Most reports of clinically significant drug interactions occurring with the barbiturates have involved
phenobarbital. However, the application of these data to other barbiturates appears valid and warrants serial blood
level determinations of the relevant drugs when there are multiple therapies.
Anticoagulants: Phenobarbital lowers the plasma levels of dicumarol (name previously used:
bishydroxycoumarin) and causes a decrease in anticoagulant activity as measured by the prothrombin time. Barbiturates
can induce hepatic microsomal enzymes resulting in increased metabolism and decreased anticoagulant response of oral
anticoagulants (e.g., warfarin, acenocoumarol, dicumarol and phenprocoumon). Patients stabilized on anticoagulant
therapy may require dosage adjustments if barbiturates are added to or withdrawn from their dosage regimen.
Corticosteroids: Barbiturates appear to enhance the metabolism of exogeneous corticosteroids
probably through the induction of hepatic microsomal enzymes. Patients stabilized on corticosteroid therapy may
require dosage adjustments if barbiturates are added to or withdrawn from their dosage regimen.
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
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
Phenytoin, sodium vaiproate, valproic acid: The effect of barbiturates on the metabolism of
phenytoin appears to be variable. Some investigators report an accelerating effect, while others report no effect.
Because the effect of barbiturates on the metabolism of phenytoin is not predictable, phenytoin and barbiturate blood
levels should be monitored more frequently if these drugs are given concurrently. Sodium vaiproate and valproic acid
appear to decrease barbiturate metabolism; therefore, barbiturate blood levels should be monitored and appropriate
dosage adjustments made as indicated.
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
Monoamine oxidase inhibitors (MAOI): M.O. prolong the effects of barbiturates probably because
metabolism of the barbiturate is inhibited.
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.