Clarithromycin 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
Clarithromycin
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 matters. Simvastatin (Zocor) is a cholesterol medicine that your body breaks down using a liver enzyme called CYP3A4. Clarithromycin (Biaxin) is an antibiotic that strongly blocks that same enzyme. When you take them together, the simvastatin can't be cleared normally, so it builds up in your blood.
Too much simvastatin can lead to serious muscle problems, including a rare but dangerous condition called rhabdomyolysis where muscle tissue breaks down. That's why these two are not meant to be taken at the same time. The good news: your care team can easily manage this by pausing your statin or picking a different one during the antibiotic course. Please talk with your pharmacist or doctor before taking both.
Contraindicated combination. Clarithromycin is a strong CYP3A4 inhibitor; simvastatin is a CYP3A4 substrate. Inhibition markedly increases simvastatin plasma concentrations (increased AUC/Cmax of active statin), raising the risk of myopathy and rhabdomyolysis.
- Direction: increased simvastatin exposure and effect (toxicity).
- Evidence: probable; supported by PK data and rare case reports of rhabdomyolysis.
- Onset: unspecified.
- Management: Do not co-administer. Suspend simvastatin during the clarithromycin course, or switch to a non-CYP3A statin such as fluvastatin. Counsel patient on muscle pain, weakness, and dark urine.
What happens
An increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Taking clarithromycin together with simvastatin (a substrate of CYP3A4) can raise the likelihood of myopathy and rhabdomyolysis, so this combination is contraindicated16; clarithromycin acts as both a substrate and a strong inhibitor of CYP3A4. When clarithromycin has been given alongside simvastatin, simvastatin plasma levels have risen, with rare reports of rhabdomyolysis10. Cases of myopathy and rhabdomyolysis have also been noted in patients (whether or not renal impairment was present) receiving other HMG-CoA reductase inhibitors either by themselves or in combination with clarithromycin789. Should clarithromycin treatment be required, discontinue simvastatin for the duration of that treatment or change to a statin whose metabolism does not rely on CYP3A, for example fluvastatin11.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated simvastatin metabolism by clarithromycin
How to manage this interaction
This combination is contraindicated, but it is very manageable with your care team's help. Do not stop or change either medicine on your own.
- Your prescriber may pause your simvastatin for the short time you are taking clarithromycin, then restart it afterward.
- Alternatively, they may switch you to a statin that is not broken down by the same enzyme, such as fluvastatin, or choose a different antibiotic.
- Tell your pharmacist or doctor right away if you notice unexplained muscle pain, tenderness, weakness, or dark-colored urine.
Ask your pharmacist to review both prescriptions before you fill them together.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A retrospective, population-based cohort study of adults over 65 years of age who were taking a statin metabolized by CYP3A (atorvastatin, 73%; simvastatin, 24%; lovastatin, 3%) found that co-prescription with clarithromycin (n=72,591) or erythromycin (n=3267) carried 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 concurrently were 0.01% and 0.26%, respectively. All-cause mortality was 0.7% among those receiving clarithromycin/erythromycin and 0.45% among those receiving azithromycin 2.
b) A 77-year-old woman developed rhabdomyolysis after simvastatin and clarithromycin were administered together. On admission she reported a 3-week history of generalized weakness that had rendered her unable to walk. Her medication regimen consisted of simvastatin 20 mg/day, telmisartan, hydroCHLOROthiazide, glibenclamide, allopurinol, bisoprolol, aspirin, and, until 3 days before admission, a 14-day course of clarithromycin 500 mg twice daily. At presentation she exhibited moderate tetraparesis, with normal tendon reflexes in the arms and absent tendon reflexes in the legs. Laboratory work showed markedly raised creatine kinase (19,486 units/L), myoglobulin (19,479 nanograms/mL), creatine kinase/AST (ratio, 32), and ALT (405 units/L). A vasculitis screen was normal. The clinical suspicion was CK-emia arising from the combined use of simvastatin and clarithromycin. Simvastatin was stopped, and within 2 weeks her paresis improved substantially and her serum creatine kinase had normalized (less than 155 units/L) 7.
