Indinavir 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
Indinavir
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. Indinavir, an HIV medicine, slows down the liver enzyme that normally breaks down simvastatin (a cholesterol medicine). When that breakdown is blocked, simvastatin can build up to much higher levels than intended.
Too much simvastatin can cause serious muscle problems. Watch for unexplained muscle pain, tenderness, or weakness, or dark, cola-colored urine. In rare cases this can harm the kidneys. The good news is your care team can manage this easily, often by pausing the statin while you are on indinavir or choosing a different cholesterol medicine. Please talk with your pharmacist or doctor before changing anything.
Contraindicated combination. Indinavir is a strong CYP3A4 inhibitor; simvastatin is a CYP3A4 substrate (an active drug, not a prodrug requiring 3A4). Inhibition reduces simvastatin metabolism, raising its plasma exposure (AUC/Cmax) and the dose-dependent risk of myopathy and rhabdomyolysis.
- Direction: increased simvastatin effect/toxicity
- Evidence: theoretical, based on the known CYP3A4 mechanism
- Onset: unspecified
- Management: avoid concurrent use; if the inhibitor is required, temporarily suspend simvastatin for the duration of indinavir therapy, or select a statin less dependent on CYP3A4. Monitor for muscle symptoms and CK if exposure occurs.
What happens
Increased simvastatin exposure and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
The combination of simvastatin with a potent CYP3A4 inhibitor, for example indinavir, is contraindicated32. Because simvastatin is a CYP3A4 substrate, giving it alongside a strong CYP3A4 inhibitor may raise its plasma concentrations, which heightens the likelihood of myopathy and rhabdomyolysis. Should the two need to be given together, simvastatin should be temporarily halted for the length of time the strong CYP3A4 inhibitor is used 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated simvastatin metabolism by indinavir
How to manage this interaction
This pairing is best avoided. Because indinavir can drive simvastatin levels up, the usual approach is to not use them together.
- Your care team may temporarily pause simvastatin while you are taking indinavir.
- They may instead choose a different cholesterol medicine that does not interact this way.
- If you are ever on both, they may watch you more closely for muscle problems.
What you should do: keep taking your medicines as prescribed for now, and contact your pharmacist or prescriber before making changes. Report any muscle pain, weakness, or dark urine right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Indinavir and Simvastatin together?
Indinavir and simvastatin should not be used together because indinavir can raise simvastatin levels and cause serious muscle damage; your care team will usually pause the statin or switch you to a safer cholesterol medicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Indinavir and Simvastatin 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 Indinavir and Simvastatin interaction managed?
This pairing is best avoided. Because indinavir can drive simvastatin levels up, the usual approach is to not use them together. Your care team may temporarily pause simvastatin while you are taking indinavir. They may instead choose a different cholesterol medicine that does not interact this way. If you are ever on both, they may watch you more closely for muscle problems. What you should do: ke… 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 Indinavir 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 (3)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Merck & CO. Inc. (Per manufacturer), Whitehouse Station, NJ, 2012. DailyMed
- Product Information: CRIXIVAN(R) oral capsules, indinavir sulfate oral capsules. Merck Sharp & Dohme Corp. (per FDA), Whitehouse Station, NJ, 2012. DailyMed
Keep reading about Indinavir
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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