Simvastatin and Cobicistat: 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
Cobicistat
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.
These two medicines should not be taken together. Cobicistat (Tybost) is a "booster" that blocks a liver enzyme called CYP3A. Simvastatin (Zocor), a cholesterol medicine, is cleared by that same enzyme. When cobicistat blocks it, simvastatin can build up to high levels in your body.
Too much simvastatin raises the risk of muscle problems, including a serious type of muscle breakdown called rhabdomyolysis. Warning signs include unexplained muscle pain, tenderness, weakness, or dark urine. The good news is this is very manageable: your care team can pause the statin while you need cobicistat, or choose a different cholesterol medicine. Never stop or change either drug on your own, just talk with your doctor or pharmacist.
Contraindicated combination. Cobicistat is a potent CYP3A inhibitor; simvastatin is a CYP3A4 substrate with high first-pass metabolism. Inhibition markedly increases simvastatin exposure (AUC/Cmax), raising the risk of dose-dependent myopathy and rhabdomyolysis. Inhibition of OATP1B1/OATP1B3/BCRP may further contribute.
- Direction: increased simvastatin effect/toxicity.
- Evidence: theoretical, but severity is high enough that coadministration is labeled contraindicated.
- Onset: unspecified.
- Management: avoid concurrent use. If cobicistat is required, temporarily suspend simvastatin for the duration of therapy, or select a statin with less CYP3A dependence per prescriber judgment. Monitor for muscle pain, weakness, and CK elevation if exposure occurs.
What happens
Increased simvastatin exposure and an increased risk of simvastatin toxicity, including an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Because of the risk of severe adverse reactions such as myopathy and rhabdomyolysis, giving cobicistat together with simvastatin is contraindicated 2. Should combined use become necessary, halt simvastatin temporarily for the entire period that cobicistat is being administered 1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of simvastatin; inhibition of OATP1B1-mediated efflux transport of cobicistat; inhibition of OATP1B3-mediated efflux transport of cobicistat; inhibition of BCRP-mediated efflux transport of cobicistat
How to manage this interaction
This pairing is best avoided. Your care team will typically not use these two together.
- If you need cobicistat, your prescriber may temporarily pause simvastatin for the whole time you are on cobicistat.
- They may instead choose a different cholesterol medicine that is safer with cobicistat.
- Keep taking your medicines exactly as prescribed until your care team tells you otherwise, and do not stop or restart either one on your own.
Ask your pharmacist or doctor before starting either drug, and report any muscle pain, tenderness, weakness, or dark-colored urine right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Simvastatin and Cobicistat together?
Cobicistat and simvastatin should not be taken together because cobicistat can push simvastatin levels high enough to cause serious muscle damage; your care team will pause the statin or pick an alternative, so check with them before combining. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Cobicistat interaction?
It is rated contraindicated. These should generally not be used together.
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 Cobicistat interaction managed?
This pairing is best avoided. Your care team will typically not use these two together. If you need cobicistat, your prescriber may temporarily pause simvastatin for the whole time you are on cobicistat. They may instead choose a different cholesterol medicine that is safer with cobicistat. Keep taking your medicines exactly as prescribed until your care team tells you otherwise, and do not stop o… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
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 Cobicistat 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)
Keep reading about Cobicistat
Keep reading about Simvastatin
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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