Drug Interactions between levomethadyl acetate and Opdivo
This report displays the potential drug interactions for the following 2 drugs:
- levomethadyl acetate
- Opdivo (nivolumab)
Interactions between your drugs
levomethadyl acetate nivolumab
Applies to: levomethadyl acetate and Opdivo (nivolumab)
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.
References (5)
- Sumimoto T, tanaka r, Murakami Y, Tatsuta R, itoh h (2024) "Clinical relevance of immune checkpoint inhibitors for the analgesic effect of opioids: a retrospective propensity score analysis." Br J Clin Pharmacol, 90, p. 1-10
- Ju M, Gao Z, liu x, et al. (2023) "The negative impact of opioids on cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis." J Cancer Res Clin Oncol, 149, p. 2699-708
- Kavgaci G, Guven DC, Kaygusuz Y, et al. (2024) "Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors." Support Care Cancer, 32, p. 467
- Deng D, Zhang T, Ma L, et al. (2025) PD-L1/PD-1 pathway: a potential neuroimmune target for pain relief. https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-024-01227-3#citeas
- Cani M, Bironzo P, Garetto F, Buffoni L, Cotogni P (2025) Immune checkpoint inhibitors and opioids in patients with solid tumours: is their association safe? A systematic literature review. https://www.mdpi.com/2227-9032/11/1/116
Drug and food interactions
levomethadyl acetate food
Applies to: levomethadyl acetate
GENERALLY AVOID: The concurrent use of levomethadyl acetate and alcohol may result in additive CNS and respiratory depression, hypotension, sedation, or coma. Grapefruit juice may increase the plasma concentrations of orally administered drugs which are substrates of the CYP450 3A4 isoenzyme, such as levomethadyl acetate. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.
MANAGEMENT: Patients who are known to abuse alcohol should be warned of the risk of potentially fatal overdose if these substances are taken concurrently. Patients who regularly consume grapefruits and grapefruit juice should be monitored for adverse effects and altered plasma concentrations of levomethadyl acetate. A 12-lead ECG should be performed before initiating therapy, 12 to 14 days after initiating therapy, and periodically thereafter. Patients should be advised to immediately seek medical attention if they experience palpitations, dizziness, lightheadedness, fainting, or seizures. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.
References (1)
- (2001) "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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