INDICATIONS AND USAGE Buprenorphine hydrochloride injection is indicated for the relief of moderate to severe pain.
CONTRAINDICATIONS Buprenorphine hydrochloride injection should not be administered to patients who have been shown to be hypersensitive to the drug.
ADVERSE REACTIONS The most frequent side effect in clinical studies involving 1,133 patients was sedation which occurred in approximately two-thirds of the patients. Although sedated, these patients could easily be aroused to an alert state. Other less frequent adverse reactions occurring in 5-10% of the patients were: Nausea Dizziness/Vertigo Occurring in 1-5% of the patients: Sweating Headache Hypotension Nausea/Vomiting Vomiting Hypoventilation Miosis The following adverse reactions were reported to have occurred in less than 1% of the patients: CNS Effect: confusion, blurred vision, euphoria, weakness/fatigue, dry mouth, nervousness, depression, slurred speech, paresthesia. Cardiovascular: hypertension, tachycardia, bradycardia. Gastrointestinal: constipation. Respiratory: dyspnea, cyanosis. Dermatological: pruritus. Ophthalmological: diplopia, visual abnormalities. Miscellaneous: injection site reaction, urinary retention, dreaming, flushing/warmth, chills/cold, tinnitus, conjunctivitis, Wenckebach block, and psychosis. Other effects observed infrequently include malaise, hallucinations, depersonalization, coma, dyspepsia, flatulence, apnea, rash, amblyopia, tremor, and pallor. The following reactions have been reported to occur rarely: loss of appetite, dysphoria/agitation, diarrhea, urticaria, and convulsions/lack of muscle coordination. Allergic Reactions Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience of buprenorphine hydrochloride injection and other buprenorphine- containing products. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to buprenorphine hydrochloride. In the United Kingdom, buprenorphine hydrochloride was made available under monitored release regulation during the first year of sale, and yielded data from 1,736 physicians on 9,123 patients (17,120 administrations). Data on 240 children under the age of 18 years were included in this monitored release program. No important new adverse effects attributable to buprenorphine hydrochloride were observed. For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical, Inc. at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions Drug interactions common to other potent opioid analgesics also may occur with buprenorphine hydrochloride. Particular care should be taken when buprenorphine hydrochloride 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 hydrochloride 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 hydrochloride. A suspected interaction between buprenorphine hydrochloride 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 hydrochloride 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 hydrochloride to patients receiving these medications and if necessary dose adjustments should be considered.