Drug Interactions between buprenorphine and olanzapine / samidorphan

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.

CONTRAINDICATED: Samidorphan is an opioid antagonist and can block the effects of opioids via competitive inhibition of opioid receptors. Opioid-containing medications may be less effective or ineffective during and shortly after discontinuing treatment with samidorphan, which has an elimination half-life of 7 to 11 hours. In patients who are dependent on opioids, samidorphan can precipitate withdrawal symptoms and opioid withdrawal syndrome that may require hospitalization. Attempts to overcome the opioid blockade with increased or repeated doses of exogenous opioids (e.g., because of ineffective analgesia or opioid withdrawal symptoms) could result in life-threatening or fatal opioid intoxication due to respiratory arrest and/or circulatory collapse, particularly if samidorphan therapy is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes. Following use of samidorphan, patients may have increased sensitivity to opioids. Therefore, patients with a history of chronic opioid use prior to receiving samidorphan may have decreased opioid tolerance when samidorphan treatment is interrupted or discontinued, which may increase the risk of overdose if opioids are resumed at previously tolerated dosages.

MANAGEMENT: The use of samidorphan is considered contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Prior to initiating samidorphan-containing medications, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids and at least a 14-day opioid-free interval from the last use of long-acting opioids. In emergency situations where opioid treatment is required for anesthesia or analgesia in a samidorphan-treated patient, it is recommended to discontinue samidorphan and have opioid therapy administered by clinicians trained in the use of anesthetic drugs and the management of the respiratory effects of opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation. The patient should be closely monitored by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency situations where a samidorphan-treated patient is expected to require opioid treatment (e.g., for analgesia during or after an elective surgical procedure), it is advisable to discontinue samidorphan at least 5 days before opioid treatment.