"The U.S. Food and Drug Administration today approved Hysingla ER (hydrocodone bitartrate), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternat"...
Impaired Respiration: As with other potent opioids, clinically significant respiratory depression may occur within the recommended dose range in patients receiving therapeutic doses of buprenorphine. Buprenex (buprenorphine) should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression). Particular caution is advised if Buprenex (buprenorphine) is administered to patients taking or recently receiving drugs with CNS/respiratory depressant effects. In patients with the physical and/or pharmacological risk factors above, the dose should be reduced by approximately one-half.
NALOXONE MAY NOT BE EFFECTIVE IN REVERSING THE RESPIRATORY DEPRESSION PRODUCED BY BUPRENEX (buprenorphine) . 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.
Interaction with Other Central Nervous System Depressants: Patients receiving Buprenex (buprenorphine) in the presence of other narcotic analgesics, general anesthetics, antihistamines, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics or other CNS depressants (including alcohol) may exhibit increased CNS depression. When such combined therapy is contemplated, it is particularly important that the dose of one or both agents be reduced.
Head Injury and Increased Intracranial Pressure: Buprenex (buprenorphine) , like other potent analgesics, may itself elevate cerebrospinal fluid pressure and should be used with caution in head injury, intracranial lesions and other circumstances where cerebrospinal pressure may be increased. Buprenex (buprenorphine) can produce miosis and changes in the level of consciousness which may interfere with patient evaluation.
Use in Ambulatory Patients: Buprenex (buprenorphine) may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery. Therefore, Buprenex (buprenorphine) should be administered with caution to ambulatory patients who should be warned to avoid such hazards.
Use in Narcotic-Dependent Patients: Because of the narcotic antagonist activity of Buprenex (buprenorphine) , use in the physically dependent individual may result in withdrawal effects.
General: Buprenex (buprenorphine) should be administered with caution in the elderly, debilitated patients, in children and those with severe impairment of hepatic, pulmonary, or renal function; myxedema or hypothyroidism; adrenal cortical insufficiency (e.g., Addison's disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; acute alcoholism; delirium tremens; or kyphoscoliosis.
Because Buprenex (buprenorphine) is metabolized by the liver, the activity of Buprenex (buprenorphine) may be increased and/or extended in those individuals with impaired hepatic function or those receiving other agents known to decrease hepatic clearance.
Buprenex (buprenorphine) has been shown to increase intracholedochal pressure to a similar degree as other opioid analgesics, and thus should be administered with caution to patients with dysfunction of the biliary tract.
Carcinogenesis, Mutagenesis And Impairment Of Fertility
Carcinogenesis: Carcinogenicity studies were conducted in Sprague-Dawley rats and CD- 1 mice. Buprenorphine was administered in the diet at doses of 0.6, 5.5, and 56 mg/kg/day for 27 months in rats. These doses were approximately equivalent to 5.7, 52 and 534 times the recommended human dose (1.2 mg) on a mg/m2 body surface area basis. Statistically significant dose-related increases in testicular interstitial (Leydig's) cell tumors occurred, according to the trend test adjusted for survival. Pair-wise comparison of the high dose against control failed to show statistical significance. In the mouse study, buprenorphine was administered in the diet at doses of 8, 50, and 100 mg/kg/day for 86 weeks.
The high dose was approximately equivalent to 477 times the recommended human dose (1.2 mg) on a mg/m2 basis. Buprenorphine was not carcinogenic in mice.
Mutagenesis: Buprenorphine was studied in a series of tests. Results were negative in Chinese hamster bone marrow and spermatogonia cells, and negative in mouse lymphoma L5178Y assay. Results were equivocal in the Ames test: negative in studies in two laboratories, but positive in frame shift mutation at high dose (5 mg/plate) in a third study.
Impairment of Fertility: Reproduction studies of buprenorphine in rats demonstrated no evidence of impaired fertility at daily oral doses up to 80mg/kg (approximately 763 times the recommended human daily dose of 1.2 mg on a mg/m2 basis) or up to 5mg/kg I.M. or S.C. (approximately 48 times the recommended human daily dose of 1.2 mg on a mg/m2 basis)
Pregnancy: Pregnancy Category C.
Teratogenic effects: Buprenorphine was not teratogenic in rats or rabbits after I.M. or S.C. doses up to 5 mg/kg/day (approximately 48 and 95 times the recommended human daily dose of 1.2 mg on a mg/m2 basis), I.V. doses up to 0.8 mg/kg/day (approximately 8 times and 15 times the recommended human daily dose of 1.2 mg on a mg/m2 basis), or oral doses up to 160 mg/kg/day in rats (approximately 1525 times the recommended human daily dose of 1.2 mg on a mg/m2 basis) and 25 mg/kg/day in rabbits (approximately 475 times the recommended human daily dose of 1.2 mg on a mg/m2 basis). Significant increases in skeletal abnormalities (e.g. extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after S.C. administration of 1 mg/kg/day and up (approximately 9.5 times the recommended human daily dose of 1.2 mg on a mg/m2 basis) and in rabbits after I.M. administration of 5 mg/kg/day (approximately 95 times the recommended human daily dose of 1.2 mg on a mg/m2 basis), but these increases were not statistically significant. Increases in skeletal abnormalities after oral administration were not observed in rats, and increases in rabbits (1-25 mg/kg/day) were not statistically significant.
Labor and Delivery: The safety of Buprenex (buprenorphine) given during labor and delivery has not been established.
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 nursing mothers treated with Buprenex (buprenorphine) .
Pediatric Use: The safety and effectiveness of Buprenex (buprenorphine) have been established for children between 2 and 12 years of age. Use of Buprenex (buprenorphine) in children is supported by evidence from adequate and well controlled trials of Buprenex (buprenorphine) in adults, with additional data from studies of 960 children ranging in age from 9 months to 18 years of age. Data is available from a pharmacokinetic study, several controlled clinical trials, and several large post-marketing studies and case series. The available information provides reasonable evidence that Buprenex (buprenorphine) may be used safely in children ranging from 2-12 years of age, and that it is of similar effectiveness in children as in adults.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/22/2008
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