Evaluation of simvastatin and CYP3A4-inhibitor interactions in an inpatient population
Authors: Boamah D , Bastian L , Wilcock M 
Published: November 2023

Abstract

Introduction
The maximum recommended dose for simvastatin in conjunction with the CYP3A4 inhibitors amiodarone, amlodipine, diltiazem, or verapamil is 20 mg/day.1 Studies have reported on the extent of potentially harmful simvastatin interactions which can increase the risk of myopathy.2 A project in a local primary care setting had identified that 42 (14%) of 305 patients prescribed simvastatin and one of these CYP3A4 inhibitors were receiving the unlicensed dose of simvastatin 40mg. We wanted to investigate if there were similar concerns for hospital inpatients.

Aim
The aim of this evaluation was to ascertain whether patients were prescribed simvastatin 40mg with one of the named interacting drugs during their hospital admission and whether any action was taken for patients on such a combination.

Methods
A search was undertaken of patients prescribed simvastatin 40mg with amiodarone, amlodipine, diltiazem, or verapamil using the electronic prescribing system (EPS) (Careflow Medicines Management) between January to October 2022. Relevant data were extracted from the EPS and discharge summaries were searched for any additional information, in particular for any notes made by the prescriber or pharmacy team that they had recognised and acted on this combination. Data were collated and analysed using Microsoft Excel. As this project falls under the definition of a service evaluation, according to UK NHS Research Ethics Committees, formal ethical approval was not required. This project was registered on the hospital’s clinical audit database.

Results
Fifty-six patients (mean age 78, range 59-94, 50% female) were prescribed a combination of interest during their admission. A further 13 who died in hospital were excluded. Thirty (54%) patients were admitted on this combination. Simvastatin 40mg appeared with amlodipine in 77% (n=43) of instances, diltiazem in 11% (n=6), amiodarone in 11% (n=6), and verapamil in 1% (n=1). Thirty-one (55%) of 56 patients were discharged on this combination, and 6 had no discharge information. Of the 19 (34%) not discharged on the combination, six were due to proactive pharmacy intervention, whilst remaining instances were due to other clinical reasons.

Discussion/Conclusion
We observed a possible lack of knowledge of these potentially hazardous interactions with some inpatients commenced on the combination, and just over half of the cohort discharged on such a combination. Such in-hospital prescribing of interacting drugs and lack of pharmacy team clinical check could be due to unawareness of the MHRA alert. Though our EPS has the functionality of triggering alerts to notify prescribers of interactions, only level 4 warnings are flagged and the interactions we examined, as a level 3 warning, remain suppressed and not easily visible to the prescriber. Our results will be shared with hospital and primary care pharmacy teams, as this is an area of prescribing that the Care Quality Commission may review when inspecting general practices.3 This evaluation will be repeated. Recognised limitations of this single centre, retrospective study include: we did not look at interactions between simvastatin and other medicines, nor interactions with other statins; we did not investigate whether these patients were suffering from muscle-related adverse events.

References
1. Medicines and Healthcare products Regulatory Agency. Simvastatin: updated advice on drug interactions. Drug Safety Update August 2012, vol 6, issue 1: S1.
2. Bakhai A, Rigney U, Hollis S, Emmas C. Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population. Pharmacoepidemiol Drug Saf 2012;21(5):485-93.
3. Care Quality Commission. GP myth buster 12: accessing medical records during inspections. London: CQC, 2023 https://www.cqc.org.uk/guidance-providers/gps/gp-mythbusters/gp-mythbuster-12-accessing-medical-records-during-inspections (accessed 2 May 2023)