Atorvastatin and Itraconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 15, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Atorvastatin
Itraconazole
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.
What happens
Increased atorvastatin exposure and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Concomitant use of atorvastatin and itraconazole may cause elevated atorvastatin exposure and may increase the risk of skeletal muscle toxicity, including rhabdomyolysis. Evaluate the benefit/risk of coadministration and if used concomitantly do not exceed atorvastatin doses of 20 mg daily12. Monitor all patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug 2.
Why it happens (mechanism)
Inhibition of BCRP-mediated efflux transport of atorvastatin; inhibition of OATP1B1-mediated efflux transport of atorvastatin; inhibition of OATP1B3-mediated efflux transport of atorvastatin; inhibition of P-gp-mediated efflux transport of atorvastatin; inhibition of CYP3A4-mediated metabolism of atorvastatin
Literature reports
5 reports — tap to read
a) A 63-year-old female with familial hypercholesterolemia and previous myocardial infarction with bypass was treated with 80 mg of lovastatin and 3 g of niacin daily for 10 years without indications of toxicity. She was also taking timolol maleate and aspirin. Two weeks after itraconazole 100 mg twice daily was added for tinea corporis, the patient developed weakness, pain on motion, and tenderness to touch in her arms, back, and legs. This was later diagnosed as drug-induced rhabdomyolysis and hepatotoxicity. Eighteen days after termination of lovastatin, niacin, and itraconazole therapy, and initiation of ubiquinone 210 mg daily, the symptoms had disappeared 3.
b) A case was reported of rhabdomyolysis in a healthy 74-year-old male three weeks following the addition of itraconazole to a stable regimen including simvastatin 40 mg daily, lisinopril, and aspirin. The patient had abnormal serum concentrations of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. After all three drugs were discontinued and the patient started to ingest large quantities of water, his condition began to improve 4.
c) Itraconazole is a potent inhibitor of CYP3A4 enzymes, and atorvastatin is at least partially metabolized by CYP3A4. Atorvastatin has two active metabolites, 2-hydroxyatorvastatin and 4-hydroxyatorvastatin. To determine the effect of coadministration of itraconazole and atorvastatin, 10 healthy volunteers ingested itraconazole 200 mg or matching placebo on days 1 through 4. Atorvastatin 40 mg was coadministered on the morning of day 4, and another dose of itraconazole or placebo was given on day 5. The AUC and the half-life (t1/2) of atorvastatin increased by 3.3-fold and 2.9-fold, respectively, in the presence of itraconazole. The Cmax and Tmax of atorvastatin were not significantly changed. Cmax of 2-hydroxyatorvastatin plummeted from 9.8 nanogram/mL (17.1 nanomol/L) during the placebo phase to 1.7 nanogram/mL (3.0 nanomol/L) during the itraconazole phase. While these results are not as dramatic as the inhibition of simvastatin and lovastatin metabolism that is seen with itraconazole administration, the risk of myopathy can not be ruled out when atorvastatin and itraconazole are given concomitantly 5.
d) The coadministration of atorvastatin and itraconazole resulted in a significant increase of atorvastatin AUC of 150%, Cmax of 38%, and half-life of 30%. In the randomized, three-way crossover study involving 18 healthy volunteers, the effect of itraconazole on the pharmacokinetics of single-dose atorvastatin 20 mg, cerivastatin 0.8 mg, and pravastatin 40 mg was assessed. The increase in atorvastatin AUC was significantly greater than the increase in the AUC of cerivastatin and of pravastatin 6.
e) Coadministration of itraconazole 200 mg once daily with single dose of atorvastatin 40 mg for 4 days increased the atorvastatin AUC by 3.32-fold and Cmax by 1.2 fold compared with atorvastatin alone 12.
Common questions
Can I take Atorvastatin and Itraconazole together?
Increased atorvastatin exposure and an increased risk of myopathy or rhabdomyolysis Always confirm with your pharmacist or prescriber before making any change.
How serious is the Atorvastatin and Itraconazole interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Atorvastatin 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: ATORVALIQ(R) oral suspension, atorvastatin calcium oral suspension. CMP Pharma Inc (per FDA), Farmville, NC, 2023. DailyMed
- Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Viatris Specialty LLC (per FDA), Morgantown, WV, 2022. DailyMed
- Lees RS & Lees AM: Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole (letter). N Eng J Med 1995; 333:664-665.
- Horn M: Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals (letter). Arch Dermatol 1996; 132:1254. PubMed
- Kantola T, Kivisto KT, & Neuvonen PJ: Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998; 64:58-65. PubMed
- Mazzu A, Lasseter K, Shamblen E, et al: Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000; 68:391-400. DOI
Keep reading about Atorvastatin
Keep reading about Itraconazole
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