Drug class	Potential interaction
Anticholinergics	Increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
Benzodiazepines	Some reports of coma and death associated with misuse of buprenorphine/naloxone (particularly via injection) and benzodiazepines 25
	Decreased ceiling effects on buprenorphine-induced respiratory depression, making the respiratory effects similar to those of full mu opioid agonists 26
Cytochrome P450 3A4 inducers (e.g., phenobarbital, carbamazepine [Tegretol], phenytoin [Dilantin], rifampin)	Increased clearance of buprenorphine could lead to decreased plasma concentrations, lack of effectiveness, or abstinence syndrome 25
Cytochrome P450 3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics, protease inhibitors, antidepressants)	Decreased clearance of buprenorphine may lead to increased plasma concentrations, resulting in increased or prolonged opioid effects; patients should be monitored for respiratory depression and sedation; dose reduction of either medication may be necessary 25
Nonbenzodiazepine muscle relaxants (e.g., carisoprodol [Soma], cyclobenzaprine [Flexeril])	Increased degree of respiratory depression
Other central nervous system depressants (e.g., sedatives, hypnotics, general anesthetics, tranquilizers, other opioids, alcohol)	Increased risk of respiratory depression, profound sedation, hypotension, coma, and death
Psychostimulant: cocaine	Increased metabolism and decreased plasma concentrations of buprenorphine 27