IVERMECTIN
Chemistry - An avermectin anthelmintic, ivermectin occurs as an off-white to yellowish powder. Itis very poorly soluble in water (4 micrograms/ml), but is soluble in propylene glycol, polyethyleneglycol, and vegetable oils.
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.
In cattle, ivermectin is approved for use in the control of: gastrointestinal roundworms (adults and4th stage larva), lungworms (adults and 4th stage larva), cat le 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 mangemites. 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, ivermectin is approved only for use as a preventative for heartworm. It is also been usedas a microfilaricide, ectoparasiticide and endoparasiticide.
Ivermectin is well distributed to most tissues, but does not readily penetrate into the CSF, therebyminimizing its toxicity. Collie-Breed dogs apparently allow more ivermectin into the CNS thanother breeds/species.
Ivermectin has a long terminal half-life in most species (see table below). It is metabolized in theliver via oxidative pathways and is primarily excreted in the feces. Less than 5% of the drug (asparent compound or metabolites) is excreted in the urine.
Pharmacokinetic parameters of ivermectin have been reported for various species:
Volume of
Total Body
Species
Bioavailability
Distribution
T 1/2 (terminal)
Clearance(F)(Vd) (L/kg)(in days)(L/kg/day)
Cattle0.45 - 2.42 - 30.79
Dogs.952.42
Swine40.5
Sheep1.0 intra-abomasal4.62 - 7.251 intra-ruminal
Ivermectin is not recommended for use in puppies less than 6 weeks old. Most clinicians feel thativermectin should not be used in Collies or Collie-mix breeds at the doses specified for treatingmicrofilaria or other parasites unless alternative therapies are unavailable. After receiving heartwormprophylaxis doses, the manufacturer recommends observing Collie-breeds for at least 8 hours afteradministration.
Because milk withdrawal times have not been established, the drug is not approved for use inlactating dairy animals or females of breeding age.
The injectable products for use in cat le and swine should be given subcutaneously only; do notgive IM or IV.
Ivermectin is considered to be safe to use during pregnancy. Reproductive studies performed indogs, horses, cattle and swine have not demonstrated adverse effects to fetuses. Reproductiveperformance in male animals is also apparently unaltered.
Onchocerca spp. microfilaria. The reaction is preventable by administering a glucocorticoid justprior to, and for 1-2 days after ivermectin. If untreated, swelling usually subsides within 7 to 10days and pruritis will resolve within 3 weeks.
Dogs may exhibit a shock-like reaction when ivermectin is used as a microfilaricide, presumablydue to a reaction associated with the dying microfilaria.
When used to treat Hypoderma bovis larva (Cattle grubs) in cat le, ivermectin can induce seriousadverse effects by killing the larva when they are in vital areas. Larva killed in the vertebral canal cancause paralysis and staggering. Larva killed around the gullet can induce salivation and bloat. Theseeffects can be avoided by treating for grubs immediately after the Heal fly (Warble fly) season orafter the stages of grub development where these areas would be affected. Cattle may alsoexperience discomfort or transient swelling at the injection site. Using a maximum of 10 ml at anyone injection site can help minimize these effects.
In birds, death, lethargy or anorexia may be seen. Orange-cheeked Waxbill Finches andbudgerigars may be more sensitive to ivermectin than other species.
For additional information refer to the Overdosage, Acute Toxicity section below.
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 heart worm 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 beconsidered for recent massive oral ingestions in dogs or cats. For more information on ivermectintoxicity 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.
Acute toxic symptoms in cats will appear within 10 hours of ingestion. Symptoms may includeagitation, vocalization, anorexia, mydriasis, rear limb paresis, tremors, and disorientation. Blindness, head-pressing, wall-climbing, absence of oculomotor menace reflex, and a slow and incompleteresponse to pupillary light may also be seen. Neurologic symptoms usually diminish over severaldays and most animals completely recover within 2-4 weeks. Symptomatic and supportive care arerecommended.
Drug/Laboratory Interactions - When used at microfilaricide dosages, ivermectin may yieldfalse-negative results in animals with occult heartworm infection.
Storage, Stability, Compatibility
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.
Pharmacology - IVERMECTIN
Ivermectin enhances the release of gamma amino butyric acid (GABA) atpresynaptic neurons. GABA acts as an inhibitory neurotransmitter and blocks the post-synapticstimulation of the adjacent neuron in nematodes or the muscle fiber in arthropods. By stimulatingthe release of GABA, ivermectin causes paralysis of the parasite and eventual death. As liver flukesand tapeworms do not use GABA as a peripheral nerve transmitter, ivermectin is ineffective againstthese parasites.Uses, Indications
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 4thstage larva), intestinal threadworms (adults) and summer sores (cutaneous 3rd stage larva)secondary to Hebronema or Draschia Spp..In cattle, ivermectin is approved for use in the control of: gastrointestinal roundworms (adults and4th stage larva), lungworms (adults and 4th stage larva), cat le 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 mangemites. 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, ivermectin is approved only for use as a preventative for heartworm. It is also been usedas a microfilaricide, ectoparasiticide and endoparasiticide.
