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Drug Interactions between fentanyl and Opdivo Qvantig

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

fentaNYL nivolumab

Applies to: fentanyl and Opdivo Qvantig (hyaluronidase / 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)
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

Major

fentaNYL food

Applies to: fentanyl

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including fentanyl. 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.

GENERALLY AVOID: Consumption of grapefruit juice during treatment with oral transmucosal formulations of fentanyl may result in increased plasma concentrations of fentanyl, which is primarily metabolized by CYP450 3A4 isoenzyme in the liver and intestine. Certain compounds present in grapefruit are known to inhibit CYP450 3A4 and may increase the bioavailability of swallowed fentanyl (reportedly up to 75% of a dose) and/or decrease its systemic clearance. The clinical significance is unknown. In 12 healthy volunteers, consumption of 250 mL regular-strength grapefruit juice the night before and 100 mL double-strength grapefruit juice one hour before administration of oral transmucosal fentanyl citrate (600 or 800 mcg lozenge) did not significantly affect fentanyl pharmacokinetics, overall extent of fentanyl-induced miosis (miosis AUC), or subjective self-assessment of various clinical effects compared to control. However, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with fentanyl. Any history of alcohol or illicit drug use should be considered when prescribing fentanyl, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with fentanyl should preferably avoid the consumption of grapefruit and grapefruit juice. In addition, patients receiving transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.

References (5)
  1. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  2. (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
  3. Kharasch ED, Whittington D, Hoffer C (2004) "Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate." Anesthesiology, 101, p. 729-737
  4. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M (1996) "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg, 82, p. 167-72
  5. Labroo RB, Paine MF, Thummel KE, Kharasch ED (1997) "Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implicaitons for interindividual variability in disposition, efficacy, and drug interactions." Drug Metab Dispos, 25, p. 1072-80

Therapeutic duplication warnings

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Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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