POTASSIUM BROMIDE (KBr)

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NOTE:  For the a quick summary of information on potassium bromide, click here.

Potassium Bromide (abbreviated as KBr) is often considered the first choice drug for any dogs with idiopathic epilepsy, and because it has no effect on the liver, is often chosen for dogs with liver damage.  Unlike Phenobarbital (Pb), which is processed by the liver, bromide works by replacing chloride throughout the body, is stored in body fluids and eliminated unchanged by the kidneys.  However, where Phenobarbital is effective almost immediately, Kbr can take up to three or four months to reach its full effect.  A loading dose may be necessary for dogs with frequent seizures or when Phenobarbital must be withdrawn rapidly because of liver disease.

John Rossmeisl and Karen D. Inzana have published a study on bromide toxicosis in 31 dogs. Two of these dogs had generalized weakness with difficulty swallowing and megaesophagus. These signs improved with reducing the dose.

Sometimes KBr and Pb are used together.  For those dogs with epilepsy  whose seizures are not well controlled by Pb alone, the addition of bromide can greatly improve seizure control.  This often allows either a decrease or total withdrawal of Phenobarbital.

There are actually two kinds of bromide -- potassium bromide and sodium  bromide -- and both are equally effective at controlling seizures.  Compounded with either potassium or sodium,  the bromide controls the  seizures.  Potassium bromide is preferred when sodium intake must be  restricted (e.g., congestive heart failure). Sodium bromide is preferred  when potassium intake may need to be restricted (e.g., hypoadrenocorticism).

Bromide is a very old anti-convulsant which was used in the 1800's as  both an anti-convulsant and a sedative.  Because it has been around for  so long and is seldom used in people, it has never received FDA approval  as a drug. Although it has not  gone through the rigorous testing  required for FDA approval, bromide has been used in dogs for a long  time, and has proven to be reliable and safe.

**For a list of pharmacies that may be able to assist you in filling a prescription for potassium bromide, please see Discount Canine Pharmacies.

Dosage:

Both potassium bromide and sodium bromide are available in liquid and  capsule form.  The liquid form, which comes in flavors, is generally  less expensive and it is easier to adjust the dose in liquid than in  capsules. The long half life of bromide, about 24 days, means that the  timing of an individual dose is much more flexible - unlike Phenobarbital (Pb), you  don't have to stick to a strict 12 hour schedule for giving the  medication. Even though the dosing can be flexible, twice daily dosing  is probably recommended because some animals cannot tolerate too much  salt in their gastrointestinal tract at once -- imagine eating a  tablespoon of sodium chloride.

If you miss a dose or even a week of doses, there is not likely to be  any adverse effect.  The missed doses can simply be made up over the  next week ( i.e. double doses for a week).   But the long half life also  means that the effectiveness of a particular dose should not be  evaluated until the patient has been on the dose for three or four months, unless a loading dose is given.  And if the dog is having seizures, adding an extra does will not help.

To avoid this wait, which simply is not tolerable in some seizing dogs, a loading dose can be administered to dogs starting potassium/sodium bromide, or to dogs whose potassium/sodium bromide concentrations are too low (if the  patient is seizing). The loading dose is intended to rapidly achieve  therapeutic concentrations.

Because absorption, distribution and speed of metabolism can vary among  dogs, published dose recommendations only serve as a general guide. Most  new patients are started at the lower end of the dose range; however,  patients with frequent or severe seizures are often best managed by  starting at the higher end of the dose range or by using a loading dose.

An average maintenance dose for potassium bromide is 20 mg to 30 mg per  kg of body weight (to convert pounds to kilograms divide your dogs  weight by 2.2 or see conversion chart) given once a day. You may divide the dose and give potassium bromide twice a day. Sodium bromide has slightly more bromide compared to an equal weight of  potassium bromide, so the dose of sodium bromide is 15% lower than for  potassium bromide.  Your veterinarian will adjust the dosage based on  blood levels, seizure activity and side effects of the medication. 

FOR VETERINARIANS:

The loading dose is based on patient volume of distribution of potassium bromide (0.3 l/kg) and the target concentration (1.5 mg/ml or 1.5 gm/l). (The loading dose is 1.5 gm/l X  0.3 l/kg or 0.450 gm/kg (450 mg/kg). This  450 mg/kg dose is divided  over 5 days (90 mg/kg/day) and added to a maintenance dose of 20 to 30  mg/kg (average of 25 mg/kg) per day.) Thus, a new patient will receive  120 mg/kg of potassium bromide each day for 5 days, and then back down  to 25 mg/kg per day. 

High chloride (salt) intake can increase the elimination of bromide,  which means that if your dog's salt intake increases, you may need to  adjust the bromide dose. It is not necessary for dogs taking bromide to  be on a low salt diet, but it is important that the salt content of the  diet not be drastically changed during treatment, as this will affect  bromide levels. (See Monitoring therapy below). Ideally, it's best to  keep the diet stable if you can.

Monitoring Therapy:

To determine the correct dose of bromide, it can be very helpful to  monitor its level in the blood .  Any change in dose should be made  based upon the actual concentration in the blood.  If you have used a  loading dose, It is recommended that your vet collect a single sample  within a week of the loading dose to see how close you came to  therapeutic levels with this loading dose, and then another sample at one  month to see if your maintenance dose is sufficient to maintain the  concentrations established by the loading dose. The maintenance dose  would be modified if the one month sample is not the same as the post-loading sample.

