RESUMEN
The identification of rhabdomyolysis as a potential fatal adverse reaction to recent COVID-19 vaccines is essential. As the symptoms of rhabdomyolysis are not specific, the threshold to actively search for this complication should be low.
RESUMEN
This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities. The relation between the event and the result of the genotype and/or phenotype was evaluated using a semi-quantitative scale. Our analysis included 243 individual genotypic and/or phenotypic explorations. Genotypes/phenotypes were mainly assessed because of an ADR (n = 145, 59.7%), and the majority of clinical situations were observed with prodrug opioids (n = 148, 60.9%). The probability of a link between an ADR or a non-response and the genotypic/phenotypic status of the patient was evaluated as intermediate to high in 40% and 28.2% of all cases, respectively. The drugs in which the probability of an association was the strongest were the prodrug opioids, with an intermediate to high link in 45.6% of the cases for occurrence of ADRs and 36.0% of the cases for non-response. This study shows that the genotypic and phenotypic approach is useful to understand ADRs or therapeutic resistance to a usual therapeutic dosage, and can be part of the evaluation of chronic pain patients.
RESUMEN
OBJECTIVES: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non-response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting. METHOD: We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations. RESULTS: One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n=93, 67.4%), followed by antipsychotics (n=28, 20.3%), benzodiazepines and hypnotics (n=13, 9.4%), and psychostimulants (n=4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n=68, 49.3%) or non-response (n=46, 33.3%). Inter-rate reliability of the scoring system between the pharmacologists was excellent (kappa=0.94). The probability of an association between ADR, TDM or non-response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non-response and ADR respectively. CONCLUSION: When indicated by clinical pharmacologists, ADR, TDM or non-response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed.
