Animal & Veterinary
CVM Adverse Drug Data Show Increase in Reports of Lack of Effectiveness for Heartworm Prevention Drugs
by Dr. Martine Hartogensis, Veterinary Medical Officer, CVM Promotion and Advertising Liaison, Office of Surveillance and Compliance
FDA Veterinarian Newsletter November/December 2005 Volume XX, No VI
The Center for Veterinary Medicine (CVM) has been receiving an increasing number of reports of lack of effectiveness in products designed to prevent heartworm disease in dogs and cats, and the best way to determine the reason for the increase is through more information that can come from routine heartworm tests and adverse drug event reporting.
The increase in the reports could be due to an increased awareness among veterinarians and pet owners about heartworm prevention effectiveness issues, leading to an increase in the number of reports while the incidence rate stayed the same. Or the increase might indicate a problem with the products.
CVM’s database of post-approval Adverse Drug Experience reports currently includes 5,794 reports of lack of effectiveness for the heartworm prevention drugs. It could be that owners are not properly administering the drugs, or some dogs might not swallow the pills or could later vomit and lose the drug.
However, the database also includes 1,301 reports that CVM specialists have analyzed and determined to be definitely related to failure of the products. These cases were well documented concerning administration of the product according to the label, proper purchase history, and negative heartworm antigen tests prior to initiation of the drug and at least seven months after beginning prevention, followed by a positive antigen test.
Routine heartworm testing, as determined by the pet’s primary veterinarian and discussion with the pet owner, can help protect the dog or cat. In addition, the tests can result in better information reaching CVM, generated through post-approval Adverse Drug Experience reports, so experts at the Center can determine why we are seeing an increase in lack of effectiveness reports.
Heartworm preventive medications intended for use in dogs and cats historically have been thought to be safe and effective. In fact, approval of a heartworm prevention product requires 100 percent efficacy in the pre-approval clinical trials.
However, the real world is not exactly like clinical trials. Real world conditions, such as patient variability, geographic considerations, and owner compliance, may be contributing to the effectiveness problems with these products.
In 2005, CVM’s Division of Surveillance asked the sponsors of all marketed heartworm preventives to refrain from claiming 100 percent effectiveness in promotion and advertising materials, due to the number of post-approval reports of lack of effectiveness for all marketed preventive products.
Heartworm disease is transmitted to dogs and cats through mosquito bites. If the mosquito is carrying the heartworm larvae when it bites a pet, the disease is likely transmitted to the pet.
The larvae migrate throughout the tissues of the infected animal. Heartworm prevention products kill the larvae before they become adult worms. Without treatment, over the course of about six months the larvae mature into adult worms, with the male heartworm growing to 4-6 inches and the female growing to 10-12 inches. They reside in the animal’s heart and lungs, and in nearby blood vessels. Even before they become mature, heartworms mate and produce microfilariae, which turn into larvae that ultimately become adult heartworms. The microfilaria must be ingested by a mosquito before continuing their life cycle.
Heartworms can kill a dog. More likely, though, heartworms will make dogs extremely sick. Dogs infected with heartworm can be successfully treated; however, such treatment may be inconvenient and emotionally stressful for the owner. If treatment is necessary, it is important to try to accomplish it with a minimum of harmful effects from the drugs and a tolerable degree of complications created by the dying heartworms. Heartworm infected dogs showing no signs or mild signs have a high success rate with treatment. Dogs with evidence of more severe heartworm disease can be successfully treated, but the possibility of complications and mortality are greater. The presence of severe heartworm disease within a patient in addition to the presence of other life-threatening diseases may prevent treatment for heartworm infection.
The best way to avoid the trouble is through proper care by the veterinarian, including routine testing. Testing is important even in dogs regularly treated with heartworm prevention products, due to the occasional reports of product ineffectiveness.
The American Heartworm Society, which was established in 1974 to generate and disseminate information about heartworm disease and treatment, has more information about the disease on its website, http://www.heartwormsociety.org.
The Heartworm Society mentions annual testing in a question-and-answer article on its website. Specifically, the Society says: “Annual testing for heartworm infection is now highly recommended. Even though heartworm preventives...are essentially 100 percent (effective) in preventing infection when administered according to instructions on the label, animals on heartworm prevention occasionally test positive for heartworms. This apparent lack of effectiveness is usually due to owner compliance failure, travel or relocation of the animal to an area of active heartworm transmission, or unknown (or misdiagnosed) prior infection. Annual testing gives owners peace of mind in knowing that their pet is free of heartworms, and in cases where the animal is infected, it assures them of early diagnosis of infection and maximal benefits from heartworm adulticide therapy.”
If the use of a heartworm prevention product results in ineffective prevention for heartworms, the treating veterinarian or animal owner should file an Adverse Drug Experience report with the drug’s sponsor, which should have its telephone number on the product’s label. The company is required to provide CVM information from all Adverse Drug Experience reports. The veterinarian or owner can instead file a report directly with CVM by calling 1-888 FDA-VETS. More information about Adverse Drug Experience reporting is available at our website.