If you have started with a regular  dosing schedule, your veterinarian will want to test the bromide levels  after about a month and then at six month intervals, once the blood  level has reached a therapeutic range. The published therapeutic or  target range for Bromide is 2 to 3 mg/ml  for dogs not on Phenobarbital at the same time, and 1.0 to 2.0 mg/ml if the dog is also receiving Phenobarbital.  Published therapeutic ranges are only an  approximation. 

If you are switching foods, please be aware of the chloride levels in  both the new and old food so that you and your vet can adjust the dose  accordingly and can closely monitor the level of bromide in the blood.  Any change in food should be done gradually.  We suggest the following as a reasonable schedule:

                 Mix 3/4 old food with 1/4 new food for 3-5 days;

                 Mix 1/2 old food with 1/2 new food for 3-5 days;

                 Mix 1/4 old food with 3/4 new food for 3-5 days;

                 100% new food.

SIDE EFFECTS:

The most common side effects of bromide therapy are sedation, ataxia  (hind end weakness and loss of coordination), increased urination and  rare skin disorders.  Increased urination, hunger and thirst are also  common for dogs taking bromide alone or with Pb. Occasionally, abnormal  behavior, such as irritability or restlessness can also require a  reduction in dose. Side effects are more common in patients whose  potassium bromide concentrations are greater than 2.5 mg/ml  and the  symptoms usually go away within a week after the dose is decreased.   If  the dog is too groggy and is on both Phenobarbital and bromide, it may  be preferable to decrease the Phenobarbital dose, rather than the  bromide.  If the dose of bromide is to be decreased, we recommend  monitoring of blood levels before any dose change in order to establish a target if seizures begin again.

Potassium bromide can also cause stomach upset, nausea and vomiting.  If  this occurs, you may wish to try giving the drug with food, or dividing  the daily dosage into two or more portions; you and your vet may also  wish to consider switching to sodium bromide which is just as effective  but doesn't cause the same stomach symptoms.  And some dogs prefer the taste of sodium bromide.

Also, Bromide should be used with caution in dogs with renal insufficiency.

Bromide toxicity is uncommon, however, it is a potential side effect of  bromide use and most of the potential side effects that have been  discussed on our list are from bromide toxicity. Bromide toxicity can  occur in dogs with renal insufficiency or those that are on a very high  dose of bromide. Signs of bromide toxicity include severe ataxia,  sedation or stupor and muscle spasms.  Usually, reducing the dose by 10%  to 25% is sufficient to take care of these signs.

DISCONTINUING THERAPY:

The decision to stop therapy must be made very carefully, but is  reasonable to consider in dogs that are seizure-free for one to two  years. The dose is gradually tapered over a period of 6 months. The  major risk of discontinuing drug therapy is seizure recurrence, which is  most likely to occur during withdrawal or within several months of  stopping therapy.

DRUG INTERACTIONS:

Bromide is eliminated from the body by the kidneys. Bromide and chloride  compete for re-absorption by the kidneys. A substantial increase in  dietary chloride (salt) will cause decreased re-absorption of bromide by  the kidneys, resulting in more bromide being eliminated. That means that  if the amount of salt in the diet increases, bromide levels will  decrease, which could lead to seizures. Conversely, switching to a diet  low in chloride will cause bromide levels to increase, which could cause  bromide intoxication.

It is not necessary for dogs taking bromide to be on a low salt diet,  but it is important that the salt content of the diet not be drastically  changed during treatment, as this will affect bromide levels.

Diuretics also increase bromide excretion and can lower the level of  bromide in the blood.

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IF ALL THIS IS MAKING YOU GLAZE OVER, HERE ARE THE BASICS:

1.  Potassium and sodium bromide are drugs given to control seizures in  dogs.  Unless you give a loading dose, it can take up to three or four months before it really begins to work.

2.  When first started, blood levels should be checked at one month and then every six months; if you have given a loading dose, then levels should be checked sooner.   

3.  The dosing schedule is more flexible than with Phenobarbital because of bromide's long half life, but please be aware of the chloride (salt) content in your dog's food and if it changes, discuss changing the dose with your veterinarian.

4.  There can be side effects, most of which disappear in a few weeks.  These can include excessive hunger, thirst and the need to urinate, lethargy and ataxia (loss of coordination). If the drug upsets your dog's stomach, try giving it with food or in two doses.  If the problem continues, discuss switching from potassium bromide to sodium bromide.

5. John Rossmeisl and Karen D. Inzana have published a study on bromide toxicosis in 31 dogs. Two of these dogs had generalized weakness with difficulty swallowing and megaesophagus. These signs improved with reducing the dose.

6.  Don't stop Kbr cold turkey unless instructed by your veterinarian.

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Sources:

William B. Thomas, DVM, MS, Common Neurologic Problems, Idiopathic Epilepsy in Dogs, Veterinary Clinics of North America: Small Animal Practice, Volume 30, Number 1, January, 2000; Texas A& M College of Veterinary Medicine, Kbr Handout, found at: http://www.cvm.tamu.edu/vcpl/publications/Kbr_handout.htm

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

Dr. W. Jean Dodds, DVM; Joanne Carson, PhD.