The Public Herbarium

Ginger (Zingiber officinale) root

Understanding Pharmacokinetic and Pharmacodynamic Mechanisms

This comprehensive guide explores the molecular mechanisms underlying herb-drug interactions, providing evidence-based information for informed decision-making in clinical and personal contexts.

Table of Contents

  1. Introduction: The Complexity of Herb-Drug Interactions
  2. Pharmacokinetic Interactions: ADME Processes
  3. Pharmacodynamic Interactions: Target-Level Effects
  4. Critical High-Risk Herbs
  5. Medication-Specific Interaction Profiles
  6. Clinical Assessment and Risk Prediction
  7. New Zealand-Specific Considerations
  8. Evidence Levels and Research Limitations

Introduction: The Complexity of Herb-Drug Interaction

The Fundamental Challenge

Unlike pharmaceutical drugs (single purified compounds), herbal medicines contain hundreds to thousands of bioactive constituents. Each constituent may interact with the body differently, creating complex multi-target, multi-pathway effects. This pharmaceutical versus herbal comparison:

Pharmaceutical Drug:

Herbal Medicine:

Result: Herb-drug interaction potential is theoretically higher than drug-drug interactions, yet clinical data is far more limited.

Prevalence and Clinical Significance

Usage statistics:

Clinical consequences:

Pharmacokinetic Interactions: ADME Processes

Pharmacokinetics describes what the body does to a drug: Absorption, Distribution, Metabolism, Excretion.

Absorption-Level Interactions

Mechanism 1: Efflux Transporter Modulation (P-glycoprotein)

P-glycoprotein (P-gp, MDR1, ABCB1) is an ATP-dependent efflux pump in intestinal epithelium that pumps drugs back into the gut lumen, limiting absorption.

Key herbs affecting P-gp:

Clinical example: St John’s Wort reduces digoxin bioavailability by 25% through P-gp induction. Digoxin is a P-gp substrate with narrow therapeutic index (0.5-2.0 ng/mL therapeutic, >2.5 ng/mL toxic).

Mechanism 2: Uptake Transporter Modulation (OATPs)

Organic Anion Transporting Polypeptides (OATPs) facilitate drug absorption. Herbs containing polyphenols can inhibit OATPs.

Example: Grapefruit juice inhibits OATP1A2, reducing absorption of fexofenadine (antihistamine), atenolol (beta-blocker), and some statins.

Mechanism 3: Chelation and Complex Formation

Metal-containing herbs can chelate drugs, preventing absorption.

Examples:

Clinical significance: Separate doses by 2-4 hours.

Mechanism 4: pH-Dependent Absorption Changes

Gastric pH affects drug ionisation and solubility.

Example: Antacids containing calcium/magnesium elevate gastric pH, reducing absorption of pH-dependent drugs (ketoconazole, atazanavir).

Metabolism-Level Interactions: Cytochrome P450 System

The Critical System: Cytochrome P450 (CYP450) enzymes metabolise 70-80% of all drugs. Major isoforms:

Enzyme Induction: The St John’s Wort Example

Hyperforin (primary constituent in Hypericum perforatum) is a potent ligand for the pregnane X receptor (PXR). PXR activation:

  1. PXR (nuclear receptor) binds hyperforin
  2. PXR translocates to nucleus
  3. PXR binds DNA response elements
  4. Upregulates transcription of CYP3A4, CYP2C9, CYP2C19, P-gp
  5. Increased enzyme protein synthesis
  6. Enhanced drug metabolism → reduced drug levels

Timeline:

Clinical magnitude: CYP3A4 induction up to 3-5 fold → drug levels reduced 40-90%

Documented interactions:

Critical point: Daily hyperforin dose >1mg produces clinically significant induction. Standard St John’s Wort extracts contain 3-6mg hyperforin per daily dose.

Enzyme Inhibition: The Grapefruit Juice Example

Furanocoumarins (bergamottin, 6′,7′-dihydroxybergamottin) in grapefruit irreversibly inhibit intestinal CYP3A4:

  1. Furanocoumarin binds CYP3A4 active site
  2. Forms covalent adduct (mechanism-based inhibition)
  3. Enzyme permanently inactivated
  4. New enzyme synthesis required (24-72 hours)
  5. Reduced first-pass metabolism → increased drug bioavailability

Clinical magnitude: Single 200mL glass can inhibit intestinal CYP3A4 >50% for 24-72 hours.

Affected drugs:

Why grapefruit affects some statins but not others:

Other CYP Inhibiting Herbs:

Important consideration: In vitro inhibition doesn’t always translate to clinical significance. Achieving sufficient systemic concentrations is required.

Phase II Metabolism: Conjugation Reactions

Phase II enzymes (UGTs, SULTs, GSTs) add polar groups (glucuronide, sulfate, glutathione) to make drugs more water-soluble for excretion.

Herb effects on Phase II:

Excretion-Level Interactions

Renal Excretion:
Some herbs affect renal drug transporters (OAT1, OAT3, OCT2) or alter urine pH:

Example: Cranberry juice acidifies urine, potentially affecting excretion of pH-sensitive drugs (though clinical significance debated).

Biliary Excretion:
Herbs inducing hepatic transporters (MRP2, BCRP) can increase biliary drug excretion.

Pharmacodynamic Interactions: Target-Level Effects

Pharmacodynamic interactions occur when herbs and drugs affect the same physiological targets, pathways, or organ systems.

Additive/Synergistic Effects

Mechanism: Herb + Drug both activate (or inhibit) the same pathway → combined effect exceeds individual effects.

