Doramectin

Macrocyclic lactone (avermectin) Antiparasitic agent (endectocide)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog SC 0.2 mg/kg Once, repeated in 2 weeks for mange Duration: Single dose or as directed
Notes: Not approved in dogs in many countries; use with caution in MDR1 mutant breeds.
Cat SC 0.2 mg/kg Once, repeated in 2 weeks for mange Duration: Single dose or as directed
Notes: Not approved in cats; use with caution.
Horse IM 0.2 mg/kg Once Duration: Single dose
Notes: Not approved in horses in some countries; use with caution.
Cattle SC 0.2 mg/kg Once Duration: Single dose
Notes: Approved for cattle; provides prolonged activity.
Sheep SC 0.2 mg/kg Once Duration: Single dose
Notes: Not approved in sheep in some countries; extra-label use.
Goat SC 0.2 mg/kg Once Duration: Single dose
Notes: Not approved in goats; extra-label use.
Rabbit SC 0.2-0.4 mg/kg Once, repeated in 10-14 days for mites Duration: Single or repeated
Notes: Off-label use; monitor for neurological signs.
Swine IM 0.3 mg/kg Once Duration: Single dose
Notes: Approved for swine in some countries.

Clinical Indications & Species Uses

General Indications
  • Broad-spectrum antiparasitic for internal and external parasites in livestock and companion animals
Dog (Canine)
  • Treatment and control of gastrointestinal nematodes (e.g., Toxocara canis, Ancylostoma caninum, Trichuris vulpis)
  • Treatment of sarcoptic mange (Sarcoptes scabiei)
  • Treatment of ear mites (Otodectes cynotis)
Cat (Feline)
  • Treatment of gastrointestinal nematodes (e.g., Toxocara cati, Ancylostoma tubaeforme)
  • Treatment of ear mites (Otodectes cynotis)
Horse (Equine)
  • Treatment of gastrointestinal strongyles (e.g., Strongylus vulgaris, Cyathostomins)
  • Treatment of lungworms (Dictyocaulus arnfieldi)
  • Treatment of bots (Gasterophilus spp.)
  • Treatment of sarcoptic and psoroptic mange
Cattle (Bovine)
  • Treatment and control of gastrointestinal roundworms (e.g., Ostertagia ostertagi, Cooperia spp., Haemonchus contortus, Trichostrongylus spp.)
  • Treatment of lungworms (Dictyocaulus viviparus)
  • Treatment of eyeworms (Thelazia spp.)
  • Treatment of warbles (Hypoderma spp.)
  • Treatment of mange mites (Sarcoptes, Psoroptes, Chorioptes)
  • Treatment of lice (Linognathus, Haematopinus, Solenopotes, Bovicola)
Small Ruminants (Sheep / Goat)
  • Treatment and control of gastrointestinal nematodes (e.g., Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus spp.)
  • Treatment of lungworms (Dictyocaulus filaria)
  • Treatment of nasal bots (Oestrus ovis)
  • Treatment of mange mites and lice
Rabbit & Small Mammals
  • Treatment of ear mites (Psoroptes cuniculi)
  • Treatment of sarcoptic mange
  • Treatment of gastrointestinal nematodes (e.g., Passalurus ambiguus)
Exotic & Other Species
  • Treatment of mites and nematodes in various exotic species (e.g., guinea pigs, rats, reptiles) - off-label use

Pharmacology & Mechanism of Action

Drug Class: Macrocyclic lactone (avermectin) | Pharmacological Group: Antiparasitic agent (endectocide)

Mechanism of Action: Doramectin is a macrocyclic lactone that binds selectively and with high affinity to glutamate-gated chloride channels in nerve and muscle cells of invertebrates. This binding increases the permeability of the cell membrane to chloride ions, leading to hyperpolarization and paralysis of the parasite. It also interacts with other ligand-gated chloride channels, such as those gated by gamma-aminobutyric acid (GABA), but the glutamate-gated channels are the primary target. The paralysis and death of the parasite result from the sustained influx of chloride ions, which disrupts neuromuscular transmission. Doramectin has no effect on GABA-gated channels in mammals because these channels are located only in the central nervous system and are protected by the blood-brain barrier, and the drug does not readily cross this barrier in most species.

Pharmacodynamics: Doramectin exhibits potent activity against a broad spectrum of nematodes and arthropods, including gastrointestinal roundworms, lungworms, and external parasites such as mites and lice. It is effective against both larval and adult stages of many parasites. The drug is highly lipophilic, which contributes to its prolonged persistence in tissues and its long-lasting efficacy. In cattle, a single subcutaneous injection provides sustained plasma concentrations for up to 28 days, offering extended protection against reinfection. The pharmacodynamic effect is dose-dependent, with higher doses providing greater efficacy and longer duration of action. Doramectin is also effective against some ectoparasites, including sarcoptic and psoroptic mange mites, and certain ticks.

