Animal Health Solutions

Brief Summary of Prescribing Information. ProHeart® 12 (moxidectin) For Extended-Release Injectable Suspension for Dogs CAUTION Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. INDICATIONS ProHeart 12 is indicated for use in dogs 12 months of age and older for the prevention of heartworm disease caused by Dirofilaria immitis for 12 months. ProHeart 12 is indicated for the treatment of existing larval and adult hookworm (Ancylostoma caninum and Uncinaria stenocephala) infections. RISK MINIMIZATION ACTION PLAN The ProHeart 12 and ProHeart 6 Risk Minimization Action Plan (RiskMAP) provides educational materials to the veterinarian, veterinary staff, and the dog owner explaining the risks and proper use of ProHeart 12 and ProHeart 6. ProHeart 12 and ProHeart 6 are the same formulation, but ProHeart 12 is three times the concentration of ProHeart 6. ProHeart 12 and ProHeart 6 are for use in dogs only and are available through a restricted distribution program to veterinarians that have completed the RiskMAP training and certification module. The ProHeart 12 and ProHeart 6 web-based training and certification module is available at http://www.proheart12.com. This website has important information on the safe and effective use of ProHeart 12 and ProHeart 6 for veterinarians. Only veterinarians and veterinary technicians/assistants that have completed the training and are certified can administer ProHeart 12 and ProHeart 6. Veterinarians are expected to report all adverse events that occur in animals or humans to the manufacturer. Important safety information is included below: CONTRAINDICATIONS ProHeart 12 is contraindicated in animals previously found to be hypersensitive to this drug or ProHeart 6. HUMAN WARNINGS Not for human use. Keep this and all drugs out of the reach of children. If contact with your skin occurs, wash thoroughly with water. May be irritating to the eyes. If product accidentally gets into your eyes, flush eyes thoroughly with water. In case of accidental ingestion, or if skin or eye irritation occurs, contact a Poison Control Center or physician for treatment advice and show the package insert to the physician. Take care to avoid accidental self-injection. In case of accidental self-injection, seek medical advice and show the package insert or the label to the physician. The Safety Data Sheet (SDS) contains more detailed occupational safety information. WARNINGS Anaphylactic and anaphylactoid reactions may occur in some dogs following administration of ProHeart 12 alone or with vaccines. In some cases, these reactions have resulted in death following administration of moxidectin microspheres (see POST-APPROVAL EXPERIENCE). Anaphylactic and anaphylactoid reactions should be treated immediately with the same measures used to treat hypersensitivity reactions to vaccines and other injectable products. Always provide Client Information Sheet and review with owners before administering ProHeart 12. The owner should be advised to observe their dog for adverse drug events including those described on the sheet. Do not administer ProHeart 12 to dogs who are sick, debilitated, underweight or who have a history of weight loss. PRECAUTIONS Prior to administration of ProHeart 12, the health of the patient should be assessed by a thorough medical history, physical examination and diagnostic testing as indicated (see WARNINGS). Caution should be used when administering ProHeart 12 in dogs with pre-existing allergic disease, including food allergy, atopy, and flea allergy dermatitis. (see WARNINGS). Caution should be used when administering ProHeart 12 concurrently with vaccinations. Adverse reactions, including anaphylaxis, have been reported following the concomitant use of moxidectin microspheres and vaccinations (see WARNINGS and POST-APPROVAL EXPERIENCE). ProHeart 12 should not be used more frequently than every 12 months. The effectiveness of ProHeart 12 has not been evaluated in dogs less than 12 months of age. Prior to administration of ProHeart 12, dogs should be tested for existing heartworm infections. Infected dogs should be treated with an adulticide to remove adult heartworms. ProHeart 12 is not effective against adult D. immitis. Caution should be used when administering ProHeart 12 to heartworm positive dogs (see ADVERSE REACTIONS). ADVERSE REACTIONS A well-controlled field study was conducted, including a total of 593 dogs (297 received two doses of ProHeart 12, 12 months apart and 296 received a monthly oral heartworm preventive as active control) ranging in age from 1 to 14 years. Over the 605-day study period, all observations of potential adverse reactions were recorded. Table 2: Number of Dogs* with Adverse Reactions Reported During the ProHeart 12 Field Study Adverse Reaction ProHeart® 12 n=297 (%) Active Control n=296 (%) Vomiting 75 (25.3) 78 (26.4) Lethargy 46 (15.5) 34 (11.5) Diarrhea (with and without blood) 43 (14.5) 46 (15.5) Anorexia 41 (13.8) 31 (10.5) Seizures 10 (3.4) 7 (2.4) Hepatopathy 8 (2.7) 3 (1.0) Hypersalivation 7 (2.4) 3 (1.0) Anaphylactoid/Hypersensitivity Reactions 6 (2.0) 4 (1.4) *Some dogs may have experienced more than one adverse reaction or more than one occurrence of the same adverse reaction during the study. Two ProHeart 12 (moxidectin) - treated dogs experienced anaphylactoid/hypersensitivity- related clinical signs within the first 24 hours following the initial treatment. Both dogs responded to symptomatic treatment. One dog experienced hives and facial swelling that resolved in 24 hours. The second dog experienced redness and swelling of the face and paws, followed by vomiting, polydipsia, and elevated heart rate and was treated symptomatically. Signs resolved within 4 days. One dog was pre-treated before the second injection of ProHeart 12, and neither dog had a reaction to the second dose 12 months later. One active control-treated dog experienced anaphylactoid/hypersensitivity-related clinical signs within the first 24 hours. The dog was withdrawn from the study prior to the second monthly dose. Mild injection site reactions occurred in six ProHeart 12-treated dogs and were observed from one to seven days post dosing and included warmth, swelling and pruritus. One of these cases included mild pruritus at the injection site that resolved spontaneously within 24 hours of administration. In a laboratory effectiveness study, dogs with 4- and 6-month-old heartworm infections administered moxidectin microspheres at a dose of 0.17 mg/kg experienced vomiting, lethargy and bloody diarrhea. These signs were more severe in the dogs with 4-month-old heartworm infections, including one dog that was recumbent and required supportive care, than in the dogs with older (6-month-old) infections. Post-Approval Experience (2018): The following adverse events are based on post-approval adverse drug experience reporting for ProHeart 6. ProHeart 12 and ProHeart 6 are the same formulation, but ProHeart 12 is three times the concentration of ProHeart 6. Not all adverse reactions are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. The following adverse events are listed in decreasing order of frequency by body system. Immune: anaphylaxis and/or anaphylactoid reactions, urticaria, head/facial edema, pruritus, pale mucous membranes, collapse, cardiovascular shock, erythema, immune-mediated hemolytic anemia, immune-mediated thrombocytopenia (signs reflected in other system categories could be related to allergic reactions, i.e. gastrointestinal, dermatologic, and hematologic) Gastrointestinal: vomiting (with or without blood), diarrhea with or without blood, hypersalivation General: depression, lethargy, anorexia, fever, weight loss, weakness Dermatological: injection site pruritus/swelling, erythema multiforme Neurological: seizures, ataxia, trembling, hind limb paresis Hematological: leukocytosis, anemia, thrombocytopenia Respiratory: dyspnea, tachypnea, coughing Hepatic: elevated liver enzymes, hypoproteinemia, hyperbilirubinemia, hepatopathy Urinary: elevated BUN, elevated creatinine, hematuria, polydipsia, polyuria Cardiopulmonary signs such as coughing and dyspnea may occur in heartworm positive dogs. In some cases, death has been reported as an outcome of the adverse events listed above. Foreign market experience with ProHeart 12 includes similar voluntarily reported adverse events, including death, following administration of ProHeart 12. For a copy of the Safety Data Sheet (SDS) or to report suspected adverse reactions, contact Zoetis at 1-888-963-8471. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae. INFORMATION FOR DOG OWNERS Always provide Client Information Sheet and review with owners before administering ProHeart 12. Owners should be advised of the potential for adverse reactions, including anaphylaxis, and be informed of the clinical signs associated with drug toxicity (see WARNINGS, ADVERSE REACTIONS and POST-APPROVAL EXPERIENCE sections.) Owners should be advised to contact their veterinarian immediately if signs of toxicity are observed. The vast majority of patients with drug related adverse reactions have recovered when the signs are recognized and veterinary care, if appropriate, is initiated. STORAGE INFORMATION Store the unconstituted product at or below 25°C (77°F). Do not expose to light for extended periods of time. After constitution, the product is stable for 8 weeks stored under refrigeration at 2° to 8°C (36° to 46°F). HOW SUPPLIED ProHeart 12 10 mL vial product is available in the following package sizes. 1-Pack 5-Pack 10-Pack 1 - 10% moxidectin sterile microspheres- 889 mg/vial 1 - Sterile vehicle - 8 mL/vial 5 - 10% moxidectin sterile microspheres- 889 mg/vial 5 - Sterile vehicle - 8 mL/vial 10 - 10% moxidectin sterile microspheres- 889 mg/vial 10 - Sterile vehicle - 8 mL/vial Approved by FDA under NADA # 141-519 Revised: April 2020 Distributed by: Zoetis Inc., Kalamazoo, MI 49007 40031204A&P

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