Prototype avermectin drug used in variety of species as an antiparasiticide
Contraindications: label specific due to lack of safety data (foals, puppies, etc) or public health safety (lactating dairy animals)
Caution in Collie-breed dogs
Adverse Effects: Horses, swelling and pruritus at the ventral mid-line can be seen approximately 24 hours after ivermectin administration due to a hypersensitivity reaction to dead Onchocerca spp. microfilaria. Dogs: may exhibit a shock-like reaction when ivermectin is used as a microfilaricide, presumably due to a reaction associated with the dying microfilaria. Cattle: ivermectin can induce serious adverse effects by killing the larva when they are in vital areas; may also cause discomfort or transient swelling at the injection site. Mice and rats: may cause neurologic toxicity at doses slightly more than usually prescribed. Birds: death, lethargy or anorexia may be seen. Orange-cheeked Waxbill Finches and budgerigars may be more sensitive to ivermectin than other species
An avermectin anthelmintic, ivermectin occurs as an off-white to yellowish powder. It is very poorly soluble in water (4 micrograms/ml), but is soluble in propylene glycol, polyethylene glycol, and vegetable oils.
Ivermectin is photolabile in solution; protect from light. Unless otherwise specified by the manufacturer, store ivermectin products at room temperature (15-30°C).
Ivermectin 1% oral solution (equine tube wormer product) is stable at 1:20 and 1:40 dilutions with water for 72 hours when stored in a tight container, at room temperature and protected from light.
Ivermectin enhances the release of gamma amino butyric acid (GABA) at presynaptic neurons. GABA acts as an inhibitory neurotransmitter and blocks the post-synaptic stimulation of the adjacent neuron in nematodes or the muscle fiber in arthropods. By stimulating the release of GABA, ivermectin causes paralysis of the parasite and eventual death. As liver flukes and tapeworms do not use GABA as a peripheral nerve transmitter, ivermectin is ineffective against these parasites.
Ivermectin is approved in horses for the control of: large strongyles (adult) (Strongylus vulgaris, S. edentatus, S. equinus, Triodontophorus spp.), small strongyles, pinworms (adults and 4th stage larva), ascarids (adults), hairworms (adults), large-mouth stomach worms (adults), neck threadworms (microfilaria), bots (oral and gastric stages), lungworms (adults and 4th stage larva), intestinal threadworms (adults) and summer sores (cutaneus 3rd stage larva) secondary to Hebronema or Draschia Spp.
In cattle, ivermectin is approved for use in the control of: gastrointestinal roundworms (adults and 4th stage larva), lungworms (adults and 4th stage larva), cattle grubs (parasitic stages), sucking lice, and mites (scabies). For a listing of individual species covered, refer to the product information.
In swine, ivermectin is approved for use to treat GI roundworms, lungworms, lice, and mange mites. For a listing of individual species covered, refer to the product information.
In reindeer, ivermectin is approved for use in the control of warbles.
In American Bison, ivermectin is approved for use in the control of grubs.
In dogs and cats, ivermectin is approved only for use as a preventative for heartworm. It is also been used as a microfilaricide, slow-kill adulticide, ectoparasiticide and endoparasiticide.
In simple-stomached animals, ivermectin is up to 95% absorbed after oral administration. Ruminants only absorb 1/4-1/3 of a dose due to inactivation of the drug in the rumen. While there is greater bioavailability after SC administration, absorption after oral dosing is more rapid than SC. It has been reported that ivermectin’s bioavailability is lower in cats than in dogs, necessitating a higher dosage for prophylaxis of heartworm in this species.
Ivermectin is well distributed to most tissues, but does not readily penetrate into the CSF, thereby minimizing its toxicity. Collie-breed dogs with a specific gene defect allow more ivermectin into the CNS than other breeds/species.
Ivermectin has a long terminal half-life in most species (see table below). It is metabolized in the liver via oxidative pathways and is primarily excreted in the feces. Less than 5% of the drug (as parent compound or metabolites) is excreted in the urine.
