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Bromide: Potassium & Sodium

By Maureen Setter

Table of Contents of frequently asked questions (FAQs)

 
 

Introduction.

Potassium bromide and sodium bromide are both anti-epileptic drugs (AEDs) but it is actually the bromide salt in each that has anti-seizure properties. KBr is the notation for potassium (K) and bromide (Br) and likewise, NaBr is the notation for sodium (Na) and bromide (Br). Of the two, KBr is more widely used. Bromide is considered the second drug of choice when it comes to controlling seizures -- PB (Phenobarbital) being the first.

Note: In this article, bromide refers to both KBr and NaBr. Whenever KBr is mentioned, the information also pertains to NaBr -- except where explicitly noted (eg. differences between KBr & NaBr).

Is Bromide therapy new?

No. As far back as 1857 bromide was used to treat catamenial (gynecologic) seizures in women. It was in the early 1900's that the more effective and less toxic AED, PB (phenobarbital) came into use. About 40 years ago they began experimenting with using bromides to control seizures in dogs. At first they recommended using bromides in refractory cases -- cases in which the seizures were difficult to control using other AEDs. In other words, as a "last ditch effort" to control the seizures.

When should bromide therapy be considered ?

Bromide therapy is still considered for dogs whose seizures are considered refractory (not controlled by another AED). For those dogs, using KBr & PB concomitantly (together) has produced some very promising results. One study reported that dogs that were refractory to PB, 86% of them had improved seizure control and 26% of the 86% became totally seizure free when adding KBr.

Other important reasons for considering bromide therapy are:

What is the difference between Kbr and NaBr?

The bromide ion is the active ingredient used for seizure control in potassium bromide and sodium bromide. There are no known differences in efficacy between the two salts. There are situations where one or the other is preferable.

What are the considerations when choosing between Kbr and Nabr

 
Potassium bromide is preferable in dogs that need to have their sodium restricted (eg. dogs with certain heart diseases, high blood pressure).
 
Sodium bromide seems to be less irritating to the stomach and is often used in dogs that suffer from nausea/vomiting with the potassium salt. Sodium bromide is also preferable in dogs with certain diseases (eg. primary hypoadrenocorticism) that cannot tolerate excess potassium.
Also, some dogs object less to the taste of sodium bromide. Except for the gastrointestinal side effects (which are due to the potassium) the side effects and the effectiveness of these two preparations are identical.
 

Are there any special considerations when giving bromide?

Yes. Bromide should be given with food and not on an empty stomach. It can simply be squirted on your dog's food or on a small piece of bread and given to your dog. Some literature says that if your dog is on PB and KBr, you only need to give the bromide once a day and if your dog is only on bromide, then it should be given twice a day. In either case, some have found that it is easier on the dog's stomach to give the bromide twice a day -- two smaller doses are easier on the stomach than one large dose. Bromide is very salty and your dog might not like it's taste. If this is the case, talk to you pharmacist about getting it flavored. Beef, liver, chicken and cherry are just a few of the many flavors available.

Are there any food considerations when using bromide?

Yes. The absorption of bromide can be affected by the chloride content of your dog's food. Chloride affects the elimination of bromide; thus increases in dietary chloride will decrease bromide levels. In one study, increasing the chloride content from that of most commercial foods (0.4% chloride on dry matter basis) to that of a high chloride diet (1.3%, comparable to some prescription diets), a three-fold increase, increased the necessary dose of bromide by almost 100%. The food's chloride content is normally not listed on the food label. Therefore, it might be necessary to contact the dog food manufacturer to obtain this information. Once bromide therapy has been started, it is suggested that the dog's diet not be changed. But if you must, you need to take into consideration the difference in the chloride content between the two foods and discuss this with your veterinarian.

Are there any considerations when switching from KBr to NaBr?

Sodium salt has a slightly higher bromide content, so the dosage for sodium bromide is about 15% less than for potassium bromide.

What are the side effects when using bromide?

Bromide is generally well tolerated in dogs. However, some of the side effects are the same as with PB. That is sedation, ataxia, increased hunger, and the 3 -P's: polydipsia (excessive thirst), polyphagia (excessive hunger) & polyuria (excessive urination). In some cases, dogs can develop a skin rash or itchy skin. As with other AEDs, these side-effects can diminish with time. If using a loading dose, these side-effects will be more noticeable. In many cases, reducing the PB or bromide can reduce or eliminate these symptoms. If a dog does show signs of toxicity, many times lowering the dosage and then gradually increasing it back up over time solves the problem. Again be sure to discuss this with your veterinarian.

How do I know if this is the side - effect of bromide?

