Science to practice
Latest highlights on drug safety and efficacy

17.2.2025

Patients who are compliant with their prescribed medication regimen may still exhibit significant variability in drug response, ranging from life-threatening adverse effects to complete lack of efficacy. This inter-individual variability is influenced by multiple factors, including co-medications that cause drug-drug interactions, liver and kidney function, age, gender, weight, and genetic variability​ (1).

Genetic variability plays a significant role in the pharmacokinetics of many cardiovascular drugs, where genes such as CYP2C9, CYP2C19, VKORC1, and SLCO1B1 affect the metabolism and efficacy of widely used medications like warfarin, clopidogrel, and statins​ (1). To mitigate the risks associated with drug use, computerised decision support systems (CDSS) have been developed to integrate patient-specific information into drug treatment recommendations (2).

Even patients who follow their prescribed medication regimen may experience vastly different drug responses, from life-threatening adverse effects to complete lack of efficacy.

Patients with a loss-of-function CYP2C19 allele may not efficiently metabolise clopidogrel to the active metabolite, leading to inadequate platelet inhibition and increased cardiovascular risk​ (3). Similarly, individuals with SLCO1B1 polymorphisms may experience statin-induced myopathy due to impaired hepatic uptake (4)​. While pharmacogenetics-driven precision medicine shows promise in studies, clinical decision support systems are needed to facilitate the implementation of pharmacogenetics and personalised drug treatment into everyday clinical practice.

Explore Medbase Knowledgebase for comprehensive insights on drug interactions, adverse effects, alternative drug and dosing recommendations, and more!

News produced by Medbase Medical Team

References

1. Ingelman-Sundberg M, Pirmohamed M. Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment. J Intern Med. 2024 May;295(5):583-598. doi: 10.1111/joim.13772. Epub 2024 Feb 11. PMID: 38343077.
2. Bakker T, Klopotowska JE, Dongelmans DA, et al. The effect of computerised decision support alerts tailored to intensive care on the administration of high-risk drug combinations, and their monitoring: a cluster randomised stepped-wedge trial. Lancet. 2024 Feb 3;403(10425):439-449. doi: 10.1016/S0140-6736(23)02465-0. Epub 2024 Jan 20. PMID: 38262430.
3. Lee CR, Luzum JA, Sangkuhl K, Gammal RS, Sabatine MS, Stein CM, Kisor DF, Limdi NA, Lee YM, Scott SA, Hulot JS, Roden DM, Gaedigk A, Caudle KE, Klein TE, Johnson JA, Shuldiner AR. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022 Nov;112(5):959-967
4. Cooper-DeHoff RM, Niemi M, Ramsey LB, Luzum JA, Tarkiainen EK, Straka RJ, Gong L, Tuteja S, Wilke RA, Wadelius M, Larson EA, Roden DM, Klein TE, Yee SW, Krauss RM, Turner RM, Palaniappan L, Gaedigk A, Giacomini KM, Caudle KE, Voora D. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022 May;111(5):1007-1021