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HOME >> API >> API List 4 >> Phenobarbital Acid >> Interaction

INTERACTION
Phenobarbital acid CAS Registry Number 50-06-6

Most reports of clinically significant drug interactions occurring with the barbiturates have involved phenobarbital.

1. Anticoagulants: Phenobarbital lowers the plasma levels of dicumarol (name previously used: bishydorxycoumarin) and causes a decrease in anticoagulant activity as measured by the prothrombin time. Phenobarbital can induce hepatic microsomal enzymes resulting in increased metabolism and decreased anticoagulant response of oral anticoagulants (e.g., warfarin, acenocournarol, dicumarol, and phenprocoumon). Patients stabilized on anticoagulant therapy may require dosage adjustments if phenobarbital is added to or withdrawn from their dosage regimen.

2. Corticosteroids: Phenobarbital appears to enhance the metabolism of exogenous corticosteroids probably through the induction of hepatic microsomal enzymes. Patients stabilized on corticosteroid therapy may require dosage adjustments if phenobarbital is added to or withdrawn from their dosage regimen.

3. Griseofulvin: Phenobarbital appears to interfere with the absorption of orally administered griseofulvin, thus decreasing its blood level. The effect of the resultant decreased blood levels of griseofulvin on therapeutic response has not been established. However, it would be preferable to avoid concomitant administration of these drugs.

4. Doxycycline: Phenobarbital has been shown to shorten the half- life of doxycycline for as long as 2 weeks after barbiturate therapy is discontinued. This mechanism is probably through the induction of hepatic microsomal enzymes that metabolize the antibiotic. If phenobarbital and doxycycline are administered concurrently, the clinical response to doxycycline should be monitored closely.

5. Phenytoin, sodium valproate, valproic acid: The effect of phenobarbital on the metabolism of phenytoin appears to be variable. Some investigators report an accelerating effect, while others report no effect. Because the effect of phenobarbital on the metabolism of phenytoin is not predictable, phenytoin and phenobarbital blood levels should be monitored more frequently if these drugs are given concurrently. Sodium valproate and valproic acid appear to decrease phenobarbital metabolism; therefore, phenobarbital blood levels should be monitored and appropriate dosage adjustments made as indicated.

6. Central nervous system depressants: The concomitant use of other central nervous system depressants including other sedatives or hypnotics, antihistamines, tranquilizers, or alcohol, may produce additive depressant effects.

7. Monoamine oxidase inhibitors (MAOIs): MAOIs prolong the effects of phenobarbital probably because metabolism of the phenobarbital is inhibited.

8. Estradiol, estrone, progesterone and other steroidal hormones: Pretreatment with or concurrent administration of phenobarbital may decrease the effect of estradiol by increasing its metabolism. There have been reports of patients treated with antiepileptic drugs (e.g., phenobarbital) who became pregnant while taking oral contraceptives. An alternate contraceptive method might be suggested to women taking phenobarbital.

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