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POTASSIUM BROMIDE (KBr)
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must be withdrawn rapidly because of liver disease. 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 must be restricted (e.g., hyperadrenocorticism). 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. 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. DISC 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. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
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. Don't
stop Kbr cold turkey unless instructed by your veterinarian.
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 Dr. W. Jean Dodds, DVM; Joanne Carson, PhD. |