POTASSIUMBROMIDE (KBr)
NOTE: For the a quick summary of information on potassium bromide, click here.
PotassiumBromide (abbreviated as KBr) is often considered the firstchoice drug for any dogs with idiopathic epilepsy, and because it has noeffect on the liver, is often chosen for dogs withliver damage. Unlike Phenobarbital (Pb), which is processed by the liver, bromideworks by replacing chloride throughout the body,is stored in bodyfluids and eliminatedunchanged by the kidneys. However, wherePhenobarbital is effective almost immediately, Kbrcan take up to three or four months to reachits full effect. A loading dose may benecessary for dogs with frequent seizures or when Phenobarbitalmust be withdrawn rapidly because of liver disease.
JohnRossmeisl andKaren D. Inzana have published a study on bromide toxicosis in 31 dogs. Two ofthese dogs had generalized weakness with difficulty swallowing andmegaesophagus. These signs improved with reducing the dose.
SometimesKBr and Pb are used together. For those dogswith epilepsy whose seizures are not wellcontrolled by Pb alone, the addition of bromidecangreatly improve seizure control. This often allows either adecrease or total withdrawal of Phenobarbital.
Thereare actually two kinds of bromide -- potassium bromide and sodium bromide -- and both are equally effective atcontrolling seizures. Compounded with eitherpotassium 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 potassiumintake may need to be restricted (e.g., hypoadrenocorticism).
Bromideis 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 neverreceived FDA approval as a drug. Although ithas not gone through the rigorous testing required for FDA approval, bromide has been usedin dogs for a long time, and has proven to bereliable and safe. **For a list of pharmacies that may be able to assist you in filling a prescription for potassium bromide, please seeDiscount Canine Pharmacies.
Dosage:
Bothpotassium 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 dosein liquid than in capsules. The long halflife of bromide, about 24 days, means that the timingof an individual dose is much more flexible - unlike Phenobarbital(Pb), you don't have to stick to a strict12 hour schedule for giving the medication.Even though the dosing can be flexible, twice daily dosingis probably recommended because some animals cannot tolerate too much salt in their gastrointestinal tract at once --imagine eating a tablespoon of sodiumchloride.
Ifyou 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 thenext week ( i.e. double doses for a week).But the long half life also means thatthe effectiveness of a particular dose should not beevaluated until the patient has been on the dose for three or four months, unless aloading dose is given. And if the dog ishaving seizures, adding an extra does will not help.
Toavoid this wait, which simply is not tolerable in some seizing dogs, a loading dose can beadministered to dogs starting potassium/sodium bromide, or to dogs whose potassium/sodiumbromide concentrations are too low (if the patientis seizing). The loading dose is intended to rapidly achieve therapeutic concentrations.
Becauseabsorption, distribution and speed of metabolism can vary among dogs, published dose recommendations only serve asa general guide. Most new patients arestarted 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 byusing a loading dose.
Anaverage maintenance dose for potassium bromide is 20 mg to 30 mg per kg of body weight (to convert pounds to kilogramsdivide 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 comparedto an equal weight of potassium bromide, sothe dose of sodium bromide is 15% lower than for potassiumbromide. Your veterinarian will adjust thedosage based on blood levels, seizureactivity and side effects of the medication.
FORVETERINARIANS:
Theloading dose is based on patient volume of distribution of potassiumbromide(0.3 l/kg) and the target concentration (1.5 mg/ml or 1.5 gm/l). (The loading dose is 1.5gm/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 (averageof 25 mg/kg) per day.) Thus, a new patient will receive120 mg/kg of potassium bromide each day for 5 days, and then back down to 25 mg/kg per day.
Highchloride (salt) intake can increase the elimination of bromide, which means that if your dog's salt intakeincreases, you may need to adjust the bromidedose. It is not necessary for dogs taking bromide tobe 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. (SeeMonitoring therapy below). Ideally, it's best to keepthe diet stable if you can.
Monitoring Therapy:
Todetermine 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 aloading dose, It is recommended that your vet collect a single sample within a week of the loading dose to see how closeyou came to therapeutic levels with thisloading dose, and then another sample at one monthto see if your maintenance dose is sufficient to maintain the concentrations established by the loading dose.The maintenance dose would be modified if theone month sample is not the same as the post-loading sample.
Ifyou have started with a regular dosingschedule, your veterinarian will want to test the bromide levels after about a month and then at six monthintervals, once the blood level has reached atherapeutic range. The published therapeutic or targetrange for Bromide is 2 to 3 mg/ml for dogsnot on Phenobarbital at the same time, and 1.0 to 2.0 mg/ml if the dog is also receivingPhenobarbital. Published therapeutic rangesare only an approximation.
