(for veterinary information only)
USES OF THIS MEDICATION
When animals have frequent seizures, medication becomes necessary. In the dog and cat, phenobarbital, a barbiturate, is probably the first choice for seizure suppression. It is effective, safe if used responsibly, reasonably priced, and conveniently dosed all of which makes it a popular choice. Since treatment with phenobarbital is generally life-long, monitoring blood tests are periodically recommended.
Phenobarbital is generally effective regardless of the underlying cause of the seizure disorder which means that is can be used for epilepsy, brain tumors, infectious diseases, or poisonings.
Phenobarbital is absorbed well into the body when given orally and it’s peak activity occurs 4-8 hours after the pill is given.
When phenobarbital is started, it takes 2-4 weeks to reach a stable blood level
The 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs includes a review of effectiveness of several anti-seizure medications. They found 82% of epileptic dogs on phenobarbital had >50% seizure reduction with a seizure-free rate of 31%. Approximately 15% of epileptic dogs on phenobarbital did not respond and needed a different treatment plan.
Excessive thirst and urination and excessive appetite are not uncommon side effects of phenobarbital. If they occur, they do not generally go away as the patient adjusts to medication. If they are severe, medication may have to be changed.
It is not unusual for some patients to demonstrate depression or sedation when phenobarbital therapy is initiated. This effect is generally transient and resolves as the patient acclimates to the medication. If this problem has not resolved after two weeks, a phenobarbital blood level can be drawn to determine if the dose is too high for the individual in question. Running a blood level sooner may not be useful as it takes a couple of weeks to achieve a stable and meaningful blood level.
Rarely, anemia (lack of red blood cells) can occur with phenobarbital exposure. Should this occur, a different seizure medication should be selected.
Chronic exposure to phenobarbital can lead to scarring in the liver and liver failure that can be irreversible. Proper monitoring tests are geared for heading off such an event in plenty of time to change medication.
Phenobarbital is able to “induce” the metabolic enzymes, thus making them more efficient at removing toxins. Part of this phenomenon involves elevation of liver enzyme tests on a blood panel. As previously mentioned, monitoring by periodic blood testing is important in catching any impending liver problems while they are still insignificant but this is complicated because elevations in liver enzymes occur with normal phenobarbital usage.
There are many monitoring protocols. Here are the recommendations from the aforementioned ACVIM Consensus Statement:
The first sample should be run two weeks after beginning medication followed by another blood level six weeks after starting medication. After that blood levels should be checked every 6 months or if the pet has >2 seizures between these times or two weeks following any change in dose. Levels are best drawn just before medication is due to be given so as to get the lowest blood level of the day (a "trough" level).
INTERACTIONS WITH OTHER DRUGS
Phenobarbital is removed from the body primarily by the liver (75% is removed by the liver, 25% by the kidney). As mentioned, in the liver, phenobarbital has a unique ability to “induce” the microsomal enzymes which means in more simple terms that chronic exposure to phenobarbital makes the liver more efficient at removing other toxins. Other medications which will not work as well in the presence of phenobarbital include: lysodren (treatment for Cushing’s disease), chloramphenicol (an antibiotic), corticosteroids (such as prednisone, dexamethasone), doxycycline (an antibiotic), estrogens, cardiac beta-blockers, quinidine (a heart rhythm medicine), theophylline (an airway dilator), cyclosporine (for immune mediated diseases), levetiracetam (another anti-seizure drug), praziquantel (dewormer), itraconazole (anti-fungal), doxorubicin (agent of chemotherapy), and metronidazole (a multi-purpose antibiotic/GI medicine).
Phenobarbital’s activity can be enhanced by concurrent administration of the following medications: chloramphenicol (an antibiotic), any anti-histamine associated with drowsiness, or any other sedative or tranquilizer.
Rifampin, a special antibiotic, may reduce the effectiveness of phenobarbital when the two are used concurrently.
When unacceptable side effects develop with phenobarbital use, phenobarbital dose may be substantially cut back or even discontinued. Potassium bromide can be used as an alternative or supplemental seizure control medication in such cases.
As mentioned, long term exposure, particularly at higher doses, can induce scarring in the liver and proper monitoring is needed to avoid this side effect. Liver toxicosis is enhanced by the use of the following drugs: rifampin (a special antibiotic), acetaminophen (pain reliever), carprofen (anti-inflammatory pain reliever), selegiline (for cognitive dysfunction), and amitraz (common ingredient in tick protection productions for dogs).
CONCERNS AND CAUTIONS
MISSING EVEN ONE PHENOBARBITAL DOSE
It is very important to comply fully with medication recommendations.
Because of the induction of microsomal enzymes previously mentioned, it is normal to see elevated liver enzymes (“AST”, “ALP”, and “ALT”) on any blood chemistry that is performed. This makes interpretation of these values somewhat difficult.
The blood level of phenobarbital attained in an individual is not completely predictable by knowing the oral dose given. With time, the patient’s liver becomes especially able to remove phenobarbital from the system and the level may go down. Or the opposite may be true and the liver becomes less efficient so that blood level goes up. For these reasons, blood levels of phenobarbital are periodically measured so as to periodically adjust the oral dose as noted above.
In patients with poor liver function or liver failure, phenobarbital may not be the best choice in seizure control.
The use of phenobarbital will interfere with thyroid function testing as well as with adrenal function testing. Monitoring hypothyroidism or Cushing’s disease in patients taking phenobarbital is extremely difficult as test results will be difficult to interpret.
Some patients are able to discontinue their phenobarbital if seizures have become infrequent. It is important not to discontinue phenobarbital "cold turkey" as doing so may precipitate severe seizuring. Your veterinarian can instruct you on how to wean off phenobarbital.
Liver toxicity is associated with blood levels of 35 ug/ml or higher. If very high blood levels of phenobarbital are required to control seizures, a second medication (usually potassium bromide) should be added so as to reduce the phenobarbital dose required.
Page last updated: 1/5/2017