How KBroVet®-CA1 Can Help Steady the Storm

KBroVet®-CA1 is the first and only conditionally approved drug for idiopathic epilepsy in dogs.

KBroVet-CA1 has received conditional approval from the FDA for the control of seizures associated with idiopathic epilepsy in dogs. KBroVet-CA1 was developed to provide a consistent and reliable source of potassium bromide for veterinary patients.

What does “Conditional Approval” mean?

KBroVet-CA1 is conditionally approved by the FDA. This means that the product has been demonstrated to be safe and that there is a reasonable expectation of effectiveness, which means that the product is reasonably expected to provide the intended effect when used under the conditions of use described in the labeling. The sponsor will continue to collect the evidence of effectiveness needed for the product to receive full approval. It is a violation of Federal Law to use this product other than as directed in the labeling. Additional information on conditional approval can be found by searching http://fda.gov for “conditional approval.”

Reasonable Expectation of Effectiveness – Pilot Study

KBroVet-CA1 has received conditional approval based on the results of a retrospective study demonstrating reasonable expectation of effectiveness. A retrospective study of 51 dogs was performed to evaluate the safety and efficacy of KBr for the treatment of idiopathic epilepsy in dogs. (Data on file)

Determination of Success

The following variables were used to compare the 30-day period before initial treatment with KBr and the 30-day period of steady state KBr dosing. These criteria were necessary to classify an individual case as a success:

  • Seizure counts – decrease of ≥50%
  • Seizure event days per month – decrease of ≥50%
  • Seizure severity scores – decrease or no change

Overall reasonable expectation of effectiveness was achieved if >50% of all cases achieved a “success” score for all three variables.

Results

Effectiveness

Based on study protocol-specified criteria, 27 of the initial 51 cases were determined to be valid for effectiveness data. As the sole anticonvulsant, potassium bromide achieved 67% overall treatment success in all three categories.

  • Seizure counts: 70% (19/27) were defined as treatment successes
  • Seizure event days per month: 67% (18/27) were defined as successes by either decreasing or showing no change
  • Seizure severity scores: 93% (25/27) were defined as successes by either decreasing or showing no change
  • Overall 67% (18/27) treatment successes

Safety

In a retrospective field study of 51 dogs diagnosed with idiopathic epilepsy clinical findings of dogs treated with KBr were documented for the initial 60 days of treatment. The most common clinical abnormalities documented in the 60-day period following the initiation of KBr therapy included increased appetite, weight gain, vomiting/regurgitation, sedation and neurologic signs.

Practitioners should tailor therapeutic regimens and clinical monitoring to each dog. Availability of an appropriately FDA-labeled, approved KBr product could provide better assurance to veterinarians and their clients of the quality, safety, and effectiveness of a product for veterinary use.

KBroVet®-CA1 Product Facts

KBroVet-CA1 is the only FDA conditionally approved drug for seizure control in dogs.

Provides better assurance to veterinarians and their clients as a reliable and trusted product, manufactured specifically for dogs, with a two-year shelf life.

KBroVet-CA1 is excreted through glomerular filtration.

An ideal choice for dogs with compromised liver function that cannot tolerate anticonvulsants that affect the liver.

KBroVet-CA1 is a liver-flavored, chewable tablet administered once a day and is formulated specifically for dogs.

May improve compliance by providing convenient once a day dosing for owners that cannot dose their dog multiple times each day.

KBroVet-CA1 has a half-life of at least 21 days,* the longest half-life of all seizure anticonvulsant options.
If owners miss a dose, fluctuation in drug concentration is unlikely to occur, minimizing the occurrence of a seizure.

KBroVet-CA1 is available in 60 count bottles.

*Boothe, D, Dewey C, Carpenter D. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. JAVMA. 2012; Vol 240, No 9. 1073-1083.

Dosage & Administration

The total recommended daily dosage range for oral administration is 25–68 mg/kg (11–31 mg/lb) of body weight. The dosage of KBroVet®-CA1 should be adjusted based on monitoring of clinical response of the individual patient. KBroVet®-CA1 may be dosed with or without food. Use of an initial loading dosage regimen may be considered on an individual patient basis, balancing the time required to achieve a therapeutic response while minimizing side effects.

Precautions

Dogs receiving KBr should be carefully monitored when changing diets, administering chloride-containing intravenous fluids, and administering concurrent medications. Careful monitoring is important in dogs that have a condition that may cause difficulty maintaining electrolyte balance.

  • Animals with decreased renal function may be predisposed to bromide toxicosis.
  • Some dogs may experience epileptic episodes that are unresponsive or refractory to KBr monotherapy and KBr alone may not be adequate for control of seizures for every dog with idiopathic epilepsy.
  • The safe use of KBroVet®-CA1 has not been evaluated in dogs that are intended for breeding, or that are pregnant or lactating. The safe use of KBr in neonates and young animals has not been established.
  • Reproductive effects of KBr have been reported in other species.
  • In dogs, ataxia, diarrhea, hematochezia, excessive salivation, shivering, skin lesions, stupor progressing to coma, and death have been.

FAQs

1. What does conditionally approved mean?

KBroVet-CA1 is conditionally approved by the FDA. This means that the product has been proven safe and has a reasonable expectation of effectiveness. The sponsor will continue to collect the evidence of effectiveness needed for the product to receive full approval. Conditionally approved animal drugs are limited to a specific use, which can be found on the package insert. Additional information on conditional approval can be found by searching http://fda.gov for “conditional approval.”