Ifyou are switching foods, please be aware of the chloride levels in both the new and old food so that you and your vetcan adjust the dose accordingly and canclosely monitor the level of bromide in the blood. Anychange in food should be done gradually. Wesuggest 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:
Themost 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 asirritability or restlessness can also require a reductionin dose. Side effects are more common in patients whosepotassium bromide concentrations are greater than 2.5 mg/ml and the symptomsusually go away within a week after the dose is decreased.If the dog is too groggy and is onboth Phenobarbital and bromide, it may bepreferable to decrease the Phenobarbital dose, rather than the bromide. Ifthe dose of bromide is to be decreased, we recommendmonitoring of blood levels before any dose change in order to establisha target if seizures begin again.
Potassiumbromide can also cause stomach upset, nausea and vomiting.If this occurs, you may wish to trygiving the drug with food, or dividing thedaily dosage into two or more portions; you and your vet may also wish to consider switching to sodium bromide whichis just as effective but doesn't cause thesame stomach symptoms. And some dogs preferthetaste of sodium bromide.
Also,Bromide should be used with caution in dogs with renalinsufficiency.
Bromidetoxicity is uncommon, however, it is a potential side effect of bromide use and most of the potential side effectsthat have been discussed on our list are frombromide toxicity. Bromide toxicity can occurin dogs with renal insufficiency or those that are on a very high dose of bromide. Signs of bromide toxicity includesevere ataxia, sedation or stupor and musclespasms. Usually, reducing the dose by 10% to 25% is sufficient to take care of these signs.
DISC ONTINUING THERAPY:
Thedecision to stop therapy must be made very carefully, but is reasonable to consider in dogs that areseizure-free for one to two years. The doseis gradually tapered over a period of 6 months. The majorrisk of discontinuing drug therapy is seizure recurrence, which is most likely to occur during withdrawal or withinseveral months of stopping therapy.
DRUG INTERACTIONS:
Bromideis eliminated from the body by the kidneys. Bromide and chloride compete for re-absorption by the kidneys. Asubstantial increase in dietary chloride(salt) will cause decreased re-absorption of bromide bythe kidneys, resulting in more bromide being eliminated. That means that if the amount of salt in the diet increases,bromide levels will decrease, which couldlead to seizures. Conversely, switching to a diet lowin chloride will cause bromide levels to increase, which could cause bromide intoxication.
Itis not necessary for dogs taking bromide to be on a low salt diet, but it is important that the salt content of thediet not be drastically changed duringtreatment, as this will affect bromide levels.
Diureticsalso increase bromide excretion and can lower the level ofbromide in the blood.
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IF ALL THIS IS MAKING YOU GLAZE OVER,HERE ARE THE BASICS:
1.Potassiumand sodium bromide are drugs given to control seizures indogs. Unless you give a loadingdose, it can take up to three or fourmonthsbefore it really begins towork.
2.Whenfirst started, blood levels should be checked at one month andthen every six months;if you have given aloading dose, then levelsshould be checkedsooner.
3.Thedosing schedule is more flexible than with Phenobarbital becauseof bromide'slong half life, but please beaware of the chloride (salt)content in yourdog's food and ifit changes, discuss changing the dosewith your veterinarian.
4. There can be side effects, most of whichdisappear in a few weeks. These can includeexcessive hunger, thirst and the need to urinate,lethargyand ataxia (loss of coordination). If the drug upsets yourdog's stomach, try giving it with food or in two doses. Iftheproblemcontinues, discuss switching frompotassium bromide tosodium bromide.
5.JohnRossmeisl andKaren D. Inzana have published a study on bromide toxicosis in 31 dogs. Two ofthese dogs had generalized weakness with difficulty swallowing andmegaesophagus. These signs improved with reducing the dose.
6.Don'tstop Kbr cold turkey unless instructed by your veterinarian.
Sources:
William B. Thomas, DVM, MS, CommonNeurologic Problems, Idiopathic Epilepsy in Dogs, Veterinary Clinics of North America:Small Animal Practice, Volume 30, Number 1, January, 2000; Texas A& M College ofVeterinary Medicine, Kbr Handout, found at:http://www.cvm.tamu.edu/vcpl/publications/Kbr_handout.htm
Rossmeisland Inzana. Clinical signs, risk factors, and outcomes associated with bromidetoxicosis (bromism) in dogs with idiopathic epilepsy. JAVMA 2009:234:1425-1431.
Dr. W. Jean Dodds, DVM; Joanne Carson, PhD.