Simvastatin and Glecaprevir: 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
Glecaprevir
No brand names on record
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.
You're taking simvastatin (a cholesterol medicine) along with glecaprevir (part of a hepatitis C treatment). The problem is that glecaprevir causes a lot more simvastatin to build up in your blood. In a study, the active form of simvastatin rose by several hundred percent.
When statin levels get that high, the main worry is muscle damage. Watch for unusual muscle pain, tenderness, weakness, or dark-colored urine. The good news: your care team can manage this easily, often by choosing a different cholesterol medicine while you're on the hepatitis C treatment. Please talk with your pharmacist or doctor before changing anything.
Effect: Glecaprevir/pibrentasvir markedly increases simvastatin exposure, raising myopathy and rhabdomyolysis risk. The combination is not recommended.
- Direction/magnitude: Simvastatin Cmax +99%, AUC +132%; simvastatin acid (active) Cmax +970%, AUC +348% (N=12).
- Mechanism: Likely OATP1B and/or CYP3A/efflux transporter inhibition by glecaprevir/pibrentasvir reducing simvastatin clearance; documented as unknown.
- Evidence: Established.
- Management: Avoid concurrent use. Consider an alternative during HCV therapy and monitor for muscle symptoms and CK if exposure occurs.
What happens
Increased simvastatin exposure and increased risk of myopathy
Interaction Deep Dive
Taking glecaprevir/pibrentasvir together with simvastatin is not advised. When given at the same time, simvastatin plasma concentrations may rise, heightening the potential for myopathy, including rhabdomyolysis. One pharmacokinetic study (N=12) evaluated simvastatin 5 mg once daily administered alongside glecaprevir 300 mg/pibrentasvir 120 mg once daily; under these conditions, the Cmax of simvastatin rose by 99% and its AUC by 132%, whereas simvastatin acid showed a 970% increase in Cmax and a 348% increase in AUC1.
Why it happens (mechanism)
Unknown
How to manage this interaction
What your care team typically does:
- Because this combination is not recommended, the usual step is choosing an alternative cholesterol medicine while you are on glecaprevir/pibrentasvir.
- Your team may monitor you more closely for muscle problems if you are on both.
What you should do:
- Keep taking both exactly as prescribed until you speak with your prescriber or pharmacist. Do not stop on your own.
- Report any muscle pain, weakness, tenderness, or dark urine right away.
- Ask your pharmacist or doctor whether a different statin or plan is right for you during your hepatitis C treatment.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a pharmacokinetic study (N=12), when simvastatin 5 mg once daily was given together with glecaprevir 300 mg/pibrentasvir 120 mg once daily, the simvastatin Cmax rose by 99% and its AUC rose by 132%, whereas the simvastatin acid Cmax rose by 970% and its AUC rose by 348% 1.
Common questions
Can I take Simvastatin and Glecaprevir together?
Glecaprevir sharply raises simvastatin levels and the risk of serious muscle damage, so this pairing is not recommended; ask your doctor or pharmacist about an alternative cholesterol medicine during hepatitis C treatment. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Glecaprevir 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 Glecaprevir interaction managed?
What your care team typically does: Because this combination is not recommended, the usual step is choosing an alternative cholesterol medicine while you are on glecaprevir/pibrentasvir. Your team may monitor you more closely for muscle problems if you are on both. What you should do: Keep taking both exactly as prescribed until you speak with your prescriber or pharmacist. Do not stop on your own… 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 Simvastatin or Glecaprevir 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: MAVYRET(R) oral tablets, oral pellets, glecaprevir pibrentasvir oral tablets, oral pellets. AbbVie Inc (per FDA), North Chicago, IL, 2023. DailyMed
Keep reading about Simvastatin
Keep reading about Glecaprevir
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