Phenobarbital and other seizure control medication used in dogs

Dietary protein and phenobarbital

Question: I have a five year old yellow lab mix, who was abandoned at four weeks old. She had four grand mal seizures on 6/11, 7/10, 7/31 and 8/1. After the second seizure, the vet suggested Hill`s L/d dog food, as it has a lower protein content than other dog foods. He advised me to stop adding chicken or any other sort of protein to her dog food. After the fourth seizure, she was put on 64.8 mg of Phenobarbital twice a day. She seemed to tolerate both the drug and the change in diet really well. On 9/23 she had her rabies vaccination. The next day she could barely walk, and had to be carried up and down the stairs to go outside. She was still eating the dry L/d, but vomited most of it up on 9/28. The vet recommended switching to Hill`s I/d, as it is easier on the digestive system. She loved the canned Hill`s I/d, and did really well on it. I was concerned about the higher protein content, and began to reintroduce some dry L/d along with the canned. After eight days she vomited again. Tried the same process and ten days later she vomited. So I went back to straight Hill`s canned I/d. She was fine on two cans per day. When I began substituting some dry I/d for the canned, she became sick again. After each vomiting episode, she`s off food for twenty-four hours, and then, over a period of days, returns to normal eating. I guess I have two questions: What do you think is going on? What is the relationship between a diet high in protein and her seizures? Thank you for your help. Sally;

Answer: Dietary protein levels have some effect on the half-life of phenobarbital, with a lower half-life of the medication reported in dogs on protein or protein and fat reduced diets (Journal of the American Veterinary Medical Association, Sept 2000, MacQuire, et.al.) but I don`t think that really has much clinical impact on the average patient being treated with phenobarbital. It is just something to consider when phenobarbital isn`t working adequately in a patient.

There is a dietary approach to seizure control in humans that is referred to as a ketogenic diet. In this diet, a patient is kept off food for several days to induce a ketoacidotic state (a situation in which fats are being broken down and producing more acidity in the blood than normal). After this state has been induced it is maintained by feeding a high fat, low carbohydrate diet. I think that protein levels are usually higher with this sort of diet than normal, not lower, though. This diet is not utilized much in dogs because it is hard to induce a ketoacidotic state in dogs by withholding food so it is questionable whether it is possible to get any benefit from the diet, in dogs.

There are dogs that are reported to have improvements in seizure control when fed diets that contain novel proteins (diets meant to rule out food allergies) and the new hypoallergenic diets with hydrolyzed proteins (HA (tm) and z/d (tm)) may be helpful in this situation. I am not sure these claims have ever really been proven, since that is hard to do because of natural variations in seizure activity. In a dog that also seems to show sensitivity to foods by vomiting or diarrhea, it really seems worthwhile to consider trying one of these foods, just to see if food sensitivity does play a role in the seizure activity or digestive problems. Truthfully, this approach hasn`t produced much benefit in our patients, that I can remember, but it doesn`t hurt to try.

The only other reason that I can think of to control dietary protein in a pet with seizures is to control seizures associated with liver disease. Reduction of dietary protein is a really important part of treatment for seizures and other central nervous system disorders associated with an inability of the liver, for whatever reason, to process ammonia properly. If this is part of the problem with your dog`s seizures, then restriction of dietary protein is important.

It is important to try to rule out treatable causes of seizure activity. It is sometimes possible to find a cause for seizures through a general blood panel or other more specific testing suggested by the lab work. If a good physical exam or the medical history suggest a possible central nervous system cause, an MRI or CT scan might be helpful in identifying a cause for seizure activity, but most patients will have normal appearing brain anatomy on these scans.

