Posaconazole 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
Posaconazole
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. Posaconazole (Noxafil) is a strong antifungal that blocks a liver enzyme called CYP3A4. Your body uses that same enzyme to break down simvastatin, a cholesterol drug. When posaconazole blocks it, simvastatin builds up in your blood, in one study by about 10 times the usual level.
That much extra statin can cause serious muscle problems, including muscle pain, weakness, and a rare but dangerous breakdown of muscle called rhabdomyolysis. The good news is this is very manageable. Your care team will usually pause your simvastatin while you are on posaconazole. Never stop or change either drug on your own, but do talk with your pharmacist or doctor.
Contraindicated combination. Posaconazole is a potent CYP3A4 inhibitor; simvastatin is a CYP3A4 substrate (active drug, not a prodrug). Inhibition markedly reduces simvastatin clearance.
- Effect: Simvastatin Cmax and AUC increased ~10-fold in healthy volunteers.
- Risk: Dose-dependent myopathy and rhabdomyolysis.
- Evidence: Established.
- Management: Do not coadminister. If posaconazole therapy is required, temporarily suspend simvastatin for the full duration of posaconazole treatment. Consider a non-CYP3A4-dependent statin if lipid therapy is needed during that window, and monitor for muscle symptoms/CK if any overlap occurs.
What happens
Increased simvastatin exposure and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Combining posaconazole, a potent CYP3A4 inhibitor, with simvastatin, a CYP3A4 substrate, is contraindicated231. A clinical study in healthy volunteers found that giving posaconazole together with simvastatin raised both the Cmax and AUC of simvastatin roughly 10-fold4, potentially heightening the likelihood of myopathy and rhabdomyolysis. Should the two agents need to be given together, simvastatin should be temporarily withheld for the entire course of posaconazole therapy1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
What your care team typically does:
- Because this pairing is contraindicated, the usual approach is to temporarily suspend simvastatin for the entire time you are taking posaconazole.
- Your team may restart simvastatin after posaconazole is finished, or choose a different cholesterol medicine if you need one during that period.
- They may ask you to watch for muscle pain, tenderness, or weakness.
What you should do: Do not stop or adjust either drug on your own. Let your pharmacist or prescriber know you take both so they can coordinate the plan. Report any unexplained muscle pain, weakness, or dark urine right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a pharmacokinetic investigation involving healthy volunteers (n=35), giving posaconazole together with simvastatin produced marked rises in the Cmax and AUC of both simvastatin and simvastatin acid. Participants were randomized to receive oral posaconazole in daily doses of 50 mg (n=11), 100 mg (n=12), or 200 mg (n=12) over 13 days. Subjects also received single oral doses of simvastatin 40 mg both alone and together with posaconazole. Relative to simvastatin given alone, the mean simvastatin Cmax rose by 7.4-fold (ratio estimate 743%; 90% CI, 565% to 976%), 9.4-fold (ratio estimate, 941%; 90% CI, 713% to 1244%), and 11.4-fold (ratio estimate, 1141%; 90% CI, 799% to 1629%) when posaconazole 50 mg, 100 mg, and 200 mg were coadministered, respectively, and the corresponding AUC values rose by 5.5-fold (ratio estimate, 565%; 90% CI, 443% to 722%), 10.3-fold (ratio estimate, 1031%; 90% CI, 840% to 1267%), and 10.6-fold (estimate ratio, 1060%; 90% CI, 863% to 1302%), respectively. Coadministration also produced 5.5-fold (ratio estimate, 552%; 90% CI, 431% to 708%), 9.2-fold (ratio estimate, 917%; 90% CI, 736% to 1143%), and 9.5-fold (ratio estimate, 951%; 90% CI, 815% to 1110%) rises in simvastatin acid Cmax values and 5.4-fold (ratio estimate, 535%; 90% CI, 418% to 684%), 7.3-fold (ratio estimate, 734%; 90% CI, 582% to 925%), and 8.5-fold (ratio estimate 848%; 90% CI, 704% to 1023%) rises in simvastatin acid AUC values, respectively, based on posaconazole dosage 4.
Common questions
Can I take Posaconazole and Simvastatin together?
Posaconazole and simvastatin should not be taken together because posaconazole can raise simvastatin levels about 10-fold and cause serious muscle damage; your care team will usually pause the simvastatin while you are on posaconazole. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Posaconazole 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 Posaconazole and Simvastatin interaction managed?
What your care team typically does: Because this pairing is contraindicated, the usual approach is to temporarily suspend simvastatin for the entire time you are taking posaconazole. Your team may restart simvastatin after posaconazole is finished, or choose a different cholesterol medicine if you need one during that period. They may ask you to watch for muscle pain, tenderness, or weakness. What… 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 Posaconazole 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 (4)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Product Information: NOXAFIL(R) PowderMix delayed-release oral suspension, posaconazole delayed-release oral suspension. Merck Sharp & Dohme LLC (per FDA), Rahway, NJ, 2024. DailyMed
- Product Information: Posaconazole oral delayed-release tablets, posaconazole oral delayed-release tablets. SpecGx LLC (per DailyMed), Webster Groves, MO, 2024. DailyMed
- Krishna G, Ma L, Prasad P, et al: Effect of posaconazole on the pharmacokinetics of simvastatin and midazolam in healthy volunteers. Expert Opin Drug Metab Toxicol 2012; 8(1):1-10. PubMed
Keep reading about Posaconazole
Keep reading about Simvastatin
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