MILBEMYCIN OXIME

Note: For information on the combination product with lufenuron (Sentinel®), see the lufenuron monograph
Chemistry - Milbemycin oxime consists of approximately 80% of the A4 derivatives and 20% ofthe A3 derivatives of 5-didehydromilbemycin. Milbemycin is considered to be a macrolideantibiotic structurally.
Storage/Stability - Store milbemycin oxime tablets at room temperature.

Pharmacology - MILBEMYCIN OXIME

Milbemycin is thought to act by disrupting the transmission of the neurotransmitter gamma amino butyric acid (GABA) in invertebrates.

Uses, Indications

Milbemycin tablets are labeled as a once-a-month heartworm preventative(Dirofilaria immitis.) and for hookworm control (Ancylostoma caninum). It also has activityagainst a variety of other parasites, including roundworms (Toxocara canis), Trichuris vulpis, andfor demodicosis. In cats, milbemycin has been used successfully to prevent larval infection of
Dirofilaria immitis.

Pharmacokinetics - MILBEMYCIN OXIME

No specific information was located. At labeled doses, milbemycin is considered effective for at least 45 days after infection by D. immitis larva.

Contraindications, Precautions, Reproductive Safety

Because some dogs with a high numberof circulating microfilaria will develop a transient, shock-like syndrome after receiving milbemycin, the manufacturer recommends testing for preexisting heartworm infections.
Studies in pregnant dogs at daily doses 3X those labeled showed no adverse effects to offspringor bitch. Milbemycin does enter maternal milk; at standard doses, no adverse effects have beennoted in nursing puppies.

Adverse Effects, Warnings

At labeled doses, adverse effects appear to be negligible in microfilaria-free dogs, including Collie breeds (see Overdosage below). There have been unconfirmedreports of an increased incidence of seizure disorders or other neurologic signs seen in dogs receiving milbemycin, but a causal relationship has not been documented at the time of this writing.
When replacing diethylcarbamazine as a heartworm preventative, milbemycin should be administered within 30 days of discontinuing DEC.
Eight week old puppies receiving 2.5 mg/kg (5X label) for 3 consecutive days showed nosymptoms after the first day, but after the second or third consecutive dose showed some ataxia andtrembling. The manufacturer states that at labeled doses the drug is safe to use in puppies as youngas 8 weeks old.

Overdosage, Acute Toxicity

Beagles have tolerated a single oral dose of 200 mg/kg (200 timesmonthly rate). Rough-coated collies have tolerated doses of 10 mg/kg (20 times labeled) withoutadversity; doses of 12.5 mg/kg (25X label) caused ataxia, pyrexia, and periodic recumbency.

Drug Interactions

No interactions were noted. The manufacturer states that the drug was usedsafely during testing in dogs receiving other frequently used veterinary products, including vaccines, anthelmintics, antibiotics, steroids, flea collars, shampoos and dips.