A Multicenter Retrospective Observational Study on Drug-Drug Interactions between Opioid Analgesics and Immune Checkpoint Inhibitors in Cancer Patients

Biol Pharm Bull. 2025;48(11):1803-1809. doi: 10.1248/bpb.b25-00515.

Abstract

Opioid analgesics are indispensable therapeutic agents for patients experiencing cancer pain. Recently, immune checkpoint inhibitors (ICIs) have made substantial progress in cancer treatment, and the range of cancer types for which they are applicable has expanded. Consequently, the combined use of ICIs with other drugs has also increased. However, it has been pointed out that ICIs may interfere with opioid nociception and weaken the analgesic effects of opioids. Therefore, in this study, we investigated the drug-drug interactions between opioid analgesics and ICIs in patients with cancer, especially their influence on analgesic effects. A multicenter collaborative study was conducted to investigate changes in pain intensity in patients with cancer pain who were prescribed opioid analgesics and ICIs. As a result, when opioids were administered to patients receiving ICIs, the median pain intensity, measured using the Numerical Rating Scale (NRS), significantly decreased from 4.5 at baseline to 3.0 on Day 1 and 2.5 on Day 7, demonstrating favorable analgesic effects. Similarly, when ICIs were administered to patients receiving opioids, the median pain intensity (NRS) significantly decreased from 3.0 at baseline to 2.0 on Day 1 and 2.75 on Day 7. These results suggest that opioids provided effective analgesia when administered alongside ICIs.

Keywords: cancer pain; drug–drug interaction; immune checkpoint inhibitor; opioid.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid* / therapeutic use
  • Cancer Pain* / drug therapy
  • Drug Interactions
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Pain Measurement
  • Retrospective Studies

Substances

  • Analgesics, Opioid
  • Immune Checkpoint Inhibitors