Canine Epilepsy - Using Phenobarbital to control seizures in dogs

Dosage	Monitoring Therapy	Side Effects
Liver Damage	Discontinuing Therapy	Drug Interactions

Phenobarbital (sometimes abbreviated as Pb or Phb) is one of the medications most commonly used to treat seizures in dogs because it is relatively inexpensive, easy to use and effective in 60 to 80% of dogs with idiopathic epilepsy. In addition to being used on a daily basis to prevent seizures, Phenobarbital can be used to stop seizures in progress. Phenobarbital's peak activity occurs 4-8 hours after the pill is given. While Pb is not FDA approved for use in dogs, it is one of two first choices for veterinarians and its use is accepted practice. Phenobarbital comes in liquid or tablet form and is available both from a veterinarian and from a regular pharmacy by prescription. When Phenobarbital is started, it takes 1 to 2 weeks to reach a stable blood level. Until that period has passed, it cannot be fully relied upon to prevent seizures. Please contact your veterinarian if your dog has more than one seizure every two weeks or the seizures last longer than five minutes.

Some manufacturers use grams and some use grains as a unit of measure. In milligrams, Phenobarbital is available in 15 mg, 30 mg, 60 mg or 100 mg tablets. Manufacturers who use grains offer 1/8 grain (8 mg), 1/4 grain (16 mg), 1/2 grain (32 mg) or 1 grain (65 mg).

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.

The initial starting dose that is frequently used is 2 mg to 3 mg per kilogram of body weight every 12 hours (to convert your dog's weight to kilograms, divide the weight by 2.2 or see conversion chart). Your veterinarian will adjust this dosage based on blood levels, seizure activity and side effects of the medication.

Your veterinarian will tell you how often to give your dog his/her medicine. As a general rule, Pb is given every 12 hours and should be given as close to every 12 hours to avoid seizures.

To determine the correct dose of Phenobarbital, it can be very helpful to monitor its level in the blood . Your veterinarian will want to test Phenobarbital levels after approximately two weeks of therapy to be sure that your dog is in a therapeutic range. It takes two weeks for Phenobarbital to reach a steady state after starting or adjusting Phenobarbital.

In most cases a single trough (low) level is collected just before a dose is administered. Published therapeutic or target ranges are only an approximation; however, according to some experts, blood serum levels below 15 mcg/ml are rarely therapeutic and levels above 45 mcg/ml increase the likelihood of liver disease. Once a therapeutic level (or control) is achieved, blood serum levels should be retested every 6 months to be sure that the blood concentrations have not drifted out of the intended range. Most important, chemistry panels with the liver enzymes GGT, ALT and Alkaline Phosphatase should be done every three or four months to monitor liver function. Of course probably the best test of whether you have hit a correct dose is whether your dog is still having seizures. Having only one seizure a month is considered good control. If the seizures are under control, it may not be necessary to adjust the dose when the dog's blood level is below therapeutic range. But levels higher than therapeutic range can lead to liver damage.

Phenobarbital inhibits seizures by decreasing the activity of neurons. Unfortunately, this effect is not specific to the neurons involved in the seizures but affects other neurons as well. Many of the potential side effects of this drug are caused by this effect on neurons. These side effects can include sedation, lethargy, excessive urination, excessive thirst and excessive hunger, hyperexcitability, ataxia (loss of coordination or hind end weakness) and restlessness. Most of these side effects diminish or disappear after the first few weeks of therapy. Excessive urination, excessive thirst and excessive hunger are the most common long-term side effects.

Chronic or long term use (over 3 months) of Phenobarbital can lead to scarring in the liver and liver failure in a small percentage of dogs. Caught early enough, liver damage can be reversed with a simple change to the liver cleansing diet, the slow reduction or elimination of Phenobarbital, and possibly the addition of milk thistle, SamE or Denysol. If left undiagnosed too long, however, liver damage can be irreversible and fatal.

