessen (this tendency towards charge 'neutralization' is termed 'depolarization' - i.e. the polarity is reduced). Once the inside of the cell reaches a negative charge of around -70 to -50 millivolts, this has the effect of triggering nearby sodium-channels to open, therefore letting in more sodium. These sodium channels, called "voltage-gated sodium channels" only open in response to the initial lessening of the negative charge. Once they open, letting in more positively-charged sodium, this triggers yet more voltage-gated sodium channels to open further down the nerve and so on until the entire length of the nerve or muscle cell has depolarized. In nerves, this series of depolarization continues completely down the length of the nerve fibre (nerve axon) until it gets to the end. The depolarisation of the end of the nerve causes it to secrete a neurotransmitter, which crosses a synapse gap to the next nerve or muscle along the chain, causing the sodium channel activation process to begin again in the next nerve or muscle. In muscles, the depolarisation causes certain internal structures of the muscle cells to secrete calcium, resulting in muscle contraction. Note: this is a super-simplified version of how nerve and muscle activation occurs. I have not included information on the role of potassium and calcium ions in all of this, nor info on how the nerve activation effect is limited and halted. The information I have given, however, should be enough for you to understand how the macrocyclic lactones go about having their toxic paralysis effects on insects. See next paragraphs. Not all neurotransmitters and their receptors are excitatory 'activation receptors'. Some neurotransmitters are inhibitory, acting to suppress the sodium influx into nerve and/or muscle cells and stop depolarisation and nerve/muscle activation from occurring. Two neurotransmitters that have this effect are the glutamate and gamma-amino-butyric-acid (GABA) neurotransmitters. These neurotransmitters act on "inhibitory receptors" that respond by letting high levels of negatively-charged chloride ions enter the target nerve or muscle cell. The increased chloride ion levels in these cells causes the cells to become "hyperpolarised" with a negative charge that is hugely increased beyond normal levels. This excessive negative charge makes it very difficult for the nerve or muscle to achieve the particular level of depolarisation (the less-negative -70 to -50 millivolts) needed to trigger the firing off of the voltage-dependent, excitatory sodium channels. Thus, activation of the nerve and muscle cells can not occur (not without massive activatory neurotransmitter input, anyway) and the affected animal is, essentially immobilised and paralysed. The inhibitory receptors that accept glutamate and GABA neurotransmitters are called "glutamate-gated chloride channels" and "GABA-gated chloride channels," respectively. The macrocyclic lactone chemicals, including Selamectin, all work by binding to and activating the inhibitory glutamate-gated chloride channels on the nerves and muscles of worms and insects. This causes an influx of chloride ions to occur into these cell-types. This, in turn, causes the nerves and muscles to be less able to depolarise appropriately in response to the activation commands of excitatory neurotransmitters, resulting in immobility and flaccid paralysis of the affected insects and worms. The parasites lose their ability to feed, become immobilised and eventually fall off the host animal (or they are swept out of the intestinal tract or bladder by normal voiding activities). The paralysed parasites die in the environment. Insects (but not worms) are also thought to have GABA-gated chloride channels, in addition to their glutamate ones, whose activation by the macrocyclic lactone compounds results in the same paralysis and elimination results. At lower doses, the macrocyclic lactone compounds are thought to merely enhance (potentiate) the effect of glutamate or GABA on the chloride channels. At high doses, however, the macrocyclic lactone compounds are thought to disregard the glutamate or GABA completely and directly activate the chloride channels themselves, resulting in a massive effect. It should be noted that macrocyclic lactones (including Selamectin in Revolution flea control) do not kill parasites rapidly. Insects and worms die over a period of days (they are most-likely shed from the host animal alive, but paralysed, such that they die in the environment). There is no fast knock-down effect seen with these chemicals. Trematodes (flukes) and cestodes (tapeworms) do not have glutamate-gated or GABA-gated chloride channels and thus the macrocyclic lactone drugs will not kill them. Effect on vertebrates: Though highly toxic to insects and certain worms, macrocyclic lactones are not generally considered to be all that toxic to vertebrate species, with the exception of fish and chelonians (turtles). They are also non-toxic to plants. The lack of toxicity to vertebrates (including man and his animals) is for several reasons. Vertebrates do not have glutamate-gated chloride channels and therefore macrocyclic lactones do not have these to act upon (i.e. no receptors for the insecticide means no toxic effect from the insecticide). Vertebrates do have GABA-gated chloride channels in the central nervous system (and some in the peripheral nervous system and gut), however, in most normal animals, the macrocyclic lactones are prevented from making contact with these channels because of the strong, exclusionary blood-brain barrier (BBB) and because of the p-glycoprotein transport molecule, which swiftly removes any macrocyclic lactone compound that makes it through the BBB and into the brain. Should Selamectin or any of the other macrocyclic lactones make it into the central nervous system of vertebrates (e.g. due to BBB damage, massive doses or defects in the p-glycoprotein transport molecule), then neurotoxic effects will be seen, similar to those that occur in insects. Toxic signs in mammals include: depression, drooling, swallowing difficulty, tongue paralysis, incoordination of the gait (ataxia), apparent blindness, tremors, seizures, coma and death. Though at first it seems odd for "excitation" signs like fits and tremors to occur with GABA-gated chloride channel activation, be aware that nerves cross-link in weird and wonderful ways and should a macrocyclic lactone cause the inhibition of a nerve that is, itself, an inhibitor, the overall result on the central nervous system might turn out to be one of excitation. The Archives of Insect Biochemistry and Physiology in December, 2003 explains the "excitation" (tremors, fits, excitement) side effects seen in mammals poisoned with macrocyclic lactones another way in its article on chloride channels and selective insecticides. According to the article, the mammalian toxicity effect is dose-related. At lower doses, the macrocyclic lactone drugs bind to the GABA-gated chloride channels of mammals, but do not actually activate them (i.e. do not cause the influx of chloride ions that suppresses the nerves). They just block the GABA from getting access to them. This results in the nerve being easily and excessively activated (there is no GABA down-regulation of the nerve) and thus, an opposite, excitatory effect is noted - often a 'coarse tremor' or convulsions. With increased concentrations (doses) and longer-term exposure to the drug, the GABA channels do get activated, similar to the effect seen in insects, with resultant suppression of target nerve activation and signs of ataxia (wobbliness), flaccid paralysis and even death. The BBB is weaker in young animals and so toxic effects are more likely to be seen in juvenile and neonatal animals, even if their p-glycoprotein transport proteins are normal. This is why there are age restrictions in place for the use of Revolution in pets. In some animals (e.g. certain breeds of dog, including collie breeds and their crosses, Murray Grey cattle), the p-glycoprotein transport proteins are defective. This is due to genetic defects of the gene (the ABCB1 gene) coding for them. Such animals are more likely to experience toxic neurological side effects from macrocyclic lactones (even at therapeutic levels) because any of the chemical that manages to cross the BBB will not be rapidly eliminated from the nervous system and brain due to the defective p-glycoprotein transport proteins. Certain medications (e.g. ketoconazole) alter the function of the p-glycoprotein transport proteins or compete with the macrocyclic lactones for them. This results in the p-glycoprotein transport proteins being less effective at clearing the macrocyclic lactones from the brain or body, resulting in a longer duration of macrocyclic lactone persistence within the body and an increased risk of neurological toxicity.
3) Parasites killed by Revolution for pets: The avermectin drugs have been around since the approval of the first commercial macrocyclic lactone drug, ivermectin, in 1981. Since then, the avermectins have been used to treat a wide range of parasitic worm and arthropod species in all manner of animal species including: livestock (cows, goats, sheep, pigs), horses, dogs, cats and even people (macrocyclic lactones have been used to treat Onchocerca eye worms in people and also the filarial condition, elephantiasis). Less typical species of animals (e.g. camels, deer, rabbits, rats, mice, guinea pigs, bison, frogs, birds) have also been given macrocyclic lactones (ivermectin, in particular), in the hope they will be cured of their internal and external parasite burdens. Although I could write extensively about the parasite applications of all the macrocyclic lactones (e.g. the many uses of ivermectin), I will restrict this section to the semi-synthetic macrocyclic lactone drug, Selamectin, as found in Revolution for pets. According to the manufacturer, Pfizer, Revolution has been approved for use in cats and dogs against the following parasites:
For example, Revolution will probably remove roundworms in dogs, but has not been officially approved for this use. Selamectin will treat Sarcoptic mange in ferrets and Psoroptic mange (ear canker) in rabbits, but has not been officially approved for these species. Revolution will treat Notoedric mange in cats, but again has not been officially approved for this parasite. Current Pharmaceutical Biotechnology in 2011 reviewed the use of "Macrocyclic Lactones in the Treatment and Control of Parasitism in Small Companion Animals" exploring the emerging off-label use of these drugs (including Selamectin) against different parasite species and in exotic and atypical pet species. 3a) Revolution kills adult fleas, their larvae and their eggs. Revolution flea control kills adult fleas present on the body of the host dog or cat. It also kills flea larvae present in the environment of the host animal and greatly reduces the viability of flea eggs. Fleas and their larvae are killed through consumption of the insecticide. The effects of Revolution flea control have mainly been studied using various strains of the cat and dog (and ferret) flea species, Ctenocephalides (Ctenocephalides felis and Ctenocephalides canis). This is because these species of flea are common, because they breed and grow rapidly in a laboratory setting (making them easy to study) and because the cat flea in particular is considered to be one of the major parasite pests affecting pets and humans worldwide. Revolution flea control works to kill fleas quite rapidly: Depending on the textbooks or journal articles you read, the time taken to achieve maximum effect and the maximum effect achieved (% of fleas killed) varies a little, however, pretty much all Revolution flea control articles state that >98% of fleas will be killed within 36 hours of dosing (this is also what the Revolution flea control information sheets put out by Pfizer claim). Many other studies have been done that support such claims. A study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. The cats were infested with fleas 2 days before the Revolution flea control was administered at label doses and then fleas were applied to the treated animals weekly for 4 doses. Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after Revolution dosing, the % kill was only 69.4%, but this improved to 99% by 24 hours. A 2000 article in Veterinary Parasitology examined the effects of Selamectin on adult and immature flea stages in dogs and cats. The study found that >98% flea kill (>98% efficacy) was achieved in dogs between 24 and 36 hours after initial dosing and that a similar % of flea kill was achieved in cats between 12 and 24 hours. In previous sections of this webpage I have mentioned that the bioavailability of topical selamectin is higher in cats than dogs with much greater plasma levels achieved more quickly. It is most likely that this is the reason why the >98% flea kill was achieved so quickly in cats compared to dogs. It is important to understand that Revolution flea control is initially slower than some other flea control products, but not by much (it does take at least 12-24 hours for significant flea kills to occur). This is shown in a 2003 article published in Veterinary Parasitology, which compared the speed of kill and percentage of flea kill between five of the major flea control products on the market at that time (Nitenpyram, Fipronil, Imidacloprid, Selamectin and Cythioate). The results for Nitenpyram were most impressive. Within 3 hours, "nitenpyram was 100% effective in cats and 99.1% effective in dogs" and 100% effective in both species at 8 hours. Cythioate (used on cats only in the study) showed a 62.4% and 97.4% flea kill at 3 and 8 hours, respectively. Selamectin (used on dogs only in the study) showed a 39.7% and 74.4% flea kill at 3 and 8 hours, respectively. It should be mentioned that Selamectin was not tested on cats in this study, however, it is expected that the speed of flea kill would have been quicker in this species. In dogs, Fipronil showed a 35.9% and 46.5% flea kill at 3 and 8 hours, respectively, whereas, in cats, the respective percentage kills were 24.3% and 62.6%. Imidacloprid in cats showed only a 26.9% flea kill at 3 hours, but then a rapid recovery response and an 82.8% flea kill at 8 hours. In dogs, a similar pattern was seen with a lower % kill (22.2%) at 3 hours, but a high % kill (95.7%) at 8 hours. The speed of flea kill does tend to wane during the month following dosing with Revolution flea control (as it does for all three major topical preparations prescribed by vets). A 2005 study published in Veterinary Therapeutics demonstrated this. It showed that Imidacloprid (Advantage flea control) had the highest % flea kill within 6 hours of initial dosing (out of Fipronil, Imidacloprid and Selamectin), but that all products had achieved a >95% flea kill by 24 hours of dosing. Fleas were re-introduced to the study cats at day 7 (to mimic a reinfestation event) and all three formulations showed a similar effect, with a 68.4% flea kill at 6 hours post flea-introduction and a massive (highly effective) 99.4% flea eradication at 24 hours. At day 21 and then again at day 28, more fleas were introduced and there was no appreciable kill of those fleas within 6 hours. The new fleas did die, but they took longer (up to 2 days were allowed before the % flea kill was determined), showing that the speed of kill declines a bit with the time passed since dosing. Another study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. The cats were infested with fleas 2 days before the Revolution flea control was administered at label doses and then fleas were applied to the treated animals weekly for 4 doses. Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after Revolution dosing, the % kill was only 69.4%, but this improved to 99% by 24 hours. After the fleas were reintroduced at day 28 (just before the next dose of Revolution was due) the study showed that 12 hours after flea introduction, the % kill was 57.3%, but this improved to 87.1% (in one version of the study) or 95.3% (in another version of the study) 24 hours after flea introduction and then 98.3% 48 hours after flea reintroduction. The study showed that Revolution still showed a high % flea kill a month after dosing, but that it took marginally longer to achieve. Revolution flea control maintains a high efficacy (% kill) for the full month - depending on the study you read: Revolution flea control is designed to maintain its high % flea killing effect for at least 1 month following dosing (after which the next dose is due). Whether this actually occurs to a moderately high degree (>90% flea kill at 30 days, as claimed by Pfizer) or a really high degree (>95% flea kills at 30 days), however, depends on the study you look at. It might also depend on the "strain" of flea the study is utilizing (for example, the 2005 study, mentioned next, was conducted on the KS1 strain) The 2005 study published in Veterinary Therapeutics (described three paragraphs above) found that, at the 28-day mark, selamectin was still achieving a 99% flea kill within 2 days of fleas being re-introduced to the treated pet. Fipronil, in contrast, only achieved an 86.4% efficacy in that time and Imidacloprid only achieved a 72.6% flea kill at the 28-day flea-re-introduction mark. Of the three, selamectin seemed to maintain its effect the best and have the highest residual activity. Another study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. The cats were infested with fleas 2 days before the Revolution flea control was administered at label doses and then fleas were applied to the treated animals weekly for 4 doses. Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after Revolution dosing, the % kill was only 69.4%, but this improved to 99% by 24 hours. After the fleas were reintroduced at day 28 (just before the next dose of Revolution was due) the study showed that 12 hours after flea introduction, the % kill was 57.3%, but this improved to 87.1% (in one version of the study) or 95.3% (in another version of the study) 24 hours after flea introduction and then 98.3% 48 hours after flea reintroduction. A 2001 study published in Veterinary Record looked at a similar thing. Animals were dosed with either selamectin, fipronil or imidacloprid and flea populations were re-introduced at days 7, 14, 21, 28 and 35 following dosing. In this study, all three treatments maintained exceptional efficacy for the full month with Selamectin (Revolution flea control) showing an 81-100% flea kill 48 hours after fleas were re-introduced on the 28th day of testing. The study showed no appreciable difference between the three products. Revolution flea control improves in efficacy with monthly use: Quite a few studies have been done whereby Revolution is given to animals monthly over several doses. These studies show that, while Revolution achieves a good effect against fleas (e.g. in a flea infested household) following the first dose (>90% effectiveness at 30 days, following a single dose), this efficacy improves dramatically with monthly dosing, proving that a consistent, monthly drug regime can be highly effective. A 2000 study in Veterinary Therapeutics examined the efficacy of Revolution flea control (Selamectin insecticide) using dogs and cats from single and multiple animal households. Animals were given the dose recommended on the Revolution packet (6mg/kg) monthly for 2 months (last dose, day 60) and flea numbers were found to be reduced by 90.6%, 97% and 98% versus the baseline adult flea levels taken on day 0 (just prior to first treatment) on days 30, 60 and 90. A 2000 study published in Veterinary Parasitology examined the effect of selamectin on fleas in a simulated, carpeted home environment. Fleas were applied to dogs and cats 3 - 4 weeks before the selamectin was dosed to give them time to breed and multiply to large numbers within the house environment. The aim of the study was to see how well the selamectin would perform in a simulated 'real life' infestation (not just in a lab). The animals were treated with three monthly doses. The results found that dogs showed a >99% flea reduction from day 14 onwards and cats showed a >92% reduction on day 29, which increased to 99% from day 44 onwards (until the end of the study). A 2008 study published in Veterinary Therapeutics compared the efficacy of Spinosad and Selamectin. The animals were divided into two groups and given monthly doses of one of the flea control medications for 3 treatments as per label instructions. At day 15 after the initial treatment, the % flea kill was 90.9% for Selamectin and at day 90, the % flea kill for Selamectin was 98.9%. Another 2000 article in Veterinary Parasitology examined the effectiveness and safety of Revolution flea control when used against both fleas and heartworms. Some of the animals studied had pre-existing signs of flea allergy dermatitis (FAD). Study animals were dosed with Selamectin (Revolution for pets) as per the label dosing regimen (6mg/kg topically every 30 days) for 2 months (days 0, 30 and 60). Similar to the situation described in the 2000 study in Veterinary Therapeutics, the efficacy of flea kill was found to be initially high, but also to improve with subsequent monthly dosing with 92.1%, 99% and 99.8% flea kills seen in dogs on sampling days 30, 60 and 90 and 92.5%, 98.3% and 99.3% flea kills seen in cats over the same period. The signs of flea allergy dermatitis were also observed to improve greatly with selamectin dosing and, with regard to heartworm, 397 dogs were placed in heartworm endemic areas and given Revolution prophylaxis and none were found to have developed heartworm positive tests over 6 months of treatment. Just over 1000 animals (dogs and cats) were studied in this test, ranging from 6 weeks to 19 years of age and no serious adverse reactions were seen. Fleas are still highly susceptible to Revolution flea control (resistance has not yet developed): It is important that the fleas are not resistant to the flea control product you are using, otherwise no fleas will be killed by it. Since Revolution flea control has been around awhile and is used so heavily, one would expect fleas to now be developing resistance to the product. Incredibly, though, this has not occurred. What does Revolution flea medication do to immature flea stages (eggs, larvae, cocoons): Revolution flea control kills flea larvae in the environment. Flea larvae in the host animal's environment become poisoned when dander (skin flakes) or flea feces (their natural diet) coated with selamectin drop into the environment from the host animal's skin. The flea larva consumes the insecticide through actual consumption of the treated dander (or flea faeces). Revolution also renders flea eggs non-viable. A 2000 article in Veterinary Parasitology examined the effects of Selamectin on adult and immature flea stages in dogs and cats. The study confirmed that Revolution flea control greatly inhibits flea egg viability (>92% reduction in flea egg hatch), larval development (inhibited by more than 95% in dogs and cats) and the emergence of adult fleas. The study also looked at the effect of medicated dander and debris shed into the environment by treated pets. Flea eggs and larvae were incubated on the dander and debris (flea feces, pet hair, scales) taken from treated dogs. The treated debris and dander was found to greatly inhibit flea egg hatching (>96%), have a high larval killing effect (>98%) and prevent the development of larvae to adults (>99%). How does Revolution flea control affect adult flea feeding times?: A 2008 study, published in the journal of Veterinary Parasitology, examined the effect of various flea control products, including Revolution flea control, on flea feeding times and blood consumption quantities. The study found that, of the products studied, only Nitenpyram (Capstar) and topical Selamectin (Revolution for pets) caused significant reduction in blood consumption by fleas. An early effect of macrocyclic lactone toxicity in parasites is to inhibit feeding and this is borne out by this study. Reducing flea feeding times makes Revolution flea control highly useful in animals suffering flea allergy dermatitis and helpful in the prevention of flea-transmitted diseases. Revolution flea control can help rid a house of an established flea infestation as well as prevent new fleas from infesting a 'clean' house: A 2000 study published in Veterinary Parasitology examined the effect of selamectin on fleas in a simulated, carpeted home environment. Fleas were applied to dogs and cats 3 - 4 weeks before the selamectin was dosed to give them time to breed and multiply to large numbers within the house environment. The aim of the study was to see how well the selamectin would perform in a simulated 'real life' infestation (not just in a lab). The animals were treated with three monthly doses. The results found that dogs showed a >99% flea reduction from day 14 onwards and cats showed a >92% reduction on day 29, which increased to 99% from day 44 onwards (until the end of the study). These results show that Revolution is capable of controlling flea infestations on pets even if they come from homes with established flea populations. It is expected that such houses will soon become free of fleas if Revolution is continued monthly. Another aspect of the study examined the effectiveness of selamectin at preventing a suitable home environment from becoming infested with fleas (e.g. as might occur if pets visited a flea-infested out-of-home environment). Fleas were added to the coats of dogs and cats 24 hours and again 7 days after Revolution flea control was given and the animals were returned to the carpeted home environment. Flea counts on days 29, 44 and 60 showed a >99% flea reduction, confirming that the Revolution had prevented the newly applied fleas setting up a persistent environmental flea burden (had there been fleas in the environment, the animals would have become reinfested once the Revolution flea control wore off and fleas should have been found at days 44 and 60). 
