(Ivermectin/Pyrantel)

Caution: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.

INDICATIONS: For use in dogs to prevent canine heartworm disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection and for the treatment and control of ascarids (Toxocara Canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma braziliense).

DOSAGE: Tri-Heart^® Plus ivermectin/pyrantel chewable tablets should be administered orally at monthly intervals at the recommended minimum dose level of 6 mcg of ivermectin per kilogram (2.72 mcg/lb) and 5 mg of pyrantel (as pamoate salt) per kg (2.27 mg/lb) of body weight. The recommended dosing schedule for prevention of canine heartworm disease and for the treatment and control of ascarids and hookworms is as follows:

Dog Weight	Chewable Tablets per Month	Ivermectin Content	Pyrantel Content	Color Coding on Blister Card and Carton
Up to 25 lbs	1	68 mcg	57 mg	Blue
26 to 50 lbs	1	136 mcg	114 mg	Green
51 to 100 lbs	1	272 mcg	227 mg	Brown

Tri-Heart Plus ivermectin/pyrantel chewable tablets are recommended for dogs 6 weeks of age and older. For dogs over 100 lbs, use the appropriate combination of these tablets.

ADMINISTRATION: Remove only one chewable tablet at a time from the blister card. Because most dogs find Tri-Heart Plus chewable tablets palatable, the product can be offered to the dog by hand. Alternatively, it may be added intact to a small amount of dry food or placed in the back of the dog's mouth for forced swallowing.

Care should be taken that the dog consumes the complete dose, and treated animals should be observed for a few minutes after administration to ensure that part of the dose is not lost or rejected. If it is suspected that any of the dose has been lost, redosing is recommended.

Tri-Heart Plus chewable tablets should be given at monthly intervals during the period of the year when mosquitoes (vectors), potentially carrying infective heartworm larvae, are active. The initial dose must be given within a month (30 days) after the dog's first exposure to mosquitoes. The final dose must be given within a month (30 days) after the dog's last exposure to mosquitoes.

When replacing another heartworm preventive product in a heartworm disease preventive program, the first dose of Tri-Heart Plus chewable tablets must be given within a month (30 days) of the last dose of the former medication.

If the interval between doses exceeds a month (30 days), the efficacy of ivermectin can be reduced. Therefore, for optimal performance, the chewable tablet must be given once a month on or about the same day of the month. If treatment is delayed, whether by a few days or many, immediate treatment with Tri-Heart Plus chewable tablets and resumption of the recommended dosing regimen minimizes the opportunity for the development of adult heartworms.

Monthly treatment with Tri-Heart Plus chewable tablets also provides effective treatment and control of ascarids (T. canis, T. leonina) and hookworms (A. caninum, U. stenocephala, A. braziliense). Clients should be advised of measures to be taken to prevent reinfection with intestinal parasites.

EFFICACY: Tri-Heart^® Plus chewable tablets given orally using the recommended dose and regimen, are effective against the tissue larval stage of D. immitis for a month (30 days) after infection and, as a result, prevent the development of the adult stage. Tri-Heart Plus chewable tablets are also effective against canine ascarids (T. canis, T. leonina) and hookworms (A. caninum. U. stenocephala, A. braziliense).

ACCEPTABILITY: In acceptability trials, Tri-Heart Plus chewable tablets were shown to be a palatable oral dosage form that was consumed at first offering by the majority of dogs.

PRECAUTIONS: All dogs should be tested for existing heartworm infection before starting treatment with Tri-Heart Plus chewable tablets which are not effective against adult D. immitis. Infected dogs must be treated to remove adult heartworms and microfilariae before initiating a program with Tri-Heart Plus chewable tablets.

While some microfilariae may be killed by the ivermectin in Tri-Heart Plus chewable tablets at the recommended dose level, Tri-Heart Plus chewable tablets are not effective for microfilariae clearance. A mild hypersensitivity-type reaction, presumably due to dead or dying microfilariae and particularly involving a transient diarrhea has been observed in clinical trials with ivermectin alone after treatment of some dogs that have circulating microfilariae.

Keep this and all drugs out of the reach of children. In case of ingestion by humans, clients should be advised to contact a physician immediately. Physicians may contact a Poison Control Center for advice concerning cases of ingestion by humans.

Store at controlled room temperature of 59-86° F (15-30° C). Protect product from light.

ADVERSE REACTIONS: In clinical field trials with ivermectin/pyrantel, vomiting or diarrhea within 24 hours of dosing was rarely observed (1.1% of administered doses). The following adverse reactions have been reported following the use of ivermectin at the recommended dose: depression/lethargy, vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, convulsions and hypersalivation.

SAFETY: Studies with ivermectin indicate that certain dogs of the Collie breed are more sensitive to the effects of ivermectin administered at elevated dose levels (more than 16 times the target use level of 6 mcg/kg) than dogs of other breeds. At elevated doses, sensitive dogs showed adverse reactions which included mydriasis, depression, ataxia, tremors, drooling, paresis, recumbency, excitability, stupor, coma and death. Ivermectin demonstrated no signs of toxicity at 10 times the recommended dose (60 mcg/kg) in sensitive Collies. Results of these trials and bioequivalency studies support the safety of ivermectin products in dogs, including Collies, when used as recommended.

Ivermectin/pyrantel has shown a wide margin of safety at the recommended dose level in dogs, including pregnant or breeding bitches, stud dogs and puppies aged 6 or more weeks. In clinical trials, many commonly used flea collars, dips, shampoos, anthelmintics, antibiotics, vaccines and steroid preparations have been administered with ivermectin/pyrantel in a heartworm disease preventive program.