March 01, 2021

Potassium bromide, used for decades to treat idiopathic epilepsy in dogs, gained its first approval in the U.S.

Food and Drug Administration officials announced Jan. 14 that the agency granted conditional approval of a chewable tablet, KBroVet-CA1, for control of seizures associated with idiopathic canine epilepsy. The condition affects about 5% of dogs, the announcement states.

Conditional approval allows a company to sell a drug while collecting efficacy data, as long as the company first provides evidence the drug is safe. The company has up to five years to collect the remaining data for approval but needs to show progress each year.

A product with the “CA1” suffix is the first conditionally approved application for that drug.

In the March 15, 2012, issue of JAVMA, FDA officials published a review of scientific literature published from 1938-2011 on the safety of potassium bromide in dogs, covering 111 sources. That article states that potassium bromide has been used to treat epilepsy in people at least since 1857 and animals since 1876.

The JAVMA article states that while potassium bromide and sodium bromide salts have been compounded into drugs and sold in the U.S., they and phenobarbital products used to treat epilepsy lacked FDA-approved uses in humans or animals in the U.S.

KBroVet-CA1’s manufacturer, Pegasus Laboratories Inc., used safety data collected in that review to support its drug application rather than conducting its own drug testing in dogs, according to the FDA announcement. Dr. Steven M. Solomon, director of the FDA Center for Veterinary Medicine, said in the announcement he was encouraged that the company could use FDA data to avoid the need to perform animal testing.

Dr. Sheila Carrera-Justiz is a clinical veterinary neurologist and neurosurgeon in the Department of Small Animal Clinical Sciences at the University of Florida College of Veterinary Medicine, and she co-authored a 2018 review article on emergency management of dogs with suspected epileptic seizures and a 2019 article on patterns of anti-epileptic drug use among neurology and emergency medicine specialists treating dogs suspected to have epilepsy. She said potassium bromide has been among the anticonvulsant drugs used for years to treat epilepsy in dogs.

Potassium bromide is a slow-acting substance with a long half-life, taking up to two months to start controlling epileptic seizures and three months to provide consistent control, Dr. Carrera-Justiz said. During that time, dog owners need to closely control their dogs’ diets and avoid any fluctuations in salt intake.

A Labrador Retriever that drinks saltwater at the beach will lose bromide in its urine, and one that vacuums up food scraps behind small children will have an unstable salt intake.

But, when owners can control for those factors, the drug does well at controlling seizures in dogs without the risk of organ damage, Dr. Carrera-Justiz said. It’s a good option for dogs with liver disease yet a poor one for dogs with kidney disease, she said.

The FDA announcement also indicates dog owners need to watch for signs of bromide intoxication. Severe intoxication can cause stumbling, stupor, hind limb weakness, behavior changes, dilated pupils, and even loss of consciousness and coma.

Other anticonvulsant drugs that have often been used include sodium bromide, phenobarbital, levetiracetam, and zonisamide, though none of these substances had approvals in the U.S. as veterinary-use anti-epileptic drugs.

FDA officials encourage veterinarians to prescribe approved drugs rather than unapproved alternatives because approved drugs meet agency standards for safety, labeling, quality, and effectiveness, according to a statement provided by agency spokesperson Siobhan DeLancey. With conditionally approved drugs­, manufacturers need to meet a lower standard of evidence for effectiveness but still need to provide reasonable assurance the drug will work as intended.

“Unapproved drugs—including compounded drugs—have not been reviewed by the FDA and do not have the same assurances,” the statement says. “However, the FDA understands that this conditionally approved tablet form and dose of KBroVet-CA1 may not be appropriate for all patients and that a veterinarian may decide to use an unapproved product to control seizures in certain dogs.”

Dr. Carrera-Justiz expects the approval will have little impact on her own prescribing practices because veterinarians also have some leeway to make decisions based on the needs of each patient.

“I can say, ‘I don’t want to use this drug because I need seizure control tomorrow, not in three months,’” she said.

But she cautioned that state rules may give varying amounts of discretion for when to use the approved drug.

An article published in February 2016 in the Journal of Veterinary Internal Medicine indicates that primidone was the only anti-epileptic drug approved for dogs in the U.S., whereas phenobarbital, imepitoin, and potassium bromide were approved in Europe. That article, a 2015 consensus statement from the American College of Veterinary Internal Medicine, provides guidelines on managing seizures in dogs.