A 70 year old PACE participant is brought to the hospital after his son found him lying on the floor of his living room, mumbling incessantly in a panicked state. Ever since the participant’s wife passed away 3 years ago, he has been drinking heavily when he is not at the Center. The hospitalist immediately initiates diazepam IV to start treating his alcohol withdrawal and to alleviate his current anxiety. The only other medication the participant was taking before being hospitalized is verapamil (sustained release, 240 mg QD) for migraine prophylaxis. The diazepam IV treatment is continued for 2 days and he is discharged on PO diazepam (scheduled 10 mg TID). Five days post-discharge, though he is still sober, the participant falls at home, breaking his hip.
When consulted, the pharmacist reminded PACE clinical staff that diazepam is extensively metabolized by CYP 3A4, and that intravenously administered diazepam bypasses first-pass metabolism. However, the participant had also been taking verapamil, which is a strong CYP 3A4 competitive inhibitor. Because diazepam has good oral bio-availability, the effect of the competitive inhibition (increase of CMax) will NOT be seen immediately with the first oral dose. However, over a period of time, the steady state levels will slowly rise (see below chart). Furthermore, because diazepam has a very long half-life (due to active metabolite) its sedative properties will be greatly pronounced days after the IV to PO switch.
The pharmacist and PACE medical director decide that the best course for the participant, as long as he could remain sober, is oxazepam po 30 mg TID for both alcohol withdrawal and depression. Oxazepam is not metabolized by the CYP system and would not be subject to metabolic inhibition by verapamil.