Category: Fellows Posters
CYP2D6 is a highly polymorphic enzyme that metabolizes numerous drugs, including various analgesics, antidepressants and beta-blockers commonly used.
Therefore, the aim of our study was:
Non-interventional, prospective study. Participation was offered to patients attending pharmacy pre-surgical consultation before hip, knee or spinal cord surgery. Informed consent was obtained from all participants. Patients´ demographics and usual treatment were compiled during the interview. Blood samples were obtained during patients´ in-hospital stay. Alleles analyzed included: *2,*3,*4,*5,*6,*7,*9,*10,*17,*29,*35,*41, amplifications and deletions. Phenotype was inferred according to activity score per Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations.
79 patients were recruited; 70% were women and the median age was 74 years(46-90).
According to CYP2D6 activity score, phenotypic distribution was: Ultra rapid Metabolizers (UM)5:6%, Extensive Metabolizers (EM)38:48%, Intermediate Metabolizers (IM): 32:40%, Poor Metabolizers(PM): 4:5%.
Patients were taking a median of 7 drugs (0-17). No patients were taking CYP2D6 inducers, but 7 were taking a CYP2D6 Inhibitor: 3 strong (paroxetine), 2 moderate (duloxetine) and 2 weak (amiodarone). These 7 patients were classified as EM 3 and IM 4, although use of inhibitors can further impair enzyme activity.
43% of the patients were receiving at least 1 CYP2D6 substrate; total: 44 drugs. CYP2D6 prescribed substrates were analgesics (45%), antidepressants (18%), beta-blockers (9%) and other drugs (27%).
Among those patients receiving CYP2D6 substrates, 1 was classified as UM (tramadol) and 3 as PM (tramadol, tamsulosin and amitriptyline). 3 patients taking CYP2D6 inhibitors were also taking CYP2D6 substrates that could be affected (tramadol and tamsulosin). Selecting alternative drugs and/or using reduced doses with close monitoring is recommended in CPIC, DPWG (Dutch Pharmacogenetics Working Group) and/or drug labels.
In our attended population, extreme CYP2D6 phenotypes, are relatively common. Use of CYP2D6 substrates is common, so close monitorization of UM and PM and coadministration of enzyme inhibitors is necessary to perform an individual risk assessment in order to make appropriate treatment adjustments.