Oral contraceptives can increase the effects of diazepam because they inhibit oxidative metabolism, thereby increasing serum concentrations of concomitantly administered benzodiazepines that undergo oxidation. Patients receiving oral contraceptive therapy should be observed for evidence of increased response to diazepam. The administration of valproic acid to patients receiving diazepam can cause an increase in diazepam serum concentrations and a concurrent increase in absence seizures. This interaction appears to be the result of inhibited metabolism of diazepam during concurrent use. If absence seizures increase in patients receiving these medications, an alternative anticonvulsant should be instituted.
Rifampin is a potent hepatic enzyme inducer and can accelerate the hepatic metabolism of diazepam.
Patients should be monitored closely for signs of reduced diazepam effects if given rifampin concomitantly. Ten patients receiving diazepam and epinephrine survived compared to one patient in a retrospective control group. Diazepam is reported to antagonize the toxic effects of chloroquine, although the mechanism is unclear. Further study is needed to confirm the usefulness of diazepam in chloroquine poisoning. Flumazenil and benzodiazepines are pharmacological opposites.