Questions and Answers
ProHeart^®6 Injectable Heartworm Product for Dogs

This content was archived on June 24, 2013.

What is ProHeart^®6?

ProHeart^®6 is an approved injectable sustained-release heartworm prevention product for dogs that can only be used under prescription by a veterinarian. ProHeart^®6 is usually administered once a year and provides protection from heartworm disease for a period of six months following injection. This veterinary drug is also approved in dogs for the treatment of infection with intestinal parasites called hookworms.

What is Heartworm Disease?

Heartworm disease is a serious and potentially fatal condition mainly in dogs. The parasite that causes heartworm disease is transmitted through infected mosquitos. In Canada, dogs are susceptible to this disease during heartworm season which occurs during the spring and summer.

What is the issue?

ProHeart^®6 was approved for sale in the United States in June 2001. On September 3, 2004, Fort Dodge Animal Health, the US-based manufacturer, issued a voluntary recall and ceased distribution of its heartworm medication ProHeart^®6 in the US. This voluntary recall was carried out at the request of the Food and Drug Administration (FDA) until the FDA's concerns about adverse reaction reports associated with the product could be resolved.

ProHeart^®6 was approved for sale in Canada in February 2002. Data (including the results of clinical trials) submitted to Health Canada in support of the New Drug Submission for ProHeart^®6 was considered satisfactory at the time of approval, in demonstrating safety and efficacy under the proposed conditions of use. ProHeart^®6 is also approved for sale in some European and Asian countries. ProHeart^®12, a similar product, is approved for sale in Australia.

It is important to note that not all adverse reactions can be identified in clinical trials, due to the relatively small number of animals and the controlled conditions of use which characterize pre-market studies. Once a veterinary drug is marketed, the Canadian Food and Drug Regulations require the manufacturer to inform Health Canada of suspected adverse reactions.

Why did Health Canada not recommend the removal of ProHeart^®6 from the Canadian market immediately following the voluntary recall of this veterinary drug in the US?

Contrary to southern States in the US where heartworm infections can be contracted year round, in Canada, dogs are only at risk of contracting heartworm disease during the spring and summer months (which represents our mosquito season). ProHeart^®6 is usually administered in the spring and only in dogs who may come in contact with infected mosquitoes. Since there was a low potential risk to animals in Canada over the fall/winter months, Health Canada determined that further investigation and analysis of the situation from a Canadian perspective were required to make a sound science-based decision.

What are the risks associated with the use of ProHeart^®6?

Based on Canadian and foreign data, the following types of adverse reactions may be associated with the use of ProHeart^®6 in dogs:

• Allergic reactions are the most frequent adverse drug reactions associated with the use of ProHeart^®6. Although rare, some of these reactions have involved anaphylaxis, a severe type of allergic reaction which may result in circulatory collapse, shock and even death. These reactions have been observed when ProHeart^®6 was the only medication administered and when this same veterinary drug was administered together with vaccines and/or other drugs.
  
  
• Symptoms of allergic reactions in dogs may include itchiness, hives, swelling of the face and ears, lack of energy, diarrhea and vomiting. Allergic reactions vary in severity and sometimes require medical attention or hospitalization.
  
  
• Various hematologic or blood abnormalities have been reported following ProHeart^®6 administration, the most frequent being increased white blood cells (leucocytosis), low red blood cells (anemia) and low platelets (thrombocytopenia).
  
  
• Seizures were the most consistently reported adverse drug reactions involving the central nervous system, with a majority of episodes occurring in the first three days after administering ProHeart^®6 injection. Other neurological signs that affect the nervous system include trembling, nervousness, confusion and weakness and may be associated with the use of ProHeart^®6.
  
  
• Evidence of injury to the liver has also been observed following ProHeart^®6 administration.

What is Health Canada doing?

Health Canada's Veterinary Drugs Directorate (VDD) closely monitors adverse reaction reports and other post-market data to ensure that veterinary drugs sold in Canada are safe and effective and that adequate directions for use are provided on product labels. Companion animal owners, caregivers and veterinarians should identify and report suspected adverse drug reactions or side effects. It is generally recognized that only a small percentage of adverse drug reactions are actually reported. Under-reporting is a key consideration in any analysis of pharmacovigilance data.

Since September 2004, VDD has worked with the Canadian manufacturer, Wyeth Animal Health, to investigate the safety of ProHeart^®6, including an in-depth analysis of Canadian adverse drug reaction reports. The frequency and severity of adverse drug reactions that have occurred and the absence of identifiable risk factors raised serious questions about the risk-benefit profile for ProHeart^®6.

Given these safety concerns, Health Canada asked the manufacturer to submit, in accordance with subsection C.01.013(1) of the Food and Drug Regulations, evidence to establish the safety of this veterinary drug under the recommended conditions of use. The manufacturer has submitted evidence to VDD regarding the safety of this product. Health Canada has evaluated the data and recommends:

• specific changes to the approved label of ProHeart^®6, and
• that Wyeth Animal Health notify veterinarians of these changes.

Wyeth Animal Health has revised the label to reflect Health Canada's safety concerns. The following advisory statement has been added to the Cautions section of the label and package insert:

Because of its potential for serious adverse drug reactions and the absence of identifiable risk factors associated with those reactions, ProHeart^®6 is only indicated for those dogs in which alternative preventatives cannot be effectively administered.

In addition, the label provides information for veterinarians about Canadian and international adverse drug reactions to ProHeart^®6.

What role does a veterinarian play in making dog owners aware of these risks?

Veterinarians have a responsibility to select the appropriate course of treatment, including preventative care, for each of their patients. They should also educate companion animal owners so that they can make informed decisions about the health of their animals.

Veterinarians and technicians are the first point of contact for adverse drug reaction reporting in clinical practice. Signs of adverse reactions, usually noticed by veterinarians and animal owners/caregivers, may be reported to the drug manufacturer or directly to Health Canada's VDD.

What role does the animal owner/caregiver play?

Clients should discuss the risks and benefits of choosing a particular veterinary drug to treat their animal with their veterinarian. With any treatment, it is important that clients are aware of any necessary follow-up care. Clients are also responsible for monitoring their animal for any adverse reactions that may occur after a veterinary drug has been administered and reporting back to their veterinarian.

Should I be concerned if my dog has been treated with ProHeart^®6 in the past?

Generally speaking, adverse drug reactions are rare events. The majority occur within the first few days after administration of a drug or vaccine. If you suspect that your dog has experienced an adverse drug reaction to ProHeart^®6, you should contact your veterinarian immediately and also report this incident to VDD's Pharmacovigilance Program at 1-877-VET-REAC (1-877-838-7322).

Suspected adverse veterinary drug reactions can be reported to the drug manufacturer or directly to Health Canada by completing an adverse drug reaction report form that is available on Health Canada's Web site and faxing or mailing it to the coordinates below. Veterinarians are encouraged to provide as much history and detail as possible, including laboratory and necropsy results. Animal owners and caregivers are encouraged to discuss their concerns with their veterinarian, who can then file a report on their behalf. Please contact Health Canada as soon as possible after the occurrence to obtain information about our program or file a report.

Fax: (613) 946-1125
Email: pharmacovigilance-vet@hc-sc.gc.ca
Toll free at: 1-877-VET-REAC (1-877-838-7322)

You may also mail an adverse drug reaction report to:
Pharmacovigilance Program
Veterinary Drugs Directorate
Health Products and Food Branch
Health Canada
Holland Cross Complex, Ground Floor
14 - 11 Holland Avenue
Ottawa, Ontario K1A OK9
Address Locator 3000A

For Your Information: Pharmacovigilance