Ticagrelor 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
Ticagrelor
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's talk about taking Brilinta (ticagrelor) and simvastatin (Zocor) together. Ticagrelor gently slows down the liver enzyme that breaks down simvastatin. Because of that, the amount of simvastatin in your blood goes up (studies show roughly one and a half times higher). More simvastatin can mean a higher chance of muscle problems, including a rare but serious muscle breakdown called rhabdomyolysis.
The good news is that this is very manageable. Your care team can keep your simvastatin dose in a safe range and watch you a bit more closely, especially in the first few months. Let them know right away if you notice unusual muscle pain, weakness, or dark-colored urine.
Effect: Ticagrelor (weak CYP3A4 inhibitor) reduces CYP3A4-mediated metabolism of simvastatin (CYP3A4 substrate), increasing simvastatin exposure and myopathy/rhabdomyolysis risk.
- Magnitude: ~1.5-fold increase in simvastatin AUC and ~1.8-fold increase in Cmax.
- Direction: Increased simvastatin effect/toxicity (neither drug is a prodrug in this pathway).
- Evidence: Established; onset unspecified.
- Management: Avoid simvastatin doses >40 mg daily with ticagrelor. With rhabdomyolysis risk factors (renal impairment, older age, hypertension, diabetes), consider a lower simvastatin dose or alternative antiplatelet. Monitor closely, especially the first few months. If rhabdomyolysis occurs, switch to another P2Y12 inhibitor if possible.
What happens
Increased simvastatin exposure and an increased risk of myopathy, including rhabdomyolysis
Interaction Deep Dive
When simvastatin (a CYP3A4 substrate) is taken together with ticagrelor (a weak CYP3A4 inhibitor), serum levels of simvastatin rise. A pharmacokinetic study demonstrated that giving simvastatin alongside ticagrelor produced roughly a 1.5-fold rise in simvastatin AUC and about a 1.8-fold rise in its Cmax2. Do not exceed simvastatin doses of 40 mg when it is combined with ticagrelor21. When factors predisposing to rhabdomyolysis exist (for example, renal impairment, advanced age, hypertension, or diabetes), it may be appropriate to use a reduced simvastatin dose or select a different antiplatelet agent. Close monitoring is warranted, particularly throughout the initial months of combined therapy. Should rhabdomyolysis develop while the two drugs are used together, transition to a different P2Y12 inhibitor where feasible3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Care teams manage this pairing routinely.
- The simvastatin dose is generally kept at 40 mg per day or lower when combined with ticagrelor, and may be individualized by your team.
- If you have risk factors like kidney problems, older age, high blood pressure, or diabetes, your team may choose a lower simvastatin dose or a different antiplatelet.
- Expect closer monitoring, especially in the first few months.
- Call your pharmacist or doctor promptly if you have new muscle pain, tenderness, weakness, or dark urine.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) An analysis of the World Health Organization pharmacovigilance database (N=9489 cases of statin use, of which 2464 also received antiplatelets) linked a higher rate of rhabdomyolysis to combined use of ticagrelor and simvastatin. In the univariate analysis, concurrent ticagrelor and simvastatin was tied to a significantly greater risk of rhabdomyolysis (reporting OR [ROR], 1.81; 95% CI, 1.19 to 2.75) versus simvastatin used alone; however, the multivariate analysis did not reach significance (ROR, 1.42; 95% CI, 0.92 to 2.18). When simvastatin was combined with other antiplatelets (such as aspirin, clopidogrel, or prasugrel), no significant difference in rhabdomyolysis risk was found compared with simvastatin alone. The majority of rhabdomyolysis cases involving combined antiplatelet and statin therapy were seen in male patients (62.5%) older than 65 years (66.5%), and most arose within the first 6 months of coadministration 3.
b) In a 2-way crossover study involving simvastatin and ticagrelor, participants received either a ticagrelor loading dose of 270 mg followed by 180 mg twice daily for 7 days plus simvastatin 80 mg on day 5, or simvastatin 80 mg alone given on day 5. Giving ticagrelor together with simvastatin raised simvastatin AUC by 56% (95% CI, 1.3 to 1.87) and Cmax by 81% (95% CI, 1.49 to 2.21) relative to simvastatin alone. In some patients, AUC and Cmax rose by as much as 2.3-fold. The changes in Cmax and AUC of ticagrelor and its metabolite were not significant. Patients taking ticagrelor should avoid simvastatin doses above 40 mg 1.
c) In a pharmacokinetic study, giving simvastatin 80 mg together with ticagrelor 180 mg twice daily produced an increase of approximately 1.5-fold in the AUC and 1.8-fold in the Cmax of simvastatin, respectively 2.
Common questions
Can I take Ticagrelor and Simvastatin together?
Ticagrelor raises simvastatin levels and muscle-injury risk, so simvastatin is usually capped at 40 mg per day with ticagrelor; keep taking both as prescribed and report any muscle pain or dark urine to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ticagrelor and Simvastatin 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 is the Ticagrelor and Simvastatin interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Care teams manage this pairing routinely. The simvastatin dose is generally kept at 40 mg per day or lower when combined with ticagrelor, and may be individualized by your team. If you have risk factors like kidney problems, older age, high blood pressure, or diabetes, your team may choose a lower simvastatin dose… 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 Ticagrelor 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 (3)
- Teng R, Mitchell PD, & Butler KA: Pharmacokinetic interaction studies of co-administration of ticagrelor and atorvastatin or simvastatin in healthy volunteers. Eur J Clin Pharmacol 2013; 69(3):477-487. PubMed
- Product Information: BRILINTA(R) oral tablets, ticagrelor oral tablets. AstraZeneca Pharmaceuticals LP (per FDA), Wilmington, DE, 2024. DailyMed
- Roule V, Alexandre J, Lemaitre A, et al: Rhabdomyolysis with co-administration of statins and antiplatelet therapies-analysis of the WHO pharmacovigilance database. Cardiovasc Drugs Ther 2024; 38(6):1191-1199. PubMed
Keep reading about Ticagrelor
Keep reading about Simvastatin
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