Grapefruit Juice 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
Grapefruit Juice
No brand names on recordSimvastatin
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.
Grapefruit juice and simvastatin (Zocor) don't mix well. Your body normally breaks down simvastatin using an enzyme in your gut and liver. Grapefruit juice blocks that enzyme, so much more of the statin ends up in your blood, in one study more than three times as much. Too much simvastatin can cause muscle pain, weakness, or, rarely, serious muscle breakdown.
The good news is this is easy to avoid. Please don't stop your simvastatin. Just talk with your pharmacist or doctor about keeping grapefruit and grapefruit juice off your menu, or about whether a different option might suit you better.
Mechanism: Grapefruit juice inhibits intestinal CYP3A4, reducing first-pass metabolism of simvastatin (an active statin, not a prodrug in the relevant sense), markedly increasing systemic exposure.
- Direction/magnitude: Increased simvastatin bioavailability; crossover data show up to ~9-fold higher Cmax and ~16-fold higher AUC.
- Onset: Rapid. Evidence: Established. Severity: Major.
- Risk: Dose-dependent myopathy and rhabdomyolysis.
- Management: Avoid grapefruit juice during simvastatin therapy. Monitor for myalgia/weakness and CK if symptomatic; consider an alternative statin less affected by CYP3A4 if grapefruit intake is unavoidable.
What happens
Increased bioavailability of simvastatin resulting in an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Concurrent administration of simvastatin and grapefruit juice should be avoided1. In a randomized crossover trial involving healthy volunteers, giving a modest quantity of grapefruit juice (200 mL once daily) together with simvastatin produced markedly higher simvastatin bioavailability (an increase of more than 3-fold) along with an elevated risk of myotoxicity2. Separately, a randomized 2-phase crossover investigation in 10 healthy volunteers found that coadministration of simvastatin with grapefruit juice, compared with water, raised the mean Cmax by 9-fold and the mean AUC by 16-fold3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
The simplest fix is dietary. Grapefruit juice greatly raises simvastatin levels, so care teams typically advise avoiding grapefruit and grapefruit juice while you take this statin.
- Keep taking your simvastatin exactly as prescribed. Do not stop it on your own.
- Avoid grapefruit and grapefruit juice unless your prescriber says otherwise.
- Report new muscle pain, tenderness, weakness, or dark urine promptly.
- Ask your pharmacist whether a different statin might be a better fit if you love grapefruit, and mention any other medicines you take.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking simvastatin together with modest amounts of grapefruit juice markedly raised simvastatin bioavailability. In a randomized crossover trial, healthy participants (n=10) consumed either 200 mL of regular-strength grapefruit juice or water over 2 days. On the third day, each participant took a single oral 40 mg dose of simvastatin at the same time as grapefruit juice or water. Blood samples were collected serially across the following 24 hours. Simultaneous intake of grapefruit juice and simvastatin markedly raised the mean Cmax and AUC of simvastatin by 393% and 355%, respectively (p less than 0.001 for both). Levels of the active metabolite simvastatin acid also rose (Cmax and AUC increased 432% and 334%, respectively; p less than 0.001 for both). The authors propose that even a single daily intake of grapefruit juice can substantially inhibit the first-pass metabolism of simvastatin, thereby raising the risk of simvastatin-associated myopathy or rhabdomyolysis 2.
b) In a randomized two-phase crossover study, 10 healthy volunteers received 200 mL of either double-strength grapefruit juice or water 3 times per day for 3 days. On the third day, each volunteer took 60 mg of simvastatin with 200 mL of grapefruit juice or water, plus another 200 mL taken at 0.5 and 1.5 hours after the simvastatin dose. The mean peak serum concentrations (Cmax) of simvastatin were 15.6 and 147 nanograms (ng)/mL (37.3 and 351 nanomol/L) with water and grapefruit juice, respectively. The mean AUC was 46.6 and 752 ng/mL/hr, respectively. Simvastatin acid measurements were likewise elevated, though to a lesser extent. The authors proposed that the probable mechanism of this interaction is inhibition of CYP3A4-mediated presystemic metabolism of simvastatin 3.
c) A crossover study with 10 volunteers was performed in which participants first took simvastatin 40 mg with water (control) or with high-dose grapefruit juice (double-strength grapefruit juice, 200 mL 3 times daily for 3 days). In addition, simvastatin 40 mg was taken 1, 3, and 7 days after the high-dose grapefruit juice. Serum concentrations of simvastatin and simvastatin acid were then measured and compared with control values. With concurrent simvastatin and grapefruit juice, the mean Cmax of simvastatin rose significantly by 12-fold and the mean AUC rose significantly by 13.5-fold. When simvastatin was given 1 day after grapefruit juice, the mean Cmax and AUC of simvastatin rose significantly by 2.4-fold and 2.1-fold, respectively. When simvastatin was given 3 days after grapefruit juice, the mean Cmax and AUC of simvastatin were not significantly increased. No difference in either value was observed after 7 days; comparable trends in simvastatin acid concentrations were seen following grapefruit juice intake 4.
d) Simvastatin AUC rose 16-fold when high-dose grapefruit juice (200 mL of double-strength) was given 3 times daily for 2 days and then coadministered with a single 60 mg dose of simvastatin, along with additional doses at 30 and 90 minutes after the single dose on day 3; the AUC of the active metabolite of simvastatin (simvastatin acid) rose 7-fold. In a separate study, simvastatin AUC rose 1.9-fold when low-dose grapefruit juice (237 mL of single-strength) was given once daily with breakfast for 3 days and coadministered with a single 20 mg dose of simvastatin taken in the evening on day 3; the AUC of simvastatin acid rose 1.3-fold 1.
Common questions
Can I take Grapefruit Juice and Simvastatin together?
Avoid grapefruit juice while taking simvastatin, since it can sharply raise statin levels and the risk of muscle damage. Keep taking your statin and talk with your pharmacist or doctor about safe options. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Grapefruit Juice 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Grapefruit Juice and Simvastatin interaction managed?
The simplest fix is dietary. Grapefruit juice greatly raises simvastatin levels, so care teams typically advise avoiding grapefruit and grapefruit juice while you take this statin. Keep taking your simvastatin exactly as prescribed. Do not stop it on your own. Avoid grapefruit and grapefruit juice unless your prescriber says otherwise. Report new muscle pain, tenderness, weakness, or dark urine pr… 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 Grapefruit Juice 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 (4)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Lilja JJ, Neuvonen M, & Neuvonen PJ: Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004; 58(1):56-60. PubMed
- Lilja JJ, Kivisto KT, & Neuvonen PJ: Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998; 64:477-483. PubMed
- Lilja JJ, Kivisto KT, & Neuvonen PJ: Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther 2000; 68:384-390. DOI
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