Pharmacogenetics of siponimod: A systematic review.

Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9 poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9 SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2 genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9 * 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not translated into a therapeutic recommendation.

Evaluation of quality indicators for nutrition and metabolism in critically ill patients: role of the pharmacist.

OBJECTIVE: To assess compliance in a Spanish intensive care unit (ICU) with 8 of the 13 quality indicators of the Spanish Society of Intensive Medicine and Coronary Units (Sociedad Española de Medicina Intensiva y Unidades Coronarias, SEMICyUC) related to nutrition and metabolism in critically ill patients. PATIENTS AND METHODS: The study included all patients over 18 years of age with an ICU stay of >48 hours between January and May 2019. The pharmacist was integrated into the daily activity of the multidisciplinary team of a 20-bed ICU to monitor and carry out the control of the quality indicators of the SEMICyUC. Studied indicators refer to: nutritional risk assessment and nutritional status (three indicators), glycaemic control, calculation of calorie-protein requirements, and use of early enteral nutrition or adequate parenteral nutrition. Compliance with each indicator was measured as the percentage of patients. RESULTS: 110 patients were included and 73 (66.4%) were male. Compliance results were: blood glucose range (90.7%), severe hypoglycaemia (0%), identification of patients at nutritional risk (58.2%) or with possible refeeding syndrome (8.9%), assessment of nutritional status at admission (58.2%), calculation of calorie-protein requirements (77.8%), early enteral nutrition (96.4%), and adequate use of parenteral nutrition (37.8%) CONCLUSION: Compliance with indicators related to glycaemic control and artificial nutrition (enteral and parenteral nutrition) was higher than reference standards, but there is a need to improve compliance with indicators related to nutritional risk and status at ICU admission. The hospital pharmacist integrated into the ICU multidisciplinary team can add value to the nutrition monitoring and quality indicators of the nutritional process of the critical patient, providing safe and effective nutritional therapy to patients.