Simvastatin and Itraconazole: 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
Itraconazole
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. Itraconazole (Sporanox) is a strong antifungal that blocks a liver enzyme called CYP3A4. That enzyme is exactly what your body uses to break down simvastatin (Zocor). So when you take both, simvastatin builds up in your blood, way higher than normal (studies showed about a 13-fold increase).
Too much simvastatin can cause serious muscle problems, including a dangerous condition called rhabdomyolysis, where muscle breaks down and can hurt your kidneys. Watch for unexplained muscle pain, weakness, or dark urine. Please don't change anything on your own, but do talk with your pharmacist or doctor soon. This is very manageable once your care team knows.
Contraindicated combination. Simvastatin is a CYP3A4 substrate; itraconazole is a potent CYP3A4 inhibitor. Inhibition markedly reduces simvastatin clearance, increasing systemic exposure and myotoxicity risk.
- Magnitude: Cmax of simvastatin and its active acid metabolite increased ~13.1-fold with itraconazole.
- Effect: increased risk of myopathy and rhabdomyolysis (case report of rhabdomyolysis within 3 weeks).
- Evidence: established.
- Management: avoid concurrent use, including up to 2 weeks after itraconazole discontinuation. If antifungal therapy is required, temporarily suspend simvastatin for the duration of itraconazole treatment.
Monitor for muscle pain/weakness and CK/renal function if inadvertent overlap occurs.
What happens
Increased simvastatin exposure and an increased risk of myopathy and rhabdomyolysis
Interaction Deep Dive
Taking itraconazole together with simvastatin, or using it within the 2 weeks following itraconazole discontinuation, is contraindicated because this combination can raise simvastatin exposure and heighten the risk of serious adverse events such as rhabdomyolysis23. When the two agents must be given together, simvastatin should be temporarily halted for the length of itraconazole therapy. The pharmacologic basis is that simvastatin is metabolized by CYP3A4, whereas itraconazole strongly inhibits that same enzyme. Coadministration with itraconazole produced a 13.1-fold rise in the Cmax of both simvastatin and its active metabolite, simvastatin acid1. A case report described a patient on a stable simvastatin-containing regimen who developed rhabdomyolysis within 3 weeks after itraconazole was introduced4.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated simvastatin metabolism by itraconazole
How to manage this interaction
This pairing is best avoided. Because itraconazole can drive simvastatin levels very high, guidance is to not use them at the same time, and to keep them separated for up to 2 weeks after itraconazole is stopped.
- Keep taking your medicines as prescribed for now, but contact your pharmacist or prescriber promptly so they can plan.
- Your care team will typically temporarily hold simvastatin while you are on itraconazole, or choose another option.
- Report any muscle pain, tenderness, weakness, or dark-colored urine right away.
Once your team knows you take both, this is straightforward to manage.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) When itraconazole 200 mg once daily for 4 days was given together with a single 80-mg dose of simvastatin, the Cmax of both simvastatin and simvastatin acid (the active metabolite) rose 13.1-fold 1.
b) One case report described a 74-year-old man who was prescribed itraconazole 200 mg for a toenail fungal infection. He had been receiving simvastatin 40 mg daily, lisinopril, and aspirin for hypertension and type IIa hyperlipidemia. Following 3 weeks of treatment, he developed pain in the lower and upper limbs and neck, muscle tenderness, and brown urine. Laboratory testing on evaluation revealed abnormal results including creatine kinase (22.8 million units/L), aldolase (423,600 units/L), lactate dehydrogenase (927,000 units/L), aspartate aminotransferase (990,000 units/L), and alanine aminotransferase (446,000 units/L). He was diagnosed with rhabdomyolysis 4.
c) In a double-blind, randomized, crossover study, 12 healthy volunteers received either 200 mg itraconazole or placebo by mouth once daily for 4 days. On the fourth day, each participant was given a single 40-mg dose of lovastatin. Plasma levels of lovastatin, lovastatin acid, itraconazole, hydroxyitraconazole, and creatine kinase were measured over a period of up to 24 hours. Itraconazole raised the Cmax and AUC of lovastatin by more than 20-fold. It also raised the mean Cmax and AUC of the active metabolite lovastatin acid by 13-fold (0 to 24) and 20-fold, respectively. During the itraconazole phase and within 24 hours after lovastatin dosing, plasma creatine kinase rose 10-fold in one participant 5.
d) A randomized, double-blind, crossover study conducted in 2 phases was used to assess how itraconazole administration affects the pharmacokinetics of simvastatin and pravastatin. Ten healthy volunteers took itraconazole 200 mg daily or placebo for 4 days and also received a single dose of simvastatin 40 mg or pravastatin on the morning of the fourth day. Itraconazole raised the Cmax and AUC of unchanged simvastatin by at least 10-fold. Itraconazole also increased the Cmax of simvastatin acid from 13 nanograms (ng)/mL to 217 ng/mL and the AUC of simvastatin acid from 52.5 ng/mL to 977 ng/mL. The pharmacokinetics of pravastatin were not significantly changed by itraconazole, indicating that CYP3A4 enzymes contribute substantially to the metabolism of simvastatin but not pravastatin 6.
Common questions
Can I take Simvastatin and Itraconazole together?
Itraconazole sharply raises simvastatin levels and the risk of serious muscle damage, so the two should not be used together. Contact your pharmacist or doctor before your next dose so they can adjust your plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Itraconazole 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 Itraconazole interaction managed?
This pairing is best avoided. Because itraconazole can drive simvastatin levels very high, guidance is to not use them at the same time, and to keep them separated for up to 2 weeks after itraconazole is stopped. Keep taking your medicines as prescribed for now, but contact your pharmacist or prescriber promptly so they can plan. Your care team will typically temporarily hold simvastatin while you… 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 Itraconazole 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 (6)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Product Information: SPORANOX(R) oral capsules, itraconazole oral capsules. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
- Product Information: SPORANOX(R) oral solution, itraconazole oral solution. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
- Horn M: Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals. Arch Dermatol 1996; 132:1254. PubMed
- Neuvonen PJ & Jalava KM: Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996; 60:54-61. PubMed
- Neuvonen PJ, Kantola T, & Kivisto KT: Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998; 63:332-341. PubMed
Keep reading about Itraconazole
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist