Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

LEVAMISOLE

Chemistry - The levo-isomer of dl-tetramisole, levamisole has a greater safety margin than doesthe racemic mixture. It is available commercially in two salts, a phosphate and a hydrochloride.
Levamisole hydrochloride occurs as a white to pale cream colored, odorless or nearly odorless, crystalline powder. One gram is soluble in 2 ml of water.

Storage, Stability, Compatibility

Levamisole hydrochloride products should be stored at roomtemperature (15-30°C), unless otherwise instructed by the manufacturer; avoid temperatures greaterthan 40°C. Levamisole phosphate injection should be stored at temperatures at or below 21°C(70°F); refrigeration is recommended and freezing should be avoided.
Levamisole tablets should not be crushed nor suspensions made from them.

Pharmacology - LEVAMISOLE

Levamisole stimulates the parasympathetic and sympathetic ganglia in susceptibleworms. At higher levels, levamisole interferes with nematode carbohydrate metabolism by blockingfumarate reduction and succinate oxidation. The net effect is a paralyzing effect on the worm whichis then expelled alive. Levamisole's effects are considered to be nicotine-like in action.
Levamisole's mechanism of action for its immunostimulating effects are not well understood. It isbelieved it restores cell-mediated immune function in peripheral T-lymphocytes and stimulatesphagocytosis by monocytes. Its immune stimulating effects appear to be more pronounced in animals that are immune-compromised.
Uses, Indications - Depending on the product licensed, levamisole is indicated for the treatment ofmany nematodes in cattle, sheep & goats, swine, poultry. In sheep and cattle, levamisole hasrelatively good activity against abomasal nematodes, small intestinal nematodes (not particularlygood against Strongyloides spp.), large intestinal nematodes (not Trichuris spp.), and lungworms.
Adult forms of species that are usually covered by levamisole, include: Haemonchus spp.,
Trichostrongylus spp., Osteragia spp., Cooperia spp., Nematodirus spp., Bunostomum spp.,
Oesophagostomum spp., Chabertia spp., and Dictyocaulus vivapurus. Levamisole is less effectiveagainst the immature forms of these parasites and is generally ineffective in cattle (but not sheep)against arrested larval forms. Resistance of parasites to levamisole is a growing concern.
In swine, levamisole is indicated for the treatment of Ascaris suum, Oesophagostomum spp.,
Strongyloides, Stephanurus, and Metastrongylus.
Levamisole has been used in dogs as a microfilaricide to treat Dirofilaria immitis infection. It has also garnered much interest as an immunostimulant in the adjunctive therapy of various neoplasms.
Because of its narrow margin for safety and limited efficacy against many equine parasites, levamisole is not generally used in horses.

Pharmacokinetics - LEVAMISOLE

Levamisole is absorbed from the gut after oral dosing and through the skinafter dermal application, although bioavailabilities are variable. It is reportedly distributedthroughout the body. Levamisole is primarily metabolized with less than 6% excreted unchanged inthe urine. Plasma elimination half-lives have been determined for several veterinary species: Cattle4-6 hours; Dogs 1.8-4 hours; and Swine 3.5-6.8 hours. Metabolites are excreted in both the urine(primarily) and feces.
Contraindications/Precautions - Levamisole is contraindicated in lactating animals (not approved). It should be used cautiously, if at all, in animals that are severely debilitated, or havesignificant renal or hepatic impairment. Use cautiously or, preferably, delay use in cattle that arestressed due to vaccination, dehorning or castration.
There is no information regarding the safety of this drug in pregnant animals. Although levamisoleis considered relatively safe to use in large animals that are pregnant, use only if the potentialbenefits outweigh the risks.

Adverse Effects, Warnings

Adverse effects that may seen in cattle can include muzzle-foamingor hypersalivation, excitement or trembling, lip-licking and head shaking. These effects aregenerally noted with higher than recommended doses or if levamisole is used concomitantly withorganophosphates. Symptoms generally subside within 2 hours. When injecting into cattle, swelling may occur at the injection site. This will usually abate in 7-14 days, but may be objectionable in animals that are close to slaughter.
In sheep, levamisole may cause a transient excitability in some animals after dosing. In goats, levamisole may cause depression, hyperesthesia and salivation. Injecting levamisole SQ in goatsapparently causes a stinging sensation.
In swine, levamisole may cause salivation or muzzle foaming. Swine infected with lungworms maydevelop coughing or vomiting.
Adverse effects that may seen in dogs include GI disturbances (usually vomiting, diarrhea), neurotoxicity (panting, shaking, agitation or other behavioral changes), agranulocytosis, dyspnea, pulmonary edema, immune-mediated skin eruptions (erythroedema, erythema multiforme, toxicepidermal necrolysis) and lethargy.
Adverse effects seen in cats include hypersalivation, excitement, mydriasis and vomiting.
Overdosage/Toxicity - Symptoms of levamisole toxicity often mimic those of organophosphatetoxicity. Symptoms may include hypersalivation, hyperesthesias and irritability, clonic seizures,
CNS depression, dyspnea, defecation, urination, and collapse. These effects are best treated bysupportive means, as animals generally recover within hours of dosing. Acute levamisole overdosage can result in death due to respiratory failure. Should respiratory failure occur, artificialventilation with oxygen should be instituted until recovery takes place. Cardiac arrhythmias mayalso be seen. If the ingestion was oral, emptying the gut and/or administering charcoal withcathartics may be indicated.
Levamisole is considered to be more dangerous when administered parenterally than when givenorally or topically. Intravenous administration is particularly hazardous, and is never recommended.
In pet birds (cockatoos, budgerigars, Mynah birds, parrots, etc.), 40 mg/kg has been reported as atoxic dose when administered SQ. IM injections may cause more severe toxicity. Depression, ataxia, leg and wing paralysis, mydriasis, regurgitation, and death may be seen after a toxic dose inbirds.

Drug Interactions

Other nicotine-like compounds (e.g., pyrantel, morantel, diethylcarbamazine), or cholinesterase-inhibitor drugs (e.g., organophosphates, neostigmine) couldtheoretically enhance the toxic effects of levamisole; use together with caution.
Levamisole may enhance the immune-reaction and efficacy to Brucella vaccines.
Fatalities have been reported after concomitant levamisole and chloramphenicol administration;avoid using these agents together.

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