3b) Revolution kills certain lice, certain mites and certain ticks. Revolution for cats and dogs is only officially labeled to kill certain species of mites, lice and ticks in dogs and cats. Off-label use, however, is common with Revolution and it has been used on a wide range of tick, lice and mite species with variable success. The mites and ticks Revolution flea control is registered to treat: Revolution flea control is registered to treat Sarcoptic mange (Sarcoptes scabiei), Otodectic mange (Otodectes cynotis) and the tick, Dermacentor variabilis. In some of these situations, a single dose of Revolution flea control will result in a complete cure, but in other cases, two or three monthly doses of Revolution may be needed for complete resolution. Revolution for pets is considered a drug of first choice for Sarcoptic mange (sometimes only a single treatment is needed, though 2 doses a month apart are generally given) and I have had excellent results with it personally (I have also treated ferrets with it and had no issues and good mange resolution). Cats with ear mites seem to respond really well to Revolution for pets too (often only a single dose is needed, as opposed to dogs who often need two doses to treat ear mites). Pfizer suggests that debris may still be present in the ears of animals with ear mites even after the mites have gone so it is recommended that ears be gently cleaned once the mites have been cured to remove the debris. In the case of ticks, Pfizer suggests giving a second dose two weeks after the first dose in situations of heavy tick infestation (to provide a fast knock-down). Monthly dosing can then resume. Articles confirming the success of Revolution flea control in treating indicated parasites: A Pfizer article in 2000 in Veterinary Parasitology looked at the effectiveness of Revolution flea control in dogs naturally affected with Sarcoptic mange. Dogs were treated monthly for two doses with either the label dose (6mg/kg) or twice that dose. The efficacy was assessed by doing mite counts (which is a little imprecise, given how difficult Sarcoptic mange is to scrape at the best of times) and also by assessing clinical improvement (which is a good way of assessing effect). By day 29 (just before the second dose was due) mite counts were already reduced by >93% and by days 44 and 60 of the study (after 2 doses), mite counts were reduced by 100% and clinical signs were resolving. The study showed that two doses of Selamectin, given at label rates (6mg/kg) were effective at treating Sarcoptic mange. A Pfizer article in 2000 in Veterinary Parasitology looked at the effectiveness of Revolution flea control in dogs and cats naturally affected with Otodectic mange (ear mites). Dogs and cats were treated with Revolution flea control at a dose range of 6-12mg/kg. Cats were given the treatment only once and dogs were treated either once or given a second dose at day 30. The different dosing is probably because a lot of studies show that ear mites in cats generally only need a single dose to resolve, whereas dogs seem to sometimes need a second dose. The efficacy was assessed by doing mite counts and also by assessing clinical improvement. The study found that Selamectin was capable of achieving a 100% mite reduction sometimes after a single dose, but certainly after a second dose given a month later. Another large study was done by the same company in 2000 and published in the August edition of Veterinary Parasitology. It looked at the efficacy of selamectin on dogs and cats with naturally acquired infestations of ear mites (dogs and cats) or sarcoptic mange (dogs only). 579 animals were studied in this trial, which took place in vet clinics. Dogs and cats were treated with Revolution flea control at a dose range of 6-12mg/kg. Cats were given only a single dose, but dogs received two doses at days 0 and 30. By day 30, >95% efficacy was recorded for sarcoptic mange cases, which increased to 100% by day 60 following the 30-day dose. By day 30, 94-100% of cats were cured of ear mites (Otodectes), whereas around 90% of dogs were cured by day 60. In 2006, the Journal of Small Animal Practice (JSAP) looked at 10 cases of 'localised' Sarcoptic mange (e.g. small pockets of mange). Selamectin was found to be an effective treatment. In 2003, Veterinary Parasitology looked at the efficacy of topical Selamectin in cats naturally infested with ear mites (Otodectes cynotis). Animals were treated with label doses (6mg/kg) at days 0 and 30 and parasites were found to be eliminated by day 17. These results show that a single dose may be all that is needed to treat cats for ear mites (though it is safe to give the second, monthly dose). A similar study was published in Germany in 2010 in Wiener Klinische Wochenschrift, looking at the efficacy of topical Selamectin in 16 cats naturally infested with ear canker (Otodectes cynotis). Animals were treated with a single dose of topical Revolution (the Stronghold brand as it is called in this country) at 6-17.3mg/kg. All cats tolerated the treatment well (there were no adverse effects noted, including local dermal effects) and all were negative for mites by days 14 and 28 after dosing. All showed clinical improvement and resolution as well. A 2005 study in Parasitology Research published by Bayer compared the efficacy and safety of imidacloprid 10% plus moxidectin 2.5% (Advocate) compared to Selamectin (Revolution flea control) in the treatment of dogs naturally infested with Sarcoptic mange or ear mites (Otodectes). Sarcoptes affected dogs were treated with label doses (6mg/kg for selamectin) of one of the respective products for two doses, one month apart, whereas Otodectes affected animals only received a second dose if their ears were still found to be positive for mites. Both treatments yielded 100% cure rate for Sarcoptic mange (by day 56, >96% of animals were clinically improved), whereas cure rates for Otodectes ear mites was 88.2% at day 56 (last dose given on day 30) for Revolution flea control (which was only slightly better than the cure rate obtained for Advocate). A second dose (if it wasn't given) or even a third (monthly) dose of Revolution was probably indicated to get a cure in these cases. A 2000 study in Veterinary Parasitology looked at the effectiveness of selamectin against two tick species, Rhipicephalus sanguineus and Dermacentor variabilis of dogs. The Revolution flea control was given weekly, 2-weekly and monthly at label doses (6mg/kg) to see which would protect the animals against weekly tick infestations (given in a lab setting). The Dermacentor variabilis ticks were also weighed in one version of the study to see how much engorgement (blood feeding) they'd managed to take in before dying (selamectin was found to reduce flea feeding). The studies found that weekly and 2-weekly dosing worked very well for both tick types with >96% efficacy reported for Dermacentor by 21 days and thereafter and 100% efficacy reported for Rhipicephalus after the same 3 weeks onwards. With monthly dosing, 90-100% efficacy was obtained for both tick types, but it took several months (several doses) to attain this level of control. Ticks were said to be well controlled for 2 weeks after each treatment. The study showed that monthly Revolution flea control would certainly help to control both species of tick, as per the label (with Dermacentor anyway), though it would seem that even more exceptional control might be achieved if the product was given 2-weekly, at least for the first couple of doses, anyway. Off-label use of Revolution flea control in the treatment of mites: Acta Veterinaria Scandinavica published a "review of the off-label use of selamectin (Stronghold/Revolution) in dogs and cats" in 2008. Aside from the labeled indications, the article reports that Selamectin will also treat notoedric mange, nasal mites (Pneumonyssoides caninum), the mite that causes "walking dandruff" in cats, dogs and rabbits (Cheyletiella spp.) and Neotrombicula autumnalis (a species of "chigger" mite or "harvest mite" found in the UK, Europe and Asia). The article reports that Revolution for pets is largely ineffective against Demodectic mange in cats or dogs. The following paragraphs are studies showing the off-label use of selamectin against a range of mite types in a range of animal species. Fur mites in mice: The Journal of the American Association for Laboratory Animal Science studied the use of selamectin for the treatment of mouse fur mites (Myocoptes musculinus) in 2008. Mice were treated with either Selamectin or Moxidectin and, though the results were thought to be faster with the Moxidectin (no adult mites found within 1 month and no egg-casings from 2 months on) than with selamectin (no adult mites found within 1 month and no egg-casings from 6 months on), both were found to be effective and safe. The study also incorporated cage changing as part of the treatment regimen (putting animals in clean, fresh cages after each treatment to reduce the chances of mice picking up eggs from the environment). Fur mites in rabbits: The Journal of the American Association for Laboratory Animal Science studied the use of selamectin for the treatment of rabbit fur mites (Leporacarus gibbus) in 2009, comparing it with an imidacloprid plus permethrin solution (Advantix). Both solutions cured the mites and were found to be 100% effective by day 13 after the single dose was given, however, Selamectin was found to be 100% effective by day 3 following treatment. Cheyletiella (walking dandruff) in cats: The Canadian Veterinary Journal looked at the efficacy of Revolution flea control at treating natural infestations of cheyletiellosis in 15 cats. Three doses of Revolution for cats (45mg vial) were given monthly and clinical signs resolved by day 60 with no recurrence noted when the cats were rechecked a year later. No side effects were noted in the cats. Cheyletiella (walking dandruff) in rabbits: In 2008, Acta Veterinaria Scandinavica looked at the effectiveness of Selamectin and Ivermectin against rabbit cheyletiellosis (Cheyletiella). This was a retrospective study, looking at the records of 53 rabbits some of which were treated with 2 to 3 subcutaneous injections of ivermectin (200-476ug/kg) around 2 weeks apart; some of which were treated with huge doses of injectable (>600ug/kg) ivermectin, followed up with large oral doses of ivermectin (>600ug/kg given every 10 days for 3-6 doses) and some of which were treated with 1-3 doses of selamectin given 2-4 weekly at doses ranging from 6-20mg/kg. Around 81% of rabbits were found to be improved with the selamectin topicals and the ivermectin injections, whereas rabbits that received the oral ivermectin didn't resolve as well. The study shows that injectable ivermectin (not oral) and topical Selamectin both show promise for this condition. A more-precise study on selamectin's effectiveness at treating rabbit cheyletiellosis was published in 2008 in Veterinary Dermatology. 23 rabbits with clinical cheyletiellosis were given selamectin at 12mg/kg, topically for a single dose. All rabbits resolved and were found negative for mites and eggs. No side effects were noted in treated rabbits. Ear mites (ear canker) in rabbits: The Journal of the American Veterinary Medical Association in 2003 looked at the effectiveness and safety of spot-on selamectin in the treatment of rabbits with natural infestations of rabbit ear mites (Psoroptes cuniculi), otherwise known as ear canker. The rabbits were treated monthly for two doses with either the label dose (6mg/kg) or a dose that was three times that dose (18mg/kg). Some rabbits just had a single dose given of either 6mg/kg or 18mg/kg (to see if one dose would be enough). The efficacy was assessed by doing mite counts and also by assessing clinical improvement. All treated rabbits were found to be free of mites from day 7 onwards and no clinical side effects were observed. In 2007, Veterinary Dermatology looked at the effectiveness of Selamectin in treating naturally-acquired infestations of psoroptic mange (ear mites) and sarcoptic mite (Sarcoptes scabiei) infestation in rabbits. Rabbits were given Selamectin at doses ranging between 6-10mg/kg. Improvement was ascertained using both mite scrapes (looking for mites or eggs) and through the assessment of clinical signs. Both types of mites were found to be significantly reduced after this treatment, compared to control groups, suggesting that Selamectin would be effective for rabbits infested with such mites. Mange in guinea pigs: The International Journal for Parasitology in 2011 looked at an outbreak of guinea pig mange mite Trixacarus caviae in an animal petting facility in Japan. Selamectin was given topically at doses of 13.6-18.75mg per guinea pig (guinea pigs weigh roughly a kilo or just over). A single dose was given and the guinea pigs resolved, however, a second outbreak occurred soon after suggesting that some animals may have remained carriers after the last treatment. The Selamectin was therefore given twice (on days 0 and 28) at lower doses than initially used (5-7.5mg/kg) and all of the guinea pigs resolved. Nasal mites in dogs: In 2004, the Journal of the American Animal Hospital Association published a study on the treatment of canine nasal mites (Pneumonyssoides caninum) using selamectin. The selamectin (Revolution flea control) was given at doses of 6-24mg/kg topically for three doses given 2 weeks apart. All treated dogs were 'cured' of their mites (except that in order to determine this for sure, the animals were euthanased and post-mortemed for this study). The Journal of Small Animal Practice also looked at two clinical cases of nasal mite in the UK in 2008. The animals had presented for sneezing and nasal itching. The two dogs both recovered with Selamectin. I have personally seen a case of nasal mite in a labrador in Sydney, which also resolved with macrocyclic lactone therapy (Ivermectin). Skin mites in canaries: The Annals of the New York Academy of Sciences in 2008 published a study on the treatment of canaries naturally infected with chicken or poultry mite (Dermanyssus gallinae) in 2008. Three types of macrocyclic lactone drugs were trialled, including ivermectin, selamectin, and moxidectin and all three were found to be equally effective at removing mite infestations in affected birds. Revolution flea control will not treat Demodex very well: In 2009, Acta Veterinaria Scandinavica looked at the treatment of Demodex gatoi, a contagious form of demodectic mite which lives outside of the hair follicles of feline pets and causes intense itchiness in cats. 21 infested cats from 6 multiple-cat households were studied. The study noted improvements with Amitraz, 2% lime sulfur dips and long-term oral ivermectin but found that Selamectin, injected ivermectin and imidacloprid-moxidectin were ineffective. Off-label use of Revolution flea control in the treatment of ticks: Revolution is only licensed to prevent the tick: Dermacentor variabilis. The following paragraphs are studies showing the off-label use of selamectin against a range of tick types in a range of animal species with variable results. Dog ticks: A 2000 study in Veterinary Parasitology looked at the effectiveness of selamectin against two tick species, Rhipicephalus sanguineus and Dermacentor variabilis of dogs. The Revolution flea control was given weekly, 2-weekly and monthly at label doses (6mg/kg) to see which would protect the animals against weekly tick infestations (given in a lab setting). The Dermacentor variabilis ticks were also weighed in one version of the study to see how much engorgement (blood feeding) they'd managed to take in before dying. The studies found that weekly and 2-weekly dosing worked very well for both tick types with >96% efficacy reported for Dermacentor by 21 days and thereafter and 100% efficacy reported for Rhipicephalus after the same 3 weeks onwards. With monthly dosing, 90-100% efficacy was obtained for both tick types, but it took several months (several doses) to attain this level of control. Ticks were said to be well controlled for 2 weeks after each treatment. The study showed that monthly Revolution flea control would certainly help to control both species of tick, as per the label (with Dermacentor anyway), though it would seem that even more exceptional control might be achieved if the product was given 2-weekly, at least for the first couple of doses, anyway. Rabbit ticks: A 2011 study published in Parasitology Research looked at whether a single dose of Selamectin at 6mg/kg would be effective at preventing rabbits from becoming infested with the adults, larvae or nymphs of the tick, Haemaphysalis concinna and, if so, for how long this effect would last. Rabbits were given the Selamectin at day 0 and at days 1, 8, 15, 22 and 29 were exposed to adult, nymph and larval ticks. 100% of larval ticks were killed from days 1-15 (2 weeks) with a 95% kill rate at day 22 and a 76.7% kill at day 29. Nymphs, likewise, suffered 100% mortality at days 1-15 with an 85% kill at day 22 and a 65% kill at day 29. Adult ticks were less susceptible, with 100% killed on day 1, 95% on day 7, 85% on day 15 and lower levels thereafter. The results show that Selamectin may be very useful at preventing rabbits from being infested with this species of tick, but that, in heavy environmental tick burdens with repeated risk of reinfestation, rabbits may need to be dosed 2-weekly to remain tick free. Revolution flea control will not work on Ixodes ticks: An article in Veterinary Therapeutics in 2002 looked at the efficacy of Selamectin against Ixodes ricinus, a major tick vector of Lyme disease in Europe. Selamectin, at label doses was not found to be very effective at killing Ixodes ricinus ticks (only 10-31% effective) and nor was it found to repel them. This study has implications for Australia where the paralysis tick, Ixodes holocyclus is a huge problem on the East coast. Selamectin is not considered to be a useful protectant against this species of tick and is not marketed as such. Off-label use of Revolution flea control in the treatment of lice: Revolution is not licensed to treat lice. The following paragraphs are studies showing the off-label use of selamectin against a range of lice types in dogs and cats with good results. Dog lice: In 2005, the Journal of the American Animal Hospital Association looked at the effectiveness of selamectin against natural infestations of sucking lice in dogs (Linognathus setosus). The animals were given a single dose of Revolution flea control at just above label doses (7.9mg/kg). Selamectin was found to be 100% effective at treating the lice infestations. In 2003, Veterinary Record looked at the effectiveness of selamectin against biting lice in dogs and cats (Trichodectes canis and Felicola subrostratus respectively). The animals were given a single dose of Revolution flea control at label doses (6mg/kg). No adverse effects were seen in the treated animals and Selamectin was found to be 100% effective at treating the lice infestations. Cat lice: In 2003, Veterinary Record looked at the effectiveness of selamectin against biting lice in dogs and cats (Trichodectes canis and Felicola subrostratus respectively). The animals were given a single dose of Revolution flea control at label doses (6mg/kg). No adverse effects were seen in the treated animals and Selamectin was found to be 100% effective at treating the lice infestations. Off-label use of Revolution flea control in the treatment of nasal bots (Oestrus ovis) in cats:: A case study published in the Australian Veterinary Journal investigated a case of nasal bot fly seen in a cat. The cat presented with nasal signs and sneezing. It resolved within 3 weeks after treatment with ivermectin and selamectin.
