Safety

Excellent safety profiles

A number of safety studies were carried out to determine the tolerance of Advocate^®/Advantage multi^® by cats and dogs.

Puppies and Kittens

Puppies and kittens were treated with Advocate at up to five times the licensed dose at two-week intervals (i.e. twice the licensed frequency of application) for a total of six treatments.

Treatment was tolerated without serious side effects, even at the highest dosage. Transient mydriasis, salivation, vomiting and rapid respiration were observed.

Adult cats and dogs

Adult cats and dogs were treated topically with up to 10 times the recommended dose of Advocate at one application, with no evidence of adverse effects or undesirable clinical signs.

Ivermectin-sensitive breeds

Studies have been performed to determine the safety of Advocate when administered to ivermectin-sensitive collies. Ivermectin-sensitive collies were treated with up to five times the recommended dose for three consecutive treatments at 28-day intervals.

There were no clinical abnormalities or adverse reactions observed in any of the dogs. Work carried out to determine the safety of accidental oral uptake of Advocate in ivermectin-sensitive breeds of dog revealed that 10% of the unit dose given orally resulted in no adverse effects, while 40% resulted in severe neurological signs.

As with any product containing macrocyclic lactones, special care should be taken with Collies, Old English Sheepdogs and related breeds or crossbreeds, to correctly administer the product. In particular, oral uptake by the recipient and/or other animals should be avoided.

Dogs with Patent Heartworm Infections

Studies were carried out to establish the safety of Advocate when administered to dogs with a patent D. immitis infection. Treatment of heartworm-positive dogs with macrocyclic lactones has, in the past, been associated with adverse reactions.

These are thought to be related to the rapid death of microfilariae and adult worms, with the subsequent occurrence of emboli. Heartworm-positive dogs were treated with Advocate at both one and five times the recommended dose at 14-day intervals for three treatments.¹ While there was no significant reduction in the number of adult D. immitis, importantly the treatment was found to be well-tolerated by both groups of dogs (only one dog receiving the 5x overdose vomited).

Nevertheless, in the interest of good clinical practice, it is recommended that all dogs 6 months of age or more, living in areas endemic for heartworm, should be tested for existing adult heartworm infections before being treated with the product.

Pregnancy and Lactation

Studies with Advocate have not been conducted in pregnant and lactating dogs or cats. Laboratory studies with either imidacloprid or moxidectin in rats and rabbits have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects.

Use only according to a risk-benefit assessment.