Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study

Mahmood Mahajna, Rami Abu Fanne*, Mahmoud Odeh, Matitiahu Berkovitch, Elias Tannous, Sara Eyal, Shlomo Vinker, Ilan Green, Ilan Matok

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol’s adverse effects. Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects. Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects. Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18–11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84–9.28), and 3.25 (95% CI 1.78–5.93), respectively. Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes.

Original languageAmerican English
Article number1358549
JournalFrontiers in Pharmacology
StatePublished - 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 Mahajna, Abu Fanne, Odeh, Berkovitch, Tannous, Eyal, Vinker, Green and Matok.


  • CYP2D6
  • database
  • O-desmethyltramadol
  • polymorphism
  • tramadol


Dive into the research topics of 'Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study'. Together they form a unique fingerprint.

Cite this