3c) Revolution prevents heartworm but does not kill already-established adult worms or their larvae. Revolution for dogs and cats is used to prevent animals from catching heartworm. It does this by effectively killing the stage 3 larvae (L3) that are inoculated into the blood of dogs and cats via the bites of infected mosquitoes. A 2000 article published by Pfizer in Veterinary Parasitology studied the prevention of heartworm infestations with Selamectin over 6 different studies using dogs and cats. Dogs were infected with L3 heartworm larvae 30 days, 45 days or 60 days before a single topical dose of Selamectin was given (6mg/kg). Cats were infected with L3 heartworm larvae 30 days before the single topical dose of Selamectin was given at label doses (6mg/kg). Some animals were even shampooed between 2 and 96 hours after treatment with revolution for pets (cats that were bathed were bathed at 24 hours after dosing). According to the abstract, "Selamectin was 100% effective in preventing heartworm development in dogs when administered as a single topical dose of ... 6mgkg at 30 days after infection, ... 6mgkg(-1) at 45 days after infection, or 6mgkg at 60 days after infection. Selamectin was 100% effective against heartworm infections in cats when administered as a single topical unit dose of 6mgkg." Bathing did not impact the effectiveness. Revolution will not kill adult heartworms very well (so it is not really effective in the treatment of heartworm disease) and nor will it kill the offspring of those adult worms (called first stage larvae or microfilariae) which circulate in the blood of infected animals waiting for mosquitoes to come along and take them up. In order to prevent heartworm, Revolution for pets must be given monthly, year-round. You can possibly miss a dose here and there and the Revolution will still be able to kill the L3 larvae (which take many months to mature into adults) and thereby prevent heartworm disease, but it is not recommended (you certainly do not want a miss a dose by over 2 months). The Pfizer literature states that the "efficacy of macrocyclic lactones decreases below 100% in dogs, if first administered >2 months after exposure to infective L3 larvae" (i.e. suggesting that it is not ideal to miss doses). For this same reason, it is recommended that puppies and kittens in heartworm endemic areas be started on heartworm prevention (e.g. Revolution flea control) within 2 months of being born (e.g. when under 8 weeks old), otherwise any L3 larvae they caught in the early days of life (e.g. puppies can be bitten by mosquitoes too) might not succumb to heartworm prevention drugs like selamectin. It is always advised that an animal be tested for heartworm infection prior to starting it on Revolution flea control for the first time. This is for two reasons. The first is safety. There is concern that an adult worm or its microfilariae may die after treatment, resulting in a potentially fatal anaphylactic reaction or pulmonary thrombosis. It should be noted, however, that because selamectin is not too effective against adult heartworms or their microfiliariae, the risks of this are very low, though still possible (Revolution for pets has been tested on heartworm positive dogs and cats and those studies showed that it was safe to give to such animals). Also, knowing that an animal does or does not have heartworm before a preventative product is given is useful in confirming that the preventative product still works. Vets and drug companies live in fear of parasites becoming resistant to vet drugs like selamectin. Should an animal be discovered to be positive for heartworm after the Revolution preventative has been given, questions will undoubtedly be raised as to whether the animal had heartworm already (which prior testing and testing again 3-4 months after starting treatment will confirm or refute) or whether the drug actually failed to work (which would be a BIG problem). Be aware that heartworm tests used in vet clinics generally detect antigens made by adult worms and the microfilarial larvae shed by them. Animals will test negative if infested with L3, L4 or juvenile adult worms that haven't matured. Therefore, though it is important to have a heartworm test performed prior to starting heartworm prevention, a negative result may not 100% indicate that the animal is negative (it could still have L3s and L4s and new adults that are slightly more resistant to heartworm drugs and which may survive them). Pfizer advises performing a second heartworm test 3-4 months after starting Revolution to confirm the negative result. It is suggested that positive animals be treated to rid them of heartworm adults prior to starting Revolution heartworm prevention. Since the removal of heartworms from cats is considered highly risky, depending on their numbers and the presence or absence of disease signs, some vets will start heartworm affected cats on Selamectin immediately to prevent them from becoming infested with more worms and not treat them for the adult heartworms at all (this is up to vet discretion though so talk to your vet if this is the situation you are in). A 2005 article in Parasitology Research looked at the safety aspects of giving Revolution flea control to cats that were already heavily infested with adult heartworms (Dirofilaria immitis). The study also looked at the safety of Advocate (10% imidacloprid + 1% moxidectin topical) in the same animals. 35 cats with proven heartworm infestation (adult heartworms were established in their hearts) were studied. 8 of them received the Revolution at label doses monthly for 3 doses. No side effects were noted and the adult worms were not killed. The off-label use of Selamectin in red pandas: In 2012, Parasitology International examined the ability of selamectin to prevent heartworm infestation in red pandas in China. The prophylaxis program effectively prevented red pandas from becoming infected with heartworm (Dirofilaria immitis) and developing signs of heartworm disease (dirofilariasis). The off-label use of Selamectin with regard to Dirofilaria repens (a relative of heartworm): A 2008 review by Acta Veterinaria Scandinavica also notes that Selamectin is a useful preventative against infestation with Dirofilaria repens. The journal, Acta Veterinaria Hungarica in 2010 examined the effectiveness of selamectin at treating animals with already-established infestations of a subcutaneous parasite (related to heartworm) called Dirofilaria repens. Selamectin, though effective at killing stage 3 Dirofilaria larvae and thereby preventing infestation with heartworm (Dirofilaria immitis) and its skin-dwelling relative, Dirofilaria repens, is not generally considered to be highly effective at treating adult Dirofilaria species or their stage 1 larvae (termed microfilaria). This study sought to confirm or refute this claim. Animals infested with adult Dirofilaria repens and with circulating microfilariae (stage 1 larvae) were treated with 2-weekly or monthly doses of Selamectin. The study lasted almost a year, after which 65% of animals showed no stage 1 larvae (i.e. were supposed to be cured), but the rest did. This indicates a response, albeit quite limited, by established Dirofilaria repens infestations to Selamectin. The drug would not be a first line of treatment against this parasite in its adult form.
3d) Revolution kills various worms all over the body (including bladder, lung and intestinal tract), except the brain. Revolution for cats and dogs is only officially labeled to kill certain species of feline intestinal worms, these being intestinal hookworm (Ancylostoma tubaeforme) and roundworm (Toxocara cati). Off-label use, however, is becoming more common with Revolution and it has been used on a wide range of intestinal, lung, bladder and other internally-dwelling worm species with variable success. Article confirming the success of Revolution flea control in treating indicated parasites: A 2000 Pfizer study published in Veterinary Parasitology examined the safety and effectiveness of selamectin at treating indicated gastrointestinal nematodes (roundworms and hookworms) in cats. Cats with natural infestations of such worms were given selamectin at label doses (6mg/kg) topically at monthly intervals for 3 doses. On day 30 (after only one dose and before the next dose), roundworms (Toxocara felis) were already reduced by 99.6-100% and on day 60 (just before the third dose), roundworms were already reduced by 99.9%-100%. Hookworms showed a similar effect with numbers reduced by 98.3% by day 30 and 100% by day 60 (just before the third dose). Off-label use of Revolution flea control against other parasitic worms: Revolution for pets has been used to treat wide range of animal species against intestinal, lung, bladder and other internally-dwelling worm species with variable success. Roundworms in dogs: A 2000 article published in Veterinary Parasitology looked at the effectiveness of Selamectin against roundworm (ascarid) infestations in dogs. The study was particularly targeted at the control of Toxocara canis and Toxascaris leonina species of canine roundworm and populations of dogs were used that either had "lab-induced" infestations with these parasites or natural infestations. Dogs were given selamectin at label doses (6mg/kg) topically at monthly intervals for 3 doses. For the lab acquired worm infestations, there was an 84.6% reduction in worm numbers after just one dose. After a second dose (given a month later) the reduction was 91.3% and after a third dose (a month later again), the reduction was 97.9%. In field studies (natural infestations occurring outside the lab environment) egg counts were reduced by 95.5% 30 days after a single dose of Revolution flea control was given (just before the next dose was due) and by 94.0% 30 days after the second monthly dose was administered. No adverse effects were noticed in the dogs. A 2000 Pfizer study published in Veterinary Parasitology examined the effectiveness of selamectin at treating and preventing Toxocara canis roundworms (and fleas) in pregnant or lactating dogs and their pups. Topical Revolution flea control was given to the dogs at 40 days and 10 days before birthing and again at 10 and 40 days after birthing (after whelping). Label doses of 6mg/kg (ranging up to 12mg/kg) were used on the mothers (the Revolution for pets was not applied to the puppies directly) and no adverse side effects of the treatment were observed in either the treated dogs or their puppies. Worm burdens were reduced by 99.7% in the mothers compared to control dogs (which didn't get the Revolution flea control) and 98.2% in the pups. Fleas were reduced by 99.8% in mothers and pups compared to controls. Intestinal nematodes in rhesus macaques: A 2008 study published in Veterinary Parasitology looked at the effectiveness of several drugs, Selamectin among them, for the treatment of gastrointestinal nematodes in rhesus macaques in China. Reductions in egg counts were found to be around 99.4% for Selamectin and Ivermectin, suggesting that these off-label treatments are quite effective. Revolution for pets may or may not control pinworms in rats and mice: In 2006, the Journal of the American Association for Laboratory Animal Science looked at the safety aspects and effectiveness of treating rats and mice for pinworms (Syphacia muris in rats and Syphacia obvelata in mice), which are not uncommon infestations seen in lab animals and rodent breeding facilities. Mice and rats with naturally acquired pinworm infestations were given either 0.6mg/kg Selamectin or 6mg/kg Selamectin or fenbendazole. No side effects were noted in the rodents using Selamectin, but neither did it have an effect on the pinworms. Only the fenbendazole was proven effective. In contrast with this, a 2009 study published in Experimental Parasitology found Selamectin to be quite effective at treating natural infections of Syphacia muris pinworms in rats. The rats were given a single dose of Selamectin orally in this study and by day 7 (when the rodents were necropsied) it was found that 100% of the adult pinworms had been eliminated (anal egg counts were reduced by 98.77% by day 6 after dosing). A 2008 study published in the Polish Journal of Veterinary Sciences also looked at this issue of rat Syphacia muris infestation, using topical selamectin. A single dose of 6mg/kg selamectin was given topically to rats naturally affected with pinworms. The drug was found to only be 40.7-63.3% effective at eliminating pinworms from rats with female rats showing more favourable results than male rats. It seems that the Selamectin may need to be given orally (higher risk of side effects and certainly against the manufacturer's recommendation) to treat pinworms in rats. Lungworms in cats: A 2005 article in Veterinary Parasitology looked at feline lungworm (Aelurostrongylus abstrusus) infestations in cats from Italy, documenting the clinical signs of disease and potential modalities of treatment. The cats, all below 12 months of age, presented with signs of coughing, breathing difficulty and weight loss. The study showed that a single dose of ivermectin was ineffective, that a single dose of selamectin (6 mg/kg) was effective at treating the lungworm in one of three cases, but that daily fenbendazole (50 mg/kg) given for just over 2 weeks was effective in all 4 cats given it. It should be noted that different results may have been achieved had several doses of selamectin (or ivermectin for that matter) been given in the study. The dose does suggest some potential for Selamectin to be given off-label as a treatment for feline lungworm. A 2008 review of off-label use of Selamectin published in Acta Veterinaria Scandinavica also mentions that Selamectin may be used as a treatment for lungworm in cats (Aelurostrongylus abstrusus). A related drug, Doramectin, has been found to accumulate in the lungs to high levels, making it a useful potential treatment for feline lungworm disease. Bladder worms (Trichosomoides crassicauda) in rats: In 2008, the Polish Journal of Veterinary Sciences examined the effect of topical selamectin at treating bladder worm infestations in lab rats. These worms live in the epithelial lining of the bladder in small tunnels they excavate themselves, causing hyperplasia (thickening) of the bladder wall and inciting chronic, painful bladder inflammation. A single dose of selamectin at 6mg/kg was applied topically to affected rats and of the 12 treated, 7 made a full recovery with just the one dose (the others may have resolved had several doses been given over time - further studies are needed here). Worms Revolution flea control will not treat: Revolution flea control is not effective against trematodes (flukes) or cestodes (tapeworms). Selamectin will not treat adult heartworm (Dirofilaria immitis) infestations and nor will it treat established infestations with a range of other adult filarial worm species including: Dirofilaria repens, Dirofilaria dracunculoides or Acanthocheilonema reconditum. This is confirmed in a 2011 German article published in Parasitology Research titled: "Diagnosis of imported canine filarial infections in Germany 2008 - 2010."