As we know, not every symptom a dog develops while taking a drug is a side effect of the drug. For example, there are many other causes of rear limb weakness. Although blood levels are certainly a guide, the only real way to tell if a particular symptom is a dose-related side effect of an AED is to decrease the dose and see if the symptom(s) goes away. For example, rear limb weakness due to bromide normally resolves within 3 to 5 days of temporarily stopping the bromide. Sometimes side-effects might not show up for five or six months or until the bromide has reached steady-state levels. If this might be the case, instead of totally eliminating the bromide (especially if you have seen good results using bromide up until this time), cut back on the dosage and if necessary, gradually build the dosage back up over time. As always, check with your veterinarian before making any changes in medication.

When adding (or increasing the dosage of) an AED, it is natural to assume that any new side-effects are due to this most recent addition. If your dog is also on another AED at the time that you add bromide, the side-effects can be caused by a combination of the two. veterinarian

Where can I obtain bromide?

Bromide (potassium or sodium) requires a prescription from your veterinarian. Most veterinarians do not carry bromide as they would have to apply to the FDA for approval to purchase the chemical. This is not practical for most veterinarians. If you have a compounding pharmacy in your area, check with them. If not, consider ordering it from a mail-order compounding pharmacy or veterinary school pharmacy. Be sure that you know what dosage (mg) your veterinarian has prescribed for your dog. Then check with the pharmacist as to the strength (mg/ml) of the solution they prepared.

Are there grades of bromide?

Yes. Chemical grades can be very confusing and is best left to the pharmacist to decipher. The bottom line is that it probably does not matter which grade the pharmacy uses. However the 'higher' the grade, the 'higher' the cost.

There are over a dozen grades of chemicals, depending on purity and intended use. Different chemical companies use slightly different grading systems. USP refers to the United States Pharmacopeia, which develops certain standards for chemicals used in drugs. ACS refers to the American Chemical Society, which develops standards for chemicals used for a variety of uses. Other countries have their own chemical grading systems.

Liquid vs capsules:

Bromide is a salt and is available in capsule form or as liquid. A bromide solution is prepared by dissolving bromide in double-distilled water . A compounding pharmacy can prepare liquid bromide in any convenient concentration (strength) you need. This could be 100 mg/ml, 200 mg/ml, 250 mg/ml, 300 mg/ml or higher. The higher the concentration, the saltier the taste. You usually don't want to go much higher than 500 mg/ml.

When having a prescription refilled, make sure that you check that you are receiving the same strength (mg/ml) as before. If it is not, discuss this with the pharmacist. It will be OK, but you need to know what adjustments need to be made in your dog's dosage. For example, if your dog was on 400 mg a day and your liquid bromide was compounded as 100 mg/ml, then you would be giving your dog a total of 4 ml a day. If the concentration went up to 200 mg/ml, then your dog would only take a total of 2 ml a day. By the way, a cc and ml are equivalent.

What are the benefits of using liquid bromide?

There are several advantages to using liquid bromide. The first is that it is easier to adjust the dosage. The next advantage is that it is much cheaper than the equivalent capsule version. Liquid bromide can be squirted on the dogs food or say on a piece of bread and given to the dog. Liquid bromide can be flavored, however some flavors can reduce the shelf-life of the solution and the flavored solution might need to be refrigerated. Even though bromide is described as being a very stable salt in solution, it wouldn't hurt to gently shake the bottle before using.

Any tips on using liquid bromide?

Bromide usually comes in a pint (or larger size) bottle. Therefore, it might be a good idea to ask your pharmacist for an additional smaller bottle to use for everyday usage. This way if you by chance would drop your small bottle, you'd still have another bottle. When running low, be sure to re-order in plenty of time so that you won't run out. Since liquid bromide is 'hand' prepared, there is a slight change that the new solution might be slightly different. Therefore, it might be a good idea when starting to use the new solution, to first mix a little of the new solution with the old, thus gradually changing over to the new solution. When giving the liquid solution, it is probably easier and more accurate to use an oral medication syringe rather than using a measuring spoon. You could also use an oral medication syringe with a bottle adapter. This is available from any pharmacy. The bottle adapter is placed into the mouth of the bottle and when the syringe is placed into the adapter. This allows you to turn the bottle upside down without spilling the liquid when withdrawing the desired amount into the syringe. When using the bottle adapter, you need to use the syringe that came with it or at least one that has a long tip. Also, if using the bottle adapter, remember that it is not childproof.

How should liquid bromide be stored?

