The treatment of refractory canine epilepsy with potassium bromide - Veterinary Practice
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The treatment of refractory canine epilepsy with potassium bromide

Dr FRANCESCA HOLLAND of Dechra discusses the use of potassium bromide in treating refractory canine epilepsy, in combination with phenobarbital, as a monotherapy or as a sole therapy

EPILEPSY is the most common chronic canine neurological disorder, affecting around 0.57% of dogs.1 Phenobarbital is the first-line treatment for canine epilepsy and is an effective monotherapy in 60-80% of dogs with idiopathic epilepsy, but phenobarbital alone does not achieve adequate seizure control in all cases.2

Potassium bromide (KBr) has been reported to be effective in the management of refractory epilepsy in the dog in combination with phenobarbital.3,4,5 It has also been found to be effective as an initial monotherapy6 or as a sole therapy following the discontinuation of phenobarbital treatment.5

KBr is licensed as Libromide 325mg Tablets (Dechra Veterinary Products). It is the only product licensed as an adjunct to phenobarbital in refractory cases of epilepsy in dogs and is indicated for cases where seizure control is unsatisfactory, despite serum phenobarbital concentrations at steady-state within the therapeutic range.

The beneficial effects of KBr have been demonstrated in a field efficacy study in which the mean seizure rate was found to reduce from 27.4 seizures per month to 2.2 seizures per month after the addition of KBr (Libromide) to the treatment protocol (Figure 1).

Halide anticonvulsant

KBr is a halide anticonvulsant. The salt dissociates after ingestion and the bromide ion is rapidly absorbed, reaching peak serum concentration 30 to 45 minutes post-oral administration.8

A starting dose of 15mg/kg KBr twice daily is recommended 3,9,10 and although bromide is water soluble and readily absorbed along the entire GI tract, it should be given with food to reduce the risk of gastrointestinal disturbances.11

Once absorbed, bromide rapidly distributes throughout the extracellular space and into cells replacing chloride in all body fluids.12,13

Its anti-epileptic activity arises from the competition between bromide and chloride for transport across nerve cell membranes. This results in membrane hyperpolarisation, which raises the seizure threshold and prevents the spread of epileptic discharges.12,13

Bromide also potentiates the effects of the inhibitory neurotransmitter GABA and so has synergistic activity with other drugs that have GABA-ergic activity such as phenobarbital.3,14

The elimination half-life of bromide is advantageously long, helping to minimise fluctuations in the serum concentration between doses. Half-lives of 46, 25 and 15 days have been reported following oral administration.8,15,16

Theoretically, “steady-state” is thought to take up to five drug halflives to achieve, and in the case of KBr, this has been suggested to equate to anywhere from 60 days16 to several months of treatment.8

When the pharmacokinetics of a veterinary-licensed formulation of KBr (Libromide) were evaluated in dogs with therapeutic plasma concentrations of phenobarbital, it was found that plasma bromide concentrations actually reached steady-state after 54 days of dosing with KBr therapy (Figure 2).

The target therapeutic range for bromide is 800-2,000µg Br – /ml 2,5,7 (laboratory ranges may vary) and serum concentrations generally enter this range before “steady-state” is reached. Plasma bromide concentrations have been shown to enter the therapeutic range approximately 24 days after starting KBr therapy (Figure 3).

In cases where urgent seizure control is required, therapeutic serum bromide concentrations can be achieved more rapidly with a loading dose protocol, although this may be associated with an increased incidence of side-effects.6

Serum bromide concentration should be measured every four weeks for the first three months of therapy. Adjustments to the dose should be made with regard to the frequency of seizures, the half-life of bromide and the serum bromide concentration.

Regular monitoring

It is useful to note that as many laboratory assays are not able to distinguish between chloride and bromide, the chloride concentration in dogs treated with KBr may be artefactually elevated.3 Once “steady-state” has been achieved, regular monitoring is necessary to ensure continued efficacy and tolerance, as many factors may cause fluctuations in an individual’s serum bromide concentration.17

Bromide does not undergo hepatic metabolism so can be considered in dogs with hepatic disease.18 It should be used with caution in dogs with renal insufficiency as it is excreted predominantly by the kidneys.19

Following glomerular filtration, bromide undergoes tubular reabsorption in competition with chloride 10,20, so a change in dietary chloride content can have a significant impact on bromide excretion.

Diets high in chloride increase bromide elimination by decreasing its renal re-absorption. The resultant reduction in the serum bromide concentration may lead to a loss of seizure control.21

Conversely, changing to a diet low in chloride will increase serum bromide concentrations and could cause bromide intoxication.

Abrupt changes in diet should therefore be avoided in dogs on KBr therapy, as should salty treats or the consumption of sea water! The rate of elimination of bromide can also be increased by the administration of intravenous fluids containing chloride 17,22 and loop diuretics (e.g. frusemide).23


In general, treatment with KBr is welltolerated, but when used as a monotherapy or in combination with phenobarbital, reported side-effects include polydipsia/polyuria, polyphagia, excessive sedation, generalised ataxia, vomiting and pancreatitis.3,6,24 Side-effects may be transient or alleviated by a reduction in dosage.6,11,15

Bromide toxicosis (bromism) is possible when a high dose is administered 17 or in animals with impaired renal function as this may prolong the elimination half-life, resulting in bromide accumulation.22 Clinical signs of bromide toxicity are predominantly neurological and include ataxia, somnolence and upper motor neuron/lower motor neuron tetraparesis/paraparesis.3,17

If overdose is suspected, the KBr dose should be immediately reduced and if necessary and appropriate, 0.9% sodium chloride solution should be administered intravenously to reduce serum bromide concentrations.17,22 Any attempts to reduce serum bromide should be monitored carefully because of the risk of breakthrough seizures.17

For many cases of refractory idiopathic epilepsy, combination KBr and phenobarbital therapy achieves acceptable seizure control and is welltolerated.

