Simvastatin and Pibrentasvir: 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
Pibrentasvir
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've been prescribed simvastatin (a cholesterol medicine) along with glecaprevir/pibrentasvir, a hepatitis C treatment. When these are taken together, the hepatitis C medicine causes much more simvastatin to build up in your blood. In a study, the active form of simvastatin rose several times higher than normal.
That extra buildup raises the risk of muscle problems, like aching, weakness, or in rare cases serious muscle breakdown. The good news is your care team knows about this combination and can manage it, often by choosing a different cholesterol medicine. Please don't stop anything on your own, just talk with your doctor or pharmacist.
Effect: Coadministration markedly increases simvastatin exposure and raises myopathy/rhabdomyolysis risk. In a PK study (N=12), simvastatin Cmax rose 99% and AUC 132%; simvastatin acid (active metabolite) Cmax rose 970% and AUC 348%.
Mechanism: Unknown per file, but consistent with glecaprevir/pibrentasvir inhibition of hepatic uptake/metabolism transporters affecting simvastatin disposition.
Direction: Increased statin effect and toxicity risk. Evidence: Established. Severity: Major.
- Concurrent use is not recommended.
- Consider an alternative lipid-lowering agent per label guidance.
- Monitor for myalgia, weakness, and CK elevation 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. Combining these agents can raise simvastatin plasma concentrations and heighten the likelihood of myopathy, including rhabdomyolysis. Findings from a pharmacokinetic study (N=12) showed that when simvastatin 5 mg once daily was given alongside glecaprevir 300 mg/pibrentasvir 120 mg once daily, the Cmax of simvastatin rose by 99% and its AUC by 132%, whereas simvastatin acid demonstrated a 970% increase in Cmax and a 348% increase in AUC1.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination is not recommended because the hepatitis C therapy pushes simvastatin levels much higher, raising the chance of muscle injury.
- Keep taking both exactly as prescribed until you speak with your care team, do not stop on your own.
- Your team will likely choose a different cholesterol medicine while you are on the hepatitis C treatment.
- Report any muscle pain, tenderness, weakness, or dark urine right away.
- Ask your pharmacist or prescriber which statin or alternative is best for you.
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), coadministration of simvastatin 5 mg once daily with glecaprevir 300 mg/pibrentasvir 120 mg once daily produced a 99% rise in simvastatin Cmax and a 132% rise in AUC, whereas simvastatin acid Cmax rose by 970% and AUC rose by 348% 1.
Common questions
Can I take Simvastatin and Pibrentasvir together?
Taking simvastatin with glecaprevir/pibrentasvir sharply raises simvastatin levels and the risk of serious muscle problems, so this pairing is not recommended. Talk with your doctor or pharmacist about a safer cholesterol option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Pibrentasvir 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 Pibrentasvir interaction managed?
This combination is not recommended because the hepatitis C therapy pushes simvastatin levels much higher, raising the chance of muscle injury. Keep taking both exactly as prescribed until you speak with your care team, do not stop on your own. Your team will likely choose a different cholesterol medicine while you are on the hepatitis C treatment. Report any muscle pain, tenderness, weakness, or… 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 Pibrentasvir 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 Pibrentasvir
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