This question can best be answered by the pharmacist. If they say refrigerate, then keep it refrigerated. However, in general, the bromide solution does NOT need to be refrigerated. It should be kept in a brown bottle, away from direct light. If there is any change in the looks of the solution, contact your veterinarian or compounding pharmacy. Sometimes the solution can become cloudy (milky). If this happens it is usually because the solution has been flavored and the solution should be refrigerated. Flavoring can also shorten the shelf-life of the solution. If crystals form, then the solution is no longer the same strength as your original prescription. This can happen if the solution's strength is say 400-500 mg/ml and can be caused by a change in temperature for the solution. If this happens contact your veterinarian or pharmacist. Depending on which pharmacist you speak to, the shelf-life of liquid bromide can be anywhere from 2-3 months up to a year. So be sure to ask.

Any special handling needed for bromide?

It is a very good idea to store your dog's medication in a different location than yours and to clearly mark your dog's medicine bottles with a colorful sticker or special marking. You should use reasonable care when administering any medication. For example, avoid getting it in your eyes, mouth or open wounds and you should probably wash your hands afterwards. Any drug should be stored out of the reach of children and pets. These recommendations would apply to any medication, for example, aspirin.

In people, one of the manifestations associated with long-term bromide overdose is psychosis. The small amount of skin exposure that would occur from giving bromide solution or capsules to a dog should not even come close to causing such an overdose in people. It is NOT neccessary to wear gloves when handling bromide, however, one needs to remember to use reasonable care when administering bromide or any medication. Bromide is a chemical and as such has its own MSDS (Material Safety Data Sheet). So does household bleach.

How is the initial dose determined?

Since most dogs do not start on bromide until they already have reached high 'steady-state' PB levels, one recommended starting bromide dosage is 20 mg/kg/day. For a 60 lb dog, this about 550 mg KBr/day. KBr trough levels should be tested in 30 days and adjusted accordingly.

Another suggested starting dosage for dogs not on PB is 30 to 40 mg/kg/day. For a 60 lb dog, this would be between 820 and 1090 mg KBr/day.

When is a loading doseage recommended?

When starting bromide at the maintenance dose, it takes a month or so to obtain therapeutic blood levels. A much higher, initial "loading" dose is sometimes used to immediately raise the blood level into the therapeutic range. This may be preferable when:

1. The dog is suffering frequent seizures, which need to be controlled quickly, or

2. When another anti-seizure drug, such as phenobarbital, must be stopped quickly (for example, due to the development of liver disease). When this happens, your veterinarian might want to hospitalize your dog.

In addition to the reasons just given, there are several other reasons why a veterinarian may hospitalize a dog during bromide loading:

1. To monitor for and treat any seizures -- uncontrolled seizures being one of the common reasons to load bromide in the first place.

2. To monitor for side effects, such as incoordination and lethargy, which are common with bromide loading. Despite being informed of these side effects, many owners become alarmed when they see this.

3. To administer the bromide and obtain a blood level after the loading dose. Some clients are unable to do this because of work schedules, etc. Some owners might be confused about the loading dosage and continuing the loading dose instead of switching to the maintenance dose, quickly causing toxicity.

How is the loading dosage determined?

There is no 'one' answer here. Some veterinarians might give 3 to 5 loading doses over a 24 to 48 hour period. Others might start by adding an additional 90 mg/kg per day for 5 days in addition to the normal dosage. In this last example, if the starting dosage was day 30 mg/kg/day and if a 90 mg/kg/day loading dosage was given, a 60 lb dog would be given 3280 mg KBr/day for 5 days and then back down to the 30mg/kg/day dosage of 820 mg KBr.

How do I know that my dog is receiving the proper doseage?

Each dog is different, so is their ability to metabolize medications. The only way to determine if your dog is receiving the proper dosage is to monitor the bromide serum concentrations (levels). This is done with a blood test. The first level is usually taken a month after initially starting bromide therapy. Sometimes if a loading dose is given, a level is taken after the first week.

Based on the level results and also on how well the seizures are controlled, the dosage can be adjusted. Levels should be taken at least twice a year, if not more often.

Checking bromide levels:

After starting bromide at a maintenance dose, it takes at least a month before blood concentration enters the therapeutic range (the level at which there is substantial anti-seizure effects) and as long as 4-5 months before steady-state levels are reached (during which blood levels are no longer changing).

What lab tests should be run?

There are two tests for measuring bromide levels. They are:

1. The gold chloride method. This method analyzes the bromide levels via the gold chloride method on a spectrophotometer. This method is "the gold standard" for analysis of bromide. Texas A&M uses this method.

2. The ion selective probe method. This method has not been shown to accurately measure bromide. It is thought that chloride levels can interfere with bromide in the probe method. Several labs use this method for measuring bromide.

Levels. What do the numbers mean?

When the lab sends your veterinarian the results from a bromide serum level test, they will also note the range that they use and the test (ie: gold chloride or ion selective probe).

