DRUG INTERACTIONS Drug Interactions
Drug interactions common to other potent opioid analgesics also may occur with buprenorphine HCl. Particular care should be taken when buprenorphine HCl is used in combination with central nervous system depressant drugs (see WARNINGS). Although specific information is not presently available, caution should be exercised when buprenorphine HCl is used in combination with MAO inhibitors. There have been reports of respiratory and cardiovascular collapse in patients who received therapeutic doses of diazepam and buprenorphine HCl. A suspected interaction between buprenorphine HCl and phenprocoumon resulting in purpura has been reported.
CYP3A4 Inhibitors: Since the metabolism of buprenorphine is mediated by the CYP3A4 isozyme, coadministration of drugs that inhibit CYP3A4 activity may cause decreased clearance of buprenorphine. Thus, patients coadministered with inhibitors of CYP3A4 such as macrolide antibiotics (e.g., erythromycin), azole antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritanovir) while receiving buprenorphine HCl should be carefully monitored and dosage adjustment made if warranted.
CYP3A4 Inducers: Cytochrome P450 inducers, such as rifampin, carbamazepine, and phenytoin, induce metabolism and as such may cause increased clearance of buprenorphine. Caution is advised when administering buprenorphine HCl to patients receiving these medications and, if necessary, dose adjustments should be considered.
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OVERDOSAGE
Manifestations
Clinical experience with buprenorphine HCl overdosage has been insufficient to define the signs of this condition at this time. Although the antagonist activity of buprenorphine may become manifest at doses somewhat above the recommended therapeutic range, doses in the recommended therapeutic range may produce clinically significant respiratory depression in certain circumstances. (See WARNINGS.)
Treatment
The respiratory and cardiac status of the patients should be monitored carefully. Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Doxapram, a respiratory stimulant, may be used. NALOXONE MAY NOT BE EFFECTIVE IN REVERSING THE RESPIRATORY DEPRESSION PRODUCED BY BUPRENORPHINE HCl. THEREFORE, AS WITH OTHER POTENT OPIOIDS, THE PRIMARY MANAGEMENT OF OVERDOSE SHOULD BE THE REESTABLISHMENT OF ADEQUATE VENTILATION WITH MECHANICAL ASSISTANCE OF RESPIRATION, IF REQUIRED.
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