Drug Interactions between buprenorphine and calcium carbonate / melatonin / valerian / vitamin e

GENERALLY AVOID: Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.