PHENOBARBITAL

(for veterinary information only)

AVAILABLE IN
15 mg (1/4 GRAIN),
30 mg (1/2 GRAIN),
60 mg (1 GRAIN),
90 mg (1 AND A HALF GRAIN)
& 100 mg TABLETS

BACKGROUND INFORMATION

When an animal has a seizure disorder, the frequency and severity of the seizures determines the need for treatment. 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.

HOW THIS MEDICATION IS USED

• 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.
  
  
• 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 employ a compounded oral liquid or transdermal gel (applied on the unhaired skin of the ear). Such special 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 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 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 blood level of phenobarbital will determine if the dose is simply too high and requires adjustment.

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

Excessive Thirst: Phenobarbital makes patients thirsty. This could become a problem if the patient drinks so much that excessive urine is produced leading to house-soiling.

UNCOMMON POSSIBLE SIDE EFFECTS OF PHENOBARBITAL

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. Liver toxicity is associated with prolonged phenobarbital blood levels of 35 ug/ml or higher. Liver toxicity appears to be a problem for dogs but not for cats.

Cats can experience facial itching 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 selected.

MONITORING

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 has a very long list of potential drug interactions so it is very important to inform your veterinarian 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 in more simple terms that chronic exposure to phenobarbital makes the liver more efficient at removing other toxins.

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 antihistamine 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.

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

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
CAN BE ENOUGH TO TRIGGER A SEIZURE.

If you accidentally skip a dose, do not double up on the next dose.

If your pet has a break-through seizure, however, you may give an extra dose
of phenobarbital when your pet is aware enough to take an oral medication.

In patients with poor liver function or liver failure,
phenobarbital may not be the best choice in seizure control.
Approximately 75% of a phenobarbital dose is removed from the body by the liver
so the liver must be working properly to process this medication.

• 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.
  
  
• 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.
  
  
• Phenobarbital should be stored at room temperature where it is protected from light (a colored pharmacy pill vial is sufficient).
  
  
• Phenobarbital is a controlled substance which means that special paperwork is necessary for its prescription.

Short version (to help us comply with "Lizzie's Law")

Page last updated: 5/21/2021