Pharmacokinetic parameters of ivermectin have been reported for various species:
The manufacturer recommends that ivermectin not be used in foals less than 4 months old, as safety of the drug in animals this young has not been firmly established. However, foals less than 30 days of age have tolerated doses as high as 1 mg/kg without symptoms of toxicity.
Ivermectin is not recommended for use in puppies less than 6 weeks old. Most clinicians feel that ivermectin should not be used in Collies or Collie-mix breeds at the doses specified for treating microfilaria or other parasites unless alternative therapies are unavailable. After receiving heartworm prophylaxis doses, the manufacturer recommends observing Collie-breeds for at least 8 hours after administration. A specific test for identifying dogs that have the gene defect (deletion mutation of the mdr1 gene) that has been seen in certain genetic lines of Collie-type breeds is now available.
Ivermectin is reportedly contraindicated in chelonian species.
Because milk withdrawal times have not been established, the drug is not approved for use in lactating dairy animals or females of breeding age.
The injectable products for use in cattle and swine should be given subcutaneously only; do not give IM or IV.
Ivermectin is considered safe to use during pregnancy. Reproductive studies performed in dogs, horses, cattle and swine have not demonstrated adverse effects to fetuses. Reproductive performance in male animals is also apparently unaltered. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.) In a separate system evaluatingthe safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: A (Probably safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)
Ivermectin is excreted in milk in low concentrations; it is unlikley to pose significant risk to nursing offspring.
In horses, swelling and pruritus at the ventral mid-line can be seen approximately 24 hours after ivermectin administration due to a hypersensitivity reaction to dead Onchocerca spp. microfilaria. The reaction is preventable by administering a glucocorticoid just prior to, and for 1-2 days after ivermectin. If untreated, swelling usually subsides within 7 to 10 days and pruritus will resolve within 3 weeks.
Dogs may exhibit a shock-like reaction when ivermectin is used as a microfilaricide, presumably due to a reaction associated with the dying microfilaria.
When used to treat Hypoderma bovis larva (Cattle grubs) in cattle, ivermectin can induce serious adverse effects by killing the larva when they are in vital areas. Larva killed in the vertebral canal can cause paralysis and staggering. Larva killed around the gullet can induce salivation and bloat. These effects can be avoided by treating for grubs immediately after the Heal fly (Warble fly) season or after the stages of grub development where these areas would be affected. Cattle may experience discomfort or transient swelling at the injection site. Using a maximum of 10 ml at any one-injection site can help minimize these effects.
In mice and rats, ivermectin may cause neurologic toxicity at doses slightly more than usually prescribed (less than 0.5 mg/kg).
In birds, death, lethargy or anorexia may be seen. Orange-cheeked Waxbill Finches and budgerigars may be more sensitive to ivermectin than other species.
For additional information refer to the Overdosage/Acute Toxicity section below.
In horses, doses of 1.8 mg/kg (9x recommended dose) PO did not produce symptoms of toxicity, but doses of 2 mg/kg caused symptoms of visual impairment, depression and ataxia.
In cattle, toxic effects generally do not appear until dosages of 30x those recommended are injected. At 8 mg/kg, cattle showed symptoms of ataxia, listless, and occasionally death.
Sheep showed symptoms of ataxia and depression at ivermectin doses of 4 mg/kg.
Swine showed symptoms of toxicosis (lethargy, ataxia, tremors, lateral recumbency, and mydriasis) at doses of 30 mg/kg. Neonatal pigs may be more susceptible to ivermectin overdosages, presumably due to a more permeable blood-brain barrier. Accurate dosing practices are recommended.
