SUBOXONE and SUBUTEX^® CIII (buprenorphine HCl sublingual tablets) should not be administered to patients who have been shown to be hypersensitive to buprenorphine, and SUBOXONE should not be administered to patients who have been shown to be hypersensitive to naloxone.

Respiratory Depression
Significant respiratory depression has been associated with buprenorphine, particularly by the intravenous route. A number of deaths have occurred when addicts have misused buprenorphine intravenously, usually with benzodiazepines concomitantly. Deaths have also been reported in association with concomitant administration of buprenorphine with other depressants such as alcohol or other opioids. Patients should be warned of the potential danger of the self-administration of benzodiazepines or other depressants while under treatment with SUBOXONE or SUBUTEX.

SUBOXONE and SUBUTEX should be used with caution in patients with compromised respiratory function (eg, chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression).

Central Nervous System (CNS) Depression
Patients receiving buprenorphine in the presence of other narcotic analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedatives/hypnotics or other CNS depressants (including alcohol) may exhibit increased CNS depression. When such combined therapy is contemplated, reduction of the dose of one or both agents should be considered.

Potential for Dependence
SUBOXONE and SUBUTEX have potential for abuse. Buprenorphine is a partial agonist at the mu-opioid receptor, and chronic administration produces dependence of the opioid type, characterized by withdrawal upon abrupt discontinuation or rapid taper. The withdrawal syndrome is milder than that seen with full opioid agonists and may be delayed in onset.

Hepatitis, Hepatic Events
Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in the addict population receiving buprenorphine both in clinical trials and in postmarketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of preexisting liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant use of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Measurements of liver function tests prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function tests during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, the drug should be carefully discontinued to prevent withdrawal symptoms and a return to illicit drug use, and strict monitoring of the patient should be initiated.

Head Injury and Increased Cranial Pressure
SUBOXONE and SUBUTEX, like other potent opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances where cerebrospinal pressure may be increased. SUBOXONE and SUBUTEX can produce miosis and changes in the level of consciousness that may interfere with patient evaluation.

Pregnancy Category C
There are no adequate and well-controlled studies of SUBOXONE and SUBUTEX in pregnant women. SUBOXONE should not be taken during pregnancy unless the potential benefit patient justifies the potential risk to the fetus. Contraception should be used while taking SUBOXONE.

Many women also have changes in menstruation when they use opioids. This may continue when the patient is taking SUBOXONE. It is important to remind patients that they can still become pregnant even with irregular periods.

Nursing Mothers
An apparent lack of milk production during general reproduction studies with buprenorphine in rats caused decreased viability and lactation indices. Use of high doses of sublingual buprenorphine in pregnant women showed that buprenorphine passes into the mother's milk. Breast-feeding is therefore not advised in mothers treated with SUBOXONE or SUBUTEX.

Use in Ambulatory Patients
SUBOXONE and SUBUTEX may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery, especially during drug induction and dose adjustment. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that buprenorphine therapy does not adversely affect their ability to engage in such activities. Like other opioids, SUBOXONE and SUBUTEX may produce orthostatic hypotension in ambulatory patients.

Commonly Reported Side Effects
Side effects of SUBOXONE and SUBUTEX are similar to those of other opioids. The most commonly reported adverse events with SUBOXONE include: headache (36%, placebo 22%), withdrawal syndrome (25%, placebo 37%), pain (22%, placebo 19%), nausea (15%, placebo 11%), insomnia (14%, placebo 16%), and sweating (14%, placebo 10%).

Pediatric Use
SUBOXONE and SUBUTEX are not recommended for use in pediatric patients. The safety and effectiveness of SUBOXONE and SUBUTEX in patients younger than 16 years have not been established.

Appropriate Use of SUBOXONE
Patients with a clinical need for analgesia should not be transferred to SUBOXONE. SUBOXONE is not indicated for pain management.