4) Revolution for dogs and cats - how to use Revolution spot-on parasite control (includes information on storage and dosing). Revolution flea control spot-ons are given to dogs and cats over weaning age (over 6 weeks of age in dogs and 8 weeks of age in cats). A full applicator of Revolution flea control is applied directly to the dog or cat's skin, usually between the shoulderblades (where it can not be licked off). The particular dose (size of applicator) chosen depends on the species and size of the animal. Animals are generally given a dosage volume every month that is equivalent to an effective dosage rate of 6mg/kg Selamectin. Revolution for puppies and kittens up to 2.5kg (Revolution mauve packet) - each monthly dose contains 15mg of Revolution for pets in 0.25ml of a 60mg/ml liquid. Revolution for cats 2.6-7.5kg (Revolution blue) - each monthly dose contains 45mg of Revolution for pets in 0.75ml of 60mg/ml liquid. Revolution for small dogs 2.6-5kg (Revolution purple/lavender) - each monthly dose contains 30mg of Revolution for pets in 0.25ml of 120mg/ml liquid. Revolution for dogs 5.1-10kg (Revolution brown) - each monthly dose contains 60mg of Revolution for pets in 0.5ml of 120mg/ml liquid. Revolution for dogs 10-20kg (Revolution red) - each monthly dose contains 120mg of Revolution for pets in 1ml of 120mg/ml liquid. Revolution for dogs 20-40kg (Revolution teal) - each monthly dose contains 240mg of Revolution for pets in 2ml of 120mg/ml liquid. Revolution for dogs 40-60kg (Revolution plum) - each monthly dose contains 360mg of Revolution for pets in 3ml of 120mg/ml liquid. If the dog you are treating is over 60kg or the cat you are treating is over 7.5kg, then you will need to use a combination of tubes to treat it. The dose you are aiming for is 6mg/kg of the active ingredient (for example, an 80kg dog will need a 480mg topical dose - i.e. one of the 360mg plum tubes and one of the 120mg red tubes). Revolution for pets is generally available in packs of 3 (to last one animal 3 months) or 6. Revolution is available at vet clinics and can usually be purchased over the counter. The cap of the Revolution flea control applicator needs to be pressed down hard onto the rest of the applicator (where the reservoir of solution is) to put a hole in the applicator. The fur is parted and the Revolution flea control solution is applied directly to the skin between the shoulder blades. Apply the entire content of the Revolution flea control vial to the one spot on the skin (not multiple spots). The skin should be clean and dry. Do not apply the solution to wet skin. Avoid applying the solution to skin that is broken or inflamed. The alcohol content of the Revolution flea control will irritate such skin. NEVER massage the solution into the skin with your fingers. Do not allow pets to the lick the solution (usually they can't reach behind their shoulders, but some can). Animals do not usually ingest much of the solution if they lick it because the taste is so bad (cats will react by salivating and frothing at the mouth or even vomiting), however, excessive ingestion can be toxic, so owners need to be mindful of not letting their animal lick. The product is considered to be waterproof 2 hours after application (after 24 hours, in cats). Bathing and shampooing the animal 2 or more hours after treatment (24 hours for cats) will not affect the product's effectiveness, though I always advise my clients to not bathe animals for a couple of days after giving any spot-on product, just to be sure. Revolution flea medicine is designed to be given monthly. It can be given 2-weekly if needed, though this is uncommon. The main indication would be in cases of high level tick infestation (a couple of doses are given 2-weekly, followed by monthly doses). Note that Revolution flea control does not kill paralysis tick (Ixodes holocyclus). If using the product to control heartworm, it is important that the product BE GIVEN MONTHLY and that no doses are missed. If using the product to remove ear mites, Sarcoptic mange or lice, a single dose may be all that is needed, however, sometimes animals need two doses (given a month apart) to achieve complete control of these parasite creatures. Revolution flea control can be used with other commonly used products and medications including: all-wormers, vaccines, antibiotics, anti-inflammatories, shampoos and some other flea control products (e.g. Lufenuron). Caution if using it with products that rely on and compete for p-glycoprotein transport molecules (e.g. ketoconazole). Do not use the product in debilitated, sick or badly underweight cats or dogs. The product is considered safe to use in breeding animals that are pregnant or lactating or that are about to be bred from. Although Selamectin is considered to be minimally harmful and well tolerated by collie breeds and their crosses (those with the ABCB1 gene defect), owners should monitor their pet carefully for any side effects the first few times they use the product on their pet (signs are usually neurological). Also,owners can get their dogs DNA-tested these days to check if their breed has the genetic defect at all (if the defect is not present, then collie breeds can usually receive such drugs without worry). Be aware that some animals may lose their hair at the site of Revolution flea control application. This is generally short-lived and the hair will usually grow back. Animals will also have sticky clumping of the hair at the site where Revolution flea control is given. Be aware that more severe signs (though rare) can be encountered, including gastrointestinal signs (vomiting, diarrhea, inappetence), lethargy (especially in cats), drooling and muscular tremors. Severe neurological signs, including seizures, have on very rare occasions been known to occur, as have side effects commensurate with allergic reaction (redness, hives, itchiness of the skin). Death has also occurred on rare occasions. All animals should be tested for heartworm infestation prior to starting them on Revolution prevention. Animals should be retested after 3-4 months to ensure that they were not harboring "almost-adult" heartworms when the Revolution flea medicine started. All canine and feline pets in the household should be treated at the same time with Revolution flea control products. This is because untreated pets can act as reservoirs for the flea life cycle. Treatment should begin in Late Winter or Early Spring at the start of the flea season. Treatment can, however, start any time fleas are noticed on our canine and feline friends. If flea numbers are very high in the environment, the Revolution flea treatment, used properly, will eventually result in decent overall flea control, due to an overall effect on adult fleas as well as the flea larvae and flea eggs in the environment. Treating the environment for fleas (flea bombs, vacuuming, steaming) is also beneficial. Revolution flea control can also be given to clean (flea and mite-free) animals to protect them when they enter a flea-risk or mite-risk environment (e.g. dog show, vet, groomer, dog training, friend's house containing fleas, nature reserve, fox or wombat habitat and so on). This will prevent the animal from catching fleas or mites and bringing these back to your house. Apply Revolution flea control about 2-3 days (no less than 24 hours) before going to the flea or mite risk environment. Though the product is not considered highly dangerous if you get it on your hands during application, it is recommended that you wash your hands thoroughly with soap and water to remove it. Some people may experience mild to severe skin irritation from the product. Never get Revolution flea control in your eyes. It is very irritant. Should you get it in your eyes, wash your eyes copiously with an eye irrigation solution, saline or just plain water if that's all you have. Seek medical advice. Caution Flammable: Revolution flea control is flammable. Never use it near open flames (including cigarettes), sparks or other sources of heat/flame that could result in ignition. For safety, Revolution flea control should be kept out of reach of children. The product is irritant to the eyes and potentially toxic if ingested or inhaled. Revolution for pets should not be consumed. Revolution flea control must be stored well away from food, drink or animal food as contamination of these products with Selamectin will render them unfit (unsafe) for human or animal consumption. Oral consumption of selamectin has been thought to damage fertility and harm developing fetuses and high doses orally have been known to cause damage to internal organs. Revolution flea control should be stored at room temp (below 30C), in a cool, dry place, well away from direct sunlight since UV light deactivates it. The product should not be exposed to high temperatures or sources of flames or ignition as the product is flammable and can catch light. Information sheets: https://animalhealth.pfizer.com/sites/pahweb/US/EN/Documents/Species%20Landing%20Page%20pdf/Dog/REVOLUTION_PI.pdf http://www.pfizeranimalhealth.co.nz/sites/pfizeranimalhealth/PAH%20Document%20Library/Pfizer%20MSDS%20-%20REVOLUTION%20for%20Puppies%20%20Kittens.pdf
5) How long does Revolution work for once it has been given? Does it really last the full month? The company that manufactures Revolution flea control topical states that the product will maintain its effectiveness for 1 month following dosing (after which the next dose is due). Whether this actually occurs to a moderately high degree (>90% flea kill at 30 days, as claimed by Pfizer, the manufacturer) or a really high degree (>95% flea kills at 30 days), however, depends on the study you look at. It might also depend on the "strain" of flea the study is utilizing (for example, the 2005 study, mentioned next, was conducted on the KS1 strain of flea). I am not sure if certain "strains" of flea are more susceptible to any one flea control chemical, however, it is always possible. In a 2005 study published in Veterinary Therapeutics, cats were treated with either Fipronil, Imidacloprid or Selamectin. All products achieved a >95% flea kill by 24 hours of dosing. Fleas were re-introduced to the study cats at day 7 (to mimic a reinfestation event) and all three formulations showed a similar effect, with a 68.4% flea kill at 6 hours post flea-introduction and a massive (highly effective) 99.4% flea eradication at 24 hours. At day 21 and then again at day 28, more fleas were introduced and there was no appreciable kill of those fleas within 6 hours. The new fleas did die, but they took longer (up to 2 days were allowed before the % flea kill was determined). The study found that, at the 28-day mark, selamectin was still achieving a 99% flea kill within 2 days of fleas being re-introduced to the treated pet. Fipronil, in contrast, only achieved an 86.4% efficacy in that time and Imidacloprid only achieved a 72.6% flea kill at the 28-day flea-re-introduction mark. Of the three, selamectin seemed to maintain its effect the best in that study and have the highest residual activity. Another study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. Cats were infested with fleas 2 days before the Revolution flea control was administered at label doses and then fleas were applied to the treated animals weekly for 4 doses (mimicking flea reinfestation events that might occur in a real household situation). Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after Revolution dosing, the % kill was only 69.4%, but this improved to 99% by 24 hours. After the fleas were reintroduced at day 28 (just before the next dose of Revolution was due) the study showed that 12 hours after flea introduction, the % kill was 57.3%, but this improved to 87.1% (in one version of the study) or 95.3% (in another version of the study) 24 hours after flea introduction and then 98.3% 48 hours after flea reintroduction. The efficacy was still very high just before the next dose of Revolution was due, it just took slightly longer to kill all the fleas. A 2001 study published in Veterinary Record looked at a similar thing. Animals were dosed with either selamectin, fipronil or imidacloprid and flea populations were re-introduced at days 7, 14, 21, 28 and 35 following dosing. In this study, all three treatments maintained exceptional efficacy for the full month with Selamectin (Revolution flea control) showing an 81-100% range of flea kill efficacy 48 hours after fleas were re-introduced on the 28th day of testing. The study showed no appreciable difference between the three spot-on products. Revolution flea control seems to improve its efficacy with repeated monthly use - very cool: Quite a few studies have been done whereby Revolution has been given to animals monthly over several doses in household situations. These studies show that, while Revolution achieves a good effect against fleas (e.g. in a flea infested household) following the first dose (>90% effectiveness at 30 days, following a single dose), this efficacy improves dramatically with regular monthly dosing. This suggests a cumulative effect (perhaps higher levels of Revolution are maintained in the skin after several doses) or perhaps the effect is due to Revolution flea control's other lethal effects on flea larvae and flea eggs in the environment (i.e. improved environmental flea control). Either way, such studies demonstrate that a consistent, monthly drug regime can be highly effective at controlling fleas in the case of Revolution. A 2000 study in Veterinary Therapeutics examined the efficacy of Revolution flea control (Selamectin insecticide) using dogs and cats from single and multiple animal households. Animals were given the dose recommended on the Revolution packet (6mg/kg) monthly for 2 months (first dose - day 0, last dose - day 60) and on days 30, 60 and 90 flea numbers were found to be reduced by 90.6%, 97% and 98% versus the baseline adult flea levels taken on day 0 (just prior to first treatment). A 2000 study published in Veterinary Parasitology examined the effect of selamectin on fleas in a simulated, carpeted home environment. Fleas were applied to dogs and cats 3 - 4 weeks before the selamectin was dosed to give them time to breed and multiply to large numbers within the house environment. The aim of the study was to see how well the selamectin would perform in a simulated 'real life' infestation (not just in a lab). The animals were treated with three monthly doses. The results found that dogs showed a >99% flea reduction from day 14 onwards and cats showed a >92% reduction on day 29, which increased to 99% from day 44 onwards (until the end of the study). A 2008 study published in Veterinary Therapeutics compared the efficacy of spinosad and selamectin. The animals were divided into two groups and given monthly doses of one of the flea control medications for 3 treatments as per label instructions. At day 15 after the initial treatment, the % flea kill was 90.9% for Selamectin and at day 90, the % flea kill for Selamectin was 98.9%. Another 2000 article in Veterinary Parasitology examined the effectiveness and safety of Revolution flea control when used against both fleas and heartworms. Some of the animals studied had pre-existing signs of flea allergy dermatitis (FAD). Study animals were dosed with Selamectin (Revolution for pets) as per the label dosing regimen (6mg/kg topically every 30 days) for 2 months (days 0, 30 and 60). Similar to the situation described in the 2000 study in Veterinary Therapeutics, the efficacy of flea kill was found to be initially high, but also to improve with subsequent monthly dosing with 92.1%, 99% and 99.8% flea kills seen in dogs on sampling days 30, 60 and 90 and 92.5%, 98.3% and 99.3% flea kills seen in cats over the same period. The signs of flea allergy dermatitis were also observed to improve greatly with selamectin dosing and, with regard to heartworm, 397 dogs were placed in heartworm endemic areas and given Revolution prophylaxis and none were found to have developed heartworm positive tests over 6 months of treatment. Just over 1000 animals (dogs and cats) were studied in this test, ranging from 6 weeks to 19 years of age and no serious adverse reactions were seen. Overall, I would be content to say that Revolution flea control maintains a very high level of effectiveness over the month following dosing and that this effectiveness is likely to only increase with subsequent doses over time (a few months). An important note on bathing dogs: The manufacturer states that Revolution flea control is capable of maintaining its month-long effectiveness in animals that are regularly wetted (swimming, bathing, rain). Revolution for pets is considered to be waterfast (resistant to washing away) 2 or more hours after application of the spot-on (24 hours for cats).
6) Is Revolution flea treatment waterproof? Can I get my dog or cat wet after using it? According to the manufacturer, Revolution flea control will maintain its efficacy after periods of wetting. The manufacturer states that dogs and cats who bathe (including shampooing), swim and who are wetted by rainfall will still be protected by Revolution so long as such wetting does not occur within 2 hours of the Revolution being applied (24 hours in cats). Revolution for pets should only be applied to clean, dry skin, never wet skin. It is recommended that dogs and cats not be bathed for at least 2 hours following application of the spot-on, however, if you want to play it safe, I recommend keeping the animal dry wherever possible for the first 2-3 days following the application of any spot-on, just to be sure. The article below (studied and sent in for publication by the Revolution manufacturer) only bathed cats 24+ hours after the spot-on was applied, so I can not say for certain whether Revolution flea control will remain effective in this species if you wet it less than a day after Revolution application. If you want to play it safe, leave cats and dogs unwetted for at least 24 hours (or, better yet, 2-3 days) after application of the Revolution for pets product (but don't panic if your pet gets wet a little sooner - Pfizer has done the tests and the product will most likely be water-fast should your pet sneak off for a quick dip in the pool a bit sooner than you expected). A 2000 article published by Pfizer in Veterinary Parasitology examined heartworm prevention using Selamectin. 6 different studies were conducted using dogs and cats. Dogs were infected with L3 heartworm larvae 30 days, 45 days or 60 days before a single topical dose of Selamectin was given (6mg/kg). Cats were infected with L3 heartworm larvae 30 days before the single topical dose of Selamectin was given at label doses (6mg/kg). Some animals were even shampooed between 2 and 96 hours after treatment with revolution for pets (cats that were bathed were bathed at 24 hours after dosing). According to the abstract, "Selamectin was 100% effective in preventing heartworm development in dogs when administered as a single topical dose of ... 6mgkg at 30 days after infection, ... 6mgkg(-1) at 45 days after infection, or 6mgkg at 60 days after infection. Selamectin was 100% effective against heartworm infections in cats when administered as a single topical unit dose of 6mgkg." Bathing did not impact the effectiveness. The abstract for the above article actually states: "Bathing with water or shampoo between 2 and 96h after treatment did not reduce the efficacy of selamectin as a heartworm prophylactic in dogs. Likewise, bathing with shampoo at 24h after treatment did not reduce the efficacy of selamectin in cats."
7) What age can dogs and cats start having Revolution for pets? Should Selamectin or any of the other macrocyclic lactones make it into the central nervous system of vertebrates (e.g. due to damage or weakness of the blood-brain barrier (BBB), massive doses or defects in the p-glycoprotein transport molecule), then neurotoxic effects will be seen, similar to those that occur in insects. Toxic signs in mammals include: depression, drooling, swallowing difficulty, tongue paralysis, incoordination of the gait (ataxia), apparent blindness, tremors, seizures, coma and death. The BBB is weaker in young animals and so toxic effects are more likely to be seen in juvenile and neonatal animals, even if their p-glycoprotein transport proteins are normal. This is why there are age restrictions in place for the use of Revolution in pets. Pfizer's own literature gives an example of an underage kitten that died from the improper application of Revolution flea control: "A kitten, estimated to be 5-6 weeks old (0.3 kg), died 8.5 hours after receiving a single treatment of REVOLUTION at the recommended dosage. The kitten displayed clinical signs which included muscle spasms, salivation and neurological signs. The kitten was a stray with an unknown history and was malnourished and underweight." It should be noted that the underweight condition of that animal may have also contributed to its death, not just its age (Pfizer recommendations state that the product should not be used in debilitated, sick or badly underweight animals). Revolution should only be given to puppies from 6 weeks of age and kittens from 8 weeks of age. The manufacturer advises that the product not be used in debilitated, sick or badly underweight cats or dogs. As such animals are often of the older age groups, be a bit cautious using the product in very geriatric animals that are starting to show signs of early or advanced old-age and illness. The product is considered safe to use in breeding animals that are pregnant or lactating or that are about to be bred from. You can use Revolution flea control on a bitch or queen that has unweaned (<6 weeks old) offspring nursing off her. Just don't apply the product directly to those young, unweaned animals. A 2000 Pfizer study published in Veterinary Parasitology examined the effectiveness of selamectin at treating and preventing Toxocara canis roundworms (and fleas) in pregnant or lactating dogs and their pups. Topical Revolution flea control was given to the dogs at 40 days and 10 days before birthing and again at 10 and 40 days after birthing (after whelping). Label doses of 6mg/kg (ranging up to 12mg/kg) were used on the mothers (the Revolution for pets was not applied to the puppies directly) and no adverse side effects of the treatment were observed in either the treated dogs or their puppies. Worm burdens were reduced by 99.7% in the mothers compared to control dogs (which didn't get the Revolution flea control) and 98.2% in the pups. Fleas were reduced by 99.8% in mothers and pups compared to controls. Safety studies (see Pfizer literature) have been done giving 6-week old puppies a topical dose of Selamectin that was 10x the dose normally given to such animals (i.e. 60mg/kg instead of 6mg/kg). No adverse effects were noted. Similarly, 6-week old kittens were given 10x the usual topical dose without effect either. A 2000 study published in Veterinary Parasitology in August looked at a wide range of safety aspects associated with the use of Selamectin in cats and kittens. The study looked at topical side effects, oral side effects (mimicking an ingestion event), Selamectin use on pregnant and lactating animals, Selamectin safety in animals already infested with heartworms and so on. Signs of toxicity were not just evaluated looking at external, clinical signs of poisoning (e.g. tremors, drooling, vomiting), but animals were also assessed using blood tests, histopathological examination of internal tissues (looking for microscopic evidence of damage) and, in breeding animals, by looking at reproductive indices (e.g. litter size, fertility and so on). With regard to age, cats were dosed from 6 weeks of age (though the recommendation is to start them on Revolution from 8 weeks) and the study abstract comments: "Cats received large doses of selamectin at the beginning of the margin of safety study when they were six weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis" and concludes by saying: "Selamectin is a broad-spectrum avermectin endectocide that is safe for use in cats starting at six weeks of age, including heartworm-infected cats and cats of reproducing age, when administered topically to the skin monthly at the recommended dosage to deliver at least 6mgkg." A 2000 study published in the August edition of Veterinary Parasitology looked at a wide range of safety aspects associated with the use of Selamectin in dogs and puppies. The study looked at topical side effects, oral side effects (mimicking an ingestion event), Selamectin use on pregnant and lactating dogs and dogs intended for breeding, Selamectin use in avermectin-sensitive collies (rough-coated collies were used in this part of the study, as opposed to beagles, which were used for the rest of the study), Selamectin safety in animals already infested with heartworms and so on. Signs of toxicity were not just evaluated looking at external, clinical signs of poisoning (e.g. tremors, drooling, ataxia), but animals were also assessed using blood tests, histopathological examination of internal tissues (looking for microscopic evidence of damage) and, in breeding animals, by looking at reproductive indices (e.g. litter size, fertility and so on). With regard to age, beagle puppies were dosed from 6 weeks of age and the study abstract comments: "Pups received large doses of selamectin at the beginning of the margin of safety study when they were 6 weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis" and concludes by saying: "Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg (6-12mgkg range) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs." Another 2000 article in Veterinary Parasitology examined the effectiveness and safety of Revolution flea control when used against both fleas and heartworms. Study animals were dosed with Selamectin (Revolution for pets) as per the label dosing regimen (6mg/kg topically every 30 days) for 2 months (days 0, 30 and 60). Similar to the situation described in a 2000 study in Veterinary Therapeutics, the efficacy of flea kill was found to be initially high, but also improve with subsequent monthly dosing with 92.1%, 99% and 99.8% flea kills seen in dogs on sampling days 30, 60 and 90 and 92.5%, 98.3% and 99.3% flea kills seen in cats over the same period. The signs of flea allergy dermatitis were also observed to improve greatly with selamectin dosing and, with regard to heartworm, 397 dogs were placed in heartworm endemic areas and given Revolution prophylaxis and none were found to have developed heartworm positive tests over 6 months of treatment. Just over 1000 animals (dogs and cats) were studied in this test, ranging from 6 weeks to 19 years of age and no serious adverse reactions were seen.