Mike Richards, DVM 11/19/2000

Potassium Bromide

Question: Dear Dr. Richards,

I found your letter very informative and timely for us.But I have a few questions regarding Potassium Bromide. I have a 65 lbs. Chocolate Lab. 18 months old, who suffers from Epilepsy since about 10 months. My vet tried the conventional medications that your have in your letter, and the combination of Diazepam and Phenobarbital seem to work for a while, but he took a cluster of seizures that really took us by surprise. So I contacted other Vets including the PEI Veterenirian College for more info on other forms of treatments. I gathered that Potassium bromide could be a good choice. However my Vet. was dead set against it on the onset, but I supplied him with much info that I had gathered both on the Net and other sources and we finally found a pharmacist in Halifax NS who carries it. He ordered the drug and we have him on 3cc of Potassium bromide twice daily,(6am & 6pm) in combination with Phenobarbital 30 mg twice daily, (9am & 9pm). But he is very limited on it`s use and knowledge of the drug, so I hope that you can help us in answering the following questions: Is my dog destined to take these drugs for his life time? And should or could the dosage change (for either drugs)? What are the side effects of the Potassium bromide? What are the danger (to us in handling the product and to my dog, and my other dogs) of this Potassium bromide? Is Potassium bromide addictive? Do having a male neutered stop the seizures? I`m lead to believe that it does, but others say it only works with females if they are spayed. True or False/ How often should I have his blood analized? And what are they looking for? Should there also be a Liver function test done? How often? What does it involve? Should the Potassium bromide be given to him on an empty stomach of after a meal? And finally do you think that the dosage that we have him on is too much or not enough? Sincerely, John

Answer: John;

I am not sure if potassium bromide is addictive. I have not seen anything that says that it is, but it is recommended that withdrawal of the medication be done slowly in a couple of sources I have seen, so that makes me think it is possible. Slow withdrawal is recommended for anti-seizure medications due to the increased possibility of seizures as control medications are withdrawn, though. So it is hard to be sure. I don`t think this is a major worry, though.

I do not know of any information that suggests that seizures can be controlled by spaying or neutering routinely, although there may be some cases in which this has happened. There is some evidence that coming into heat can make seizure activity worse in female dogs, so perhaps that is what you are referring to. I think this is thought to be due to stress but I am not certain of that.

I don`t think it matters if potassium bromide is given with food or not but our clients that have used potassium bromide have mixed it with the food and it was well tolerated. It can cause gastrointestinal upset, which might be a little less likely when mixed with food.

The recommended dosage range of potassium bromide is 20 to 80mg/kg/day, usually given as a single dosage per day but sometimes split into two doses. There are two reasons for the wide dose range. The first is that the lower dosage range is usually used when combining potassium bromide with phenobarbital and the second is that the dosage has to be adjusted over time based on serum bromide levels. This is also true for phenobarbital.

The usual recommended therapeutic dosage range for potassium bromide is 0.5 to 2 mg/ml (50 to 200 mg/dl -- some labs report in these values) but some dogs require levels as high as 2.5 mg/ml in the serum to have control of seizures and most dogs probably do fine in the 0.5 to 1.5 mg/ml range, especially if combined with phenobarbital. It is usually recommended that serum levels be checked after a month, then again at four months (when a more steady state level has been achieved) and then at an interval that you and your vet are comfortable with. So the dose of this medication is adjusted based on how well an individual dog absorbs it and gets it into the serum. If the serum levels are low, the dose is increased, if they are high, the dose is decreased.

The therapeutic serum levels for phenobarbital are reported to be between 20 and 40 ug/ml. There are a lot of recommendations as to when to check these levels. In the "Handbook of Small Animal Practice" by Rhea Morgan, the recommendation is to test on the 14th, 45th and 90th days after starting phenobarbital and then every 6 months. The test should be done at a time that should be the low point for the day --- so as long after the morning pill as possible (at least 8 hours later). The dosage of phenobarbital appears to be low, as 1 to 2mg per pound of body weight, or more, is usually necessary to achieve therapeutic doses, but if serum levels have been OK with this dose, it would not be advisable to increase the dosage.

Video: Rottweiler Epileptic seizure phenobarbital

The usual recommendation is to check a serum chemistry panel, including liver enzymes, after 30 to 45 days and then at six month intervals when using phenobarbital.