The most commonly used units of measurement for bromide are:

milligrams per decaliter (mg/dl),
milligrams per milliliter (mg/ml), and
micrograms per milliliter (mcg/ml or ul/ml)

The range 1-2 mg/ml equals 100-200 mg/dl, which equals 1000-200 mcg/ml

The target range for dogs taking bromide and phenobarbital is usually around 100-200 mg/dl. This is equivalent to 1-2 mg/ml or 1000-2000 ug/ml. Dogs taking bromide alone may require levels as high as 300 mg/dl. A few dogs can tolerate blood levels over 400 mg/dl with no side effects, but most dogs show some signs of toxicity at levels above 300 mg/dl.

As you can see, the effects of bromide blood levels vary quite a bit in different dogs.

In general the low level of the therapeutic range means that 50% of the dogs at the low level will exhibit some benefit (ie: seizure control) from the bromide. Likewise, 50% of the dogs that are at the upper limit will NOT show signs of bromide toxicity. As you can see, these lower and upper therapeutic ranges are a little vague. Therefore it is just as important to take into consideration your dog's seizure control and side effects rather than just relying on the numbers.

Trough and peak levels:

Because bromide has such a long half-life (24 days), tough and peak levelsare not as significant as they are with PB (32- 75 hours). If your dog is also on PB, just have the bromide levels checked at the same time as you havethe PB levels done.

The seizures are now well controlled can I redce the doseage?

This should ONLY be done under the direct supervision of your veterinarian. You should NEVER do this on your own without consulting with your veterinarian. If your dog is under the care of several veterinarians (say a 'traditional' practitioner and an 'alternative' practitioner) it is necessary that each of them are aware of what the other is recommending. This is very important. One of the causes of status (status epilepticus) is reducing the AED - so reduction should be done very carefully and with the knowledge and approval of your veterinarians.

If your dog is on PB and KBr (NaBr), each are at steady-state levels and has been seizure free for 6 months, then you can try to slowly reduce the PB. According to one reference, the desired bromide serum level is 200 mg/dl or higher and PB trough level of 25. It is possible for dogs to be totally 'weaned' off the PB. But again this should only be done under the strict
supervision of your veterinarian.

Is there anything to do if I think I my dog may have a seizure?

Because bromide has such a long half-life, giving extra bromide at the time will not prevent a seizure like giving other AEDs (PB, Valium, etc) can.

What if I miss a doseage or are late in giving it?

Because of the long half-life of bromide, this is not a critical issue like it is with other AEDs. Though it is not advised, skipping a dosage for a day or two is not critical.

What if my dog and I are out of town and I forget the bromide?

It will be next to impossible to obtain bromide away from home. Not giving bromide for a few days is not a critical issue. However, do check with your veterinarian, especially for dogs that are on bromide as their only AED.

What if my dogs seizures are not well controlled by bromide?

For some dogs it can take up to 6 months or longer to get the therapeutic benefit from bromide. If bromide is the only AED that your dog is on, you should look into adding PB. You could look into using clorazepate. There are some newer AEDs too, though currently expensive, look promising in controlling seizures in dogs. They are felbamate and gabapentin.

 

Are there ongoing bromide studies?

Texas A&M College of Veterinary Medicine recently completed a study to evaluate the efficacy (effectiveness), safety, and dosing requirements of bromide as an add-on AED -- that is using bromide concomitantly (together) with another AED. And they are currently evaluating bromide as a 'first choice' AED (that is not using with another AED).

 

I'd like to read more about KBr and Bromide Therapy, any recommendations?

Yes, see the article "Seizures in Dogs" by Dr Michael Podell, MSc, DVM that appeared in the July 1996 issue of Veterinary Clinics of North America: Small Animal Practice, Vol 26, Number 4 (pages 779-809). Also check out Texas A&M's article on potassium bromide at http://www.cvm.tamu.edu/vcpl/bromide.ht

 

Please note: On Epil-K9 have been a few reported cases of Pancreatitis and Megasophagus in dogs who are on Potassium Bromide.

Pancreatitis and bromide.

One study has suggested a possible link between bromide and pancreatitis in dogs. Pancreatitis is inflammation of the panaceas. Signs include abdominal pain and vomiting. In this study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy had probable pancreatitis. Only 0.3% of dogs receiving phenobarbital alone had probable pancreatitis. Further studies are necessary to tell if there is a true cause-and-effect relationship between bromide and pancreatitis.

Gaskill-CL; Cribb-AE. Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs.
Canadian-Veterinary-Journal. 2000, 41: 7, 555-558

WB Thomas DVM
Dipl.ACVIM(Neurology)
University of Tennessee
Knoxville, TN
wthomas@utk.edu

 

The above information is NOT intended to replace that provided by your veterinarian. Always discuss any changes regarding your dog's health or medication with your veterinarian.

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Page last update: 05/31/2011

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