8) Can Revolution Selamectin be used on pregnant or lactating animals? According to the manufacturer, Revolution flea control is safe to use in pregnant and lactating animals and animals intended for breeding. A 2000 Pfizer study published in Veterinary Parasitology examined the effectiveness of selamectin at treating and preventing Toxocara canis roundworms (and fleas) in pregnant or lactating dogs and their pups. Topical Revolution flea control was given to the dogs at 40 days and 10 days before birthing and again at 10 and 40 days after birthing (after whelping). Label doses of 6mg/kg (ranging up to 12mg/kg) were used on the mothers (the Revolution for pets was not applied to the puppies directly) and no adverse side effects of the treatment were observed in either the treated dogs or their puppies. Worm burdens were reduced by 99.7% in the mothers compared to control dogs (which didn't get the Revolution flea control) and 98.2% in the pups. Fleas were reduced by 99.8% in mothers and pups compared to controls. A 2000 study published in Veterinary Parasitology in August looked at a wide range of safety aspects associated with the use of Selamectin in cats and kittens. The study looked at topical side effects, oral side effects (mimicking an ingestion event), Selamectin use on pregnant and lactating animals, Selamectin safety in animals already infested with heartworms and so on. Signs of toxicity were not just evaluated looking at external, clinical signs of poisoning (e.g. tremors, drooling, vomiting), but animals were also assessed using blood tests, histopathological examination of internal tissues (looking for microscopic evidence of damage) and, in breeding animals, by looking at reproductive indices (e.g. litter size, fertility and so on). The study abstract concludes by saying: "Selamectin is a broad-spectrum avermectin endectocide that is safe for use in cats starting at six weeks of age, including heartworm-infected cats and cats of reproducing age, when administered topically to the skin monthly at the recommended dosage to deliver at least 6mgkg." A 2000 study published in the August edition of Veterinary Parasitology looked at a wide range of safety aspects associated with the use of Selamectin in dogs and puppies. The study looked at topical side effects, oral side effects (mimicking an ingestion event), Selamectin use in pregnant and lactating dogs and dogs intended for breeding, Selamectin use in avermectin-sensitive collies (rough-coated collies were used in this part of the study, as opposed to beagles, which were used for the rest of the study), Selamectin safety in animals already infested with heartworms and so on. Signs of toxicity were not just evaluated looking at external, clinical signs of poisoning (e.g. tremors, drooling, ataxia), but animals were also assessed using blood tests, histopathological examination of internal tissues (looking for microscopic evidence of damage) and, in breeding animals, by looking at reproductive indices (e.g. litter size, fertility and so on). The study abstract concludes by saying: "Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mg/kg (6-12mg/kg range) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs." According to the MSDS, the chemical, Selamectin, has, at very high doses (and high frequencies - i.e. given daily) been found to cause a range of reproductive effects, including: fetal toxicity and death, developmental deformities and maternal toxicity (poisoning of the mother). Some of these effects may not be solely related to the Selamectin, but the alcohol components also contained within the Revolution flea control product. It should be noted that, even though no 100% guarantee can be made that a pregnant or lactating animal treated with Revolution flea control will not have some form of adverse reaction (e.g. a deformed fetus), the company has approved the product for use in pregnant and lactating animals. The studies done on rodents (as mentioned in the MSDS), which showed the reproductive side effects mentioned above, were done using massive doses of the product (well beyond that which a pet owner or vet would ever conceive of giving) and doses were often given orally (Revolution flea control is not marketed for oral use) for days at a time. At normal dose rates, given topically and monthly, Revolution for pets should be safe to use in pregnant animals and animals intended for breeding (see MSDS publications), though, of course, no 100% guarantee could ever be given. To give an example of the kinds of doses we are talking about here, the LOAEL level for fetal death and maternal toxicity of the Isopropyl alcohol component of the product was 1000mg/kg/day orally in rats. The LOAEL is the "lowest observed adverse effect level" and it refers to the lowest dosage of a substance (e.g. selamectin) whereby an adverse effect will be seen. For the butylated hydroxytoluene component of the product, the LOAEL for causing teratogenicity (birth deformities) was 6000mg/kg and this was an oral dose too. The NOAELs for selamectin were 10mg/kg/day with regard to rat fetotoxicity and developmental toxicity, but 40mg/kg/day oral dosing for maternal toxicity. The NOAEL is the "The no observable adverse effect level" and it refers to the highest dosage of a substance that can be given whereby no "biologically or statistically significant" adverse effect will be noted. Above this concentration, adverse effects will start to be noted. Now, 10mg/kg does not sound like a big dose when it comes to selamectin (after all, dogs in studies were getting 6-12mg/kg doses), however, these doses were being given every day for long periods of time without causing reproductive side effects (the side effects kick in above these levels). Other macrocyclic lactones might be toxic to pregnant and lactating animals: Although selamectin does not seem to cause issues in pregnant and lactating animals, the same can not necessarily be said of all the avermectin group. In studies conducted using such products as ivermectin and eprinomectin at high doses, death of the fetus or mother often occurred before any teratogenicity (birth defect) issues could be seen, however, when they did occur, birth defects seen included: cleft palates, wavy ribs and failure of ossification (bone formation). Toxicity was seen in one nursing pup when the mother was given eprinomectin and in baby rats when the mother was dosed with ivermectin. In these situations, the macrocyclic lactones were thought to have gone into the babies via the milk.
9) Revolution has been used successfully in many species, not just the dog and cat. Aside from its registered use in dogs and cats, studies have also been conducted on a range of other animal species, showing that selamectin (the active ingredient of Revolution flea control) is well-tolerated by a range of vertebrate species including: rodents (e.g. rats, mice, guinea pigs), red pandas, rabbits, ferrets, monkeys, birds (canaries) and others. Revolution flea and heartworm control is only officially registered for use in dogs and cats, however, and the use of this product on other species is therefore "off-label" and can not be in any way guaranteed or advised (see your vet for information and doses). Users should also be aware that the potential for collie-type avermectin sensitivity does exist in some other species. For example, Murray Grey cattle are thought to be sensitive to macrocyclic lactones. Another thing to be aware of is that, due to its packaging (packs of 3 or 6 doses), Revolution flea control may not be the most cost-effective way of treating large herds or flocks (e.g. big rabbit, bird or rodent populations) for parasites. Ivermectin is far cheaper and is often available in multi-dose formulations (e.g. as drenches, spot-ons or injectables) that can be administered to large numbers of animals in a herd or flock situation (important note - the dose for ivermectin is NOT the same as the dose for selamectin and their spectrum of activity and safety profile is not identical either). Mice and rats and Revolution flea control: Fur mites: The Journal of the American Association for Laboratory Animal Science studied the use of selamectin for the treatment of mouse fur mites (Myocoptes musculinus) in 2008. Mice were treated with either Selamectin or Moxidectin and, though the results were thought to be faster with the Moxidectin (no adult mites found within 1 month and no egg-casings from 2 months on) than with selamectin (no adult mites found within 1 month and no egg-casings from 6 months on), both were found to be effective and safe. The study also incorporated cage changing as part of the treatment regimen (putting animals in clean, fresh cages after each treatment to reduce the chances of mice picking up eggs from the environment). The drug may or may not treat pinworms: In 2006, the Journal of the American Association for Laboratory Animal Science looked at the safety aspects and effectiveness of treating rats and mice for pinworms (Syphacia muris in rats and Syphacia obvelata in mice), which are not uncommon infestations seen in lab animals and rodent breeding facilities. Mice and rats with naturally acquired pinworm infestations were given either 0.6mg/kg Selamectin or 6mg/kg Selamectin or fenbendazole. No side effects were noted in the rodents using Selamectin, but neither did it have an effect on the pinworms. Only the fenbendazole was proven effective. In contrast with this, a 2009 study published in Experimental Parasitology found Selamectin to be quite effective at treating natural infections of Syphacia muris pinworms in rats. The rats were given a single dose of Selamectin orally in this study and by day 7 (when the rodents were necropsied) it was found that 100% of the adult pinworms had been eliminated (anal egg counts were reduced by 98.77% by day 6 after dosing). A 2008 study published in the Polish Journal of Veterinary Sciences also looked at this issue of rat Syphacia muris infestation, using topical selamectin. A single dose of 6mg/kg selamectin was given topically to rats naturally affected with pinworms. The drug was found to only be 40.7-63.3% effective at eliminating pinworms from rats with female rats showing more favourable results than male rats. It seems that the Selamectin needs to be given orally (higher risk of side effects and certainly against the manufacturer's recommendation) to treat pinworms in rats. Bladder worms: In 2008, the Polish Journal of Veterinary Sciences examined the effect of topical selamectin against bladder worm infestations in lab rats. These worms live in the epithelial lining of the bladder in small tunnels they excavate themselves, causing hyperplasia (thickening) of the bladder wall and inciting chronic, painful bladder inflammation. A single dose of selamectin at 6mg/kg was applied topically to affected rats and of the 12 treated, 7 made a full recovery with just the one dose (the others may have resolved had several doses been given over time - more study is needed here). Rabbits and Revolution for pets: Rabbit fur mites: The Journal of the American Association for Laboratory Animal Science studied the use of selamectin for the treatment of rabbit fur mites (Leporacarus gibbus) in 2009, comparing it with an imidacloprid plus permethrin solution (Advantix). Both solutions cured the mites and were found to be 100% effective by day 13 after the single dose was given, however, Selamectin was found to be 100% effective by day 3 following treatment. Rabbit Cheyletiella: In 2008, Acta Veterinaria Scandinavica looked at the effectiveness of Selamectin and Ivermectin against rabbit cheyletiellosis (Cheyletiella). This was a retrospective study, looking at the records of 53 rabbits some of which were treated with 2 to 3 subcutaneous injections of ivermectin (200-476ug/kg) around 2 weeks apart; some of which were treated with huge doses of injectable (>600ug/kg) ivermectin, followed up with large oral doses of ivermectin (>600ug/kg given every 10 days for 3-6 doses) and some of which were treated with 1-3 doses of selamectin given 2-4 weekly at doses ranging from 6-20mg/kg. Around 81% of rabbits were found to be improved with the selamectin topicals and the ivermectin injections, whereas rabbits that received the oral ivermectin didn't resolve as well. The study shows that injectable ivermectin (not oral) and topical Selamectin both show promise for this condition. A more-precise study on selamectin's effectiveness at treating rabbit cheyletiellosis was published in 2008 in Veterinary Dermatology. 23 rabbits with clinical cheyletiellosis were given selamectin at 12mg/kg, topically for a single dose. All rabbits resolved and were found negative for mites and eggs. No side effects were noted in treated rabbits. Rabbit ear mites (Psoroptes): The Journal of the American Veterinary Medical Association in 2003 looked at the effectiveness and safety of spot-on selamectin in the treatment of rabbits with natural infestations of rabbit ear mites (Psoroptes cuniculi), otherwise known as ear canker. The rabbits were treated monthly for two doses with either the label dose (6mg/kg) or a dose that was three times that dose (18mg/kg). Some rabbits just had a single dose given of either 6mg/kg or 18mg/kg (to see if one dose would be enough). The efficacy was assessed by doing mite counts and also by assessing clinical improvement. All treated rabbits were found to be free of mites from day 7 onwards and no clinical side effects were observed. In 2007, Veterinary Dermatology looked at the effectiveness of Selamectin in treating naturally-acquired infestations of psoroptic mange (ear mites) and sarcoptic mite (Sarcoptes scabiei) in rabbits. Rabbits were given Selamectin at doses ranging between 6-10mg/kg. Improvement was ascertained using both mite scrapes (looking for mites or eggs) and through the assessment of clinical signs. Both types of mites were found to be significantly reduced after this treatment, compared to control groups, suggesting that Selamectin would be effective for rabbits infested with such mites. Rabbit ticks: A 2011 study published in Parasitology Research looked at whether a single dose of Selamectin at 6mg/kg would be effective at preventing rabbits from becoming infested with the adults, larvae or nymphs of the tick, Haemaphysalis concinna and, if so, for how long this effect would last. Rabbits were given the Selamectin at day 0 and at days 1, 8, 15, 22 and 29 were exposed to adult, nymph and larval ticks. 100% of larval ticks were killed from days 1-15 (2 weeks) with a 95% kill rate at day 22 and a 76.7% kill at day 29. Nymphs, likewise, suffered 100% mortality at days 1-15 with an 85% kill at day 22 and a 65% kill at day 29. Adult ticks were less susceptible, with 100% killed on day 1, 95% on day 7, 85% on day 15 and lower levels thereafter. The results show that Selamectin may be very useful at preventing rabbits from being infested with this species of tick, but that, in heavy environmental tick burdens with repeated risk of reinfestation, rabbits may need to be dosed 2-weekly to remain tick free. Guinea pigs and Revolution for pets: Guinea pig mange: The International Journal for Parasitology in 2011 looked at an outbreak of guinea pig mange mite Trixacarus caviae in an animal petting facility in Japan. Selamectin was given topically at doses of 13.6-18.75mg per guinea pig (guinea pigs weigh roughly a kilo or just over). A single dose was given and the guinea pigs resolved, however, a second outbreak occurred soon after suggesting that some animals may have remained carriers after the last treatment. The Selamectin was therefore given twice (on days 0 and 28) at lower doses than initially used (5-7.5mg/kg) and all of the guinea pigs resolved. Canaries and Revolution flea treatment: Skin mites in canaries: The Annals of the New York Academy of Sciences in 2008 published a study on the treatment of canaries naturally infected with chicken or poultry mite (Dermanyssus gallinae) in 2008. Three types of macrocyclic lactone drugs were trialled, including ivermectin, selamectin, and moxidectin and all three were found to be equally effective at removing mite infestations in affected birds. Red Pandas and Revolution flea control: Heartworm prevention: In 2012, Parasitology International examined the ability of selamectin to prevent heartworm infestation in red pandas in China. The prophylaxis program effectively prevented red pandas from becoming infected with heartworm (Dirofilaria immitis) and developing signs of heartworm disease (dirofilariasis). Rhesus Macaques and Selamectin: Intestinal nematodes: A 2008 study published in Veterinary Parasitology looked at the effectiveness of several drugs, Selamectin among them, for the treatment of gastrointestinal nematodes in rhesus macaques in China. Reductions in egg counts were found to be around 99.4% for Selamectin and Ivermectin, suggesting that these off-label treatments are quite effective. Agoutis and Selamectin: In 2008, Veterinary Parasitology, published an article whereby propoxur and selamectin were used successfully to treat severe burdens of "stickfast" or "sticktight" Echidnophaga fleas in captive agoutis. Bullfrogs and Selamectin: Because parasites are common causes of illness and disease in captive amphibians, the Oklahoma City Zoo conducted a study into the use of the drug, Selamectin, on the common American bullfrog to see what tolerance the amphibians had for it and the drug levels in the blood that could be achieved. The results were published in the Journal of Zoo and Wildlife Medicine in 2007. The frogs were given 6mg/kg selamectin topically and none of them showed any clinical or histological (tissue level) signs of toxicity. High plasma levels of the drug were achieved (so an effect on parasites should be expected). Selamectin may be of use in the future as a treatment for certain parasites in captive and pet frogs and toads. Fish and Turtles: The macrocyclic lactones are considered to be highly toxic to fish and chelonian (turtle) species. For this reason, care must be taken to ensure that Selamectin and other such macrocyclic lactone chemicals are not allowed to contaminate water supplies and outdoor environments where such sensitive aquatic species live. Macrocyclic lactones are classed as "very toxic to the aquatic environment". The LC50 of selamectin for Rainbow Trout is 266 ug/L over 96 hours (4 days). The LC50 is the concentration of the chemical (selamectin in this case) in water that will kill 50% of the test animals (trout in this case) within a specified time. LC50 studies are usually done over 4 days. Invertebrates and selamectin insecticide: Selamectin and the other macrocyclic lactones are not particularly selective when it comes to insects and, just as they kill fleas and ticks, so too will they also kill a wide range of pest and beneficial terrestrial and aquatic insect species. These chemicals will kill crop, orchard and garden pests like beetles, aphids, mites and certain worms, but so too will they kill insects that are of benefit to gardens, crops, soil and water courses, including: dung beetles, bees and parasitoid wasps. For this reason, such chemicals are rated as being "very toxic to terrestrial environments" and "very toxic to soil environments." Additionally, such chemicals, being water insoluble (hard to flush away), are thought to bind tightly to soil and sediment and to thus persist in the environment for long periods of time, potentially exerting an accumulative, long-term toxic effect on the environment. Dung-dwelling beetles and flies (which act to break down feces in the environment) are considered highly susceptible to macrocyclic lactones, as are various parasitoid wasps (wasps that prey on pest insect species) and arthropod nymphs that live in waterways. For example, the larvae of the dung-feeding fly Tricharea die during pupation after exposure to such chemicals and dung beetle larvae show impeded development and deformities. For this reason, care must be taken to ensure that Selamectin does not contaminate water supplies, soil and terrestrial environments with valuable, non-pest insect populations. Selamectin must never be allowed to contaminate beehives and major pollen sources as bees are susceptible to poisoning. The LC50 of selamectin for Daphnia magna (an aquatic arthropod) is 26 ng/L in only 48 hours (2 days). The species is highly susceptible. The LC50 of selamectin for Mysid Shrimp (an aquatic crustacean) is 28 ng/L in 4 days. Additionally, sublethal doses of macrocyclic lactone insecticides can also be harmful to beneficial insect populations without actually killing them outright. Sublethal levels of selamectin can: inhibit feeding by insects (resulting in poor growth and development), disrupt insect reproduction (reduced mating, reduced egg numbers, reduced egg survival and even permanent sterility of males and females have all been recorded), create abnormal developmental processes (failure of the molting process, interference with pupation, poor metamorphosis and increased development time from juvenile to adult have all been observed). Male Lucilia cuprina flies (a form of blowfly) showed abnormal mating behaviour with fewer mating attempts and longer duration copulation noted. Tsetse flies (Africa) actually aborted their eggs and larvae after exposure to sublethal doses of macrocyclic lactone drugs. Note: Of the macrocyclic lactones, emamectin and abamectin are considered to be potentially less toxic to beneficial bug populations and so production systems are altering in some regions to take this differing environmental toxicity into account. Current Pharmaceutical Biotechnology in 2011 did a review on the "toxicity and non-target effects of macrocyclic lactones in terrestrial and aquatic environments." The paper reviews the "present knowledge about the acute and chronic ecotoxicological effects of macrocyclic lactones on organisms, mainly invertebrates, in the terrestrial and aquatic environment" and is well worth the read for those of you interested in this aspect of chemical parasite control. Because selamectin is pretty much restricted to use in the dog and cat and, thus, gets little chance to contaminate outdoor environments like some of the livestock and plant preparations do, the article does not include Selamectin in the review, however, it is still worth the read. Info on the effects of these chemicals on dung-dwelling insect species is included.
