Moderate
Alprazolam × duloxetine
Benzodiazepines. Short-to-medium-acting anxiolytics×SNRI
Mechanism
Additive CNS depression. Duloxetine weakly inhibits CYP2D6 with no CYP3A4 effect — no pharmacokinetic interaction with alprazolam.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk.
Management
On starting the combination, begin alprazolam at the minimum dose. In anxiety with chronic pain (neuropathy, fibromyalgia), the combination is reasonable, but for long-term therapy assess feasibility of benzodiazepine discontinuation via CBT. Avoid the combination in older patients — fall risk.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.