There are no significant dangers that I am aware of from administering potassium bromide or phenobarbital, as long as you don`t take the medications yourself.

Potassium bromide can cause increased drinking, increased urination, increased hunger, sleepiness, lethargy, loss of balance, hind leg weakness and depression. Usually the only effects that are chronic are the first three, but it may take several weeks for lethargy and balance problems to disappear.

It is very possible that your dog will require anti-seizure therapy for life. Some dogs do stop having seizures, though. If there are no seizures for a year, it is reasonable to taper off the medications and see what happens.

Hope this helps.

Mike Richards, DVM 9/13/2000

Phenobarbital levels and difficulty standing in St Bernard

Question: Dr. Mike;

I have a recue St. Bernard, 9 years, we have had him for 3.5 years, and he has epilepsy that responds well to phenobarb and KBr, he is on 2 pills TID and 10ml KBr in the am.

He had been on 20ml of KBr for quite some time then we noticed that he was dopeyier than usual and staggered and ran blood on him to find out that his levels were too high so we reduced his KBr to 10ml. That was last year about this time.

He now is having problems with the ability to stand or urinate, he sags in in back end until he is down to the ground, when up and walking he weaves some and has an exagerated high step. I realize that his age may be a factor but he runs and gets up with no problem, could this inability to stand fairly stable be a result from once again to high levels of KBr?

We did not give him his KBr this am. do you know what the withdrawel time is for this get out of system? and how should we measure it. The vet that admin. the pheno and the KBr is not my vet and is far away. My vet is willing to try most anything but has limited experience with Potassium Bromide and it affects.

to date if my dog has any seizure activity it is basically he gets a little dopey then may lay down and have a very short seizure then get up and be fine. we have not had any episodes for well over 3 months, he usually urinates so we can tell if he when he is wet.

Is there any clinical work or info we can find to read on Potassium Bromide. thanks, C.

Answer: C.;

There is definitely a chance that the potassium bromide, or the phenobarbital levels, may be high enough to produce the weakness and wobbliness you are seeing now. There is also a good chance that a herniated disc, lumbosacral instability or even degenerative myelopathy could be causing the signs. In addition there would be some chance of liver damage due to phenobarbital contributing to this clinical sign. Your vet can help sort through these problems with a good physical exam, a blood chemistry test to check on liver and kidney function and checking serum levels of phenobarbital and potassium bromide.

Potassium bromide (KBr) has a "half life" of about 24 days. This means that in an overdosage situation it is sometimes necessary to use intravenous saline or at least added salt in the diet to help get rid of the KBr since it will stay at high levels for a long time. On the other hand, it also means that once a stable dosage has been established that it will usually stay about where it is since it takes a long time to get much change. It also means that it doesn`t matter much what time during the day blood samples are taken to evaluate the bromide level.

Phenobarbital levels should also be tested. Recent studies indicate that timing of the blood test for phenobarbital levels isn`t critical, either. (Levitski as reported in ACVIM research abstracts in "DVM Magazine".

The mechanism of action of potassium bromide is still unknown. It is used fairly often in combination with phenobarbital and can be used alone with good success in a number of dogs. The serum level that is usually considered to be useful to control seizures is 1000-2000 ug/mL.

I really think a good physical exam and general blood chemistry exam are important, too. The other problems mentioned are probably just as likely as a problem with KBr or phenobarbital.

Hope this helps.

