Available in 15 mg (1/4 grain), 30 mg (1/2 grain), 60 mg (1 grain), and 90 mg (1 and one-half grain) tablets

Background 

When an animal has a seizure disorder, the frequency and severity of the seizures determine the need for treatment. In dogs and cats, the barbiturate phenobarbital is probably the first choice to suppress seizures. It is effective, safe if used responsibly, reasonably priced, and conveniently dosed, all of which make it a popular choice. Since treatment with phenobarbital is generally life-long, monitoring blood tests is periodically recommended.

Phenobarbital is generally effective regardless of the underlying cause of the seizure disorder, which means that it can be used for epilepsy, brain tumors, infectious diseases, or poisoning.

• Phenobarbital is given as a tablet 2-3 times daily. Most patients take it twice daily as this schedule is relatively convenient for most pet owners. If a dose is accidentally skipped, give the dose when it is remembered and give the subsequent dose at the appropriate time interval. If a breakthrough seizure occurs, an additional dose may be given at that time.

• Keep away from light and store at room temperature. Do not refrigerate.

• Phenobarbital can be given with or without food.

• Cats can be difficult when it comes to pills twice daily long term so it may be helpful to use a compounded oral liquid or transdermal gel (applied on the unhaired skin of the inner ear). Such formulations are custom-made by compounding pharmacies. A commercially available oral solution exists but has too high an ethanol content to be useful in pets.

Monitoring blood tests are important for long-term use of phenobarbital (see below).

Common Possible Side Effects of Phenobarbital

Sedation: The goal of seizure therapy is to end the seizures, not sedate the patient. Most patients will not show noticeable sedation while on phenobarbital, and if they do, there is a good chance the dose is too high. Some patients cannot find an effective dose of phenobarbital that is not sedating and these patients may need a different medication, or simply a reduction of the phenobarbital dose and addition of a second medication.

Sedation During Initial Therapy: It is not unusual for some patients to appear depressed or sedated when phenobarbital therapy is begun. This effect is generally temporary and resolves as the patient gets used to the medication. If this problem has not been resolved after two weeks, a blood test can determine if the dose is simply too high and needs to be changed.

Excessive Appetite: Phenobarbital makes patients very hungry. This can be problematic if the patient becomes obese or overly focused on food.

Excessive Thirst: It makes patients thirsty. This could become a problem if the patient drinks so much water that house soiling becomes a problem.

Uncommon Possible Side Effects of Phenobarbital

Chronic exposure to phenobarbital can lead to scarring in the liver and liver failure, which can be irreversible. Monitoring tests can head off such an event in plenty of time to change medication. Liver toxicity is associated with prolonged high phenobarbital blood levels. Liver toxicity appears to be a problem for dogs but not for cats.

Cats can get itchy faces on phenobarbital. This can be problematic enough to require a medication change.

Rarely, anemia (lack of red blood cells) can occur with phenobarbital exposure. Should this occur, a different seizure medication should be used.

Monitoring

Phenobarbital is able to induce metabolic enzymes, thus making them more efficient at removing toxins. Part of this phenomenon involves elevating 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. The recommendations from the American College of Veterinary Internal Medicine Consensus Statement are:

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 six months, if the pet has more than two seizures between these times, or two weeks following any change in dose. Levels are best drawn just before medication is due to be given to get the lowest blood level of the day (a "trough" level).

Interactions with Other Drugs

Phenobarbital has a long list of potential drug interactions, so your veterinarian must know about all the drugs and supplements your pet is taking.

As mentioned, in the liver, phenobarbital has a unique ability to “induce” the microsomal enzymes, which means that long-term exposure to phenobarbital makes the liver more efficient at removing other toxins, including other drugs.

Medications that will not work as well when taking 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), levitracitam (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 giving the following medications at the same time: chloramphenicol (an antibiotic), any antihistamine associated with drowsiness, or any other sedative or tranquilizer.

Rifampin, an antibiotic, may reduce the effectiveness of phenobarbital when the two are used concurrently.

If phenobarbital is used with griseofulvin (treatment for ringworm), the griseofulvin may not be absorbed well into the body and may not be as effective.

When unacceptable side effects develop with phenobarbital use, the 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. Potassium bromide is contraindicated for use in cats.

As mentioned, long-term exposure, particularly at higher doses, can induce scarring in the liver and monitoring is needed to avoid this side effect. Liver toxicosis is made more likely by the following drugs: rifampin (an 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

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 results. This makes interpreting 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 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 the blood level goes up. For these reasons, blood levels of phenobarbital are periodically measured so as to adjust the oral dose as noted above.

Some patients can discontinue phenobarbital if seizures have become infrequent. It is important not to discontinue phenobarbital cold turkey as doing so may precipitate severe seizures. 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 to reduce the phenobarbital dose required. Potassium bromide can be given to dogs, but is not to be used for cats. 

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