NutriStack
Fluconazole and Milk Thistle, a caution.
Silymarin from milk thistle inhibits CYP3A4, CYP2C9, UGT enzymes, and P-glycoprotein in vitro, and clinical pharmacokinetic studies have shown modest interactions with substrates such as losartan and nifedipine. Because fluconazole itself inhibits CYP3A4 and CYP2C9, layering milk thistle may amplify suppression of drug metabolism while doing little to mitigate fluconazole hepatotoxicity risk in any RCT-proven way.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Fluconazole and Milk Thistle
- Pair type
- Caution
- Evidence (highest tier)
- Emerging
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Emerging evidence
Caution
What is happening. Silymarin from milk thistle inhibits CYP3A4, CYP2C9, UGT enzymes, and P-glycoprotein in vitro, and clinical pharmacokinetic studies have shown modest interactions with substrates such as losartan and nifedipine. Because fluconazole itself inhibits CYP3A4 and CYP2C9, layering milk thistle may amplify suppression of drug metabolism while doing little to mitigate fluconazole hepatotoxicity risk in any RCT-proven way.
Mechanism. Silymarin inhibits CYP3A4 and CYP2C9 in vitro and is itself extensively metabolized. Stacking with fluconazole increases combined inhibition of these enzymes.
Recommendation. If you take milk thistle for liver support, discuss with your prescriber before continuing during fluconazole therapy. Do not rely on it to prevent fluconazole-induced liver injury; instead monitor liver enzymes as your prescriber advises.
Sources (2)
- Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 2009;121(2):185-93. PMID 19041708
- Hermann R, von Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med. 2012;78(13):1458-77. PMID 22855269
Stack Score
How this pair moves the number.
Effect on the composite score
If both Fluconazole and Milk Thistle are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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