Amitriptyline × Ritonavir

Ritonavir strongly inhibits CYP3A4, and at full antiretroviral doses it probably inhibits CYP2D6 as well (ritonavir SmPC). The liver breaks down amitriptyline mainly through CYP2D6 and CYP2C19, and to a lesser degree through CYP3A4 (amitriptyline SmPC). The ritonavir SmPC expects higher amitriptyline levels, and the amitriptyline SmPC expects a clinically relevant interaction with strong CYP3A4 inhibitors, naming ritonavir. Neither document gives the size of the rise.

Dry mouth, constipation, urinary retention, accommodation disturbance, tachycardia. In older patients: delirium and confusion risk. QT prolongation with torsades risk.

The combination is allowed but needs monitoring. With ritonavir at full antiretroviral doses, watch the therapeutic and adverse effects of amitriptyline closely (ritonavir SmPC). The amitriptyline dose may need to be lowered (US Food and Drug Administration (FDA) ritonavir label). When a tricyclic antidepressant is combined with a strong CYP2D6 inhibitor, the amitriptyline SmPC advises considering plasma level monitoring and adjusting the dose if needed. Use amitriptyline with caution in significant bradycardia, decompensated heart failure and with other drugs that prolong the QT interval (amitriptyline SmPC). After ritonavir is stopped, amitriptyline levels may fall and a higher antidepressant dose may be needed (FDA amitriptyline label).