Simvastatin and Voriconazole: 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
Voriconazole
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 can push each other's levels up. Voriconazole (Vfend) is an antifungal that blocks the liver enzyme that breaks down simvastatin (Zocor). When that happens, simvastatin can build up in your body. Too much simvastatin raises the risk of muscle problems, including a serious condition called rhabdomyolysis that can harm your kidneys.
At the same time, simvastatin can slow how you clear voriconazole, so that drug can build up too and cause more side effects. Because of this, the two are usually not taken together. Please don't change anything on your own. Talk with your pharmacist or doctor, who can safely manage this for you.
Bidirectional CYP interaction; coadministration is contraindicated.
- Mechanism: Voriconazole inhibits CYP3A4-mediated metabolism of simvastatin, increasing statin exposure and myopathy/rhabdomyolysis risk. Simvastatin inhibits CYP2C9, potentially increasing voriconazole exposure and adverse reactions.
- Direction: Both agents' exposure (AUC/Cmax) increases; neither is a prodrug here, so effects are amplified.
- Evidence: Theoretical, with one case report of cholestatic hepatitis.
- Onset: Unspecified (case onset within ~2 weeks).
- Management: Avoid combination. If antifungal therapy is required, temporarily suspend simvastatin for the duration of voriconazole treatment. If both used, adjust/individualize voriconazole dosing and monitor closely (CK, hepatic function, myopathy symptoms).
What happens
Increased simvastatin exposure, an increased risk of simvastatin adverse effects an increased risk of rhabdomyolysis, increased voriconazole exposure and an increased risk of voriconazole-related adverse reactions
Interaction Deep Dive
Because simvastatin acts as a CYP3A4 inhibitor and voriconazole is a CYP3A4 substrate, giving the two together is contraindicated, since doing so can raise simvastatin exposure and heighten the likelihood of myopathy and rhabdomyolysis. When the pair must be given together, simvastatin should be temporarily withheld throughout the period of voriconazole therapy1. Simvastatin also inhibits CYP2C9, so combining it with voriconazole may raise voriconazole exposure as well; in that case, adjust the voriconazole dose and monitor closely and often for adverse reactions 2. In one report, a 44-year-old man who had been on voriconazole 200 mg twice daily over the long term for invasive aspergillosis developed cholestatic hepatitis within 2 weeks of starting simvastatin 10 mg once daily. Fifteen days after both voriconazole and simvastatin were stopped, the voriconazole concentration was still within the therapeutic range 3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin; inhibition of CYP2C9-mediated metabolism of voriconazole
How to manage this interaction
This combination is generally avoided. Your care team can handle it safely, so keep taking your medicines as prescribed until you speak with them.
- If you need voriconazole for a fungal infection, your team may temporarily pause simvastatin for the length of that treatment.
- If both must be used, your voriconazole dose may be adjusted and individualized, and your team may monitor you more closely for side effects.
- Report muscle pain, weakness, dark urine, unusual tiredness, or yellowing of the skin or eyes right away.
- Ask your pharmacist or prescriber before starting or stopping either drug.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A 44-year-old man who had been on voriconazole 200 mg twice daily over the long term for invasive aspergillosis experienced cholestatic hepatitis within 2 weeks of starting simvastatin 10 mg once daily. He was also receiving prednisone, trimethoprim/sulfamethoxazole, and insulin. After developing nausea, malaise, and severe jaundice, the patient stopped both voriconazole and simvastatin on his own, and liver function tests during this episode showed the following: AST 823 milliunits/mL; ALT 893 milliunits/mL; alkaline phosphatase 789 milliunits/mL, total bilirubin 15.4 mg/dL (263 micromol/L), and direct bilirubin 11.3 mg/dL (193 micromol/L). These values reached their highest point 13 days after simvastatin was discontinued and normalized after 1 month. The voriconazole concentration was in the therapeutic range at 4.1 mcg/mL measured 15 days after simvastatin was stopped. Both voriconazole levels and liver function stayed normal 7 months after voriconazole and the other drugs, apart from simvastatin, were resumed. The Naranjo score for this interaction was determined to be 9, signifying that simvastatin was definitely responsible for the cholestatic hepatitis. In addition, the patient had experienced a separate episode 16 months earlier that was probably linked to the start of lansoprazole (Naranjo score of 7). In that instance, voriconazole was stopped and later reintroduced once liver function tests had normalized, while lansoprazole was discontinued permanently 3.
b) In a drug interaction study, giving oral voriconazole (400 mg every 12 hours for 1 day, followed by 200 mg every 12 hours for 2.5 days) together with oral fluconazole (a CYP2C9 inhibitor) (400 mg on day 1, then 200 mg every 24 hours for 4 days) to 6 healthy male subjects produced an average rise in the Cmax and AUC(tau) of voriconazole of 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively. In a subsequent clinical study with 8 healthy male subjects, lowering the dose and/or frequency of voriconazole and fluconazole did not remove or lessen this effect 2
Common questions
Can I take Simvastatin and Voriconazole together?
Voriconazole and simvastatin can each raise the other's levels, increasing the risk of serious muscle damage and other side effects, so this combination is usually avoided. Do not change either medicine on your own; let your pharmacist or doctor manage it. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Voriconazole 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 Voriconazole interaction managed?
This combination is generally avoided. Your care team can handle it safely, so keep taking your medicines as prescribed until you speak with them. If you need voriconazole for a fungal infection, your team may temporarily pause simvastatin for the length of that treatment. If both must be used, your voriconazole dose may be adjusted and individualized, and your team may monitor you more closely fo… 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 Voriconazole 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: VFEND(R) oral tablets, oral suspension, intravenous injection, voriconazole oral tablets, oral suspension, intravenous injection. Roerig (per FDA), New York, NY, 2025. DailyMed
- Lopez JL & Tayek JA: Voriconazole-induced hepatitis via simvastatin-and lansoprazole-mediated drug interactions: a case report and review of the literature. Drug Metab Dispos 2016; 44(1):124-126. PubMed
Keep reading about Voriconazole
Keep reading about Simvastatin
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