Milbemycin Oxime

5-didehydromilbemycin derivatives (A4 and A3)

Macrolide AntiparasiticPOtopicalDogsCatsReptiles

Also known as: Interceptor · Sentinel · Milbemite · CGA-179246

Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference

0.5 mg/kg PO once a monthPO· q30d

Body weight— 🐕

Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.

Dosing by species

🌎 NA — North America🌍 EU — Europe

Dogs

Indication	Dose	Route	Frequency	Duration	Region
Heartworm prophylaxis, control of adult hookworms, roundworms, and whipworms	0.5 mg/kg PO once a month	PO	q30d	—	🌎 NA
Microfilaricide chemotherapy (in adulticide-pretreated dogs)	0.5 mg/kg PO	PO	once	—	🌎 NA
Treatment of generalized demodicosis	1-3 mg/kg/day PO	PO	q24h	Until resolved	🌎 NA
Treatment of cheyletiellosis	2 mg/kg PO every 7 days for 3 doses	PO	q7d	3 doses	🌎 NA
Treatment of scabies	2 mg/kg PO every 7 days for 3 doses or 0.75 mg/kg once daily for 30 days	PO	q7d or q24h	3 doses or 30 days	🌎 NA
Chronic rhinitis caused by Pneumonyssus caninum	1 mg/kg PO once every 10 days for 3 treatments	PO	q10d	3 treatments	🌎 NA

Heartworm prophylaxis, control of adult hookworms, roundworms, and whipworms: Minimum dosage. Can also be used with nitenpyram for flea control.
Microfilaricide chemotherapy (in adulticide-pretreated dogs): Repeat in 2 weeks if necessary. Give approximately one month after melarsomine.
Treatment of generalized demodicosis: Begin at 1 mg/kg/day with skin scraping after 30 days. Increase to 2 mg/kg if minimal improvement, then 3 mg/kg if needed. Dogs homozygous for MDR1 mutation can show neuro side effects at 1-2.2 mg/kg/day.

Cats

Indication	Dose	Route	Frequency	Duration	Region
Prevention of heartworm; treat adult hookworm and adult roundworms	2 mg/kg PO once monthly	PO	q30d	—	🌎 NA

Reptiles

Indication	Dose	Route	Frequency	Duration	Region
Nematodes	0.5-1 mg/kg PO; repeat in 2 weeks	PO	once, repeat in 14 days	Until clear	🌎 NA

Nematodes: If 14 days after second dose fecal is positive, a third dose is given. Appears to be safe in chelonians (unlike ivermectin).

Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.

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Overview

Milbemycin oxime is a macrolide anthelmintic (macrocyclic lactone) widely used in veterinary medicine.

Primary use: Monthly heartworm (Dirofilaria immitis) prophylaxis and intestinal parasite control (hookworms, roundworms, whipworms).
Off-label uses: Treatment of generalized demodicosis, scabies, cheyletiellosis, and nasal mites.

Clinical Pearl: While generally safe, caution is required when using high, daily doses for demodicosis in breeds with the ABCB1 (MDR1) mutation (e.g., Collies, Australian Shepherds, Shelties), as they are more susceptible to neurologic toxicity. It is often considered a safer alternative to ivermectin for these breeds, but genetic testing is still recommended before initiating high-dose therapy.

Mechanism of action

Milbemycin acts primarily on the nervous system of invertebrates.

Binds to glutamate-gated chloride channels and GABA receptors in the parasite's nervous system.
This binding increases membrane permeability to chloride ions → hyperpolarization of nerve and muscle cells.
Results in flaccid paralysis and death of the parasite.

Note: Mammals are generally protected because their GABA receptors are confined to the central nervous system, and intact P-glycoprotein (P-gp) pumps at the blood-brain barrier prevent the drug from accumulating in the CNS.

Safety & warnings

Contraindications

Puppies less than 4 weeks of age or less than 2 lbs
Kittens less than 6 weeks of age or less than 1.5 lbs

Adverse effects

Transient shock-like syndrome (in microfilaremic animals)
Ataxia
Trembling
Mydriasis
Hypersalivation
Lethargy
Pyrexia
Seizures
Coma

Precautions

Because some dogs with a high number of circulating microfilaria will develop a transient, shock-like syndrome after receiving milbemycin, testing for preexisting heartworm infections is recommended before use. If using at doses greater than labeled in breeds susceptible to the ABCB1 genetic mutation, genetic testing is recommended before initiating therapy. Safety in breeding, pregnant, and lactating queens and breeding toms has not been established.

Drug interactions

Benzodiazepines

Effects may be potentiated by milbemycin; concurrent use is not advised in humans and warrants caution in animals.

P-glycoprotein inhibitors (Amiodarone, Ketoconazole, Cyclosporine, Diltiazem, Erythromycin, Clarithromycin, Quinidine, Spironolactone, Tamoxifen, Verapamil)

May inhibit the efflux pump at the blood-brain barrier, increasing the risk of milbemycin neurotoxicity, particularly in dogs at risk for the ABCB1-1 (MDR1) mutation.

Monitoring

Heartworm status (prior to initiation of therapy)
Neurologic signs (especially in susceptible breeds or at high doses)
Skin scrapings (if treating demodicosis)

Overdose

Beagles have tolerated a single oral dose of 200 mg/kg (200 times monthly rate). Rough-coated collies have tolerated doses of 10 mg/kg (20 times labeled) without adversity. Toxic doses can cause mydriasis, hypersalivation, lethargy, ataxia, pyrexia, seizures, coma, and death. There is no specific antidotal treatment; supportive therapy is recommended.

Available products

Formulations

Oral tablets
Otic solution

Veterinary

Interceptor Flavor Tabs: 2.3 mg, 5.75 mg, 11.5 mg, 23 mg
Sentinel Flavor Tabs (milbemycin/lufenuron): 46 mg/115 mg/230 mg/460 mg milbemycin/lufenuron combinations
Milbemite 0.1% otic solution

Regulatory status

No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU

Storage & stability

Store milbemycin oxime tablets at room temperature.

Client information

Compliance is key: Give this medication exactly as prescribed, usually once a month on the same day.
Watch them eat it: Ensure your pet completely consumes the tablet. If they spit it out, they will not be protected.
Testing required: Your pet must have a negative heartworm test before starting this medication.
Side effects: Very rare at standard monthly doses. If your pet is being treated for mange at higher daily doses, watch for and immediately report any stumbling, tremors, excessive drooling, or extreme lethargy.

VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.