In dogs, symptoms of acute toxicity rarely occur at single dosages of 2 mg/kg (2000 micrograms/kg) or less. At 2.5 mg/kg, mydriasis occurs, and at 5 mg/kg, tremors occur. At doses of 10 mg/kg, severe tremors and ataxia are seen. Deaths occurred when dosages exceeded 40 mg/kg, but the LD50 is 80 mg/kg. Dogs (Beagles) receiving 0.5 mg/kg PO for 14 weeks developed no signs of toxicity, but at 1-2 mg/kg for the same time period, developed mydriasis and had some weight decreases. Half of the dogs receiving 2 mg/kg/day for 14 weeks developed symptoms of depression, tremors, ataxia, anorexia, and dehydration.
The Collie breed appears to be more sensitive to the toxic effects of ivermectin than other canine breeds. This may be due to a more permeable blood-brain barrier to the drug or drug accumulation in the CNS of this breed. At the dosage recommended for heartworm prophylaxis, it is generally believed that the drug is safe to use in Collies.
Dogs who receive an overdosage of ivermectin or develop signs of acute toxicity (CNS effects, GI, cardiovascular) should receive supportive and symptomatic therapy. Emptying the gut should be considered for recent massive oral ingestions in dogs or cats. For more information on ivermectin toxicity in dogs, refer to the following reference: Paul, A., and W. Tranquilli. 1989. Ivermectin. In Current Veterinary Therapy X: Small Animal Practice. Edited by R. W. Kirk. 140-142. Philadelphia: WB Saunders.
Ivermectin has a large safety margin in cats. Kittens receiving doses of at least 110 mcg/kg and adult cats receiving at least 750 mcg/kg showed no untoward effects. Acute toxic symptoms associated with massive overdoses in cats will appear within 10 hours of ingestion. Symptoms may include agitation, vocalization, anorexia, mydriasis, rear limb paresis, tremors, and disorientation. Blindness, headpressing, wall climbing, absence of oculomotor menace reflex, and a slow and incomplete response to pupillary light may also be seen. Neurologic symptoms usually diminish over several days and most animals completely recover within 2-4 weeks. Symptomatic and supportive care is recommended.
Drug/Laboratory InteractionsWhen used at microfilaricide dosages, ivermectin may yield false-negative results in animals with occult heartworm infection.
As a preventative for heartworm:
1. 0.006 mg/kg (6 mcg/kg) PO once monthly (Hribernik 1989)
2. 6-12 mcg/kg PO once monthly (Knight 2000)
3. Minimum dosage of 5.98 micrograms/kg (0.00598 mg/kg) PO per month (Rawlings and Calvert 1989)
4. Minimum dosage of 6 micrograms/kg (0.006 mg/kg) PO per month. Three tablet sizes are available: For dogs up to 25 lbs (68 micrograms); 26-50 lbs (136 micrograms); and 51-100 lbs (272 micrograms). Dogs weighing more than 100 lbs. should receive additional drug so that the minimum dosage is covered. (Package insert; Heartgard 30®–MSD)
As a microfilaricide:
1. 3-4 weeks after adulticide therapy, admit to hospital and administer 0.05 mg/kg (Dilute 10 mg/ml solution (Ivomec®) to a 1:10 solution with propylene glycol). Monitor for symptoms of toxicity (depression, mydriasis, ataxia, vomiting, diarrhea, and shock) throughout the day. If adverse effects are severe, (usually less than 5% of the time), treat with fluids and corticosteroids. If no adverse effects are noted, animal may be sent home to return in 3 weeks for microfilaricide concentration test. If negative at that time, begin prophylaxis therapy. If positive, recheck in one week. If 4 weeks after therapy microfilaria persist, reevaluate for adult heartworms. See the complete reference for more information. (Hribernik 1989)
2. 50-200 micrograms/kg (0.05-0.2 mg/kg) as a single dose; contraindicated in collies (Knight 1988)
3. 4 weeks after adulticide therapy, give 50 micrograms/kg PO (dilute as in “a” above) in the morning. Monitor for adverse effects throughout the day; if no serious effects, may discharge in late afternoon. Do not use in Collies or Collie-Mix breeds. (Rawlings and Calvert 1989)
