Do Rhodiola Rosea, Eleuthero Root, Schisandra Berry, and Licorice Root interact with fluconazole (antifungal medication)?

Herb-Fluconazole Interactions

None of these four herbal supplements—Rhodiola Rosea, Eleuthero Root, Schisandra Berry, or Licorice Root—have clinically significant documented interactions with fluconazole based on available evidence.

Fluconazole's Primary Interaction Profile

Fluconazole's drug interactions occur through specific mechanisms that do not involve these herbs:

• Fluconazole primarily inhibits CYP2C9, CYP2C19, and moderately inhibits CYP3A4 enzymes 1
• The clinically significant interactions involve CYP450-metabolized drugs including warfarin, phenytoin, certain antiepileptics, and drugs metabolized via CYP2C9/CYP3A4 pathways 1, 2
• Higher doses of fluconazole (≥200-400 mg/day) pose greater risk for interactions due to more potent enzyme inhibition 2

Rhodiola Rosea Specific Considerations

While Rhodiola Rosea does have documented enzyme interactions, these do not overlap with fluconazole's mechanism:

• Rhodiola Rosea contains rhodiosin and rhodionin, which are potent CYP2D6 inhibitors (IC50 values of 0.761 μM and 0.420 μM respectively) 3
• These compounds act as non-competitive inhibitors of CYP2D6 with Ki values of 0.769 μM and 0.535 μM 3
• Critically, CYP2D6 is NOT involved in fluconazole's metabolism or interaction profile 1
• Rhodiola's traditional adaptogenic effects involve neurotransmitter modulation, HPA-axis regulation, and protein kinase interactions—none of which interact with fluconazole's antifungal mechanism 4

Other Herbs: Absence of Evidence

• Eleuthero Root, Schisandra Berry, and Licorice Root do not appear in any major fluconazole interaction databases or guidelines 1
• No published studies document CYP450 interactions between these herbs and azole antifungals in the reviewed literature

Clinical Management Algorithm

For patients taking fluconazole with any of these four herbs:

1. Continue both the herbal supplement and fluconazole without dose adjustment based on interaction concerns alone 1
2. Monitor for fluconazole's known interactions with other medications (warfarin, phenytoin, other CYP2C9/CYP3A4 substrates) 1, 2
3. If using high-dose fluconazole (≥400 mg/day), the increased risk applies to CYP450-metabolized drugs, not these herbs 1

Important Caveats

• Quality control issues with Rhodiola products are significant: approximately 20% of commercial products claiming to contain Rhodiola rosea do not contain the key marker compound rosavin, and 80% appear adulterated with other Rhodiola species 5
• The lack of standardization in herbal supplements means actual content may vary significantly from labeled claims 5
• While these herbs don't interact with fluconazole pharmacologically, always consider the underlying condition being treated and whether herbal supplementation is appropriate during antifungal therapy