Major
ritonavir × Tamsulosin
HIV protease inhibitor / pharmacokinetic booster×Alpha-adrenergic blockers for prostatic disorders
Mechanism
Tamsulosin is a CYP3A4 substrate. Ritonavir is a potent CYP3A4 inhibitor. Tamsulosin plasma levels rise 5-fold or more; orthostatic hypotension and syncope emerge.
Symptoms
Sudden blood pressure drop on standing, syncope, dizziness. Older patients: fall and fracture risk.
Management
Avoid the combination. Alternative for benign prostatic hyperplasia on ritonavir: a 5α-reductase inhibitor (finasteride, dutasteride; minimal CYP3A4 dependence) or an α1-blocker with less CYP3A4 dependence (alfuzosin with caution).