Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: update of a systematic review.

Abstract

Introduction: Drug-drug interactions (DDIs) are among factors that may affect the efficacy and safety of opioid treatment. Data on clinically manifested DDIs are scarse, and recommendations that might guide physicians are presently lacking. The aim of this study was to update a systematic review (2015) on studies reporting clinically significant DDIs involving opioids used for pain treatment in adult patients with cancer.

Methods: Systematic literature searches in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from the start of the databases through 18 September 2023.

Results: Of the 1968 retrieved papers, 16 were included in the final analysis, together with five papers identified through hand-searching of reference lists. Nineteen publications were case reports or case series. Nine, sixteen, and eight patients presented adverse effects from opioids, impaired pain control, or opioid withdrawal, respectively. The main mechanisms underlying DDIs were alteration of cytochrome P450 3A4 activity and pharmacodynamic antagonism resulting from concurrent use of an opioid analgesic and a peripheral mu-opioid receptor antagonist (PAMORA).

Conclusion: Knowledge about clinically significant DDIs associated with opioids in cancer patients is currently mostly based upon case reports. These cases give information about drug combinations that should be recognized as potentially harmful by physicians prescribing opioids.

Prospero id: CRD42023481103.