Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Opioid analgesics may reduce the efficacy of immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 monoclonal antibodies and/or inhibitors of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1). The mechanism of this interaction has not been fully elucidated, but may involve the ability of opioids to modify cellular functions of the immune system (T-cells), potentially affecting tumor growth. Additionally, ICIs can suppress the efficacy of opioids leading to an increase in opioid use via inhibition of the PD-1/PD-L1 signaling pathway. In a meta-analysis review of 7 studies (531 studies screened), it was observed that the use of opioids in patients treated with ICIs was negatively associated with overall survival (OS) and significantly reduced progression-free survival (PFS). Similarly, an observational, retrospective study including 375 patients with recurrent or metastatic cancer treated with anti-PD-1 or anti-PD-L1 monoclonal antibodies noted that patients who were not treated with opioid analgesics had significantly longer median PFS (6.83 vs. 4.30 months) and median OS (17.05 vs 7.68 months) compared to patients who were treated with opioid analgesics. Furthermore, a retrospective, single-center, observational cohort study observed that the median amount of change in opioid dose from baseline was significantly higher in patients who were treated with ICIs as compared to patients who were treated with non-ICI anticancer therapies (22.5 vs. 15.0 morphine mg equivalents). Multiple regression analysis and propensity score matching identified ICI administration as an independent factor associated with the amount of increase in opioid dose.

MANAGEMENT: Until more information is available, caution and clinical monitoring for reduced efficacy of immune checkpoint inhibitors (ICIs) and opioid analgesics are advised if concomitant therapy is required. Opioid analgesic use should be limited to clinically appropriate indications and durations. Clinicians should consult relevant literature, local and national treatment guidelines, and package labeling for further guidance.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur. In addition, alcohol may affect opioid release from sustained-release formulations.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with opioid analgesics. Any history of alcohol or illicit drug use should be considered when prescribing an opioid analgesic, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension.