Fluconazole and Simvastatin interaction

Fluconazole and Simvastatin: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Simvastatin (ZOCOR) label · effective 2025-03-28

Major

ZOCOR is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] .

Contraindicationsby drug classView label on DailyMed
Major

Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) ( 4 , 7.1 )

Contraindicationsby drug classView label on DailyMed
Major

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis The concomitant use of strong CYP3A4 inhibitors with ZOCOR is contraindicated.

Warnings and precautionsby drug classView label on DailyMed
Major

Intervention: Concomitant use of strong CYP3A4 inhibitors with ZOCOR is contraindicated [see Contraindications (4) ] .

Drug interactionsby drug classView label on DailyMed
Major

If treatment with a CYP3A4 inhibitor is unavoidable, suspend ZOCOR during the course of strong CYP3A4 inhibitor treatment.

Drug interactionsby drug classView label on DailyMed

From the Fluconazole label · effective 2026-04-02

Moderate

HMG-CoA reductase inhibitors The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin (decreased hepatic metabolism of the statin).

Drug interactionsby drug classView label on DailyMed
Moderate

HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatinine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected.

Drug interactionsby drug classView label on DailyMed
Moderate

Dose reduction of statins may be needed.

Drug interactionsby drug classView label on DailyMed
Minor

Refer to the statin-specific prescribing information for details.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.