OBJECT DRUGS

Anxiolytics (CYP3A4 Substrates):

• Alprazolam (Xanax, etc.)
• Buspirone (BuSpar)
• Clonazepam (Klonopin)
• Clorazepate (Tranxene, etc.)
• Diazepam (Valium, etc.)
• Estazolam (ProSom)
• Flurazepam (Dalmane)
• Halazepam (Paxipam)
• Midazolam (Versed, oral)
• Prazepam (Centrex)
• Quazepam (Doral)
• Triazolam (Halcion)

PRECIPITANT DRUGS

Calcium Channel Blockers:

• Diltiazem (Cardizem, etc.)
• Verapamil (Isoptin, etc.)

Comment:

When given orally, alprazolam, midazolam and triazolam undergo extensive first pass metabolism by CYP3A4 in the gut wall and liver. Other benzodiazepines such as clonazepam, clorazepate, diazepam, flurazepam, halazepam, prazepam and quazepam are also at least partly metabolized by CYP3A4, and may also interact with CYP3A4 inhibitors, Intravenous midazolam is much less affected than when it is given orally. The primary risk of these interactions is impairment of motor skills that could result in falls or motor vehicle accidents.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Benzodiazepines: Consider other benzodiazepines: temazepam (Restoril), oxazepam (Serax), and lorazepam (Ativan) are largely glucuronidated, and are unlikely to be affected by CYP3A4 inhibitors.
• Calcium Channel Blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit the metabolism of benzodiazepines.
• Monitor: Monitor for altered benzodiazepine response if the CYP3A4 inhibitor is initiated, discontinued, or changed in dosage. Warn patients about increased sedative effects.