FORMULARY-

BROMIDE

Bromide is an old anticonvulsant drug. It works by replacing negatively charged chloride ions through the chloride channels causing neuronal hyperpolarisation. Bromide has synergistic effect with drugs that enhance chloride conduction (such as phenobarbital). Bromide is usually administered as the potassium salt (KBr) but sodium salts may be used in patients with adrenal insufficiency and renal dysfunction.

 

Bromide is slowly excreted by the kidneys without the requirement for hepatic biotransformation. Bromide has a very long half-life (25 to 46 days) in dogs so steady state serum concentration is not reached for 3 to 6 months.

 

Indications

Bromide is commonly used in combination with phenobarbital in refractory epileptics or in patients that have suffered liver disease. It should be used with caution in patients with impaired renal function.

 

Dose

Recommended oral dosage in dogs is 30 mg/kg once daily. Therapeutic serum concentrations are 880 to 3000 mg/l as a solitary agent and 810 to 2400 mg/l in combination with phenobarbital.

 

If adequate serum concentrations are needed rapidly, a loading dose of bromide can be used. An oral dose of 120 to 150 mg/kg for 5 days should achieve a serum concentration of 1 – 1.5 mg/ml. For a more rapid effect than that obtained with oral maintenance dosing regimes, a per rectum loading protocol has been devised. Intrarectal administration may be preferred in the patient that is heavily sedated from prior diazepam and phenobarbital administration. The side-effects seen with the use of this regime may be transient diarrhoea and sedation.

 

The maintenance dose should achieve steady state concentrations so check serum levels at 1 week and 1 month post loading. These concentrations should be identical. Steady state concentrations reached at about 6-8 weeks if no loading dose administered and then single (trough) samples are suitable for monitoring. Therapeutic range of 1-3.5 mg/ml should be tailored in individual patients based on tolerance and effect.

 

Once bromide concentrations are stable at 1.5mg/ml phenobarbital dose may be reduced in 25% increments if required (particularly if sedation is a problem).

 

In rare circumstances may be used as sole agent in which case target concentrations are higher (2-2.5 mg/ml).

 

Side effects

Tend to be dose-dependent and include: polyuria, polydipsia, polyphagia, transient sedation or ataxia during the first 2 to 3 weeks (before tolerance develops). Hyperactivity and pruritus may be seen occasionally. Overdosage may be associated with ataxia, depression, tremors, neuropathies, stupor or coma (bromism) – sodium chloride IV or orally accompanied by furosemide may be considered.

 

Bromide is a gastric irritant and may cause vomiting – this may be minimised by administering bromide with or shortly after feeding.

References:

Cox SK, Whiton AM, Bowman HL (2008) Determination of bromide in canine plasma using ion chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 870(2), 255-258. - PubMed -

 

Nichols ES, Trepanier LA, Linn K (1996) Bromide toxicosis secondary to renal insufficiency in an epileptic dog. JAVMA 208, 231-233. - PubMed -

 

Papich MG, Davidson G, Schnatz RG (2009) Appreciation for study on bromide administration in dogs. JAVMA. 235(6):659; author reply 659. - PubMed -

 

Podell M, Fenner WR (1993) Bromide therapy in refractory canine idiopathic epilepsy. JVIM 7, 318-327. - PubMed -

 

Rossmeisl JH, Inzana KD (2009) Clinical signs, risk factors, and outcomes associated with bromide toxicosis (bromism) in dogs with idiopathic epilepsy. JAVMA 234(11):1425-31. – PubMed -

 

Rossmeisl JH, Inzana KD (2009) Clinical signs, risk factors, and outcomes associated with bromide toxicosis (bromism) in dogs with idiopathic epilepsy. JAVMA 234(11), 1425-1431. - PubMed -

 

Shaw N, Trepanier LA, Center SA et al (1996) High dietary chloride content associated with loss of therapeutic serum bromide concentrations in an epileptic dog. JAVMA 208, 234-236. - PubMed -

 

Yohn SE, Wallace BM, Sharp PE (1992) Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizures. JAVMA 201, 468-470. - PubMed -

 

 

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