We have included the stories of some of our members' dogs - members who have generously agreed to have their stories included so that others can avoid the heartbreak of irreversible liver damage in their dogs.

What we have learned from our other members is that we have a better chance of avoiding severe liver damage with proactive monitoring -- blood tests to check that the level of Phenobarbital is not above the therapeutic range (run two weeks after beginning therapy and then every six months); and, MOST IMPORTANT, pre and post bile acid tests as early in therapy as possible for a baseline and then chemistry panels with the liver enzymes ALT, GGT and Alkaline Phosphatase every three or four months. These tests are used because they can indicate the beginning of a problem in plenty of time to change medication and take appropriate action. Some vets will say that a chemistry panel is sufficient to determine liver damage. Unfortunately, we have seen instances where the liver/chemistry panel was normal and by the time changes appeared in those tests, it was too late. Bile acid testing every 6 months can provide an earlier indication of a problem so that adjustments can be made before it is too late. Liver enzymes to watch in a chemistry panel are: ALT (SGPT), GGT, Alkaline Phosaphatase and AST.

Whatever you and your vet may decide to do about monitoring, here is a list of symptoms of liver damage. Early signs can be as general as loss of appetite, weight loss and chronic intermittent diarrhea and vomiting - vomiting is more common. While an increase in drinking and urinating can also signal liver problems, these are common with Pb and it may be difficult to tell the difference. Later signs of liver failure are jaundice (the whites of the eyes turn yellow as well as the mucous membranes on the gums and tongue), swollen belly, lethargy and dark brown urine along with either pale gray or mustard colored stools.

The decision to stop Phenobarbital must be made very carefully but is reasonable to consider with dogs that are seizure-free for one to two years, who are having side effects that affect their quality of life, who develop liver disease or where you wish to incorporate Potassium Bromide into the dog's treatment and eliminate or reduce the Pb dosage. The dose should be gradually tapered off over a period of about 6 months. If the dog has developed liver disease, the reduction can be by as much as 25 % a week. If there is no urgency, some vets suggest a reduction of 10% every week or so. The major risk of discontinuing drug therapy is seizure recurrence, which is most likely to happen during withdrawal or within several months of stopping therapy.

Phenobarbital speeds up liver activity and, when used with other medications that are normally broken down by the liver, may cause them to be metabolized more rapidly, therefore requiring them to be given at a higher dosage. Some of these drugs include antibiotics like chloramphenicol and doxycycline, heart medications like digitoxin, corticosteroids and antiparasitic drugs such as metronidazole (Flagyl). It is also reported to decrease intestinal absorption of the commonly used anti-fungal product, griseofulvin.

1. Phenobarbital is one of the drugs given to control seizures in dogs. After your dog has begun Phenobarbital, CONSULT WITH YOUR VETERINARIAN RIGHT AWAY IF: the dog has more than one seizure every two weeks or if the seizures last longer than five minutes.

2. When first started, blood levels should be checked after a week or two, then every six months.

3. You generally need to give it to your dog as close as you can to 12 hours apart.

4. There can be side effects, most of which disappear in a few weeks. The most common side effects are excessive hunger, thirst and need to urinate, excitability, restlessness, lethargy and ataxia (loss of coordination).

5. PLEASE PLEASE monitor Liver functions by having pre and post bile acid tests done every 3 to 4 months when your dog is on Pb. Caught very early, liver disease can be reversed. Signs of severe liver damage which is irreversible include: loss of appetite, weight loss, chronic diarrhea or vomiting, jaundice, swollen belly, lethargy, dark brown urine and pale gray or mustard colored stools.

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

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;

Dr. W. Jean Dodds, DVM; James M. Griffin, MD and Liisa D. Carlson, DVM, Dog Owner's Home Veterinary Handbook, 3^rd Edition, NY: 2000; Kate A. W. Roby, VMD, Lenny Southam, DVM, The Pill Book Guide to Medication for your Dog and Cat, NY: 1998