Tetracyclines and anticonvulsants


The serum levels of doxycycline are reduced and may fall below the accepted therapeutic minimum in patients on long-term treatment with barbiturates, phenytoin or carbamazepine. Other tetracyclines appear to be unaffected.

Clinical evidence
A study in 14 patients taking phenytoin (200-500 mg daily) and/or carbamazepine (300-1000 mg daily) showed that the half-life of doxycycline was approximately half that in nine other patients not taking anticonvulsants (7.1 compared with 15.1 h).
Similar results were found in 16 other patients on anticonvulsant therapy with phenytoin, carbamazepine and phenobarbitone. The serum doxycycline levels of almost all of them fell below 0.5 g/ml during the 12-24 h period following their last dose of doxycycline (100 mg). Tetracycline, methacycline, oxytetracyclme, demeclocydine and chlortetracycline were not significantly affected by these anti-convulsants. Other studies confirm this interaction between the anticonvulsant barbiturates (and in one case the hypnotic amylobarbitone) and doxycycline.

Mechanism
Uncertain. These anticonvulsants are known enzyme-inducing agents and it seems probable that they increase the metabolism of the doxycycline by the liver, thereby hastening its clearance from the body.

Importance and management
The doxycycline-anticonvulsant interactions are established. The extent to which concurrent use affects treatment with doxycycline seems not to have been studied, but serum doxycycline levels below 0.5 g/ml are less than the accepted minimum inhibitor concentration (MIC). It seems likely that the antibiotic will fail to be effective. The suggestion has been made that the interaction can be accommodated by increasing the doxycycline dosage or by giving it twice daily. Alternatively, tetracyclines which are reported not to be affected by the anticonvulsants could be used: tetracycline, methacycline, oxytetracydine, demeclocydine and chlortetracycline.