Drug Interactions between aspirin / carisoprodol / codeine and voriconazole

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

MONITOR: Coadministration with voriconazole may increase the plasma concentrations of drugs that are substrates of CYP450 2C19, 2C9, and/or 3A4. The mechanism is decreased clearance due to inhibition of those isoenzymes by voriconazole. Increased plasma levels and/or pharmacologic effects of drugs such as cyclosporine, sirolimus, tacrolimus (3A4 substrates), and warfarin (2C9 substrate) have been reported during coadministration with voriconazole.

MANAGEMENT: Caution is advised if voriconazole must be used concomitantly with medications that undergo metabolism by CYP450 2C19, 2C9 and/or 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever voriconazole is added to or withdrawn from therapy. The manufacturer specifically recommends that a dosage reduction be considered for benzodiazepines, statins, long-acting opiates, and vinca alkaloids that are metabolized by the affected isoenzymes when used with voriconazole.