Alprazolam × Itraconazole

The liver breaks down alprazolam mainly through the enzyme CYP3A4, and itraconazole and its main metabolite hydroxy-itraconazole strongly inhibit this enzyme. In a study with alprazolam 0.8 mg, itraconazole raised the alprazolam area under the curve (AUC) 2.8-fold, while peak concentration did not change. More alprazolam stays in the blood, and its sedative effect becomes stronger and may last longer. The inhibition reaches full strength only when itraconazole reaches steady state, after about 15 days with the capsules. After itraconazole is stopped, it takes 7–14 days to leave the blood.

Too much alprazolam shows as drowsiness, slurred speech, poor coordination, confusion, lethargy, low muscle tone and low blood pressure. Severe poisoning can bring respiratory depression and, rarely, coma. The risk is higher if the person also takes alcohol or other drugs that depress the nervous system.

The combination is contraindicated. The alprazolam label forbids use with strong inhibitors of the enzyme CYP3A4 and names itraconazole (alprazolam label, US Food and Drug Administration, FDA). The Spanish alprazolam label does not recommend it with itraconazole or other azole antifungals (alprazolam label, Spanish Agency of Medicines and Medical Devices, AEMPS). The itraconazole documents are milder: they list alprazolam among drugs to use with caution, with close monitoring and a lower dose if needed (itraconazole labels, AEMPS and FDA). After itraconazole is stopped, it takes 7–14 days to leave the blood, and longer in liver cirrhosis. Take this into account when starting alprazolam after a course of itraconazole (itraconazole label, AEMPS). If the two have been taken together, watch for drowsiness, slurred speech, poor coordination, low blood pressure and slowed breathing (alprazolam and itraconazole labels, AEMPS). Alcohol is not recommended with alprazolam because it adds to the sedation (alprazolam label, AEMPS). In a serious overdose, support breathing and circulation. Flumazenil, a benzodiazepine receptor antagonist, may help (alprazolam label, AEMPS).