As an ectoparasiticide (miticide):
1. For treatment of Sarcoptes scabiei or Otodectes cynotis infestations: 300 micrograms/kg (0.3 mg/kg) SC or PO; repeat in 14 days (Paradis 1989)
2. For demodicosis: 400-600 mcg/kg PO daily. Consider using the test dose method: Start at 100 mcg/kg PO and increase by 100 mcg/day until target dose is reached. Treatent typically required for 2-4 months. If toxicity is noted, discontinue. Do not use in collies, Shelties, Old English Sheepdogs and other herding dogs. (DeManuelle 2000)
3. As scabicide: 300-400 mcg/kg PO or SC once weekly for weeks. If using the 1% injection, 1 ml = 10,000 mcg. Beware in sensitive breeds (e.g. Collies, etc.; “white feet, don’t treat”). Check heartworm status prior to treatment. Adverse effects are rare outside of sensitive breeds. (Foil 2003c)
As an endoparasiticide:
1. For treatment of parasitic lung disease (Capillaria spp.): 0.2 mg/kg PO once (Bauer 1988)
2. For Oslerus osleri: 0.4 mg/kg SC once (Reinemeyer 1995)
3. For Eucoleus boehmi: 0.2 mg/kg PO once (Reinemeyer 1995)
4. For Pneumonyssoides caninum: 0.2 mg/kg SC once (Reinemeyer 1995)
As a preventative for heartworm:
1. Minimum effective dosage: 0.024 mg/kg (24 micrograms/kg) PO every 30-45 days (Note: also controls hookworms at this dosage) (Knight 1995)
For Aelurostrongylus abstrusus:
1. 0.4 mg/kg SC once (Reinemeyer 1995); (Hawkins 2000)
For prevention of heartworm disease:
1. 0.02 mg/kg PO monthly (Hoeffer 2000)
1. Rabbits: For Sarcoptes scabiei, Notoedres cati: 0.3-0.4 mg/kg SC, repeat in 14 days For ear mites (Psoroptes) 0.2-0.44 mg/kg PO, SC repeat in 8-18 days (Ivey and Morrisey 2000)
2. Rabbits: For treatment of ear mites: 200 mcg/kg SC and repeated in two weeks. All rabbits in colony should be treated and cages cleaned and disinfected. (Burke 1999)
3. Rodents and lagomorphs: For treatment of sarcoptoid and some fur mites: 200-250 mcg/kg SC. Cages should be thoroughly cleaned and disinfected. (Burke 1999)
4. Mice, Rats, Gerbils, Guinea pigs, Chinchillas: 200 mcg/kg SC or PO every 7 days for 3 weeks Hamsters: 200-500 mcg/kg SC or PO every 14 days for 3 weeks (Adamcak and Otten 2000)
For susceptible parasites:
1. 200 micrograms/kg SC. Doses greater than 10 ml should be given at two separate sites. (Paul 1986)
2. For psoroptic mange: 200 mg/kg IM (Note: Reference was written before approval of the SC labeled bovine product); isolate from other cattle for at least 5 days after treatment. (Mullowney 1986)
3. 200 micrograms/kg (0.2 mg/kg) SC under the loose skin in front of or behind the shoulder (Product Information; Ivomec® Inj. for Cattle 1%–MSD)
For susceptible parasites:
1. 200 micrograms/kg (0.2 mg/kg) PO using oral paste or oral liquid (Product Information; Eqvalan®–MSD)
2. 0.2 mg/kg PO; 0.2 mg/kg PO at 4 day intervals for lice and mange (Robinson 1987)
3. As a larvicidal for arterial stages of S. vulgaris: 0.2 mg/kg once (Herd 1987)
For susceptible parasites:
1. 300 micrograms/kg (0.3 mg/kg) SC in the neck immediately behind the ear (Product Information; Ivomec® Inj. for Swine 1%–MSD)
2. For general control of endo- and ectoparasites in potbellied pigs: 300 micrograms/kg SC or IM once for internal parasites and repeated in 10-14 days for external parasites (only partially effective against whipworms–see fenbendazole) (Braun 1995)
For susceptible parasites:
1. 200 micrograms/kg for nasal bot infection (Bennett 1986)
2. 200 micrograms/kg SC for one dose (goats also) (Upson 1988)
For susceptible parasites:
1. 0.2 mg/kg PO or SC for one dose (Cheney and Allen 1989), (Fowler 1989)
For susceptible parasites:
1. For ascarids, Capillaria and other intestinal worms, Knemidocoptes pilae (scaly face and leg mites): Dilute to a 2 mg/ml concentration. After diluting product, use immediately.