Mike Richards, DVM 11/5/99

Epilepsy and phenobarbital

Q: Dr. Mike--My questions are about epilepsy. My 28 month old Lhasa, Zak, has been having seizures for the last 9 months. They were grand mal seizures and he had them one at a time every two to three weeks. Our vet put Zak on Primidone. Zak continued to have grand mal seizures but then started to cluster also. Our vet was reluctent to try anything else, he just changed the dosage. So we went for a second opinion on June 1st and the new vet wanted to try Phenobarb, which we started with 1/2 grain, twice a day. Then on June 13th Zak had one seizure and then about midnight June 15th Zak started to having seizures one right after another and continued non-stop, totaling 20-30 seizures, for about two hours until we got him 60 miles away to the closest animal emergency hospital. He was given valium that night and I took him to the vet the next day and the vet increased the Phenobarb to 1 grain, three times a day and a valium protocol when he had seizures. Zak continued to have seizurers on and off for three more days. This all really took a toll on Zak but he has eventually made a total comeback. Since this episode we had Zak tested for low thryoid function and he does have low thyroid and now he also takes 0.3mg of Thyrozine two times a day. Zak went the entire month on July without a seizure and then had two seizurers, (no cluster) two weeks apart in August. We gave him liquid and then oral valium and he came right out of it. And then in September he had a seizure on the 10th and another on the 13th. These seizurers were so mild that he really fought us when we tried to give him the liquid valium (rectally). Now I have all these questions--It has been brought to my attention that this is alot of Phenobarb to be giving to a dog Zak`s size, he weighs about 28lbs. I have had his Phenobarb levels tested and the was 41.1, which I was told was a very good level but what about liver damage with this much Phenobarb? I`ve heard about adding Potassium Bromide? If he takes Potassium Bromide can he take less Phenobarb? And how about the herbal milkthistle? Does it help protect the liver from damage? And should it be taken before there is any damage or wait until there is a problem? And what about the problems we are having giving Zak the liquid valium, it really does help keep him from clustering but if the seizurers are so mild and he stays so allert he just won`t let us give it to him, is there anything else we can do? Sorry there are so many questions but this is all totally new to us and we want to the best we can for Zak. Any input you might have would be greatly appreciated--Thank you C. C. and Zak

A: Cathy;

I`ll try not to miss a question, but if I do, feel free to write again.

The phenobarbital dosage is producing a serum phenobarbital level in the high end of the therapeutic dosage range, which is good considering the experience with seizures in the past. It is OK to give higher than normal dosages of phenobarbital if that is what it takes to get the blood values in the range necessary to control seizures. It is best to keep it below 45 micrograms/ml. In some dogs, it is necessary to give phenobarbital at dosages as high as 8mg/lb of body weight per day to control seizures.

There are several medications that can be used in conjunction with phenobarbital to control seizures but diazepam (Valium Rx) and potassium bromide are two of the more common ones. It is often the goal to reduce the need for high phenobarbital dosages when combining potassium bromide and phenobarbital and this can work. In some dogs it is even possible to switch to potassium bromide alone but I don`t think you could count on that in Zak`s case due to the severity of the seizure history.

We will dispense injectable diazepam, in some circumstances, for seizure control (same liquid, you just give it in the muscle by injection instead of rectally). If the seizure activity is mild enough that you can give diazepam orally by pill that would be OK, too.

Phenobarbital causes liver damage in some dogs. It is not predictable when this will happen and I don`t think that preventative medications are useful in that circumstance so I guess I wouldn`t recommend using milk thistle or any other liver medication unless problems occurred.

Phenobarbital is generally considered to be less likely to cause liver problems than primidone, so it was good to switch medications, especially considering the dosage necessary to control Zak`s seizures.

It may be worth asking for referral to a veterinary neurologist for help with this problem. They have the most experience with dogs resistant to seizure control. Your vet seems to be doing a good job and so I don`t think this is absolutely necessary but it can sometimes be helpful.

It is a good idea to check the phenobarbital serum levels periodically, especially when you are having to use high dosages.

Mike Richards, DVM 9/24/99

Phenobarbital, seizure, excessive drinking and urination

Q: Dear Dr. Mike,

Our 6 year old German Shepherd started around Thanksgiving with increased thirst, two weeks later she had a grand mal seizures lasting about 3 minutes. Our vet did blood work and a urinalysis. All were normal.

One week later she had two grand mal seizures about 1 hour apart. She was hospitalized and had several more tests including an ultra sound to check for tumors. She was also started on Phenobarbitol 1 gram.