Pharmacokinetics - IVERMECTIN
In simple-stomached animals, ivermectin is up to 95% absorbed after oraladministration. Ruminants only absorb 1/4 - 1/3 of a dose due to inactivation of the drug in therumen. While there is greater bioavailability after SQ administration, absorption after oral dosing ismore rapid than SQ. It has been reported that ivermectin's bioavailability is lower in cats than indogs, 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, therebyminimizing its toxicity. Collie-Breed dogs apparently allow more ivermectin into the CNS thanother breeds/species.
Ivermectin has a long terminal half-life in most species (see table below). It is metabolized in theliver via oxidative pathways and is primarily excreted in the feces. Less than 5% of the drug (asparent compound or metabolites) is excreted in the urine.
Pharmacokinetic parameters of ivermectin have been reported for various species:
Volume of
Total Body
Species
Bioavailability
Distribution
T 1/2 (terminal)
Clearance(F)(Vd) (L/kg)(in days)(L/kg/day)
Cattle0.45 - 2.42 - 30.79
Dogs.952.42
Swine40.5
Sheep1.0 intra-abomasal4.62 - 7.251 intra-ruminal
Contraindications, Precautions, Reproductive Safety
The manufacturer recommends thativermectin not be used in foals less than 4 months old, as safety of the drug in animals this younghas not been firmly established. However, foals less than 30 days of age have tolerated doses ashigh as 1 mg/kg without symptoms of toxicity.Ivermectin is not recommended for use in puppies less than 6 weeks old. Most clinicians feel thativermectin should not be used in Collies or Collie-mix breeds at the doses specified for treatingmicrofilaria or other parasites unless alternative therapies are unavailable. After receiving heartwormprophylaxis doses, the manufacturer recommends observing Collie-breeds for at least 8 hours afteradministration.
Because milk withdrawal times have not been established, the drug is not approved for use inlactating dairy animals or females of breeding age.
The injectable products for use in cat le and swine should be given subcutaneously only; do notgive IM or IV.
Ivermectin is considered to be safe to use during pregnancy. Reproductive studies performed indogs, horses, cattle and swine have not demonstrated adverse effects to fetuses. Reproductiveperformance in male animals is also apparently unaltered.
Adverse Effects, Warnings
In horses, swelling and pruritis at the ventral mid-line can be seenapproximately 24 hours after ivermectin administration due to a hypersensitivity reaction to deadOnchocerca spp. microfilaria. The reaction is preventable by administering a glucocorticoid justprior to, and for 1-2 days after ivermectin. If untreated, swelling usually subsides within 7 to 10days and pruritis will resolve within 3 weeks.
Dogs may exhibit a shock-like reaction when ivermectin is used as a microfilaricide, presumablydue to a reaction associated with the dying microfilaria.
When used to treat Hypoderma bovis larva (Cattle grubs) in cat le, ivermectin can induce seriousadverse effects by killing the larva when they are in vital areas. Larva killed in the vertebral canal cancause paralysis and staggering. Larva killed around the gullet can induce salivation and bloat. Theseeffects can be avoided by treating for grubs immediately after the Heal fly (Warble fly) season orafter the stages of grub development where these areas would be affected. Cattle may alsoexperience discomfort or transient swelling at the injection site. Using a maximum of 10 ml at anyone injection site can help minimize these effects.
In birds, death, lethargy or anorexia may be seen. Orange-cheeked Waxbill Finches andbudgerigars may be more sensitive to ivermectin than other species.
For additional information refer to the Overdosage, Acute Toxicity section below.
Overdosage, Acute Toxicity
In horses, doses of 1.8 mg/kg (9X recommended dose) PO did notproduce 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 heart worm 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 beconsidered for recent massive oral ingestions in dogs or cats. For more information on ivermectintoxicity 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.
Acute toxic symptoms in cats will appear within 10 hours of ingestion. Symptoms may includeagitation, vocalization, anorexia, mydriasis, rear limb paresis, tremors, and disorientation. Blindness, head-pressing, wall-climbing, absence of oculomotor menace reflex, and a slow and incompleteresponse to pupillary light may also be seen. Neurologic symptoms usually diminish over severaldays and most animals completely recover within 2-4 weeks. Symptomatic and supportive care arerecommended.
Drug Interactions
None were located.Drug/Laboratory Interactions - When used at microfilaricide dosages, ivermectin may yieldfalse-negative results in animals with occult heartworm infection.