Most birds: Inject 220 micrograms/kg IM.
Parakeets: 0.02 mg/30 g (2000 micrograms/30 gram) IM.
Amazons: 0.1 mg IM
Macaws: 0.2 mg IM
Finches:0.02 mg (Stunkard 1984)
2. For ascarids, coccidia and other intestinal nematodes, Oxysipura, gapeworms, Knemidocoptes pilae (scaly face and leg mites): Dilute bovine preparation (10 mg/ml) 1:4 with propylene glycol.
For most species: 200 micrograms/kg IM or orally; repeat in 10-14 days.
Budgerigars:0.01 ml of diluted product (see above) IM or PO (Clubb 1986)
3. 200 micrograms/kg (0.2 mg/kg) SC; dilute using propylene glycol. (Sikarskie 1986)
4. Ratites: 200 mcg/kg PO, IM or SC. Has efficacy against Chandlerella quiscali in emus. (Jenson 1998)
For most nematodes, ectoparasites:
1. For lizards, snakes, and alligators: 0.2 mg/kg (200 mg/kg) IM, SC, or PO once; repeat in 2 weeks Note: Ivermectin is toxic to chelonians (Gauvin 1993)
1) Clinical efficacy; 2) Adverse effects/toxicity (see Adverse Effects and Overdosage Sections)
When using large animal products the manufacturer recommends not eating or smoking and to wash hands after use. Avoid contact with eyes. Dispose of unused products and containers by incineration or in approved-landfills. Ivermectin may adversely affect fish or other water-borne organisms if disposed in water.
Contact veterinarian if any treated animal exhibits symptoms of toxicity (see Adverse effects and Overdosage sections above).
Veterinary Approved Products:
Note: As ivermectin is no longer patent protected in the USA, there are a variety of “generic” products available with many trade names. The following may not be a complete listing.
Ivermectin for Injection 1% in 50 ml, 200 ml and 500 ml packs. Approved for use in swine. Slaughter withdrawal (at labeled doses) = 18 days. Ivomec® 1% Injection for Swine (Merial); (OTC)
Ivermectin for Injection 10 mg/ml (1%) and Clorsulon 100 mg/ml; Ivomec® Plus Injection for Cattle (Merial); (OTC). Approved for use in cattle (not female dairy cattle of breeding age). Slaughter withdrawal (at labeled doses) = 40 days. No milk withdrawal has been established.
Ivermectin for Injection 10 mg/ml (1%) in 50 ml, 200 ml, 500 ml bottles; Ivomec® 1% Injection for Cattle and Swine (Merial), Double Impact® (AgriLabs); Ultramectrin® Injection (RXV); (OTC). Approved for use in cattle (not female dairy cattle of breeding age) and swine. Slaughter (when used as labeled): cattle = 35 days, swine = 18 days, reindeer = 56 days, bison = 56 days. No milk withdrawal time has been established.
