Moderate
Alprazolam × tacrolimus
Benzodiazepines. Short-to-medium-acting anxiolytics×Calcineurin inhibitor (immunosuppressant)
Mechanism
Tacrolimus is a weak CYP3A4 inhibitor; alprazolam is a CYP3A4 substrate. Alprazolam levels may rise moderately. Additive sedative effect.
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 0.25 mg at bedtime. In transplant patients, prefer buspirone or CBT for anxiety over benzodiazepines. If unavoidable, tacrolimus monitoring is unchanged, but check sedation at 1 and 2 weeks after starting alprazolam.