Vadadustat 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
Simvastatin
Vadadustat
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.
Here's what's going on: Vadadustat (Vafseo) can slow down how your body moves simvastatin (Zocor) out, so more of the statin builds up in your blood. Studies showed simvastatin levels roughly doubled when the two were taken together.
More simvastatin in your system means a higher chance of statin side effects, like muscle aches, weakness, or (rarely) muscle damage. The good news is this is very manageable. Your care team may start your simvastatin at a lower dose and keep it capped, and they'll watch how you feel. Please don't stop either medicine on your own, just let your pharmacist or doctor know you take both so they can tailor your dose.
Mechanism: Vadadustat inhibits BCRP-mediated efflux of simvastatin (a BCRP substrate), increasing systemic exposure. Neither drug's activity depends on prodrug conversion relevant here.
Magnitude: Coadministration increased simvastatin AUC ~2.0-fold and Cmax ~1.2-fold.
Direction: Increased simvastatin exposure, raising risk of myopathy/rhabdomyolysis and hepatotoxicity.
- Evidence: Probable; onset unspecified.
- Management: Limit simvastatin starting dose to 5 mg/day and do not exceed 20 mg/day. Monitor for muscle symptoms (myalgia, weakness), and check CK if symptomatic; reduce simvastatin dose as needed.
What happens
Increased simvastatin exposure and an increased risk of simvastatin-related adverse effects
Interaction Deep Dive
Taking vadadustat together with simvastatin, which is a BCRP substrate, may raise both the maximal concentration (Cmax) and the AUC of simvastatin, thereby potentially heightening the likelihood of simvastatin-related adverse reactions. When the two were coadministered, the influence of vadadustat on the pharmacokinetics of the BCRP substrate was investigated. The presence of vadadustat produced an increase of roughly 2.0-fold in the AUC and about 1.2-fold in the Cmax of simvastatin (BCRP substrate). Watch for indications of adverse effects from the coadministered simvastatin, and lower the simvastatin dose if warranted. The simvastatin initial dose should be 5 mg/day, and its maximum daily dose should not go beyond 20 mg1.
Why it happens (mechanism)
Inhibition of BCRP-mediated efflux transport of simvastatin
How to manage this interaction
This interaction is manageable with dosing limits and monitoring. Keep taking both medicines as prescribed unless your care team tells you otherwise.
- Your prescriber may start simvastatin low (around 5 mg/day) and keep the daily dose capped (not above 20 mg/day) while you're on vadadustat.
- Your dose may be adjusted and individualized by your care team, and they may monitor you more closely.
- Tell your pharmacist or doctor right away if you notice new muscle pain, tenderness, weakness, or dark-colored urine.
- Make sure both prescribers know you take these two medicines together.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of vadadustat on the pharmacokinetics of a BCRP substrate was evaluated during coadministration. When given with vadadustat, the AUC and Cmax of simvastatin (a BCRP substrate) rose by roughly 2.0-fold and 1.2-fold, respectively 1.
Common questions
Can I take Vadadustat and Simvastatin together?
Vadadustat can roughly double simvastatin levels, so your care team will likely cap the simvastatin dose (5 mg to start, max 20 mg/day) and watch for muscle side effects. Keep taking both as prescribed and report any muscle pain or weakness. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Vadadustat 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 Vadadustat and Simvastatin interaction managed?
This interaction is manageable with dosing limits and monitoring. Keep taking both medicines as prescribed unless your care team tells you otherwise. Your prescriber may start simvastatin low (around 5 mg/day) and keep the daily dose capped (not above 20 mg/day) while you're on vadadustat. Your dose may be adjusted and individualized by your care team, and they may monitor you more closely. Tell y… 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 Vadadustat 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 (1)
- Product Information: VAFSEO(R) oral tablets, vadadustat oral tablets. Akebia Therapeutics (Per Manufacturer), Cambridge, MA, 2024. DailyMed
Keep reading about Simvastatin
Keep reading about Vadadustat
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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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