Erythromycin and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Erythromycin
Simvastatin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Let me explain this one, because it's important. Erythromycin is an antibiotic that slows down a liver enzyme (called CYP3A4) that your body uses to break down simvastatin, your cholesterol medicine. When that breakdown slows, simvastatin builds up in your blood, in one study by several times the normal amount.
Too much simvastatin can cause serious muscle problems, including muscle breakdown (called rhabdomyolysis) that can harm your kidneys. Watch for unusual muscle pain, weakness, or dark urine. The good news is your care team can manage this easily, often by pausing your statin while you take the antibiotic. Please talk with your pharmacist or doctor before combining these two.
Contraindicated combination. Erythromycin is a potent CYP3A4 inhibitor; simvastatin is a CYP3A4 substrate. Inhibition reduces simvastatin metabolism, raising systemic exposure.
- Direction: Increased simvastatin exposure and pharmacodynamic effect.
- Magnitude: In 12 healthy volunteers, simvastatin Cmax rose ~3.4-fold and AUC(0-24h) ~6.2-fold.
- Risk: Dose-dependent myopathy and rhabdomyolysis.
- Evidence: Established.
- Management: Avoid concurrent use. If erythromycin is necessary, suspend simvastatin during the antibiotic course. Monitor for muscle pain/weakness and consider CK if symptomatic.
What happens
Increased simvastatin exposure, an increased risk of simvastatin-related adverse reaction and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Because of the risk of grave reactions including myopathy and rhabdomyolysis, giving erythromycin and simvastatin together (a CYP3A4 substrate paired with an HMG CoA reductase inhibitor) is contraindicated and may provoke serious adverse effects 3451. Taking the two agents at the same time can also raise simvastatin exposure 6. In a pharmacokinetic study of 12 healthy volunteers, erythromycin raised the mean Cmax of simvastatin 3.4-fold and increased the AUC from 0 to 24 hours by 6.2-fold 7. When erythromycin treatment cannot be avoided, discontinue simvastatin for the duration of that treatment 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
This pairing is best avoided, but it is very manageable with your care team's help.
- Keep taking your medicines only as directed, and do not stop anything on your own.
- A common approach is that your prescriber will pause simvastatin during the short course of erythromycin, since the antibiotic is usually temporary.
- Your team may also choose a different antibiotic or a different statin if that fits your situation better.
- Report right away any new muscle pain, tenderness, weakness, or dark-colored urine.
Ask your pharmacist or doctor before starting erythromycin while on simvastatin so they can adjust things safely.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a retrospective, population-based cohort study involving adults over 65 years of age who were taking a statin metabolized by CYP3A (atorvastatin, 73%; simvastatin, 24%; lovastatin, 3%), simultaneous use with clarithromycin (n=72,591) or erythromycin (n=3267) was linked to a hospitalization rate for rhabdomyolysis of 0.03% and a hospitalization rate for acute kidney injury of 0.46%. The equivalent rates when azithromycin (n=68,478) was given together were 0.01% and 0.26%, respectively. The all-cause mortality rate came to 0.7% in the clarithromycin/erythromycin group and 0.45% in the azithromycin group 2.
b) In a randomized, double-blind crossover study, 12 young healthy volunteers took either erythromycin 500 mg 3 times daily, verapamil 80 mg 3 times daily, or placebo over 2 days. On the second day, simvastatin 40 mg was also given. In the presence of erythromycin, the simvastatin Cmax rose from 10.5 nanograms (ng)/mL to 36.3 ng/mL and the AUC from 0 to 24 hours increased from 17.7 ng/mL/hr to 110 ng/mL/hr 7.
Common questions
Can I take Erythromycin and Simvastatin together?
Erythromycin sharply raises simvastatin levels and the risk of serious muscle damage, so these are not used together; your doctor will typically pause the statin during the antibiotic course. Report any muscle pain, weakness, or dark urine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Erythromycin and Simvastatin interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Erythromycin and Simvastatin interaction managed?
This pairing is best avoided, but it is very manageable with your care team's help. Keep taking your medicines only as directed, and do not stop anything on your own. A common approach is that your prescriber will pause simvastatin during the short course of erythromycin, since the antibiotic is usually temporary. Your team may also choose a different antibiotic or a different statin if that fits… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Erythromycin or Simvastatin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2023. DailyMed
- 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
- Product Information: Erythromycin Lactobionate IV injection lyophilized powder for solution, erythromycin lactobionate IV injection lyophilized powder for solution. Nexus Pharmaceuticals (per DailyMed), Lincolnshire, IL, 2024.
- Product Information: Erythromycin oral delayed-release capsules, erythromycin oral delayed-release capsules. Dr. Reddy's Laboratories Inc. (per DailyMed), Princeton, NJ, 2025. DailyMed
- Product Information: ERYTHROMYCIN ETHYLSUCCINATE oral suspension granule, erythromycin ethylsuccinate oral suspension granule. ANI Pharmaceuticals, Inc (per DailyMed), Baudette, MN, 2025. DailyMed
- Product Information: Eryped oral suspension, erythromycin ethylsuccinate oral suspension. Abbott Laboratories, North Chicago, IL, 2011. DailyMed
- Kantola T, Kivisto KT, & Neuvonen PJ: Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 1998; 64:177-182. DOI
Keep reading about Erythromycin
Keep reading about Simvastatin
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