Please use this identifier to cite or link to this item: https://hdl.handle.net/11000/32544

Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness

Title:
Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness
Authors:
Muriel, J
Escorial, Mónica  
Carratalá, C
Margarit, César
Barrachina, Jordi  
López, A
Kringen, Marianne K  
Peiró, Ana  
Editor:
Elsevier
Department:
Departamentos de la UMH::Farmacología, Pediatría y Química Orgánica
Issue Date:
2024-06-14
URI:
https://hdl.handle.net/11000/32544
Abstract:
Background: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. Materials and Methods: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. Results: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. Conclusion: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.
Keywords/Subjects:
Analgesic opioids
Pharmacogenetics
CYP2D6
Drug-drug interactions
Chronic non cancer pain
Substrates/inhibitors
Knowledge area:
CDU: Ciencias aplicadas: Medicina: Farmacología. Terapéutica. Toxicología. Radiología
Type of document:
application/pdf
Access rights:
info:eu-repo/semantics/openAccess
DOI:
https://doi.org/10.1016/j.biopha.2024.116882
Appears in Collections:
Artículos Farmacología, Pediatría y Química Orgánica



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