If seizure control is inadequate, despite high therapeutic range serum concentrations of phenobarbital and bromide, other anti-epileptic medications such as gabapentin, levetiracetam or zonisamide can be considered; although they are not licensed for veterinary use.


  1. Löscher, W., Schwartz-Porsche, D., Frey, H. H. and Schmidt, D. (1985) Evaluation of epileptic dogs as an animal model of human epilepsy. Arzneimittel-Forschung 35: 82-87.
  2. Thomas, W. (2010) Idiopathic Epilepsy in Dogs and Cats. Veterinary Clinics of North America: Small Animal Practice 40: 161-179.
  3. Podell and Fenner (1993) Bromide therapy in refractory canine epilepsy. Journal of Veterinary Internal Medicine 7: 318-327.
  4. Pearce, L. K. (1990) Potassium bromide as an adjunct to phenobarbital for the management of uncontrolled seizures in dogs. Progress in Veterinary Neurology 1: 95-101.
  5. Trepanier, L. A. (1998) Therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide alone or in combination with other anti-convulsants: 122 cases (1992-1996). JAVMA 10: 1,449-1,453.
  6. Boothe, D. M., Dewey, C. and Carpenter, D. M. (2012) Comparison of phenobarbital with bromide as a first-choice anti-epileptic drug for treatment of epilepsy in dogs. JAVMA 240: 1,073-1,083.
  7. Dechra Veterinary Products: internal report LIB001.
  8. Trepanier, L. A. and Babish, J. G. (1995) Pharmacokinetic properties of bromide in dogs after the intravenous and oral administration of single doses. Research in Veterinary Science 58: 248-251.
  9. Dechra Veterinary Products: internal report LIB002.
  10. Trepanier, L. A. and Babish, J. G. (1995) Effect of dietary chloride content on the elimination of bromide by dogs. Research in Veterinary Science 58: 252-255.
  11. Baird-Heinz, H. E., Van Schoick, A. L., Francis, R., Pelsor, F. R., Ranivand, D. L. and Hungerford, L. L. (2012) A systematic review of the safety of potassium bromide in dogs. J Am Vet Med Assoc 240: 705-715.
  12. Dowling, P. M. (1994) Management of canine epilepsy with phenobarbital and potassium bromide. The Canadian Veterinary Journal 35: 724-725.
  13. Yohn, S. E., Morrison, W. B. and Sharp, P. E. (1992) Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizures. JAVMA 201: 468-470.
  14. Woodbury, D. M. and Pippenger, C. E. (1982) Antiepileptic Drugs. Woodbury, Penry and Pippenger, eds. (New York, Raven Press), pp791-801.
  15. Schwartz-Porsche, D., Jurgens, N., May, T., Gerhardt, M., Boenigk, H. E. and Krebs, B. (1990) Pharmacokinetics of bromide and bromide therapy in canine epilepsy. Proceedings of the 4th Annual European Society of Veterinary Neurology. Bern, Switzerland: pp32-34.
  16. March, P. A., Podell, M. and Sams, R. A. (2002) Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy beagles. J Vet Pharmacol Therap 25: 425-432.
  17. Rossmeisl Jr, J. H. and Inzana, K. D. (2009) Clinical signs, risk factors and outcomes associated with bromide toxicosis (bromism) in dogs with idiopathic epilepsy. JAVMA 234: 1,425-1,431.
  18. Chandler, K. (2011) Treatment and monitoring of epilepsy in dogs. In Practice 33: 98-104.
  19. Trepanier, L. A. (1995) Use of bromide as an anticonvulsant for dogs with epilepsy. JAVMA 207: 163-166.
  20. Palmer, J. W. and Clarke, H. T. (1933) The elimination of bromides from the bloodstream. J Biol Chem 99: 435-444.
  21. Shaw, N., Trepanier, L. A., Center, S. A. and Garland, S. (1996) High dietary chloride content associated with loss of therapeutic serum bromide concentrations in an epileptic dog. JAVMA 208: 234-236.
  22. Nichols, E. S., Trepanier, L. A. and Linn K (1996) Bromide toxicosis secondary to renal insufficiency in an epileptic dog. JAVMA 208: 231-233.
  23. Schmitt, G. W., Maher, J. F. and Schreiner, G. E. (1966) Ethacrynic acid enhanced bromuresis: a comparison with peritoneal and hemodialysis. J Lab Clin Med 68: 913-922.
  24. Gaskill, C. L. and Cribb, A. E. (2000) Pancreatitis associated with potassium bromide/Phenobarbital combination therapy in epileptic dogs. Can Vet J 41: 555-558.

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