Elephant specific information, if available, is in blue.

Chemistry – 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.

 

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 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.

 

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 4th stage 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 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, ivermectin is approved only for use as a preventative for heartworm. It is also been used as a microfilaricide, ectoparasiticide and endoparasiticide.

 

Pharmacokinetics – 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 SQ administration, absorption after oral dosing is more rapid than SQ. 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 apparently 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:

 

Species	Bioavailability (F)	Volume  of Distribution (Vd) (L/kg)	T 1/2 (terminal) (in days)	Total Body Clearance (L/kg/day)
Cattle		0.45 – 2.4	2 – 3	0.79
Dogs	.95	2.4	2
Swine		4	0.5
Sheep	1.0 intra-abomasal .251 intra-ruminal	4.6	2 – 7

 

Contraindications/Precautions/Reproductive Safety – 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.

 

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 to be 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.

 

Adverse Effects/Warnings – In horses, swelling and pruritis 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 pruritis 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 also 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 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.

 

Overdosage/Acute Toxicity – 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 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 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.

 

Acute toxic symptoms in cats will appear within 10 hours of ingestion. Symptoms may include agitation, vocalization, anorexia, mydriasis, rear limb paresis, tremors, and disorientation. Blindness, head-pressing, 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 are recommended.

 

Drug Interactions – None were located.

 

Drug/Laboratory Interactions – When used at microfilaricide dosages, ivermectin may yield false-negative results in animals with occult heartworm infection.

 

Doses –

Horses:

For susceptible parasites:

a)   200 micrograms/kg (0.2 mg/kg) PO using oral paste or oral liquid. (Product Information; Eqvalan®—MSD)

b)   0.2 mg/kg PO; 0.2 mg/kg PO at 4 day intervals for lice and mange. (Robinson 1987)

c)   As a larvacidal for arterial stages of S. vulgaris: 0.2 mg/kg once. (Herd 1987)

 

Elephants:

For lice infestation:

a) 0.059 – 0.087 mg/kg administered orally using the injectable preparation; may re-treat at 5- 6 weeks. (Karesh and Robinson, 1985).

 

For helminths:

b) 0.1 mg/kg SQ for strongyles and other helminths (Tuntasuvan, 2003).

 

c) 0.1 mg/kg PO for strongyles and other helminths (Mikota and Bartlett, 2003).

 

 

Elephant References:

 

 

a Karesh,W.B. and Robinson,P.T. 1985. Ivermectin treatment of lice infestations in two elephant species. Journal of the American Veterinary Medical Association 187:(11):1235-1236  Summary:  Infestation by the elephant louse, Haematomyzus elephantis was diagnosed in 5 Asian elephants and 4 African elephants. The elephants were treated orally with an injectable ivermectin preparation.  Dosages ranged from 0.059 mg/kg to 0.087 mg/kg. Within 48-72 hours the lice became easier to remove manually.  Seven days post-treatment lice were not found.  Five to six weeks after he first treatment, ivermectin was given again using the same route and same dose.  At the time of the second treatment, a few lice were present but no eggs were found.  Previously, ivermectin administered by the intramuscularly route was found to be effective against lice, however, it caused local inflammation and soreness at the injection site and use of this route was discontinued.

b) Darunee Tuntasuvan B.Sc., D.V.M., Ph.D. (personal communication) 2003. In an unpublished study, Dr. Tantasuvan found a mixture of 1% ivermectin and 10% Clorsulon (Ivomec – F) administered subcutaneously at a dose of 0.1 mg/kg to be 100 % effective against helminths. Flotation and sedimentation techniques were performed and eggs / gram determined at 0, 1, and 2 days and at weekly intervals for 6 weeks. This dose was not effective against flukes. For further information contact tdarunee@hotmail.com

         c) Susan Mikota DVM and Susie Bartlett DVM 2003. In an unpublished study, an ivermectin dose of 0.1 mg/kg administered orally was found to be effective against strongyles in Asian elephants. Egg counts were reduced to zero two weeks post worming (n=10).

Monitoring Parameters –

1)   Clinical efficacy

2)   Adverse effects/toxicity (see Adverse Effects and Overdosage Sections)

 

Client Information – 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).

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

 

Veterinary Approved Products –

Ivermectin for Injection 10 mg/ml (1%) in 50 ml, 200 ml, 500 ml and 1000 ml bottles

Ivomec®  1% Injection for Cattle (MSD-AgVet); (OTC) Approved for use in nonlactat­ing dairy cattle, beef cattle and reindeer. Slaughter withdrawal = 35 days (cattle); 56 days (reindeer and bison)

 

Ivermectin for Injection 10 mg/ml (1%) & Clorsulon 100 mg/ml; Ivomec® Plus  Injection(MSD-AgVet); (OTC) Approved for use in cattle.

 

Ivermectin Oral Paste 0.153% (1.53 mg/gram) in 10.4 oz tubes; Ivomec® Cattle Paste 0.153% (MSD-AgVet); (OTC)  Approved for use in nonlactating dairy cattle, and beef cattle. Slaughter withdrawal = 24 days

 

Ivermectin for Injection 10 mg/ml (1%) in 50 ml, 200 ml, 500 ml bottles; Ivomec® 1% Injection for Swine (MSD-AgVet); (OTC)  Approved for use in swine. Slaughter withdrawal = 18 days

 

Ivermectin for Injection 2.7 mg/ml (0.27%) in 200 ml bottles; Ivomec®  0.27% Injection for Feeder and Grower Pigs (MSD-AgVet); (OTC)  Approved for use in swine. Slaughter withdrawal = 18 days

 

Ivermectin Oral Paste 1.87% (18.7 mg/gram) in 6.08 g syringes; Eqvalan®  Paste 1.87% (MSD-AgVet), Zimectrin® Paste (Farnam); (OTC)  Approved for use in horses (not intended for food purposes).

 

Ivermectin Liquid 1% (10 mg/ml) in 50 ml and 100 ml btls (for tube administration; not for injection);Eqvalan® Liquid for Horses (MSD-AgVet); (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 or 9 packs; Heartgard 30®  (MSD-AgVet) (Rx)  Approved for use in dogs.

 

Ivermectin/Pyrantel Oral Tablets 68 mcg/57 mg, 136 mcg/114mg, 272 mcg/228 mg) in  packs; Heartgard 30® Chewables Plus (MSD-AgVet) (Rx)  Approved for use in dogs.