Ivermectin for Injection 2.7 mg/ml (0.27%) in 200 ml bottles; Ivomec® 0.27% Injection for Feeder and Grower Pigs (Merial); (OTC). Approved for use in swine. Slaughter (when used as labeled) = 18 days
Ivermectin Oral Paste 1.87% (18.7 mg/gram) in 6.08 g syringes; Equimectrin® Paste 1.87% (Farnam), Eqvalan® Paste 1.87% (Merial), Rotectin® 1 Paste 1.87% (Farnam), Zimectrin® Paste (Farnam); (OTC). Approved for use in horses (not intended for food purposes).
Oral Paste containing 1.87% ivermectin and 14.03% of praziquantel in oral syringes (sufficient to treat one 1320 lb horse); Equimax®;(Pfizer); (OTC). Approved for use in horse or ponies not intended for food purposes.
Oral Paste containing 1.55% ivermectin and 7.75% of praziquantel in oral syringes; Zimecterin Gold®;(Merial); (OTC). Approved for use in horse or ponies not intended for food purposes.
Ivermectin Liquid 1% (10 mg/ml) in 50 ml and 100 ml btls (for tube administration; not for injection); Amtech Phoenectin® Liquid for Horses (Phoenix Scientific), Eqvalan® Liquid (Merial), Ivercide®Liquid for Horses (Phoenix Pharmaceutical); (Rx). Approved for use in horses (not intended for food purposes).
Ivermectin Oral Tablets 68 micrograms, 136 micrograms, 272 micrograms (Plain or Chewable) in 6 chewables in carton in 10 carton trays, Heartgard® Tablets (Merial), Heartgard® Chewables (Merial); (Rx). Approved for use in dogs.
Ivermectin Oral Chewable Tablets 55 mcg or 165 mcg in cartons of 6 in 10 cartons per tray. Heartgard® for Cats (Merial); (Rx)
Ivermectin/Pyrantel Oral Tablets 68 mcg/57 mg, 136 mcg/114mg, 272 mcg/228 mg); Heartgard® Plus Chewables (Merial); Tri-Heart® Plus Chewable Tablets (Schering); (Rx). Approved for use in dogs.
Ivermectin 0.08% Oral Solution: in 960 ml and 4,800 ml containers. Approved for use in sheep. Slaughter withdrawal time = 11 days. Ivomec® Sheep Drench (Merial); (OTC)
Ivermectin 1.72 g Bolus. Approved for use in cattle (not female dairy cattle of breeding age). Slaughter withdrawal time = 180 days. No milk withdrawal time has been established. Ivomec® SR Bolus (Merial); (OTC)
Ivermectin Medicated feeds: Ivomec® Premix for Swine Type A Medicated Article (Merial) 0.6% in 50 lb. Ivomec® Premix for Swine Type C Medicated Feed 0.02% (Merial) in 20 lb one-ton bag and 40 lb two-ton bag, Ivomec® Premix for Swine Type C medicated feed 0.1% (Merial) in 20 lb one-ton bag. Approved for use in swine. Slaughter withdrawal = 5 days
Ivermectin Topical Parasiticide Pour-on for Cattle; 5 mg/ml 250 ml, 500 ml, 1 liter and 1 gallon bottles. Approved for use in cattle (not female dairy cattle of breeding age). Slaughter withdrawal time = 48 days, milk withdrawal has not been established. Amtech Phoenectin® Pour-on for Cattle (Phoenix Scientific), Bimectin® Pour-On (Bimeda), Ivercide® Pour-On for Cattle (Phoenix Pharmaceutical), Ivermectin® Pour-On (Aspen, Durvet), Ivomec® Eprinex® Pour-on for Beef and Dairy Cattle and Ivomec® Pour-on for Cattle (Merial), Prozap®Ivermectin Pour-on (Loveland), Top Line® (AgriLabs), Ultramectrin® Pour-On (RXV); (OTC)
Ivermectin Tablets: 3 mg and 6 mg; Stromectol® (Merck); (Rx)
Ivermectinmay also be known by the following trade names: Mectizan®, Revectina®, and Securo®.