10) Revolution flea medicine safety and side effects - How safe is Selamectin for pets? Though highly toxic to insects and certain worms, macrocyclic lactones are not generally considered to be all that toxic to vertebrate species, with the exception of fish and chelonians (turtles). The lack of toxicity to vertebrates (including man and his animals) is for several reasons. Vertebrates do not have glutamate-gated chloride channels and therefore the macrocyclic lactones do not have these to act upon (i.e. no receptors for the insecticide means no toxic effect from the insecticide). Vertebrates do have GABA-gated chloride channels in the central nervous system (and some in the peripheral nervous system and gut), which could be acted upon by the insecticide, however, in most normal animals, the macrocyclic lactones are prevented from making contact with these channels because of the strong blood-brain barrier (BBB) and because of the p-glycoprotein transport molecules which live in the BBB and work to swiftly eject any macrocyclic lactone compound that happens to make it through the BBB and into the brain space. Studies done showing Selamectin's high degree of safety: Safety studies (see Pfizer literature) have been done whereupon 6-week old puppies were given a topical dose of Selamectin that was 10x the dose normally given to such animals (i.e. 60mg/kg instead of 6mg/kg). No adverse effects were noted (in one study, puppies were given this dose for 7 months without issue). Similarly, 6-week old kittens were given 10x the usual topical dose without effect either. The NOAEL for cats and dogs is 60mg/kg selamectin (i.e. 10x the label dose). The NOAEL is the "The no observable adverse effect level" and it refers to the highest dosage of a substance that can be given whereby no "biologically or statistically significant" adverse effect will be noted. Above this concentration, adverse effects may start to be observed. In mice and rat toxicity studies, Selamectin is often given orally. Mice given 30mg/kg orally showed no side effects, but developed drooling, weakness and an increase in respiratory rate with doses of 100mg/kg and 300mg/kg. No deaths were recorded at this rate. The LD50 for both rats and mice with selamectin is >1600mg/kg (monster dose). The LD50 is the dose needed to cause death in 50% of the test population. A 2000 study published in Veterinary Parasitology in August looked at a wide range of safety aspects associated with the use of Selamectin in cats and kittens (from 6 weeks old and up). The study examined Revolution flea control given topically (at normal doses) and orally (mimicking an ingestion event) and examined its effect on pregnant and lactating animals, on animals already infested with heartworms and so on. Signs of toxicity were not just evaluated looking at external, clinical signs of poisoning (e.g. tremors, drooling, vomiting), but animals were also assessed using blood tests, histopathological examination of internal tissues (looking for microscopic evidence of damage) and, in breeding animals, by looking at reproductive indices (e.g. litter size, fertility and so on). With regard to age: "Cats received large doses of selamectin at the beginning of the margin of safety study when they were six weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis". Similarly, no adverse effects were noted in the breeding parameters of male and female cats nor in animals already infested with heartworm. The drug did cause mild, transient, non-harmful salivation and vomiting in cats given the drug orally. The study abstract concludes by saying: "Selamectin is a broad-spectrum avermectin endectocide that is safe for use in cats starting at six weeks of age, including heartworm-infected cats and cats of reproducing age, when administered topically to the skin monthly at the recommended dosage to deliver at least 6mgkg." A 2000 study published in the August edition of Veterinary Parasitology looked at a wide range of safety aspects associated with the use of Selamectin in dogs and pups (from 6 weeks old and up). The study examined Revolution flea control given topically (at normal doses) and orally (mimicking an ingestion event) and assessed its effect on pregnant and lactating animals and animals intended for breeding, on animals already infested with heartworms and on avermectin-sensitive collies (rough-coated collies were used in this part of the study, as opposed to beagles, which were used for the rest of the study) and so forth. Signs of toxicity were not just evaluated looking at external, clinical signs of poisoning (e.g. tremors, drooling, vomiting), but animals were also assessed using blood tests, histopathological examination of internal tissues (looking for microscopic evidence of damage) and, in breeding animals, by looking at reproductive indices (e.g. litter size, fertility and so on). With regard to age: "Pups received large doses of selamectin at the beginning of the margin of safety study when they were 6 weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis". Similarly, no adverse effects were noted in the breeding parameters of male and female dogs nor in animals already infested with heartworm. The drug, given orally, caused no adverse effects. No effects were seen on avermectin-sensitive collies either. The study abstract concludes by saying: "Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg (6-12mgkg) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs." A Pfizer study published in Veterinary Parasitology in 2000 looked at the "efficacy and safety of selamectin against gastrointestinal nematodes in cats presented as veterinary patients." 202 cats affected with roundworms and/or hookworms were treated with topical Revolution flea control at normal doses (6mg/kg). Parasite kills were excellent and side effects were not remarkable. Another 2000 article in Veterinary Parasitology examined the effectiveness and safety of Revolution flea control when used against both fleas and heartworms. Study animals were dosed with Selamectin (Revolution for pets) as per the label dosing regimen (6mg/kg topically every 30 days) for 2 months (days 0, 30 and 60). Just over 1000 animals (dogs and cats) were studied, ranging from 6 weeks to 19 years of age and no serious adverse reactions were seen. In other studies, an 18mg/kg dosage (3x dose rate) of selamectin was found to have no effect on male or female reproduction and, with regard to collie toxicity (discussed below), three, monthly, doses of 30mg/kg (5x the normal dose rate for Revolution flea control) were found to have no adverse effect on avermectin-sensitive collies. A 2002 Journal of Veterinary Pharmacology and Therapeutics article also examined the bioavailability, bodily distribution, peak plasma levels and clearance of Selamectin when given to dogs and cats by oral and intravenous routes. Since Revolution for cats and dogs is not given by these means, I will not comment further on these routes of administration here. One comment I will make is that quite high doses of Selamectin (24mg/kg, which is 4x the normal dose) were given to dogs and cats by both topical and oral routes in this study and no adverse effects were noted in the test subjects. This suggests a good safety profile for the drug. The major signs of macrocyclic lactone toxicity, should they occur, are neurological: Should Selamectin or any of the other macrocyclic lactones make it into the central nervous system of vertebrates (e.g. due to BBB damage, massive overdoses or defects in the exclusionary p-glycoprotein transport molecule), then neurotoxic effects will be seen, similar to those that occur in insects. Toxic signs in mammals include: depression, drooling (hypersalivation), swallowing difficulty, tongue paralysis, incoordination of the gait (ataxia), pupil dilation (sometimes pupil constriction), apparent blindness, vocalisation (seen in cats), high heart rate, high respiratory rate and muscle tremors. In severe cases (e.g. sensitive collies given ivermectin), respiratory depression, difficulty breathing, slow heart rate, cyanosis (a blue appearance of the gums caused by a lack of oxygen in the body), seizures, recumbancy, coma and death can occur. Cattle given an overdose of ivermectin showed similar signs. Though at first it seems odd for "excitation" signs like fits and tremors to occur with GABA-gated chloride channel activation, be aware that nerves cross-link in weird and wonderful ways and should a macrocyclic lactone cause the inhibition of a nerve that is, itself, an inhibitor, the overall result on the central nervous system might turn out to be one of excitation. The Archives of Insect Biochemistry and Physiology in December, 2003 explains the "excitation" (tremors, fits, excitement) side effects seen in mammals poisoned with macrocyclic lactones another way in its article on chloride channels and selective insecticides. According to the article, the mammalian toxicity effect is dose-related. At lower doses, the macrocyclic lactone drugs bind to the GABA-gated chloride channels of mammals, but do not actually activate them (i.e. do not cause the influx of chloride ions that suppresses the nerves). They just block the GABA from getting access to them. This results in the nerve being easily and excessively activated (there is no GABA down-regulation of the nerve) and thus, an opposite, excitatory effect is noted - often a 'coarse tremor' or convulsions. With increased concentrations (doses) and longer-term exposure to the drug, the GABA channels do get activated, similar to the effect seen in insects, with resultant suppression of target nerve activation and signs of ataxia (wobbliness), flaccid paralysis and even death. Author's note: long-term, repeat-dosing studies have been done on dogs using several of the macrocyclic lactone drugs. Though I haven't found data for selamectin, degeneration of the cerebellum and pons has been noted in dogs given long-term, repeated-dosing of eprinomectin and degeneration of the peripheral and central nerve cells has been noted with emamectin. Certain animals are more sensitive to macrocyclic lactone poisoning (young animals and collies): The BBB (blood-brain barrier) is weaker in young animals and so toxic effects are more likely to be seen in juvenile and neonatal animals, even if their p-glycoprotein transport proteins are normal. This is why there are age restrictions in place for the use of Revolution in pets. Puppies should not be given Revolution flea control if under 6 weeks of age and kittens should not be given Revolution flea control if under 8 weeks of age (see section 7 for more info on Revolution flea control in young animals). The product should not be used in sick, debilitated or underweight animals. It can be used in pregnant and lactating animals (see section 8 for more). Animals on certain medications may also be more susceptible to macrocyclic lactone toxicity. Certain medications (e.g. ketoconazole) alter the function of the p-glycoprotein transport proteins or compete with the macrocyclic lactones for them. This results in the p-glycoprotein transport proteins being less effective at clearing the macrocyclic lactones from the brain or body, resulting in a longer duration of macrocyclic lactone persistence within the body and an increased risk of neurological toxicity. In some animals (e.g. certain breeds of dog, including collie breeds and their crosses, Murray Grey cattle, the CF-1 strain of lab mouse), the p-glycoprotein transport proteins are defective. This is due to defects in the gene (the ABCB1 gene) coding for them. Such animals are more likely to experience toxic neurological side effects from macrocyclic lactones (even at therapeutic levels) because any of the chemical that manages to cross the BBB will not be rapidly eliminated from the nervous system and brain because of the defective p-glycoprotein transport proteins. It should be noted that, while ivermectin is considered to be of high risk to collie-type breeds and their crosses with the ABCB1 gene defect (11 breeds are known to carry the defect), Selamectin is considered to be minimally harmful and well tolerated (Pfizer has even done studies to confirm this) by avermectin-sensitive breeds. Side effects may potentially occur in sensitive individuals, however, even with topical selamectin. Owners should monitor their pet carefully for any side effects the first few times they use the product on their pet (signs are usually neurological). Also, owners can get their dogs DNA-tested these days to check if their breed has the genetic defect (if the defect is not present, then the collie can usually receive such drugs without worry). To get an idea of how sensitive at-risk collies can be, ivermectin toxicity tends to be seen at doses anywhere from 100-2500ug/kg (0.1mg/kg to 2.5mg/kg). To put that in context, although collies rarely react to the level of ivermectin used to prevent heartworm infestation (6ug/kg dose monthly), when vets treat animals for mange, much bigger doses are given - in the order of 0.2-0.6mg/kg. These doses are usually well-tolerated by normal dogs, but avermectin sensitive collies can certainly react to them. Selamectin, however, seems to be better tolerated by sensitive collies. The Pfizer literature states: "In a topical safety study conducted with avermectin-sensitive collies at 1, 3 and 5 times the recommended dose of Revolution, salivation was observed in all treatment groups, including the vehicle control." Nothing more severe was noted and since the control dogs had the same signs, it is unlikely the Revolution was to blame. A 2000 study published in the August edition of Veterinary Parasitology looked at a wide range of safety aspects associated with the use of Selamectin in dogs and pups (from 6 weeks old and up). The study examined the effect of Revolution for pets on avermectin-sensitive collies (rough-coated collies were used in this part of the study, as opposed to beagles) and concluded by saying: "Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg (6-12mgkg) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs." Another 2000 study published in Veterinary Parasitology comments of Selamectin: "it is well tolerated at higher dosages than 22,23-dihydroavermectin B1a (DHAVM) or milbemycin oxime in Collies, which is a breed known to exhibit idiosyncratic sensitivity to avermectins." Treatment of animals poisoned by macrocyclic lactones, including Selamectin: There is no specific antidote for animals poisoned with macrocyclic lactone drugs like Selamectin. All that can really be offered is decontamination (ridding the stomach or skin of the drug if poisoning was recent) and then supportive care (treatment of the symptoms) until the animal recovers. All you, as the owner should know is, if you suspect a poisoning (regardless of whether signs are yet present or not - e.g. you find an eaten packet of Revolution), you must seek veterinary advice. Decontamination: If the drug was given by injection (e.g. heartworm injectable product, ivermectin injection) and the bleb of solution can still be felt, the skin region can be excised (cut out) to remove the remaining product. This is an extreme solution, but may be required in dogs experiencing severe side effects. If the drug was ingested (eaten) within 2 hours and the animal is not yet symptomatic, vomiting can be induced. If the animal is markedly symptomatic, however, anaesthetising the animal and lavaging the stomach contents out may be safer. Charcoal binding: Macrocyclic lactones bind really well to organic matter like charcoal. Activated charcoal helps to trap the macrocyclic lactone drugs and stop the body from reabsorbing them. Charcoal is useful even in situations where the product was not administered orally. This is because the drug undergoes enterohepatic recycling - macrocyclic lactones get secreted into the intestines via the bile, but up to 20% of the secreted drug may be absorbed back into the bloodstream via the intestine, creating ongoing side effects. Drenching the charcoal regularly (four times daily for 2-3 days) can help to mop up any macrocyclic lactone drug secreted into the intestine via the bile (thus preventing reabsorption). Monitor sodium levels if doing this as hypernatraemia (excessive blood sodium) has been associated with prolonged charcoal administration. Supportive care: Poisoned animals are placed onto IV fluids and given a soft bed. If they can not sit upright, they need to be turned every 4 hours and monitored for pressure sores and urine scalding (their bladder may need to be expressed manually). Their airways need to be monitored carefully (such animals are at risk of inhaling saliva or vomit and developing aspiration pneumonia), as does their heart rate (atropine can be helpful if the HR drops too low), respiration depth and neurological function. Animals with seizures need to be treated to control the seizures and animals need to be kept very quiet since they are often quite hypersensitive (they will tend to over-react violently to sound, light and movement). For longer-term patients, tube-feeding may be required. There are reports of IV lipid emulsions (20% emulsions used for IV feeding of animals) helping in the treatment of lipid soluble poisons (a puppy with moxidectin poisoning was helped with this in 2009). The lipid in the bloodstream helps to bind up the macrocyclic lactones (the MLs are attracted to the fat) making them unavailable to harm the rest of the body. The treatment does come with an increased risk of: pancreatitis, fat embolism, hepatic lipidosis, air embolism and vessel thrombosis. Other potential side effects and precautions associated with Revolution for pets: Be aware that other marked signs (though rare) can sometimes be encountered, including gastrointestinal signs (vomiting, diarrhea with blood in it, inappetence), lethargy (especially in cats), increased respiratory rates and drooling. Side effects commensurate with acute allergic reaction (redness, hives, itchiness of the skin, rashes, fever) can also occur and need veterinary attention. The product contains alcohol and will irritate skin that is broken or inflamed. Revolution flea control should therefore not be used on damaged skin. Studies have found that the product is non-hypersensitising (i.e. animals tested didn't start to react to it with repeated use), however, skin sensitivity and irritation reactions have been known to occur (see side effects section) in individual animals and humans exposed to Revolution for pets. Many skin irritation studies are done on rabbits (Revolution flea control is no different) and such studies have found all ingredients (except the selamectin itself) contained in the Revolution flea control product to be capable of causing mild to moderate skin irritation. The product is irritant to the eyes and should be washed out immediately with saline or even clean water if any contact with a pet's eye occurs. Medical advice should then be sought. Most eye irritation studies are done on rabbits (Revolution flea control is no different) and these studies have found all ingredients contained in the flea control product to cause mild to severe eye irritation. Be aware that some animals may lose their hair (alopecia) at the site of Revolution flea control application. This is generally short-lived and the hair will usually grow back. Animals will also have sticky clumping or discolouration of the hair at the site where Revolution flea control is given. Pets allowed to lick the solution, particularly cats, may react by salivating profusely (frothing at the mouth) or even vomiting. This is not normally harmful, however, excessive ingestion of the product can result in signs of toxicity, so it is not advised to let pets consume the product. It should be noted that Pfizer has studied the oral ingestion of Revolution flea control in both cats and dogs (because accidents do happen) and did find it to be safe to eat at label doses (6mg/kg). The literature states: "Oral administration of Revolution at the recommended topical dose in 5- to 8-month-old beagles did not cause any adverse reactions." Similar findings were