Drug Interactions between Lybalvi and propoxyphene

MONITOR CLOSELY: Sedatives, tranquilizers, muscle relaxants, antidepressants, and other central nervous system (CNS) depressants may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly, and the risk was further increased by concomitant use of psychotropic agents (sedatives, antidepressants, neuroleptics), presumably due to additive psychomotor impairment. Therefore, these drugs may constitute a dangerous combination in certain susceptible populations. Pharmacokinetically, propoxyphene is an inhibitor of CYP450 2D6 and may increase the plasma concentrations of many psychotropic agents that are metabolized by the isoenzyme such as phenothiazines, haloperidol, risperidone, phenobarbital, and some tricyclic antidepressants and serotonin reuptake inhibitors.

MANAGEMENT: Caution is advised if propoxyphene is used with sedatives, tranquilizers, muscle relaxants, antidepressants, and other CNS depressants, particularly in the elderly and in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. Dosage reductions may be appropriate. Patients should be monitored for potentially excessive or prolonged CNS and respiratory depression and other CNS adverse effects. Patients should be warned not to exceed recommended dosages, to avoid alcohol, and to avoid activities requiring mental alertness until they know how these agents affect them.

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.