Subutex is metabolized to norbuprenorphine by cytochrome CYP 3A4. Because CYP 3A4 inhibitors may increase
plasma concentrations of buprenorphine, patients already on CYP 3A4 inhibitors such as azole antifungals (e.g.
ketoconazole), macrolide antibiotics (e.g. erythromycin), and HIV protease inhibitors (e.g. ritonavir, indi-navir and
saquinavir) should have their dose of SUBUTEX or SUBOXONE adjusted.
Based on anecdotal reports, there may be an interaction between buprenorphine and benzodiazepines. There have been
a number of reports in the post-marketing experience of coma and death associated with the concomitant intravenous
misuse of buprenorphine and benzodiazepines by addicts. In many of these cases, buprenorphine was misused by
self-injection of crushed SUBUTEX tablets. SUBUTEX and SUBOXONE should be prescribed with caution to patients on
benzodiazepines or other drugs that act on the central nervous system, regardless of whether these drugs are taken on
the advice of a physician or are taken as drugs of abuse. Patients should be warned of the potential danger of the
intravenous self-administration of benzodiazepines while under treatment with SUBOXONE or SUBUTEX.