also found for cats, except that cats sometimes vomited or salivated. Revolution flea control is flammable and should never be used near flames or high heat. Animals freshly treated with Revolution for pets should also not be exposed to such sources of ignition, just in case the product catches fire before it has dried. Revolution flea control can be used with other commonly used products and medications including: all-wormers, vaccines, antibiotics, anti-inflammatories, shampoos and some other flea control products (e.g. Lufenuron). Caution should be exercised if using Revolution with products that rely on and compete for p-glycoprotein transport molecules (e.g. ketoconazole). Tests on laboratory animals and cell cultures have determined that the chemical, Selamectin (Revolution flea control) does not cause cancer. According to the MSDS, Revolution flea control, has, at very high doses (and high frequencies - i.e. given daily) been found to cause a range of reproductive effects, including: fetal toxicity and death, developmental deformities and maternal toxicity (poisoning of the mother). Some of these effects may not be solely related to the Selamectin, but to the alcohol components also contained within the Revolution flea control product. It should be noted that, even though no 100% guarantee can be made that a pregnant or lactating animal treated with Revolution flea control will not have some form of adverse reaction (e.g. a deformed fetus), the company has studied and approved the product for use in pregnant and lactating animals. The studies done on rodents (as mentioned in the MSDS), which showed the reproductive side effects mentioned above, were done using massive doses of the product (well beyond that which a pet owner or vet would ever conceive of giving) and doses were often given orally (Revolution flea control is not marketed for oral use) for days at a time. At normal dose rates, given topically and monthly, Revolution for pets should be considered safe to use in pregnant animals and animals intended for breeding (see MSDS publications), though, of course, no 100% guarantee could ever be given (see section 8 for more on Revolution flea control and breeding animals). Revolution flea control and heartworm testing: It is always advised that an animal be tested for heartworm infection prior to starting it on Revolution flea control for the first time. This is for two reasons. The first is safety. There is concern that an adult worm or its microfilariae may die after treatment, resulting in a potentially fatal anaphylactic reaction or pulmonary thrombosis. It should be noted, however, that because selamectin is not too effective against adult heartworms or their microfiliariae, the risks of this are very low, though still possible (Revolution for pets has been tested on heartworm positive dogs and cats and those studies showed that it was safe to give to such animals). Also, knowing that an animal does or does not have heartworm before a preventative product is given is useful in confirming that the preventative product still works. Vets and drug companies live in fear of parasites becoming resistant to vet drugs like selamectin. Should an animal be discovered to be positive for heartworm after the Revolution preventative has been given, questions will undoubtedly be raised as to whether the animal had heartworm already (which prior testing and testing again 3-4 months after starting treatment will confirm or refute) or whether the drug actually failed to work (which would be a BIG problem). Be aware that heartworm tests used in vet clinics generally detect antigens made by adult worms and the microfilarial larvae shed by them. Animals will test negative if infested with L3, L4 or juvenile adult worms that haven't matured. Therefore, though it is important to have a heartworm test performed prior to starting heartworm prevention, a negative result may not 100% indicate that the animal is negative (it could still have L3s and L4s and new adults that are slightly more resistant to heartworm drugs and which may survive them). Pfizer advises performing a second heartworm test 3-4 months after starting Revolution to confirm the negative result. It is suggested that heartworm positive animals (especially dogs, who tend to get larger burdens of worms than cats) be treated to rid them of heartworm adults prior to starting them on Revolution heartworm prevention. Since the removal of heartworms from cats is considered highly risky, depending on the worm numbers and the presence or absence of heartworm disease signs, some vets will start heartworm affected cats on Selamectin immediately to prevent them from becoming infested with more worms and not treat them for the adult heartworms at all (this is up to vet discretion though so talk to your vet if this is the situation you are in). This is supported by the Pfizer literature which states: "Cats already infected with adult heartworms can be given Revolution monthly to prevent further infections." A 2005 article in Parasitology Research looked at the safety aspects of giving Revolution flea control to cats that were already heavily infested with adult heartworms (Dirofilaria immitis). The study also looked at the safety of Advocate (10% imidacloprid + 1% moxidectin topical) in the same animals. 35 cats with proven heartworm infestation (adult heartworms were established in their hearts) were studied. 8 of them received the Revolution at label doses monthly for 3 doses. No side effects were noted and the adult worms were not killed. Pfizer has studied the use of Revolution flea control in both cats and dogs infested with adult heartworms and has not reported adverse effects. The Pfizer Revolution literature adds: "Hypersensitivity reactions have not been observed in dogs with patent heartworm infections administered 3 times the recommended dose of Revolution."
11) How safe is Selamectin for people? Can I touch it? Although Revolution flea control is not considered highly dangerous if you get it on your hands during application, it is recommended that you wash your hands thoroughly with soap and water to remove the product. This is because some individuals may experience mild to severe skin irritation from the product. Some people have been known to show significant allergic reactions to topical Revolution for pets, including: rashes, itching and hives. People who suffer from skin hypersensitivity reactions to the product should probably avoid using it because, even if you wear gloves during application (so as not to touch it), you will no doubt want to pat your animal. Residues of revolution will be present on the coats of pets so patting treated animals could be a risk to highly allergic people. Never get the product in your eyes. It is very irritant. Should you get it in your eyes, wash your eyes copiously with an eye irrigation solution, saline or just plain water if that's all you have. Seek medical advice. For safety, Revolution flea control should be kept well out of reach of children. The product is potentially toxic if ingested or inhaled. Seek medical advice should such an event occur. Revolution for pets should not be consumed. Do not eat or drink while applying the product to pets. Revolution flea control must be stored well away from food, drink or animal food as contamination of these products with Selamectin will render them unfit (unsafe) for human or animal consumption. Oral consumption of selamectin has been thought to damage fertility and harm developing fetuses and high doses orally have been known to cause damage to internal organs. Should someone be found to have ingested the Revolution flea product, medical advice should be sought. At certain doses the drug can potentially be harmful if given orally. It is not advised for vomiting to be induced, but the mouth should be washed out thoroughly. Signs of human poisoning with selamectin include: drowsiness, dizziness and headache, however this can potentially progress to more severe neurological signs if enough of the chemical is taken up. Caution Flammable: Revolution flea control is flammable. Never use it near open flames (including cigarettes), sparks or other sources of heat/flame that could result in ignition. Revolution flea control should be stored at room temp (below 30C), in a cool, dry place. The product should not be exposed to high temperatures or sources of flames or ignition. Should a fire occur - you need to use dry chemical, foam, or carbon dioxide to put it out. Do not put water on a fire involving Revolution flea control as it is similar to an oil fire. There is a risk of low-level exposure to Revolution flea control on the coats of treated pets: A study published in Toxicology Mechanisms and Methods in 2005 looked at the "human exposure to selamectin from dogs treated with Revolution". Dogs were treated with topical Revolution flea control (240mg/dog - the actual dose rate is not stated in the abstract) and residue levels of selamectin insecticide in the dog's blood and on the fur (sampled during a 5-minute patting session using a collection glove) were sampled at 0, 24 and 72 hours and then weekly. Selamectin was not detected in the blood after 72 hours and transferable residues were present on the fur out to 4-5 weeks post-dosing (which is expected, given the product is designed to last for a full month as per the manufacturer's design). It should be noted that highest dermal residues were collected 24 hours after applying Revolution flea control and levels fell dramatically after this. It is thus expected that humans who treat their animals with Revolution flea control will inevitably be exposed to selamectin residue on the coats of their animals, particularly during periods of patting and close interaction. Whether this low-level chronic exposure will pose a health risk to pet owners and other animal handlers (e.g. vets) remains to be seen. The dogs showed no signs of selamectin toxicity during the trial.
12) Is Revolution flea treatment useful in dogs and cats suffering Flea Allergy Dermatitis (FAD)? Animals with flea allergy dermatitis are allergically sensitized to fleas such that they have a severe skin reaction (itching, scratching, rashing) each time a flea bites them. In such animals, the immune system is reacting inappropriately and extremely to antigens present in the flea's saliva and/or feces. The usual thinking has always been that it can take a single flea bite to set a flea allergic animal off on a path of scratching (you might not even see any fleas on the animal - the flea has simply jumped on, bitten and then jumped off again, leaving the animal to itch away), though in veterinary circles there is still debate occurring about whether or not the "single bite" theory is perfectly true. In most instances of flea allergy dermatitis I see, it is not a simple case of a single flea biting an otherwise uninfested dog or cat, but animals crawling with fleas because owners have not bothered to treat their animals correctly (e.g. using good products) or treat the environment. Such animals may not be so much "sensitive" or "allergic" to fleas rather than overwhelmed by them. Treating the fleas properly tends to do wonders for these animals. The best flea control products for helping flea allergic dogs and cats are those that kill all adult fleas (i.e. high effectiveness) in a very short period of time (fast-acting), whilst at the same time limiting adult flea feeding times (which is where allergic sensitization occurs - when the animal is exposed to the flea's saliva and droppings). Those that also rapidly wipe out flea populations in the home environment (i.e. those that also kill flea larvae or stop flea eggs from hatching) get extra points because, once a flea population is gone from a household, it is highly likely that flea allergy dermatitis problems will resolve. Revolution flea control works to kill fleas quite rapidly: Depending on the textbooks or journal articles you read, the time taken to achieve maximum effect and the maximum effect achieved (% of fleas killed) varies a little, however, pretty much all Revolution flea control articles state that >98% of fleas will be killed within 36 hours of dosing (this is also what the Revolution flea control information sheets put out by Pfizer claim). Many other studies have been done that support such claims. Whilst this speed of kill is not as fast as Nitenpyram or Imidacloprid, 24-36 hours is still really good, particularly when you consider that many flea allergy dermatitis animals have been suffering with fleas for weeks, months or even years before they get treated. A study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. Cats were infested with fleas 2 days before Revolution flea control was administered at label doses and then fleas were re-applied to the treated animals weekly for 4 doses. Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after initial Revolution dosing, the % flea kill was only 69.4%, but this improved to 99% by 24 hours. A 2000 article in Veterinary Parasitology examined the effects of Selamectin on adult and immature flea stages in dogs and cats. The study found that >98% flea kill (>98% efficacy) was achieved in dogs between 24 and 36 hours after initial dosing and that a similar % of flea kill was achieved in cats between 12 and 24 hours. It is important to realise that Revolution flea control is initially slower than certain other flea control products (it does take at least 12-24 hours for significant flea kills to occur), but not by much. This is shown in a 2003 article published in Veterinary Parasitology, which compared the speed of kill and percentage of flea kill between five of the major flea control products on the market at that time (Nitenpyram, Fipronil, Imidacloprid, Selamectin and Cythioate). The results for Nitenpyram were most impressive. Within 3 hours, "nitenpyram was 100% effective in cats and 99.1% effective in dogs" and 100% effective in both species at 8 hours. Cythioate (used on cats only in the study) showed a 62.4% and 97.4% flea kill at 3 and 8 hours, respectively. Selamectin (used on dogs only in the study) showed a 39.7% and 74.4% flea kill at 3 and 8 hours, respectively. It should be mentioned that Selamectin was not tested on cats in this study, however, it is expected that the speed of flea kill would have been quicker in this species. In dogs, Fipronil showed a 35.9% and 46.5% flea kill at 3 and 8 hours, respectively, whereas, in cats, the respective percentage kills were 24.3% and 62.6%. Imidacloprid in cats showed only a 26.9% flea kill at 3 hours, but then a rapid recovery response and an 82.8% flea kill at 8 hours. In dogs, a similar pattern was seen with a lower % kill (22.2%) at 3 hours, but a high % kill (95.7%) at 8 hours. The speed of flea kill also tends to wane during the month following dosing with Revolution flea control (as it does for all three major topical preparations prescribed by vets). A 2005 study published in Veterinary Therapeutics demonstrated this. It showed that Imidacloprid (Advantage flea control) had the highest % flea kill within 6 hours of initial dosing (out of Fipronil, Imidacloprid and Selamectin), but that all three products had achieved a >95% flea kill by 24 hours of dosing. Fleas were re-introduced to treated cats at day 7 (to mimic a reinfestation event) and all three formulations showed a similar effect, with a 68.4% flea kill at 6 hours post flea-introduction and a massive (highly effective) 99.4% flea eradication at 24 hours. At day 21 and then again at day 28 (just before next dose was due), more fleas were introduced to the treated cats and there was no appreciable kill of those fleas within 6 hours. The new fleas did die, but they took longer (up to 2 days were allowed before the % flea kill was determined), showing that the speed of kill declines with the time passed since dosing. Another study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. Cats were infested with fleas 2 days before Revolution flea control was administered at label doses and then fleas were applied to the treated animals weekly for 4 doses. Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after Revolution dosing, the % kill was only 69.4%, but that this improved to 99% by 24 hours. After the fleas were reintroduced at day 28 (just before the next dose of Revolution was due) the study showed that 12 hours after flea introduction, the % kill was 57.3%, but this improved to 87.1% (in one version of the study) or 95.3% (in another version of the study) 24 hours after flea introduction and then 98.3% 48 hours after flea reintroduction. The study showed that Revolution still showed a high % flea kill a month after dosing, but that it took a little longer to achieve. Revolution flea control maintains a high efficacy (% kill) for the full month - depending on the study you read: Revolution flea control is designed to maintain its high % flea killing effect for at least 1 month following dosing (after which the next dose is due). Whether this actually occurs to a moderately high degree (>90% flea kill at 30 days, as claimed by Pfizer) or a really high degree (>95% flea kills at 30 days), however, depends on the study you look at. The 2005 study published in Veterinary Therapeutics (described above) found that, at the 28-day mark, selamectin was still achieving a 99% flea kill within 2 days of fleas being re-introduced to the treated pet. Fipronil, in contrast, only achieved an 86.4% efficacy in that time and Imidacloprid only achieved a 72.6% flea kill at the 28-day flea-re-introduction mark. Of the three, selamectin seemed to maintain its effect the best and have the highest residual activity. Another study published in Parasites and Vectors in 2011 looked at the efficacy of Selamectin against the KS1 strain of Ctenocephalides. Cats were infested with fleas 2 days before Revolution flea control was administered at label doses and then fleas were applied to the treated animals weekly for 4 doses. Flea counts were taken at 12 and 24 and 48 hours after fleas were reintroduced to the treated animals. The study showed that 12 hours after Revolution dosing, the % kill was only 69.4%, but that this improved to 99% by 24 hours. After the fleas were reintroduced at day 28 (just before the next dose of Revolution was due) the study showed that 12 hours after flea introduction, the % kill was 57.3%, but this improved to 87.1% (in one version of the study) or 95.3% (in another version of the study) 24 hours after flea introduction and then 98.3% 48 hours after flea reintroduction. A 2001 study published in Veterinary Record looked at a similar thing. Animals were dosed with either selamectin, fipronil or imidacloprid and flea populations were re-introduced at days 7, 14, 21, 28 and 35 following dosing. In this study, all three treatments maintained exceptional efficacy for the full month with Selamectin (Revolution flea control) showing an 81-100% flea kill 48 hours after fleas were re-introduced on the 28th day of testing. The study showed no appreciable difference between the three products. Revolution flea control improves in efficacy with monthly use: Quite a few studies have been done whereby Revolution flea control is given to animals monthly over several doses. These studies show that, while Revolution achieves a good effect against fleas (e.g. in a flea infested household) following the first dose (>90% effectiveness at 30 days, following a single dose), this efficacy improves dramatically with monthly dosing, proving that a consistent, monthly drug regime can be highly effective. Since animals with flea allergic dermatitis (FAD) do need ongoing treatment, this cool "improving" effect of Revolution flea control will certainly be of use in such animals. A 2000 study in Veterinary Therapeutics examined the efficacy of Revolution flea control (Selamectin insecticide) in dogs and cats from single and multiple animal households. Animals were given the dose recommended on the Revolution packet (6mg/kg) monthly for 2 months (last dose, day 60) and flea numbers were found to be reduced by 90.6%, 97% and 98% versus the baseline adult flea