Anxiol Drug Interactions

Enhanced sedation or respiratory and cardiovascular depression may occur if diazepam is given with other drugs that have CNS depressant properties; these include alcohol, antidepressants, antihistamines, antipsychotics, general anesthetics, other hypnotics or sedatives, and opioid analgesics. The sedative effect of diazepam may also be enhanced by Cisapride. Adverse effects may also be produced by concomitant administration with drugs which interfere with the metabolism of diazepam. Drugs which have been reported to alter the pharmacokinetics of diazepam are the following: Analgesics: Diazepam used with opioid analgesics in anesthetic or analgesic regimens is expected to produce additive sedative effect.
Antibacterials: Rifampicin has decreased the half life of diazepam.
Anticoagulants: Plasma binding of diazepam and desmethyldiazepam was reduced, and free concentrations increased, immediately following heparin intravenously.
Antidepressants: Plasma concentrations of diazepam are affected by fluvoxamine. It has been suggested that patients taking fluvoxamine who require benzodiazepine should preferentially receive one such as lorazepam which has a different metabolic pathway.
Fluoxetine can increase the plasma concentrations of diazepam but the plasma concentrations of desmethyldiazepam are reduced and it is considered that the overall effect is likely to be mirror.
Antiepileptics: Carbamazepine, Phenobarbital and Phenytoin are all inducers of hepatic drug-metabolising enzymes. Therefore in patients receiving long-term therapy with these drugs the metabolism of benzodiazepines may be enhanced.
Sodium valproate has been reported to displace diazepam from plasma-protein binding sites.
Antivirals: The non-nucleoside reverse transcriptase inhibitors delavirdine and efavirenz, and HIV-protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir may inhibit the hepatic microsomal systems involved in the metabolism of some benzodiazepines. Prolonged administration of protease inhibitors may also induce these metabolic systems; interactions may therefore be complex and difficult to predict. Concomitant administration requires monitoring with dosage adjustments for the benzodiazepine or else should be avoided. Diazepam should not be used concomitantly with HIV-protease inhibitors.
Beta blockers: A clear pattern of interaction between benzodiazepines and beta blocker has not emerged. Propranolol and metoprolol may inhibit the metabolism of diazepam.
Clozapine: There have been reports of cardiorespiratory collapse in patients taking clozapine and benzodiazepines. Hypersalivation associated with clozapine and benzodiazepines may be exacerbated when these drugs are used together.
Digoxin: Raised serum-digoxin concentrations have been reported in patients also taking diazepam. The clearance of digoxin was reduced clearance.
Disulfiram: Chronic treatment with disulfiram can inhibit the metabolism of diazepam leading to a prolonged half-life and reduced clearance.
Gastrointestinal drugs: Cimetidine can inhibit the hepatic metabolism of diazepam. The clearance of diazepam has generally been decreased and the half-life prolonged. Some studies have also demonstrated impaired metabolic clearance of desmethyldiazepam.
Continuous omeprazole administration affects the pharmacokinetics of a single intravenous dose of diazepam. Omeprazole decreases the clearance and prolongs the elimination half-life of diazepam; in addition both the formation and elimination of desmethyldiazepam appear to be decreased. The effects may be greater in rapid than in slow metabolisers of omeprazole and vary between ethnic groups.
Levodopa: Reversible deterioration of parkinsonism has been reported in patients receiving levodopa who were given benzodiazepines such as diazepam.
Neuromuscular blockers: There are conflicting reports of the effect of diazepam on neuromuscular blockers; potentiation or antagonism of neuromuscular block, and a lack of interaction have all been reported.
Oral contraceptives: Some studies with diazepam have supported suggestions that oral contraceptives may inhibit the biotransformation of benzodiazepines metabolized by oxidation.
Penicillamine: Phlebitis associated with intravenous diazepam resolved with local heat but recurred on two separate occasions after oral penicillamine.
Smooth muscle relaxants: Intracavernosal papaverine produced prolonged erection in 2 patients who had been given intravenous diazepam as an anxiolytic before the papaverine.
Tobacco smoking: Drowsiness as a side effect of diazepam is less frequent in smokers than non-smokers.
Xanthines: Reports of aminophylline give intravenously reversing the sedation from intravenous diazepam. Xanthine-containing beverages may be expected to decrease the incidence of benzodiazepine-induced drowsiness because of their CNS-stimulating effects and their ability to induce hepatic drug-metabolising enzymes.