Atorvastatin with Erythromycin Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased atorvastatin exposure and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

The coadministration of erythromycin with atorvastatin significantly increased atorvastatin exposure[1]. Clinically significant rhabdomyolysis has been cited in case reports of patients treated concomitantly with atorvastatin and clarithromycin [2][3]. Similar to clarithromycin, erythromycin is a known inhibitor of cytochrome P450-3A4 [4], for which atorvastatin is a substrate. Use caution with the concomitant use of atorvastatin and erythromycin; consider using lower initial and maintenance doses of atorvastatin due to an increased risk of myopathy/rhabdomyolysis. Evaluate the benefit and risk of coadministration. Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). If myopathy or rhabdomyolysis is diagnosed or suspected, or if creatine kinase (CK) levels show a marked increase, temporarily withhold or discontinue atorvastatin [1].

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Use caution with the concomitant use of atorvastatin with erythromycin; consider using lower initial and maintenance doses of atorvastatin due to an increased risk of myopathy/rhabdomyolysis. Evaluate the benefit and risk of coadministration. Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during upward dosage titration of either drug. If myopathy or rhabdomyolysis is diagnosed or suspected, or if creatine kinase (CK) levels show a marked increase, temporarily withhold or discontinue atorvastatin[1].

Mechanism Of Interaction

Inhibition of cytochrome P450 3A4-mediated atorvastatin metabolism by erythromycin

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 [5].

B) Subjects receiving a single dose of atorvastatin 10 mg who were coadministered erythromycin 500 mg 4 times daily for 7 days had a 33% increase in atorvastatin AUC and a 38% increase in Cmax [1].

References

1 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Pfizer (Per FDA), New York, NY, 2012.

2 ) Sipe BE, Jones RJ, & Bokhart GH: Rhabdomyolysis causing AV blockade due to possible atorvastatin, esomeprazole, and clarithromycin interaction. Ann Pharmacother 2003; 37:808-811.

3 ) Ming JB & Gill MJ: Drug-induced rhabdomyolysis after concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir in a patient with HIV. AIDS Patient Care and STDs 2003; 17(5):207-210.

4 ) Product Information: PCE(R) oral tablets, erythromycin oral tablets. Arbor Pharmaceuticals (per FDA), Atlanta, GA, 2012.

5 ) Patel AM , Shariff S , Bailey DG , et al: Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med 2013; 158(12):869-876.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

Atorvastatin Overview

• Atorvastatin 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. Atorvastatin 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. Atorvastatin 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). Atorvastatin 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 atorvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin 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.

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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.