NutriStack
Berberine and Fluconazole, a caution.
Berberine inhibits CYP3A4 (and to a lesser extent CYP2D6), the same family of enzymes that fluconazole also inhibits. Stacking two CYP3A4 inhibitors can raise the systemic levels of co-prescribed CYP3A4 substrates (statins, calcium channel blockers, benzodiazepines, certain immunosuppressants) and prolong fluconazole's own half-life, increasing the risk of dose-related adverse effects such as hepatotoxicity and QT prolongation.
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
- Berberine and Fluconazole
- 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. Berberine inhibits CYP3A4 (and to a lesser extent CYP2D6), the same family of enzymes that fluconazole also inhibits. Stacking two CYP3A4 inhibitors can raise the systemic levels of co-prescribed CYP3A4 substrates (statins, calcium channel blockers, benzodiazepines, certain immunosuppressants) and prolong fluconazole's own half-life, increasing the risk of dose-related adverse effects such as hepatotoxicity and QT prolongation.
Mechanism. Berberine is a moderate, partly quasi-irreversible inhibitor of CYP3A4 and CYP2D6 in human liver microsomes. Combined with fluconazole's own CYP3A4/2C9 inhibition, the result is additive impairment of oxidative drug metabolism.
Recommendation. Avoid starting berberine during a fluconazole course. If you take berberine for blood sugar, hold it while on fluconazole and resume a few days after the course ends. Tell your prescriber about every CYP3A4 substrate you take.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Berberine and Fluconazole 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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