Cookie policy: This site uses cookies (small files stored on your computer) to simplify and improve your experience of this website. Cookies are small text files stored on the device you are using to access this website. For more information please take a look at our terms and conditions. Some parts of the site may not work properly if you choose not to accept cookies.


Subscribe or Register

Existing user? Login

Drug interactions that can occur with statins and macrolide antibacterials

by Karen Baxter, Alison Marshall and Jennifer Sharp (Stockley's Drug Interactions)

An elderly woman with a history of hyperlipidaemia and hypertension presents with a fast heart rate, and new-onset atrial fibrillation (AF) is diagnosed. Initial therapy with a beta blocker fails to control the AF, so diltiazem is prescribed. Aspirin is also started, and the patient’s usual medication of ramipril 5mg daily and simvastatin 40mg daily is continued.

A respiratory tract infection is also diagnosed, and so she is given a seven-day course of amoxicillin and clarithromycin. A week later she presents with fatigue, muscle weakness and dark urine, and on admission to hospital her creatine kinase level is 15,000units/L. A diagnosis of rhabdomyolysis is made, and the simvastatin is stopped.

Statins are commonly prescribed for the treatment of hyperlipidaemia and in the prevention of cardiovascular disease. Simvastatin is primarily metabolised by the cytochrome P450 isoenzyme CYP3A4 and its metabolism may be significantly affected by drugs that can inhibit or induce CYP3A4.

Drugs that are potent inhibitors of CYP3A4 can, therefore, lead to a large increase in simvastatin levels, increasing the risk of developing serious adverse effects such as myopathy and rhabdomyolysis. Drugs that are moderate inhibitors of CYP3A4 can also increase the levels of these statins but have less effects than clarithromycin.

The patient in this case was taking both a potent and a moderate inhibitor of CYP3A4 (clarithromycin and diltiazem, respectively) with simvastatin 40mg daily. She should have been advised to omit her simvastatin while taking the clarithromycin. A maximum dose of simvastatin 40mg is advised when prescribed with diltiazem, so no dose adjustment is needed for this patient in the long term.

Other macrolides, such as erythromycin and telithromycin, are expected to interact with simvastatin in the same way as clarithromycin, because they are also moderate to potent inhibitors of CYP3A4. Simvastatin should also be temporarily stopped if these antibacterials are required. Azithromycin does not inhibit CYP3A4 and, therefore, would not be expected to interact with simvastatin.

Not all statins are metabolised in the same way as simvastatin. Atorvastatin is metabolised by CYP3A4 but to a lesser extent than simvastatin. It can therefore interact with similar drugs, but usually to a lesser extent.

Fluvastatin, pravastatin and rosuvastatin are not significantly metabolised by CYP3A4 and are, therefore, are not expected to interact to a clinically relevant extent with CYP3A4 inhibitors. However, pravastatin levels have been reported to be moderately raised by clarithromycin and erythromycin, although the mechanism for this effect is not yet understood.

The Table (in the PDF file) illustrates the metabolic routes of the statins, and their interactions with the macrolide antibacterials.

Rarely, cases of rhabdomyolysis have been seen with pairs of statins and macrolides not expected to interact. Therefore, all patients taking statins should be counselled about the risks of myopathy. They should be encouraged to report any muscle pain, tenderness, or weakness, especially if accompanied by malaise, fever or dark urine. This warning should be reinforced if a CYP3A4-inhibiting macrolide is given concurrently.

Citation: The Pharmaceutical Journal URI: 10017578

Have your say

For commenting, please login or register as a user and agree to our Community Guidelines. You will be re-directed back to this page where you will have the ability to comment.

Recommended from Pharmaceutical Press

  • Drugs of Abuse

    Drugs of Abuse

    A concise, easy-to-read guide for healthcare professionals who encounter drug abuse.

    £38.00Buy now
  • Adverse Drug Reactions

    Adverse Drug Reactions

    A practical guide to the drug reactions that affect particular organ systems, and the management of these reactions.

    £38.00Buy now
  • English Delftware Drug Jars

    English Delftware Drug Jars

    This beautiful book illustrates the art and history of the collection of English delftware drug jars in the Museum of the Royal Pharmaceutical Society of Great Britain.

    £54.00Buy now
  • Paediatric Drug Handling

    Paediatric Drug Handling

    Written for new pharmaceutical scientists, this book provides a background in paediatric pharmacy and a comprehensive introduction to children's medication.

    £33.00Buy now
  • Introduction to Renal Therapeutics

    Introduction to Renal Therapeutics

    Introduction to Renal Therapeutics covers all aspects of drug use in renal failure. Shows the role of the pharmacist in patient care for chronic kidney disease.

    £38.00Buy now

Search an extensive range of the world’s most trusted resources

Powered by MedicinesComplete
  • Print
  • Share
  • Comment
  • Save
  • Print Friendly Version of this pagePrint Get a PDF version of this webpagePDF

Supplementary information

Jobs you might like

Newsletter Sign-up

Want to keep up with the latest news, comment and CPD articles in pharmacy and science? Subscribe to our free alerts.