Simvastatin and Voclosporin: 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
Simvastatin
Voclosporin
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.
These two medicines can add up in a way we watch closely. Voclosporin (Lupkynis) slows down the transporters your liver uses to clear simvastatin (Zocor). That means simvastatin can build up in your body and reach higher levels than usual.
When statin levels climb, the main concern is your muscles. This can raise the risk of muscle pain, weakness, or, rarely, a serious muscle breakdown called rhabdomyolysis. Please don't stop either medicine on your own. The good news is your care team can manage this easily, often by keeping your simvastatin dose lower and checking in on how your muscles feel. Tell them right away if you notice unusual muscle aches, tenderness, or dark urine.
Effect: Voclosporin inhibits OATP1B1 and OATP1B3, hepatic uptake transporters for which simvastatin is a substrate. This reduces hepatic uptake and increases systemic simvastatin exposure, raising the risk of myopathy and rhabdomyolysis (dose-dependent statin toxicity). Neither drug is a prodrug relevant here; direction is increased statin effect/toxicity.
- Severity: Major; evidence: probable; onset: unspecified.
- Management: If coadministered, limit simvastatin to 20 mg/day, or 40 mg/day only for patients who tolerated 80 mg/day for at least 1 year without muscle toxicity.
- Monitor: muscle symptoms and CK; counsel on myalgia, weakness, dark urine.
What happens
Increased simvastatin exposure and an increased risk of myopathy and rhabdomyolysis
Interaction Deep Dive
When voclosporin, which inhibits OATP1B1 and OATP1B3, is given together with simvastatin, a substrate of OATP1B1 and OATP1B3, the exposure to simvastatin may rise, potentially raising the likelihood of adverse effects such as myopathy and rhabdomyolysis. Should the two drugs need to be used together, restrict simvastatin to a maximum of 20 mg per day; a dose of 40 mg daily may be used in patients who have tolerated simvastatin 80 mg daily for a minimum of one year without any sign of muscle toxicity1.
Why it happens (mechanism)
Inhibition of OATP1B1-mediated efflux transport of simvastatin; inhibition of OATP1B3-mediated efflux transport of simvastatin
How to manage this interaction
This is manageable with dose limits and monitoring. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
- Your team will typically cap the simvastatin dose (commonly no more than 20 mg daily, or up to 40 mg daily only if you have already tolerated 80 mg daily for at least a year without muscle problems).
- They may monitor you more closely for muscle-related side effects.
- Report promptly: unexplained muscle pain, tenderness, weakness, or dark-colored urine.
Ask your pharmacist or prescriber to confirm your simvastatin dose is appropriate now that you're also on voclosporin.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When voclosporin (an OATP1B1 inhibitor) 23.7 mg twice daily was given together with simvastatin acid (an OATP1B1 substrate), the AUC of simvastatin acid rose by 1.84-fold and the Cmax rose by 3.10-fold. Giving voclosporin with simvastatin raised the Cmax of the parent compound simvastatin by 1.6-fold but produced no change in the AUC of simvastatin 1.
Common questions
Can I take Simvastatin and Voclosporin together?
Voclosporin raises simvastatin levels and the risk of muscle injury, so the simvastatin dose is usually capped (often 20 mg daily) and your muscles watched. Keep both medicines as prescribed and report any muscle pain, weakness, or dark urine right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Voclosporin 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 Simvastatin and Voclosporin interaction managed?
This is manageable with dose limits and monitoring. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your team will typically cap the simvastatin dose (commonly no more than 20 mg daily, or up to 40 mg daily only if you have already tolerated 80 mg daily for at least a year without muscle problems). They may monitor you more closely for muscle-related side effec… 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 Simvastatin or Voclosporin 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 (1)
- Product Information: LUPKYNIS(TM) oral capsules, voclosporin oral capsules. Aurinia Pharma US Inc (per FDA), Rockville, MD, 2024. DailyMed
Keep reading about Simvastatin
Keep reading about Voclosporin
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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