⚡ Pharmacokinetics Summary

Absorption: Doramectin is well absorbed after subcutaneous or intramuscular injection, with peak plasma concentrations reached within 24-48 hours. Oral absorption is also good in some species, but the injectable route is most commonly used in veterinary practice. The absorption profile is characterized by a slow release from the injection site, contributing to its prolonged half-life.
Distribution: Doramectin is widely distributed throughout the body, with high concentrations in fat and liver due to its lipophilic nature. It crosses the blood-brain barrier to a limited extent in most species, but in collies and other dogs with the MDR1 gene mutation, it can accumulate in the central nervous system, leading to neurotoxicity. It is distributed into milk and crosses the placenta.
Metabolism: Doramectin is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, to various hydroxylated and polar metabolites. The metabolites are less active than the parent compound. The metabolism is species-dependent, with cattle and swine metabolizing it more rapidly than sheep and goats.
Excretion: Doramectin is excreted primarily in the feces, with a smaller amount eliminated in urine. In lactating animals, a significant portion is excreted in milk. The elimination half-life is long, ranging from 3-8 days in cattle, 4-6 days in swine, and 2-4 days in sheep and goats.
Half-Life: Cattle: 3-8 days; Swine: 4-6 days; Sheep/Goats: 2-4 days; Dogs: 1-2 days (but may be prolonged in MDR1 mutants)
Bioavailability: Subcutaneous injection: nearly 100% bioavailability; Oral: approximately 50-70% in some species.
Protein Binding: Doramectin is highly protein-bound, with approximately 90-95% bound to plasma proteins.

Available Formulations & Strengths

Injectable Solution 1% (10 mg/mL) (SC, IM)
Oral Paste Not commonly available (PO)
Pour-on Solution 0.5% (5 mg/mL) (Topical)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to doramectin or other macrocyclic lactones
  • Do not use in dogs with known MDR1 gene mutation (e.g., Collies, Australian Shepherds) due to risk of severe neurotoxicity
  • Do not use in animals with compromised blood-brain barrier
  • Do not use in lactating animals if milk is intended for human consumption unless withdrawal times are observed
  • Do not use in animals with severe hepatic impairment
Warnings & Clinical Precautions:
  • Use with caution in young animals, as safety has not been fully established
  • Avoid use in sick or debilitated animals
  • Do not administer intravenously
  • Use with caution in animals with a history of seizures
  • In food animals, observe withdrawal times
  • Do not use in horses intended for human consumption
  • In dogs, use only when other treatments are not available and with extreme caution
  • Wash hands after handling
  • Keep away from children

Adverse Effects & Reactions

Common:

  • Transient pain or swelling at injection site
  • Salivation (if oral)
  • Lethargy
  • Mild gastrointestinal upset (vomiting, diarrhea)

Serious / Severe:

  • Neurotoxicity (ataxia, tremors, seizures, coma) especially in MDR1 mutant dogs
  • Respiratory depression
  • Death (in overdose or sensitive breeds)

Rare:

  • Allergic reactions (urticaria, anaphylaxis)
  • Hepatotoxicity
  • Bone marrow suppression

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other macrocyclic lactones (e.g., ivermectin, moxidectin) Additive toxicity and increased risk of adverse effects High
P-glycoprotein inhibitors (e.g., ketoconazole, itraconazole, cyclosporine) Increased plasma concentrations of doramectin and risk of neurotoxicity High
GABAergic drugs (e.g., barbiturates, benzodiazepines) Potential additive CNS depression Moderate
Organophosphates or other cholinesterase inhibitors Potential additive toxicity Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Ataxia
  • Tremors
  • Mydriasis
  • Depression
  • Coma
  • Respiratory failure
  • Death

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. In cases of recent oral ingestion, induce emesis (if appropriate) and administer activated charcoal. Provide intravenous fluids, respiratory support, and anticonvulsants (e.g., diazepam) if seizures occur. In severe cases, consider lipid emulsion therapy to enhance elimination of lipophilic drugs. Monitor vital signs and neurological status closely.

Food Animal Withdrawal Times

🥩 Meat: 35 days🥛 Milk: 24 days

Withdrawal times vary by country and formulation. For cattle: meat 35 days, milk 24 days. For swine: meat 7 days. For sheep/goats: not approved, extra-label withdrawal times may be longer (e.g., 45 days meat, 30 days milk). Always consult local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F)

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light. Keep container tightly closed. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in cattle and swine in the US. Not approved for dogs, cats, horses, sheep, goats, or other species.

Extra-Label (Off-Label) Use: In the US, doramectin is approved for cattle and swine. Extra-label use in other species is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) only with a valid veterinarian-client-patient relationship and must follow established withdrawal times. Use in minor species may be allowed under the Minor Use and Minor Species (MUMS) Act.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Doramectin is a highly effective endectocide with a long duration of action, making it particularly useful in livestock for controlling parasites with a single treatment. Its lipophilicity allows for sustained tissue concentrations, providing prolonged protection. However, its use in companion animals is limited due to safety concerns, especially in breeds with MDR1 mutations. In dogs and cats, alternative avermectins like ivermectin or milbemycin are often preferred. For horses, doramectin is effective but not approved in some regions; careful consideration of withdrawal times is necessary. In food animals, strict adherence to withdrawal times is essential to prevent drug residues in meat and milk. Resistance to macrocyclic lactones has been reported in some gastrointestinal nematodes, particularly in sheep and goats, so rotational deworming strategies are recommended. Always perform a fecal egg count reduction test to monitor efficacy. When using doramectin, ensure accurate dosing based on body weight to avoid underdosing, which can promote resistance, or overdosing, which can cause toxicity.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)