An Analysis of Risk Associated to Concomitant Use of Potential Inhibitors of Statins Metabolism Volume 3 - Issue 2

Carlos Treceño Lobato^1,2*, María-Isabe^l Jiménez-Serranía², Javier Herradón Muñoz¹, Elena Valles Martín² and José Luis Nájera García¹

• ¹Council of Professional Colleges of Pharmacists of Castilla y León, Castile and Leon, Spain
• ²ADViSE Research Group. Department of Health Sciences, Faculty of Health Sciences, Miguel de Cervantes European University (UEMC), Spai

Received:June 27, 2023;   Published: July 03, 2023

Corresponding author: Carlos Treceño Lobato, Council of Professional Colleges of Pharmacists of Castilla y León. Castile and Leon,Spain

DOI: 10.32474/LOJPCR.2023.03.000159

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Abstract

Background: Some statins are metabolised by CYP3A4 pathway and concomitant treatments with potential inhibitors of this isoenzyme could influence in the occurrence of adverse drug reactions (ADR) related to an increase in dose. Objective: To evaluate the ADR incidence rate of statins combined with CYP3A4 inhibitors and to detect new signals of ADR in real-life ambulatory settings.
Methods: The authors performed an observational cross-sectional study of surveyed patients treated with statins (atorvastatin, lovastatin, simvastatin –CYP3A4 metabolized-, fluvastatin, pitavastatin, pravastatin, rosuvastatin –other metabolization pathways-) and CYP3A4 inhibitors (amiodarone, cyclosporine, cilostazol, diltiazem, dronedarone, fluoxetine, verapamil). Descriptive, clinical, and ADRs incidence data were reported and analyzed through a bivariate and applied an adaptation of Bayesian methodology (BCPNN) to detect new signals.
Results: A total of 112 patients were surveyed, the mean concomitant number of treatments per patient was 7,5±3,7 and 56,3% were on atorvastatin. The authors obtained higher risk of musculoskeletal or limb pain (0.58; 95% confidence interval 0.17-1.92) and paresthesias-myasthenia (0.67; 0.22–2.32) with CYP3A4 metabolised statins and higher risk of myalgia (OR,1.41; 0.42–4.74) with non-CYP3A4 metabolised statins. These results are confirmed with detection of positive signals of musculoskeletal or limb pain linked to atorvastatin (FDR=0.016). A signal of osteoporosis linked to [atorvastatin+fluoxetine] (FDR=0.011) was also detected.
Conclusion: The risk profile of statins metabolised by CYP3A4 did not largely differ with concomitant isoenzyme inhibitors, being the most reported ADR the musculoskeletal or limb pain. Caution is recommended with calcium antagonists and cyclosporine. Atorvastatin-fluoxetine combination enhance the risk of osteoporosis.

Keywords:Statin; CYP3A4 inhibitor; musculoskeletal pain; osteoporosis; interaction

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