c) The combined use of clarithromycin and simvastatin produced myopathy and rhabdomyolysis. A 64-year-old African American man presented with the classic features of rhabdomyolysis, including muscle tenderness, myalgia, swelling, weakness, raised serum myoglobin, raised serum CPK, and dark brown urine due to myoglobinuria. He had been on simvastatin for roughly 6 months. Clarithromycin had been started for sinusitis three weeks before admission. Treatment consisted of aggressive IV hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy showed necrotizing myopathy caused by a toxin. The patient experienced recurrent polymicrobial nosocomial infections and died 3 months after admission from infectious complications 8.
d) Rhabdomyolysis developed following the concurrent use of cycloSPORINE, simvastatin, and clarithromycin, each of which is metabolized by the cytochrome P450 enzyme system. A 62-year-old cadaveric renal transplant patient was receiving prednisoLONE, azaTHIOprine, cycloSPORINE, and simvastatin. Clarithromycin was added when the patient developed a respiratory tract infection with atypical features. At the conclusion of a 10-day antibiotic course her serum cycloSPORINE level increased to 240 nmol/L and her serum creatinine to 330 micromol/L. Severe muscle weakness developed 10 days afterward, accompanied by a rise in serum creatine kinase to 7500 international units/L. The patient's muscle enzymes and symptoms resolved soon after simvastatin was discontinued 9.
Common questions
Can I take Clarithromycin and Simvastatin together?
Taking clarithromycin with simvastatin lets the statin build up and can cause serious muscle damage, so this pairing is contraindicated. Your care team will typically pause the simvastatin during the antibiotic course or use a safer alternative. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clarithromycin 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 Clarithromycin and Simvastatin interaction managed?
This combination is contraindicated, but it is very manageable with your care team's help. Do not stop or change either medicine on your own. Your prescriber may pause your simvastatin for the short time you are taking clarithromycin, then restart it afterward. Alternatively, they may switch you to a statin that is not broken down by the same enzyme, such as fluvastatin, or choose a different anti… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Clarithromycin 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 (11)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. 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: BIAXIN(R) XL Filmtab(R) oral extended-release tablets, clarithromycin oral extended-release tablets. AbbVie Inc (per FDA), North Chicago, IL, 2018. DailyMed
- Product Information: BIAXIN(R) Filmtab(R) oral tablets, clarithromycin oral tablets. AbbVie Inc. (per FDA), North Chicago, IL, 2015. DailyMed
- Product Information: BIAXIN(R) Granules oral suspension, clarithromycin oral suspension. AbbVie Inc. (per FDA), North Chicago, IL, 2015. DailyMed
- Product Information: VOQUEZNA(TM) TRIPLE PAK(TM) oral kit, vonoprazan oral tablets, amoxicillin oral capsules, clarithromycin oral tablets kit. Phathom Pharmaceuticals (per FDA), Buffalo Grove, IL, 2023. DailyMed
- Wagner J, Suessmair C, & Pfister HW: Rhabdomyolysis caused by co-medication with simvastatin and clarithromycin. J Neurol 2009; 256(7):1182-1183. PubMed
- Lee A & Maddix D: Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromcyin. Ann Pharmacother 2001; 35:26-31.
- Stirling C & Isles C: Rhabdomyolysis due to simvastatin in a transplant patient: are some statins safer than others?. Nephrol Dial Transplan 2001; 16:873-874. PubMed
- Product Information: BIAXIN(R) Filmtab(R) oral film coated tablets, clarithromycin oral film coated tablets. Abbott Pharmaceuticals (per FDA), Barceloneta, PR, 2011. DailyMed
- Product Information: BIAXIN(R) XL Filmtab(R) oral extended-release tablets, clarithromycin oral extended-release tablets. AbbVie Inc. (per FDA), North Chicago, IL, 2015. DailyMed
Keep reading about Clarithromycin
Keep reading about Simvastatin
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