Table 4.

CYP3A4 enzyme inhibitors and inducers reported to have caused clinically significant drug–drug interactions with opioids metabolized by CYP3A4 (oxycodone, methadone, fentanyl) in papers included in the present review24,27–33,37–39,44

Drugs	Effect on CYP3A4 activity	Resulting effects when coadministered with opioid	Resulting effects after withdrawal of interacting drug
CYP3A4 inhibitors
Voriconazole	Strong
Itraconazole	Strong
Fluconazole Clarithromycin Diltiazem	Moderate Strong Moderate	Decreased rate of opioid metabolism, increased opioid effect, increased risk of opioid toxicity	Increased opioid metabolism, decreased clinical effect of opioid
Cyclosporine	Weak
Cimetidine	Weak
CYP3A4 inducers
Rifampin Carbamazepine	Strong Strong	Increased metabolism of opioid, requirement for higher opioid doses, deterioration of pain control	Decreased rate of opioid metabolism, increased risk of opioid overdose