Simvastatin and Darunavir: 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
Darunavir
No brand names on recordSimvastatin
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. Darunavir is an HIV medicine that slows down a liver enzyme (called CYP3A) that normally breaks down simvastatin, your cholesterol medicine. When that enzyme is blocked, simvastatin can build up to much higher levels than intended.
Too much simvastatin can cause serious muscle problems. This can range from muscle pain and weakness to a rare but dangerous condition called rhabdomyolysis, where muscle breaks down and can harm your kidneys. The good news is your care team has safe options. Don't stop either medicine on your own, but do talk with your doctor or pharmacist soon so they can pick a cholesterol medicine that works safely with darunavir.
Contraindicated combination. Darunavir is a potent CYP3A4 inhibitor; simvastatin is a CYP3A4 substrate with an active acid metabolite. Inhibition markedly increases simvastatin systemic exposure (AUC/Cmax), raising the risk of dose-dependent myopathy and rhabdomyolysis.
- Direction: increased simvastatin effect/toxicity
- Mechanism: inhibition of CYP3A-mediated simvastatin metabolism
- Evidence: theoretical, but mechanistically robust; labeled as contraindicated
- Onset: unspecified
Management: Do not coadminister. Select a statin with less CYP3A dependence (e.g., pravastatin, rosuvastatin) per the prescriber, and counsel patients to report muscle pain, tenderness, weakness, or dark urine.
What happens
Increased simvastatin exposure; increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Because darunavir inhibits CYP3A and simvastatin is metabolized by CYP3A, taking these two agents together is contraindicated, given the potential for severe adverse effects such as myopathy and rhabdomyolysis1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated simvastatin metabolism
How to manage this interaction
This pairing is not recommended. Because darunavir raises simvastatin levels enough to risk serious muscle injury, care teams typically avoid using them together.
- Your prescriber will usually choose a different cholesterol medicine that is safer with darunavir.
- Keep taking both medicines as prescribed until you speak with your care team, and do not stop the HIV medicine on your own.
- Bring this up promptly with your pharmacist or doctor so a safe alternative can be arranged.
Right away, report any muscle pain, tenderness, weakness, or dark-colored urine to a healthcare provider.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Simvastatin and Darunavir together?
Darunavir and simvastatin should not be taken together because darunavir can raise simvastatin to dangerous levels and cause serious muscle damage. Contact your doctor or pharmacist so they can switch you to a safer cholesterol medicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Darunavir 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 Darunavir interaction managed?
This pairing is not recommended. Because darunavir raises simvastatin levels enough to risk serious muscle injury, care teams typically avoid using them together. Your prescriber will usually choose a different cholesterol medicine that is safer with darunavir. Keep taking both medicines as prescribed until you speak with your care team, and do not stop the HIV medicine on your own. Bring this up… 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 Darunavir 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: PREZCOBIX(TM) oral tablets, darunavir cobicistat oral tablets. Janssen Pharmaceuticals, Inc. (per manufacturer), Titusville, NJ, 2015. DailyMed
Keep reading about Darunavir
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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