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Opioids: Due to additive pharmacologic effect, the concomitant use of opioids with benzodiazepines increases the risk of respiratory depression, profound sedation, coma and death.
The concomitant use of opioids and benzodiazepines increases the risk of respiratory depression because of actions at different receptor sites in the central nervous system that control respiration. Opioids interact primarily at μ-receptors, and benzodiazepines interact at GABAA sites. When opioids and benzodiazepines are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate (see Precautions).
Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.
Benzodiazepines produce additive CNS depressant effects when co-administered with alcohol or other drugs producing CNS depression (see Precautions).
Pharmacokinetic interactions can occur when alprazolam is administered along with drugs that interfere with its metabolism. Compounds which inhibit certain hepatic enzymes (particularly cytochrome P4503A4) may increase the concentration of alprazolam and enhance its activity. Data from clinical studies with alprazolam, in vitro studies with alprazolam, and clinical studies with drugs metabolized similarly to alprazolam provide evidence for varying degrees of interaction and possible interaction with alprazolam for a number of drugs. Based on the degree of interaction and the type of data available, the following recommendations are made: The co-administration of alprazolam with ketoconazole, itraconazole, or other azole-type antifungals is not recommended.
Caution and consideration of dose reduction is recommended when alprazolam is co-administered with nefazodone, fluvoxamine, and cimetidine.
Caution is recommended when alprazolam is co-administered with fluoxetine, propoxyphene, oral contraceptives, diltiazem, or macrolide antibiotics such as erythromycin and troleandomycin.
Interactions involving human immunodeficiency virus (HIV) protease inhibitors (e.g., ritonavir) and alprazolam are complex and time dependent. Low doses of ritonavir resulted in a large impairment of alprazolam clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of alprazolam.
Increased digoxin concentrations have been reported when alprazolam was given, especially in elderly (>65 years of age). Patients who receive alprazolam and digoxin should therefore be monitored for signs and symptoms related to digoxin toxicity.
