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Milbemycin Oxime
Revised: June 27, 2024
Published: January 01, 2000

Brand name: Interceptor, Milbemite

Also combined with other anti-parasite ingredients in Trifexis, Sentinel, Interceptor Plus, Sentinel Spectrum, Milbemax and Milbeguard

Available in:
2.3 mg, 5.75 mg, 11.5 mg, and 23 mg tablets
An ear formula for cats


It is hard to imagine a time when heartworm prevention for dogs was handled with daily pills, but that was what dog ownership involved up until the mid-1980s.

 Skipping even one dose would leave a dog vulnerable to a terrible infection.  When ivermectin became commercially available for dogs, heartworm (as well as hookworm and roundworm infection) could be prevented by a monthly chewable, as is commonly done today. It was an amazing development in pet care. Milbemycin oxime became commercially available shortly after with the added benefit of covering not only hookworms, heartworms, and roundworms but also whipworms. As of this writing, milbemycin oxime is also available as an ear drop for cats to be used against ear mites. It has activity against many parasites, and it has been combined with other anti-parasite medications to create even broader spectrum parasite protection.

How this Medication is Used

How this medication is used depends on the target parasite.

Heartworms, Hookworm, Roundworms, and, for dogs, Whipworms:
A monthly tablet for dogs and cats. Puppies should be at least 2 lbs by weight and at least 4 weeks of age. Kittens should be at least 6 weeks of age and one and a half pounds of weight. Oral use of milbemycin oxime for parasites other than these is considered off-label, and higher doses may be involved.

Demodectic Mange Mites: Canine demodex mites are sensitive to milbemycin oxime but medication must be given daily.

Sarcoptic Mange Mites: Sarcoptic mange mites are sensitive to milbemycin oxime, but a special off-label protocol is needed.

Ear Mites: Ear mites are sensitive to milbemycin oxime given orally but a special protocol is likely necessary. In cats, a milbemycin oxime ear drop is commercially available.

Milbemycin oxime may be given with or without food.

Interactions with Other Drugs:

Contact your veterinarian in the event of a skipped dose so as to obtain proper instructions.

There are no meaningful drug interactions except in dogs with the MDR1 mutation. Breeds that are most commonly involved are collie-related breeds but other breeds can be involved.

The MDR1 mutation (recently renamed the ABCB-1 mutation) concerns the function of something called the P-glycoprotein. In normal patients, the P-glycoprotein is involved in keeping drugs out of certain tissues and is important in keeping milbemycin oxime out of the patient's nervous system. A healthy P-glycoprotein system is what allows milbemycin oxime to be safe for mammals, even in very high doses. 

The MDR1 mutation can create dangerous milbemycin oxime sensitivity. Normal commercial heartworm preventives do not use high enough doses for this issue to come into play; it is usually in the treatment of demodectic or sarcoptic mange when the issue comes up. Similarly, as mentioned, certain drug combinations involving milbemycin oxime are issues in dogs with the MDR1 mutation. Drugs that can combine with milbemycin oxime to create a toxic situation in an MDR1 mutation dog include:

Testing for the MDR1 Mutation

Because of the prevalence of the P-glycoprotein gene mutation, genetic testing is recommended for dogs of the following breeds: Collie, Shetland sheepdog, Australian Shepherd, Old English Sheepdog, Long-Haired Whippet, and possibly other herding breeds. Genetic testing can be done. This is a DNA test using an oral swab. Test kits can be ordered directly from the Washington State University Veterinary School.

Side Effects

If milbemycin oxime is given to a heartworm-positive dog with circulating microfilariae (baby heartworms swimming in the bloodstream), the young worms may die abruptly, causing a shock-like reaction in the dog. A slower microfilariae kill with ivermectin is a safer method for clearing heartworm microfilariae.

Dogs with the MDR1 mutation can have serious neurologic reactions to milbemycin oxime if medication is used at a dose higher than the labeled heartworm preventive dose. 

Toxic reactions (as in overdose) include dilated pupils, drooling, incoordination, fever, seizures, coma, and death.

Special Cautions

Milbemycin oxime is not approved for use during pregnancy and lactation. 

Milbemycin oxime tablets should be stored in the blister packs provided by the manufacturer. Store at room temperature. 

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