PHENOBARBITAL DOSING
AND PRECAUTIONS

The ideal anti-seizure medicine should suppress seizures completely without side effects or toxicity. Unfortunately, such a drug does not exist.

Phenobarbital is an effective, inexpensive drug for treating seizures in dogs and cats. It can have side effects, and, according to Ned Patterson, DVM, 20% of the dogs on long term phenobarbital develop some liver dysfunction.  In order to obtain maximum effects from this medicine, and to insure safe administering, it is our responsibility as caregivers to provide and administer this drug properly and test periodically for liver damage. Milk Thistle will not protect against liver dysfunction.

TESTING FOR LIVER DAMAGE
It is extremely important to have a chemistry panel done every 3 to 4 months for dogs on phenobarbital. If any of the three liver enzymes [ALT (SGPT), GGT and Alkaline Phosphatase] are elevated, you need to immediately do a urine bile acid test through Dr. Dodds. (Please see Dr. Dodds Instruction Form for Submitting Blood for Testing and Dr. Dodds' Information Form.) If detected early enough, liver damage can be reversed. You cannot rely on symptoms for liver damage to warn you.  Unfortunately, when the symptoms are visible, it is often too late.

REMINDER: Based on studies of liver disease and those epileptic dogs we have lost to it, we recommend a chemistry panel be done every 3 to 4 months.  If the liver enzymes are elevated then a urine bile acid should be done immediately.  Here is the link for the urine bile acid test:
http://canine-epilepsy-guardian-angels.com/urine_bile_acid_testing.htm

Make sure the chemistry panel has the liver enzymes: Alkaline Phosphatase, ALT (SGPT)  and GGT.  Also make sure you receive a copy of the test results for your files so that you can determine for yourself that the liver enzymes are in the normal range. Since you pay for the tests, you should automatically get a copy of the results.  If not, ask for one for your files. Please do not expect your vet to tell you if the liver enzymes are normal or not. This is your responsibility and it cannot be stressed strongly enough. Your pup's life depends on it....

MONITORING BLOOD LEVELS
To insure proper AND safe administering of phenobarbital, it is very important to monitor the level in the blood. This is done by obtaining a blood sample 4-5 hours AFTER a dose (peak).

*Therapeutic range is 15-45 ug/mL. for dogs taking only phenobarbital.  For dogs taking both phenobarbital and bromide, the phenobarbital range is 9-36 ug/mL. Phenobarbital levels should be done every 6 months to a year. 

*Different foods, changes in environment or even the addition of supplements can change phenobarbital levels. If adding thyroid medication, check phenobarbital levels after 2 to 3 weeks.  Thyroid medication raises the metabolism and could lower phenobarbital levels.

PRECAUTIONS
Due to this relatively short half-life of phenobarbital in the dog, it is very important to administer the phenobarbital dose at least EVERY 12 hours. This does not mean "twice a day," such as a morning dose and another dose "sometime" in
the afternoon. This DOES mean dosing as close to every 12 hours as possible. Wide fluctuations in dosing or even a single missed dose can initiate a seizure.  You can also dose every 8 hours for better seizure control.

Even when a dog has been taking the same drug for a long time and the blood levels are in equilibrium, the levels will fluctuate over the course of the day. Depending on the rate of absorption of the drug and factors that influence the absorption rate (e.g., taking some drugs after meals slows absorption), there will be peaking (high points) in the blood level and troughs (low points) shortly before or immediately after a dose is taken.

Dose-related adverse effects are more likely to occur at times of peak levels, and a seizure is more likely to occur at times of trough levels.

DOSAGES
The most commonly recommended dose in dogs is 2-3 mg phenobarbital per kilogram of body weight given every 12 hours. In some cases, it helps to divide the daily dose into three equal doses given every 8 hours.

Each patient is different and only the attending veterinarian should make specific recommendations.  Never make any changes in the dosage without consulting your veterinarian.

To determine your dog's weight in kilograms, divide the weight in pounds by 2.2.
(Or use our conversion table:  CONVERSION TABLE)

EXAMPLE:   A 50 lb. dog equals 22.7 kg  (50 divided by 2.2 = 22.7)
                   Calculating a 2 mg dose:  2 x 22.7 = 45.4 or 45 mg phenobarbital given every 12 hours.
                   Calculating a 3 mg dose:  3 x 22.7 = 68.1 or 68 mg phenobarbital given every 12 hours.
(If you are dosing phenobarbital in grains, 1 grain is equal to approximately 60-65 mgs)

Successful treatment depends heavily on client education and cooperation. Treatment failures often result from inadequate client education or poor client compliance.  In order to understand the importance of regularly scheduled dosing, it will be helpful to understand the term "half-life" and other common terms.

HALF LIFE - is defined as the amount of time (usually expressed in hours) that it takes for the quantity of a drug in the body to be reduced by 50%.

PEAK LEVELS - are when the drug is at it's highest. Peak levels occur 4-5 hours after oral administration in dogs.  (Compared to 8-12 hours in humans.)  Phenobarbital is given every 12 hours in most dogs. Some dogs may require dosing every 8 hours.

TROUGH LEVELS - Although there are various protocols and opinions concerning WHEN to test, a "trough" level should be obtained 3-4 weeks after the initiation of therapy followed by similar testing at least every 6 months. A tough level is taken just prior to a dose of phenobarbital.

Peak and trough levels also allow estimation of half-life so that the dosing interval can be modified if necessary.

OVERALL MONITORING
Monitoring by periodic testing is important in catching any impending liver problems while still insignificant and treatable. Testing should include routine chemistry panels with the liver enzymes GGT, ALT and Alkaline Phosphatase.  If the liver enzymes are more than slightly elevated you will need a liver function test that can show the accurate health of the liver (PRE- and POST-MEAL BILE ACIDS OR URINE BILE ACIDS). This testing is VITALLY IMPORTANT and should also be done if there are more than slight evelvations in the liver enzymes ALT, GGT and Alkaline Phosphatase. 

In addition to proper dosing and diligent testing, it is imperative that you observe your dog closely at all times. Learn his or her behavior. Know when the slightest change occurs so that it can alert you to impending side effects or signs of toxicity. If things are "off," contact your veterinarian IMMEDIATELY. Proper care and monitoring can insure that your dog will lead a normal, happy life.

We feel that proper understanding of this medication as well as the addition of helpful "dosing reminders" (daily or weekly medication dispensers, calendars, etc.) can help us realize the importance of calculating and implementing accurate dosing.


References:
Antech, W.J. Dodds, DVM
"Applied Pharmacology for the Veterinary Technician," Boyce P. Wanamaker, Christy L. Pettes, 1996
Canine Epilepsy Network, Ned Patterson, 2002
"Epilepsy:  Patient and Family Guide," Orrin Devinsky, M.D., 2002
"Handbook of Veterinary Neurology," Oliver, Lorenz, and Kornegay, 1997
"Idiopathic Epilepsy In Dogs," Wm. B. Thomas, DVM MS, Veterinary Clinics of North America: Small Animal Practice, 2000
"Veterinary Drug Handbook," Donald C. Plumb, 1994