Video: Dog with Epilepsy having a Seizure :(

She continues to have cluster seizures every three weeks. Each episode is more severe and contains more seizures. The last one was 16 seizures in a 24 hours period with 8 of them being very severe grand mal seizures. She is now on 3 grains of Pheno BID and 6 cc potassium bromide SID. She has been on this dose about 3 weeks and was very unsteady the first week. Then she adapted to it and was doing quite good.

About 1 week ago she started drinking literally gallons of water and leaking urine constantly. Also she has also started being very unsteady particularily on her left rear leg. All blood work and another urinalysis were again normal.

Our vet is treating it as diabetes insipidus hoping to get the water intake and leakage under control. He doesn`t feel that these things are connected.

I am very afraid that we might be looking at some kind of brain tumor. Do you have any suggestions or ideas. We have already decided that we will not have a cat scan and spinal done on her.

Judy A

A: Judy;

We have seen excessive drinking and urination as a side effect of phenobarbital administration in a few dogs. It can be very difficult to figure out if there is a problem because of the phenobarbital or in addition to the original problem of seizures. Since the increase in drinking seems to slightly predate the seizures it does seem likely that it may be a problem in its own right, though.

There is a very high probability of a brain tumor or brain injury in a dog that develops seizures after it is five years old. The MRI and CT scans are the best way to look for tumors but sometimes there are other identifiable signs of damage to the brain that can help identify the presence of a tumor, such as head pressing, circling, balance problems or changes in behavior or mentition. When seizures do not respond to medication there is also a high correlation with brain tumors. I know that both of those prognostic signs are bad.

It is often possible to control diabetes insipidus even when it is occurring in conjunction with other diseases. It makes it a lot easier to handle the other problems when constant drinking and urinating are under control.

If there is a veterinary neurologist in your area it may be worth getting an opinion from him or her even if you do not wish to have further diagnostic tests. Neurologists are often better at discerning very subtle signs of neurologic dysfunction than general practitioners and may be able to give you a better idea of the prognosis.

I don`t know of a better combination of medications than phenobarbital and potassium bromide.

I wish that I could help more with this.

Mike Richards, DVM 4/14/99

Phenobarbital levels - seizure control

Q:My Lhasa Apso is 9 years old and has had 3 seizures in 9 months. She lies down and convulses (not too hard) for a short time, gets up, seems disorientated and after a short time becomes herself again. My vet started her on 15 mg. of pheno twice a day. She was a little tire for the first few days and that has leveled off, but she is very thirsty, drinks a lot, urinates quite frequently now and has developed a large appetite. When I asked my vet if this would level off as the listlesness did, he advised me to take her off the medication for a week to see if the symptoms disappeared and then resume at half the dosage. If the symptoms recur then we know it is from the medication. She had blood tests in May and everything was normal. He suggested blood tests again, but as much as my dog is part of my family as my husband and daughter, I hesitate to spend $165.00 so soon again. What do you think. Also my dog weighs 14 lbs.

A: Dear SM;

Increased drinking and urinating can be associated with the use of phenobarbital. It also occurs as a natural consequence of diabetes, kidney failure, hyperadrenocorticism and several other conditions. Sometimes an increased appetite does also occur. So there is a good chance that the signs you are seeing are due to the medication.

I do think that testing the serum phenobarbital levels is the best approach to monitoring the dosage of phenobarbital and that it should be a routine part of the management of seizure disorders with phenobarbital. The amount of phenobarbital that must be administered orally in order to achieve proper blood levels varies a lot from dog to dog. It takes a couple of weeks for phenobarbital levels to stabilize, though, so the testing should be done after the medication has been used for that time. It is also a good idea to check the liver enzyme levels in the serum on a routine basis (once or twice a year, at least) when using phenobarbital.

If the phenobarbital causes side effects that are difficult to live with it is worth evaluating the need for seizure control against these side effects. My dog seizures three or four times a year and I do not medicate her to control the seizures because I think that the seizures are less of a problem than the medications to control them, at that level of seizure activity. You might want to discuss the need for the medications with your vet again.

Good luck with this.

Mike Richards, DVM

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