Atorvastatin and Ranolazine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 15, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Atorvastatin
Ranolazine
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.
What happens
Increased ranolazine exposure, an increased atorvastatin exposure and increased risk of myopathy
Interaction Deep Dive
Concomitant use of ranolazine and atorvastatin (P-gp inhibitor) may increase ranolazine exposure. Titrate ranolazine based on clinical response in patients concomitantly treated with atorvastatin1. Concomitant use may also increase the risk of myopathy. A case report described myopathy following coadministration of ranolazine in a patient already receiving atorvastatin. If concomitant use is necessary, monitor serum creatine kinase levels and perform muscle strength assessment at baseline in patients receiving statins before initiating ranolazine 2.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of ranolazine; inhibition of CYP3A4-mediated metabolism of atorvastatin
Literature reports
2 reports — tap to read
a) In a drug interaction study, in healthy volunteers coadministration of ranolazine 1000 mg twice daily and simvastatin 80 mg once daily, a CYP3A4 substrate resulted in increased simvastatin and its active metabolite exposure by 100%. Similarly, mean exposure to atorvastatin (CYP3A4 substrate) (80 mg daily) is increased by 40% following coadministration with ranolazine (1000 mg twice daily) in healthy volunteers. However, in one subject the exposure to atorvastatin and metabolites was increased by approximately 400% in the presence of ranolazine 1.
b) Concurrent use of ranolazine and atorvastatin led to myopathy with increased creatine kinase (CK) levels in an 86-year-old woman. The patient's medical history was complicated and included hyperlipidemia, coronary artery disease, and pulmonary hypertension, among other conditions. The patient was restarted on atorvastatin, after having been off simvastatin for a year, and had no issues for 4 months; however, within 1 week of adding ranolazine, she presented with progressive back and leg pain, weakness in both legs, and a change in gait. Examination revealed leg and hip muscle weakness on both sides. Lab test results showed increased CK (1875 units/L; baseline, 64 to 101 units/L). Muscle membrane instability and small short-duration motor unit potentials were evident on electromyography and edema in multiple muscles was noted on MRI. Within 1 week of discontinuing both drugs, her CK levels declined to 151 units/L. One month later, the patient had symptomatic and neurological improvement. Two months later, her serum CK level was 85 units/L and her edema decreased. Even though the patient had several comorbidities and was receiving multiple medications, based on the timing of myopathy onset upon adding ranolazine, and the improvement upon discontinuing both drugs, the interaction between atorvastatin and ranolazine was considered the primary etiology of the reaction. Although CYP3A4 inhibition by ranolazine is weak, the interaction could become clinically significant in the elderly 2.
Common questions
Can I take Atorvastatin and Ranolazine together?
Increased ranolazine exposure, an increased atorvastatin exposure and increased risk of myopathy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Atorvastatin and Ranolazine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
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 Atorvastatin or Ranolazine 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 (2)
- Product Information: RANOLAZINE oral extended-release tablets, ranolazine oral extended-release tablets. Viona Pharmaceuticals Inc. (per Dailymed), Cranford, NJ, 2023. DailyMed
- Correa D & Landau M: Ranolazine-induced myopathy in a patient on chronic statin therapy. J Clin Neuromuscul Dis 2013; 14(3):114-116. PubMed
Keep reading about Atorvastatin
Keep reading about Ranolazine
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