Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients (2019). Basic & Clinical Pharmacology & Toxicology, 124, 439-448.

Javier Muriel (Alicante Institute for Health and Biomedical Research), César Margarit (Alicante-General Hospital), Jordi Barrachina (Occupational Observatory, Miguel Hernández University of Elche), Pura Ballester (Alicante Institute for Health and Biomedical Research), Andrea Flor (Alicante-General Hospital), Domingo Morales (Miguel Hernández University of Elche), José F. Horga (Alicante-General Hospital), Eduardo Fernández (Miguel Hernández University of Elche) and Ana M. Peiró (Alicante-General Hospital).
Abstract. The threats involved in the long‐term opioid treatment of chronic non‐cancer pain (CNCP) have increased notably. Strategies to identify at‐risk patients are important because there is no clear evidence showing which screening or deprescription programmes are appropriate. Our aim was to evaluate the evidence provided by pharmacogenetics applied to predict an analgesic toxicity profile in prescription opioid use disorder (POUD) patients participating in an opioid deprescription programme. Pharmacogenetic markers were analysed in an observational, prospective deprescription programme for POUD patients (n = 88) treated for CNCP. It consisted of monitoring visits (baseline, follow‐up and final), opioid rotation or discontinuation and the recording of adverse events and suspected adverse drug reactions (ADRs). Variants in OPRM1 (A118G), ABCB1 (C3435T), COMT (G472A), OPRD1 (T921C) and ARRB2 (C8622T) genes were tested by real‐time PCR. Ethics committee approved the study. Wild‐type OPRM1‐AA genotype carriers reported a significantly higher number of adverse events than OPRM1‐AG/GG (median [p25 75], 7 [5‐11] vs 5 [3‐9]), particularly gastrointestinal system events (90% vs 63%) such as nausea (33% vs 0%). Suspected ADRs (affecting 17% of the patients) were three times higher in males than in females (30% vs 11%). The deprescription programme was effective and safe, and it achieved a significant progressive reduction in the morphine equivalent daily dose, strong opioids and other analgesics’ use, without causing any changes in pain intensity or opiate abstinence syndrome. OPRM1 gene polymorphisms could identify the risk of gastrointestinal adverse events in POUD patients. Deprescription programmes including pharmacogenetic analysis should be considered during the follow‐up of this population.
Keywords. Adverse events; Chronic pain; Opioid use disorder; Pharmacogenetics; Prescription opioids