levels taken on day 0 (just prior to first treatment) on days 30, 60 and 90. A 2000 study published in Veterinary Parasitology examined the effect of selamectin on fleas in a simulated, carpeted home environment. Fleas were applied to dogs and cats 3 - 4 weeks before the selamectin was dosed to give them time to breed and multiply to large numbers within the house environment. The aim of the study was to see how well the selamectin would perform in a simulated 'real life' infestation (not just in a lab). The animals were treated with three monthly doses. The results found that dogs showed a >99% flea reduction from day 14 onwards and cats showed a >92% reduction on day 29, which increased to 99% from day 44 onwards (until the end of the study). A 2008 study published in Veterinary Therapeutics compared the efficacy of spinosad and selamectin. The animals were divided into two groups and given monthly doses of one of the flea control medications for 3 treatments as per label instructions. At day 15 after the initial treatment, the % flea kill was 90.9% for Selamectin and at day 90, the % flea kill for Selamectin was 98.9% (99.9% spinosad). Another 2000 article in Veterinary Parasitology examined the effectiveness and safety of Revolution flea control when used against both fleas and heartworms. Some of the animals studied had pre-existing signs of flea allergy dermatitis. Study animals were dosed with Selamectin (Revolution for pets) as per the label dosing regimen (6mg/kg topically every 30 days) for 2 months (days 0, 30 and 60). The efficacy of flea kill was found to be initially high, but to also improve with subsequent monthly dosing with 92.1%, 99% and 99.8% flea kills seen in dogs on sampling days 30, 60 and 90 and 92.5%, 98.3% and 99.3% flea kills seen in cats over the same period. The signs of flea allergy dermatitis were also observed to improve greatly with selamectin dosing, confirming that the product is highly effective for managing this condition. Revolution flea control kills immature flea stages (eggs and larvae) for improved flea eradication: Revolution flea control kills flea larvae in the environment. Flea larvae in the host animal's environment become poisoned when dander (skin flakes) or flea feces (their natural diet) coated with selamectin drop into the environment from the host animal's skin. The flea larva consumes the insecticide through actual consumption of the treated dander (or flea faeces). Revolution also renders flea eggs non-viable. With flea allergy dermatitis (FAD), you do want to aim for rapid and complete destruction and removal of the flea life stages (flea eggs, larvae and cocoons) present in the pet's environment. Adult fleas only come from the immature flea stages present in the environment and if these are nullified, adult fleas will stop hatching out of the environment and thus flea control will be achieved. With no adult fleas about, the animal with flea allergic dermatitis will improve and most likely its condition will resolve significantly. A 2000 article in Veterinary Parasitology examined the effects of Selamectin on adult and immature flea stages in dogs and cats. The study confirmed that Revolution flea control greatly inhibits flea egg viability (>92% reduction in flea egg hatch), larval development (inhibited by more than 95% in dogs and cats) and the emergence of adult fleas. The study also looked at the effect of medicated dander and debris shed into the environment by treated pets. Flea eggs and larvae were incubated on the dander and debris (flea feces, pet hair, scales) taken from treated dogs. The treated debris and dander was found to greatly inhibit flea egg hatching (>96%), have a high larval killing effect (>98%) and prevent the development of larvae to adults (>99%). Revolution flea control reduces adult flea feeding times: If the theory is true (currently debated) that a "single flea bite" can set a flea allergic dog or cat off on a path of scratching, then the best products for treating flea allergic animals would seem to be those that stop adult fleas from feeding. The odd thing is, almost all flea prevention products require fleas to bite the pet at least once in order for the flea-killing chemical to be taken up into the flea's body (i.e. to kill it). Thus, most flea control products can not claim to "prevent" fleas from biting. The better products, therefore, merely act to reduce flea feeding times, but even those that do not (imidacloprid, fipronil) have still been proven highly effective in treating FAD animals, throwing into question whether reducing flea feeding times is all that important (it appears to be more important that the product just eradicates fleas with high speed and high efficacy). Still, it happens to be the case that Revolution flea control does reduce flea feeding times. It is thus highly useful in animals suffering flea allergy dermatitis and helpful in the prevention of flea-transmitted diseases. A 2008 study, published in the journal of Veterinary Parasitology, examined the effect of various flea control products, including Revolution flea control, on flea feeding times and blood consumption quantities. The study found that, of the products studied, only Nitenpyram (Capstar) and topical Selamectin (Revolution for pets) caused significant reduction in blood consumption by fleas. An early effect of macrocyclic lactone toxicity in parasites is to inhibit feeding and this is borne out by this study. The other thing to note is that Revolution flea control medicine does destroy flea larvae and eggs, which is a good thing in cases of flea allergy. With flea allergy dermatitis, you do want to aim for rapid and complete destruction and removal of the flea life stages (flea eggs, larvae and cocoons) present in the pet's environment. Adult fleas only come from the immature flea stages present in the environment and if these are nullified, adult fleas will stop hatching out of the environment and thus flea control will be achieved. With no adult fleas about, the animal with flea allergic dermatitis will improve and most likely its condition will resolve significantly. At that stage, it will no longer matter if the product allowed fleas to feed for 2 minutes or 20, because no fleas means no bites at all! Advantage flea control has been studied in real-life situations and on animals with flea allergy dermatitis: A 2000 study published in Veterinary Parasitology examined the effect of selamectin on fleas in a simulated, carpeted home environment. Fleas were applied to dogs and cats 3 - 4 weeks before the selamectin was dosed to give them time to breed and multiply to large numbers within the house environment. The aim of the study was to see how well the selamectin would perform in a simulated 'real life' infestation (not just in a lab). The animals were treated with three monthly doses. The results found that dogs showed a >99% flea reduction from day 14 onwards and cats showed a >92% reduction on day 29, which increased to 99% from day 44 onwards (until the end of the study). These results show that Revolution is capable of controlling flea infestations on pets even if they come from homes with established flea populations. It is expected that such houses will soon become free of fleas if Revolution is used monthly. Another 2000 study in Veterinary Therapeutics examined the efficacy of Revolution flea control (Selamectin insecticide) using dogs and cats from single and multiple animal households (i.e. real life flea infestation situations). Animals were given the dose recommended on the Revolution packet (6mg/kg) monthly for 2 months (last dose, day 60) and flea numbers were found to be reduced by 90.6%, 97% and 98% versus the baseline adult flea levels taken on day 0 (just prior to first treatment) on days 30, 60 and 90. Over time, flea allergy animals in those households would be expected to improve dramatically. A 2000 article in Veterinary Parasitology examined the effectiveness and safety of Revolution flea control used against both fleas and heartworms. Some of the animals studied had pre-existing signs of flea allergy dermatitis. Study animals were dosed with Selamectin (Revolution for pets) as per the label dosing regimen (6mg/kg topically every 30 days) for 2 months (days 0, 30 and 60). The efficacy of flea kill was found to be initially high, but also improve with subsequent monthly dosing with 92.1%, 99% and 99.8% flea kills seen in dogs on sampling days 30, 60 and 90 and 92.5%, 98.3% and 99.3% flea kills seen in cats over the same period. The signs of flea allergy dermatitis were also observed to improve greatly with selamectin dosing, confirming that the product is highly effective for managing this condition. Although the theory has always been that 'a single bite' can be enough to get a flea allergy animal scratching for weeks, it may be the case that a bit more is needed (a number of bites, perhaps, sustained over time). Revolution flea control does not 100% prevent flea bites and yet it has been shown to resolve the signs of flea allergy dermatitis in a large study (above). This suggests that a rapid and high % flea kill sustained over a full month, along with a major effect at reducing the flea populations in the animal's environment are as important, if not more so, than merely stopping individual fleas from biting. Revolution flea control can help prevent new fleas from infesting a 'clean' house: Another aspect of the 2000 study, published in Veterinary Parasitology, examined the effectiveness of selamectin at preventing a suitable home environment from becoming infested with fleas (e.g. as might occur if pets visited a flea-infested out-of-home environment). Fleas were added to the coats of dogs and cats 24 hours and again 7 days after Revolution flea control was given and the animals were returned to the carpeted home environment. Flea counts on days 29, 44 and 60 showed a >99% flea reduction, confirming that the Revolution had prevented the newly applied fleas setting up a persistent environmental flea burden (had there been fleas in the environment, the animals would have become reinfested once the Revolution flea control wore off and fleas should have been found at days 44 and 60). Revolution flea control is thus an effective product for preventing a recovering or recovered flea allergy animal from becoming reinfested with fleas from outside environments. In summary - Revolution flea control is a good product to use on animals with flea allergic dermatitis: Overall, it would seem that Revolution flea treatment is a very sound flea control product to give to pets suffering from flea allergy dermatitis. It works relatively quickly, gives a high % flea kill, maintains a high % flea kill for a full month, improves in its % flea kill when given over a period of months (reaches an exceptionally high level), reduces flea feeding and it neutralises flea eggs laid by treated fleas and kills flea larvae in the environment, thereby helping to cripple the flea life cycle and flea population. Additionally, Revolution flea medication is compatible with corticosteroid administration (prednisolone, dexamethasone and so on). Corticosteroids are commonly given to flea allergy dogs and cats to reduce the severity of the allergic skin reaction and lessen the signs of skin irritation associated with the flea allergy dermatitis condition.
13) Selamectin insecticide and the environment - things to be aware of. The macrocyclic lactone chemicals are considered to pose a significant environmental safety risk to terrestrial and aquatic environments if allowed to contaminate them. This is because they are lethal to a wide range of terrestrial, soil and aquatic invertebrate species as well as to certain aquatic vertebrates, including fish and turtles. For this reason, care must be taken to ensure that Selamectin and other such macrocyclic lactone chemicals are not allowed to contaminate water supplies and outdoor environments where such sensitive species live. Macrocyclic lactones are classed as "very toxic to the aquatic environment" and to the soil and terrestrial (land) environments. Whilst selamectin is not generally available in a form that could pose huge risks to the environment (i.e. most owners will only put a small vial of the product on their pet and put the applicator in the bin), large stockpiles of the product probably would pose significant risks if a large spill or contamination event was to occur. Selamectin is toxic to fish and turtles: The macrocyclic lactones are considered to be highly toxic to fish and chelonian (turtle) species. For this reason, care must be taken to ensure that Selamectin and other such macrocyclic lactone chemicals are not allowed to contaminate water supplies and outdoor environments where such sensitive aquatic species live. The LC50 of selamectin for Rainbow Trout is 266 ug/L over 96 hours (4 days). The LC50 is the concentration of the chemical (selamectin in this case) in water that will kill 50% of the test animals (trout in this case) within a specified time. LC50 studies are usually done over 4 days. Selamectin is toxic to invertebrates: Selamectin and the other macrocyclic lactones are not particularly selective when it comes to insects and, just as they kill fleas and ticks, so too will they also kill a wide range of pest and beneficial terrestrial and aquatic insect species. These chemicals will kill crop, orchard and garden pests like beetles, aphids, mites and certain worms, but so too will they kill insects that are of benefit to gardens, crops, soil and water courses, including: dung beetles, bees and parasitoid wasps. For this reason, such chemicals are rated as being "very toxic to terrestrial invertebrates" and "very toxic to soil environments." Additionally, such chemicals, being water insoluble (hard to flush away), are thought to bind tightly to soil and sediment and to thus persist in the environment for long periods of time, potentially exerting an accumulative, long-term toxic effect on the environment. It is important to note that macrocyclic lactone chemicals (Ivermectin, Selamectin), regardless of how they are administered (orally, topically, by injection and so on) to the flea or parasite infested host animal (e.g. horses, livestock, pets) are all excreted from that animal via the feces. When you treat a dog with Revolution flea control, the Selamectin that you applied to the skin will leave that animal via its droppings. Consequently, insects that feed on dung (e.g. dung beetles) are highly likely to be poisoned by such treated dung. Such drenches (e.g. Ivermectin), commonly used to control worms in livestock animals, are considered a major cause of dung-beetle declines in the environment. Dung-dwelling beetles and flies (which act to break down feces in the environment) are considered highly susceptible to macrocyclic lactones, as are various parasitoid wasps (wasps that prey on pest insect species) and arthropod nymphs that live in waterways. For example, the larvae of the dung-feeding fly Tricharea die during pupation after exposure to such chemicals and dung beetle larvae show impeded development and deformities. For this reason, care must be taken to ensure that Selamectin does not contaminate water supplies, soil and terrestrial environments with valuable, non-pest insect populations. Selamectin must never be allowed to contaminate beehives and major pollen sources as bees are susceptible to poisoning. The LC50 of selamectin for Daphnia magna (an aquatic arthropod) is 26 ng/L in only 48 hours (2 days). The species is highly susceptible. The LC50 of selamectin for Mysid Shrimp (an aquatic crustacean) is 28 ng/L in 4 days. Additionally, sublethal doses of macrocyclic lactone insecticides can also be harmful to beneficial insect populations without actually killing them outright. Sublethal levels of selamectin can: inhibit feeding by insects (resulting in poor growth and development), disrupt insect reproduction (reduced mating, reduced egg numbers, reduced egg survival and even permanent sterility of males and females have all been recorded), create abnormal developmental processes (failure of the molting process, interference with pupation, poor metamorphosis and increased development time from juvenile to adult have all been observed). Male Lucilia cuprina flies (a form of blowfly) showed abnormal mating behaviour with fewer mating attempts and longer duration copulation noted. Tsetse flies (Africa) actually aborted their eggs and larvae after exposure to sublethal doses of macrocyclic lactone drugs. Note: Of the macrocyclic lactones, emamectin and abamectin are considered to be potentially less toxic to beneficial bug populations and so production systems are altering in some regions to take this differing environmental toxicity into account. Current Pharmaceutical Biotechnology in 2011 did a review on the "toxicity and non-target effects of macrocyclic lactones in terrestrial and aquatic environments." The paper reviews the "present knowledge about the acute and chronic ecotoxicological effects of macrocyclic lactones on organisms, mainly invertebrates, in the terrestrial and aquatic environment" and is well worth the read for those of you interested in this aspect of chemical parasite control. Because selamectin is pretty much restricted to use in the dog and cat and, thus, gets little chance to contaminate outdoor environments like some of the livestock and plant preparations do, the article does not include Selamectin in the review, however, it is still worth the read. Info on the effects of these chemicals on dung-dwelling insect species is included. Should a spill occur (info from Revolution MSDS): Should a large scale spill occur, the main concerns are worker safety and preventing the spill from contaminating waterways, drains and soil environments. Relevant authorities must be contacted immediately to get advice on the finer points of how to confine and manage the spill. The information contained below is just a basic outline (info is based on MSDS advice), but as I am not qualified to instruct people on managing a major chemical spill, seeking professional advice pertinent to your local area and safety and environmental laws is a must! Should spillage of selamectin insecticide occur, all personnel involved in the clean-up should wear protective clothing, including respiratory protection and eye protection. Unprotected and non-essential people should be evacuated from the site of the spill. Spillage should not be allowed to spread or enter soil, water courses or drains. Absorbent materials like sand or vermiculite should be used to bind up any spillage and this bound insecticide/binder mix should then be scooped into sealable containers. Detergent, along with small amounts of water (not enough to produce run-off which could enter drains), can be used to clean surfaces. The water and detergent and insecticide mix, along with any cleaning implements, should then be put into similar sealable containers. Relevant authorities must be contacted for safe disposal of the insecticide-containing waste. "Contaminated material must be disposed of in accordance with local, regional and national requirements." Relevant authorities must be notified should a spill enter a waterway or drain, as the effects of such a contamination event could be wide and far-reaching.
Revolution flea control links: To go from this Revolution flea treatment page to my detailed Flea Control Page, click here. To go from this Revolution flea medicine page to the Flea Pictures page, click here. Pfizer Revolution Flea Control Product Sheets and MSDS: https://animalhealth.pfizer.com/sites/pahweb/US/EN/Documents/Species%20Landing%20Page%20pdf/Dog/REVOLUTION_PI.pdf http://www.pfizeranimalhealth.com.au/documents/e/969/4173,Revolution.pdf http://www.pfizeranimalhealth.co.nz/sites/pfizeranimalhealth/PAH%20Document%20Library/Pfizer%20MSDS%20-%20REVOLUTION%20for%20Cats.pdf
Revolution Flea Control References and Suggested Reading: 1) Arthropods. In Bowman DD, Lynn RC, Eberhard ML editors: Parasitology for Veterinarians, USA, 2003, Elsevier Science.
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