Clarithromycin with Simvastatin Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Simvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 10, 2023

Interaction Effect

An increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concomitant use of clarithromycin with simvastatin may increase the risk of myopathy and rhabdomyolysis, and is contraindicated. Simvastatin is a CYP3A4 substrate and clarithromycin is both a substrate and strong inhibitor of CYP3A4. The coadministration of clarithromycin with simvastatin has resulted in increased simvastatin plasma concentrations and rare reports of rhabdomyolysis . Myopathy and rhabdomyolysis have been observed in patients (with or without renal impairment) treated with other HMG-CoA reductase inhibitors alone or concomitantly with clarithromycin . If clarithromycin therapy is necessary, suspend simvastatin during the course of treatment or switch to a statin that is not dependent on CYP3A metabolism, such as fluvastatin. If concomitant use cannot be avoided, use the lowest possible dose of simvastatin .

Severity

Contraindicated

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

The concurrent use of clarithromycin and simvastatin is contraindicated. If clarithromycin therapy is necessary, suspend simvastatin during the course of treatment or switch to a statin that is not dependent on CYP3A metabolism, such as fluvastatin. If concomitant use cannot be avoided, use the lowest possible dose of simvastatin .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated simvastatin metabolism by clarithromycin

Literature Reports

A) In a retrospective, population-based cohort study of adults older than 65 years taking a statin metabolized by CYP3A (atorvastatin, 73%; simvastatin, 24%; lovastatin, 3%), concomitant administration with clarithromycin (n=72,591) or erythromycin (n=3267) was associated a rate of hospitalization for rhabdomyolysis of 0.03% and a rate of hospitalization for acute kidney injury of 0.46%. Corresponding rates with concomitant administration of azithromycin (n=68,478) were 0.01% and 0.26%, respectively. The all-cause mortality rate was 0.7% in the clarithromycin/erythromycin group and 0.45% in the azithromycin group .

B) Rhabdomyolysis was described in a 77-year-old woman following the concomitant administration of simvastatin and clarithromycin. At admission, the patient had a 3-week history of generalized weakness, which left her unable to walk. Her medications included simvastatin 20 mg/day, telmisartan, hydrochlorothiazide, glibenclamide, allopurinol, bisoprolol, aspirin, and, up until 3 days before admission, a 14-day course of clarithromycin 500 mg twice daily. At presentation, she had moderate tetraparesis, with unremarkable tendon reflexes in the upper extremities and absent tendon reflexes in the legs. Laboratory testing revealed significantly elevated creatine kinase (19,486 units/L), myoglobulin (19,479 nanograms/mL), creatine kinase/AST (ratio, 32), and ALT (405 units/L). A vasculitis screen showed no irregularities. The patient was suspected to have CK-emia due to the concurrent administration of simvastatin and clarithromycin. Simvastatin was discontinued, and within 2 weeks, her paresis greatly improved and her serum creatine kinase had returned to normal levels (less than 155 units/L) .

C) Coadministration of clarithromycin and simvastatin resulted in myopathy and rhabdomyolysis. A 64-year-old African American man presented with classic symptoms of rhabdomyolysis consisting of muscle tenderness, myalgia, swelling, weakness, elevated serum myoglobin concentrations, elevated serum CPK, and dark brown urine secondary to myoglobinuria. The patient had been receiving simvastatin for approximately 6 months. Three weeks prior to admission, clarithromycin was initiated for sinusitis. The patient received aggressive IV hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy revealed necrotizing myopathy secondary to a toxin. The patient suffered from recurrent polymicrobial nosocomial infections and died 3 months after admission secondary to infectious complications .

D) Rhabdomyolysis occurred as a consequence of the coadministration of cyclosporin, simvastatin, and clarithromycin, all metabolized by the cytochrome P450 enzyme system. A 62-year-old cadaveric renal transplant patient was being treated with prednisolone, azathioprine, cyclosporine, and simvastatin. Clarithromycin was initiated after the patient developed a respiratory tract infection with atypical features. At the end of a 10-day antibiotic course her serum cyclosporin level rose to 240 nmol/L and serum creatinine to 330 micromol/L. Profound muscle weakness ensued 10 days later with a rise in serum creatine kinase to 7500 international units/L. The patients muscle enzymes and symptoms resolved shortly after discontinuing simvastatin .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Simvastatin Overview

• Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.