Ivermectin and Herbal Interactions: Comprehensive Overview

    Ivermectin is a widely used antiparasitic agent with systemic activity, especially in the treatment of onchocerciasis, scabies, strongyloidiasis, and off-label use in viral illnesses. Its pharmacokinetics involve metabolism primarily via the CYP3A4 enzyme and is also a known substrate of P-glycoprotein (P-gp). These two pathways are the main targets for potential herbal interactions.

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Herb-Drug Interactions with Ivermectin

    Below is a breakdown of known or theoretically possible interactions between herbal medicines and ivermectin, based on mechanisms such as CYP3A4 modulation, P-gp inhibition, or toxicity potentiation:

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1. St John's Wort (Hypericum perforatum)

• Interaction Mechanism: Potent CYP3A4 and P-glycoprotein inducer.

• Effect: May significantly reduce ivermectin plasma concentrations, leading to subtherapeutic effect.

• Evidence: Well-documented for drug interactions in general due to induction effects.

• Management: Avoid concurrent use; may reduce efficacy of ivermectin.

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2. Grapefruit (Citrus paradisi)

• Interaction Mechanism: CYP3A4 inhibitor in the gut wall.

• Effect: May increase plasma ivermectin levels, potentially leading to CNS toxicity.

• Management: Avoid excessive grapefruit consumption within 24–48 hours of ivermectin dosing.

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3. Goldenseal (Hydrastis canadensis)

• Interaction Mechanism: CYP3A4 inhibitor.

• Effect: Potential increase in ivermectin bioavailability and CNS side effects.

• Management: Avoid concurrent use or monitor closely for adverse effects like dizziness or ataxia.

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4. Turmeric / Curcumin (Curcuma longa)

• Interaction Mechanism: Inhibits P-gp and CYP3A4 to some extent.

• Effect: Theoretically may increase ivermectin blood levels and enhance risk of neurotoxicity (e.g., sedation, confusion).

• Management: Use with caution, especially in elderly or those on multiple CNS-acting drugs.

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5. Kava (Piper methysticum)

• Interaction Mechanism: CNS depressant with weak CYP450 inhibition.

• Effect: May synergize CNS depressant effects of ivermectin, especially at high doses.

• Management: Avoid combination due to risk of excessive sedation or motor impairment.

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6. Licorice Root (Glycyrrhiza glabra)

• Interaction Mechanism: Can influence P-gp expression and affect cortisol metabolism.

• Effect: Potentially increased ivermectin CNS exposure; caution in hypertensive or hypokalemic individuals.

• Management: Monitor blood pressure and avoid chronic use in high doses with ivermectin.

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7. Ginkgo (Ginkgo biloba)

• Interaction Mechanism: May alter P-gp activity.

• Effect: Variable—could increase or decrease ivermectin concentration depending on preparation.

• Management: Use cautiously; avoid in seizure-prone individuals due to theoretical proconvulsant risk.

Safe or Possibly Beneficial Herbs (with Caution)

These herbs show no major metabolic interactions with ivermectin but still should be evaluated case-by-case:

• Andrographis paniculata – Antiviral and immune modulating, no strong CYP450 interaction noted.

• Elderberry (Sambucus nigra) – Immunostimulant, no P-gp or CYP3A4 inhibition known.

• Neem (Azadirachta indica) – Used for parasitic infections; minimal CYP interaction, but may potentiate ivermectin's antiparasitic effects.

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Mechanism Summary

• CYP3A4 modulation affects hepatic metabolism of ivermectin.

• P-gp inhibition or induction alters intestinal absorption and blood-brain barrier penetration of ivermectin.

• These can lead to toxicity (if inhibited) or therapeutic failure (if induced).

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Practical Recommendations

• Avoid combining ivermectin with:

  • St. John's Wort

  • Grapefruit juice

  • Kava

• Use caution with:

  • Turmeric, Goldenseal, Ginkgo, Licorice

• Time separation may help mitigate some interactions (e.g., spacing turmeric or grapefruit by 12–24 hrs), but this is not always reliable.