Posted on April 25th, 2012 by FindRetrievers.com Admin
By Melanie McLean, DVM, Center for Veterinary Medicine, FDA
“Daisy,” an 8-year-old, female spayed Dalmatian with a history of idiopathic epilepsy, and her owner are in Exam Room 1. The owner says that Daisy’s having frequent seizures, even on daily phenobarbital therapy. What’s the next step to control the dog’s seizures? Likely, it’s adding potassium bromide.
For over a century, potassium bromide, or KBr, has been used in human and veterinary medicine as an anti-seizure medication. Phenobarbital, or PB, has also been used for years to treat seizures. Despite both drugs’ long history of common use, neither is approved by FDA to treat seizures in people or animals.
The lack of FDA approval means that no drug company has presented information to the agency to prove that KBr or PB is safe and effective to treat seizures. It also means that no drug company has proven to FDA that either drug can be consistently manufactured according to quality standards. Without FDA approval, veterinarians and pet owners may be unaware of the risks of these drugs.
As part of FDA’s unapproved animal drugs initiative, several agency employees reviewed published literature on the safety of potassium bromide in dogs. They recently published the results of their review in the Journal of the American Veterinary Medical Association.1
By evaluating 111 references that provided data on the safety of potassium bromide, the authors “identified a considerable body of pharmacological, primary, and supportive evidence regarding the in vivo safety of KBr” in dogs. The authors summarized their findings by body system affected and clinical signs observed.
Body Systems and Clinical Signs
Based on data in published literature, the authors found that the body system in dogs most commonly affected by potassium bromide is neurologic. Adverse neurologic signs include sedation, ataxia, and behavioral changes. These signs are reversible and usually resolve within several days by lowering the phenobarbital dose (if the dog is on both KBr and PB) or within hours by giving intravenous saline.
The authors also discuss the effects of potassium bromide on other body systems in dogs, including:
Traditional Safety Studies
As part of the animal drug approval process, a drug company traditionally would conduct laboratory-based studies to collect safety information on the drug. These studies would evaluate the clinical and pathological changes in four groups of healthy laboratory dogs. Each group would receive 0, 1, 3, or 5 times the therapeutic dose of the drug. The results would provide detailed individual data, but might miss subtle adverse signs or those signs that occur after long-term use of the drug.
New and Innovative Methods
While 0-1-3-5X safety studies remain the gold standard for evaluating the safety of an animal drug before approval, they may not be the only way for a drug company to prove a drug’s safety.
A review of published literature, such as the one done by FDA for potassium bromide, is an example of a new and innovative method to potentially show the safety of a particular use of a drug. Literature reviews may be especially helpful for an unapproved animal drug that has a long history of use and many literature references, like KBr.
The authors reviewed more than 50 years of published literature on the use of potassium bromide in dogs. The vast amount of literature gave FDA “a volume and variety of evidence that far exceeded the data traditionally available to determine the safety of new animal drugs.”
Client-owned pets provided much of the safety data in the literature. These pets had idiopathic epilepsy and were treated with KBr, PB, or both “under conditions of clinical use,” meaning in real-world settings. While the data collected on each animal were less detailed than in a traditional safety study, the reports by the pet owners often included information that may be missed in a laboratory setting. Also, the pet owner reports offered a look at the long-term effects of potassium bromide in a large number of animals, which a short-term clinical trial involving only a small, select group of dogs may not detect.
What’s next for Potassium Bromide?
The best next step is for a drug company to seek FDA approval of potassium bromide for use as an anti-seizure medication in dogs. With an FDA-approved KBr product, veterinarians would be assured that the drug they prescribe is safe and effective to treat seizures in dogs, and that it is manufactured according to accepted quality standards.
1 Baird-Heinz HE, Van Schoick AL, Pelsor FR, et al. A systematic review of the safety of potassium bromide in dogs . J Am Vet Med Assoc 2012; 240:705-715.
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