2. How does conditional approval differ from traditional/formal approval?

The FDA, following successful demonstration of efficacy, safety and manufacturing protocols, grants drug approvals. A conditional approval is granted for only certain types of treatments for serious or life-threatening conditions where demonstrating effectiveness requires complex or difficult studies.  Once safety and manufacturing protocols have been proven, the FDA will consider an approval when there is a reasonable expectation of effectiveness for use.  The conditional approval is for one year, must be renewed annually after showing progress toward full approval for up to four additional years.

3. What are the differences between KBroVet-CA1 (potassium bromide chewable tablets) and the former KBroVet® tablets?

The two products are labeled differently due the FDA’s conditional approval of KBroVet-CA1. Please see the full product label and package insert for details.  Additionally, the tablets are no longer scored, nor contain cyanocobalamin (vitamin B-12).  All other ingredients remain the same.

4. As a veterinarian, can I transition a patient from the previous bottle of KBroVet tablets directly to the new KBroVet-CA1 tablets without a washout or transition period?

Yes.

5. As a veterinarian, can I transition a patient from compounded potassium bromide directly to the new KBroVet-CA1 tablets without a washout or transition period?

The total recommended daily dosage range for oral administration is 25–68 mg/kg (11–31 mg/lb) of body weight. The dosage of KBroVet-CA1 should be adjusted based on monitoring of clinical response of the individual patient. KBroVet-CA1 may be dosed with or without food.

6. Is there a “washout” period for this KBroVet-CA1 tablets?

No.

7. How do KBroVet-CA1 tablets work to control seizures?

The active ingredient, potassium bromide, is thought to exert its antiepileptic activity by passing through neuronal chloride ion channels, thereby hyperpolarizing neuronal membranes. With the neuronal membranes more negatively charged, this decreases the action potential across the synapse, thus raising the seizure threshold and stabilizing neurons against excitatory input from epileptic foci.

8. Once starting a patient on KBroVet-CA1 tablets, do I need to monitor blood work? How often?

Based on the ACVIM Small Animal Consensus Statement on Seizure Management in Dogs (Podell, 2016), potassium bromide serum concentrations are recommended 6-12 weeks after starting therapy then on an annual basis. Blood work should also be considered if patients experience > 3 seizures – before the next scheduled evaluation or signs of toxicity are suspected.

9. Are there any special diet implications to keep in mind when prescribing KBroVet-CA1?

Dogs taking potassium bromide should use caution with chloride-containing medications and foods.

10. What are side effects of KBroVet-CA1?

Dogs taking potassium bromide should use caution with chloride-containing medications and foods.

11. Are there contraindications for other medications in which KBroVet-CA1 should not be used?

KBroVet-CA1 should not be used in animals with a history of hypersensitivity to bromide. Please see full product label and package insert for all labeled contraindications, warning and precautions.

12. What are the precautions that I should be aware of as a prescribing veterinarian?

Animals with decreased renal function may be predisposed to bromide toxicosis. Safe use has not been evaluated in dogs that are intended for breeding, or that are pregnant or lactating. The safe use of KBr in neonates and young animals has not been established.   Death has been reported with a dose of 200 to 500 mg/kg a day for 4 to 26 weeks. Please see full product label and package insert for all labeled contraindications, warning and precautions.

13. With KBroVet-CA1, do I need to have the same concerns when prescribing for patients with moderate to severe liver damage/impairment?

The active ingredient in KBroVet-CA1, potassium bromide, does not induce or increase hepatic enzymes. KBroVet-CA1 does not contain a contraindication or precaution against use in patients with decreased liver function.

14. Can I administer KBroVet-CA1 with other anti-epileptic drugs?

The reasonable expectation of efficacy and safety sections of KBroVet-CA1’s conditional approval only evaluated use as a sole anti-epileptic drug. However, within the Precautions section of the drug’s package insert, it is acknowledged that “Some dogs may experience epileptic episodes that are unresponsive or refractory to KBr monotherapy and KBr alone may not be adequate treatment for every dog with idiopathic epilepsy.”

15. If the patient’s seizure frequency increases, can I increase the dose of KBroVet-CA1?

Please consult your veterinarian if seizure frequency increases. The total recommended daily dosage range for oral administration is 25–68 mg/kg (11–31 mg/lb) of body weight. The dosage of KBroVet-CA1 should be adjusted based on monitoring of clinical response of the individual patient.

16. What is a recommended loading dose guidance for KBroVet-CA1?

Use of an initial loading dosage regimen may be considered on an individual patient basis, balancing the time required to achieve a therapeutic response while minimizing side effects. For guidance on loading dose recommendations, please consult with your referring veterinary neurologist or the most updated reference veterinary materials (e.g. The Merck Veterinary Manual or the 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs.)

17. Are KBroVet-CA1 tablets flavored?

Yes, the tablets contain a proprietary chicken-liver flavor to increase acceptance by dogs. The tablets do not contain ingredients of bovine or porcine origin.

18. Are the new KBroVet-CA1 tablets scored? Can I split KBroVet-CA1 tablets?

Tablets are not scored, nor can tablet uniformity across the tablet be guaranteed. It is not recommended that the tablets be split.

19. How should KBroVet-CA1 tablets be stored?

Store at controlled room temperature 20–25°C (68–77°F). Keep out of reach of children and animals.  Additionally, clients should be advised to keep KBroVet-CA1 in a secured location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

20. I’ve been using KBroVet for years and I thought it was already approved. Was it not? Is this a step backward for the product?

By way of a close partnership with the FDA due to a recognized marketplace need, PRN® Pharmacal has manufactured KBroVet for nearly a decade as an unapproved drug, while working toward completion of a formal approval. At this juncture, the FDA granted conditional approval based on reasonable expectation of efficacy, demonstrated safety and approval of manufacturing controls.  This is a step forward for the product in the eyes of the FDA. 

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