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Interactions of benzodiazepines with warfarin
British Medical Journal
|September 9, 1972
Summary
Nitrazepam, diazepam, and chlordiazepoxide do not affect warfarin levels or anticoagulant control in patients, indicating safety for concurrent use. However, chlordiazepoxide may affect cortisol metabolism in some individuals.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Drug Interactions
Background:
- Warfarin is a common anticoagulant requiring careful management.
- Benzodiazepines are frequently prescribed, necessitating evaluation of potential drug interactions.
Purpose of the Study:
- To investigate the effects of nitrazepam, diazepam, and chlordiazepoxide on warfarin pharmacokinetics and anticoagulant control.
- To assess the safety of co-administering these benzodiazepines with long-term oral anticoagulation.
Main Methods:
- Patients on long-term warfarin therapy received nitrazepam, diazepam, or chlordiazepoxide.
- Warfarin plasma concentrations, half-life, and anticoagulant control were monitored.
- Urinary 6 beta-hydroxycortisol excretion was measured.
- Rat studies assessed liver microsomal enzyme activity.
Main Results:
- Nitrazepam, diazepam, and chlordiazepoxide did not alter warfarin steady-state plasma concentrations, half-life, or anticoagulant control.
- Two of five patients showed increased urinary 6 beta-hydroxycortisol excretion with chlordiazepoxide.
- Chlordiazepoxide, but not diazepam or nitrazepam, induced liver microsomal enzymes in rats.
Conclusions:
- Nitrazepam, diazepam, and chlordiazepoxide appear safe for patients on long-term oral anticoagulants regarding warfarin efficacy.
- Chlordiazepoxide may influence cortisol metabolism and liver enzyme activity, warranting further investigation.
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