Drug Interactions between olanzapine / samidorphan and oliceridine

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.

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.