Example 1: GABAergic Sedation

Mechanism:

Result: Enhanced CNS depression → excessive sedation, impaired coordination, respiratory depression (in severe cases)

Clinical relevance: Moderate. Most reports are case-level. The combination isn’t absolutely contraindicated but requires caution.

Example 2: Antiplatelet/Anticoagulant Effects

Coagulation cascade: Complex system with multiple targets for intervention.

Drugs:

Herbs with antiplatelet/anticoagulant properties:

Result: Increased bleeding risk. Documented cases of spontaneous bleeding, increased INR, prolonged bleeding time.

Clinical significance: Varies by herb and dose:

Practical protocol:

Antagonistic Effects

Mechanism: Herb and drug have opposing actions → reduced therapeutic effect.

Example: Immunosuppressants + Immune Stimulants

Drugs: Cyclosporine, tacrolimus, azathioprine, methotrexate
Purpose: Suppress immune system (transplant rejection, autoimmune disease)

Herbs: Echinacea, astragalus, medicinal mushrooms (reishi, maitake)
Effect: Stimulate immune system (increase T-cell, NK cell, macrophage activity)

Concern: Immune stimulation could:

  1. Counteract immunosuppression → transplant rejection risk
  2. Exacerbate autoimmune conditions

Evidence level: Theoretical concern based on mechanisms. Limited clinical case reports. Conservative approach warranted given severity of potential outcomes (organ rejection).

Recommendation: Avoid immune-stimulating herbs when taking immunosuppressants.

Serotonin Syndrome Risk

Mechanism: Excessive serotonergic activity at 5-HT receptors in CNS and periphery.

Classic triad: Altered mental status, autonomic hyperactivity, neuromuscular abnormalities

Symptoms: Confusion, agitation, restlessness, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremor, hyperreflexia, hyperthermia. Severe: seizures, rhabdomyolysis, DIC, death.

Drugs increasing serotonin:

Herbs increasing serotonin:

Result: Combining St John’s Wort with SSRIs can produce serotonin syndrome. Multiple case reports documented.

Critical point: St John’s Wort creates a paradox:

  1. Pharmacodynamic interaction: Increases serotonin (risk of serotonin syndrome)
  2. Pharmacokinetic interaction: Induces CYP enzymes, reducing SSRI levels (treatment failure)

Recommendation: Never combine St John’s Wort with antidepressants.

Critical High-Risk Herbs

St John’s Wort (Hypericum perforatum): The Major Offender

St. John’s Wort (Hypericum perforatum) leaves and flowers
St. John’s Wort (Hypericum perforatum)

Active constituents: Hypericin, hyperforin, flavonoids

Interaction mechanisms:

  1. Enzyme induction: CYP3A4, CYP2C9, CYP2C19, CYP1A2, UGT1A1 (via PXR activation)
  2. Transporter induction: P-gp, MRP1 (multidrug resistance protein)
  3. Neurotransmitter re-uptake inhibition: Serotonin, norepinephrine, dopamine (via hyperforin)

Documented major interactions:

Drug ClassSpecific DrugEffectClinical Consequence
ImmunosuppressantsCyclosporine, tacrolimus↓ AUC 46-62%Transplant rejection (documented cases)
AntiretroviralsIndinavir, efavirenz↓ AUC 57-81%HIV treatment failure
Oral contraceptivesEthinyl estradiol↓ AUC 13-15%Breakthrough bleeding, unintended pregnancy
AnticoagulantsWarfarin↓ INRThrombosis risk
AnticancerImatinib, irinotecan↓ levels 30-40%Treatment failure
CardiacDigoxin, ivabradine↓ levels 25-33%Loss of therapeutic effect
AntidepressantsSSRIs, TCAsVariable (↓ levels + ↑ serotonin)Serotonin syndrome or treatment failure

Dose-dependency: Hyperforin content determines interaction severity:

Standard extract: LI-160 contains ~5mg hyperforin per daily dose (900mg total extract).

Time course:

Conservative recommendation: Avoid St John’s Wort if taking any prescription medication.

Grapefruit Juice (Citrus × paradisi): CYP3A4 Inhibitor

botanical drawing of Grapefruit (Citrus x paradisi) showing cut and uncut fruit
Grapefruit (Citrus x paradisi)

Active constituents: Furanocoumarins (bergamottin, 6′,7′-dihydroxybergamottin)

Mechanism: Irreversible intestinal (not hepatic) CYP3A4 inhibition → increased drug bioavailability for drugs with high first-pass metabolism.

Timeline: Single glass (200mL) inhibits intestinal CYP3A4 for 24-72 hours.

Major interactions:

DrugMechanismMagnitudeRisk
Simvastatin, lovastatinHigh first-pass CYP3A4 metabolism↑ AUC up to 16-foldRhabdomyolysis (documented deaths)
Felodipine, nifedipineHigh first-pass CYP3A4 metabolism↑ AUC 2-4 foldSevere hypotension, headache
CyclosporineCYP3A4 substrate↑ levels 50-200%Nephrotoxicity risk
BuspironeHigh first-pass metabolism↑ AUC 9-foldExcessive sedation

Important: Grapefruit affects drugs taken orally (not IV). Effect is intestinal, not systemic hepatic.

Alternative citrus:

Ginkgo biloba: Bleeding Risk

Gingko (Gingko biloba) leaves
Gingko (Gingko biloba)

Active constituents: Ginkgolides (terpenoids), bilobalide, flavonoids

Mechanisms:

  1. PAF antagonism: Ginkgolides are platelet-activating factor (PAF) receptor antagonists → reduced platelet aggregation
  2. Fibrinolytic activity: May enhance fibrinolysis
  3. Potential CYP2C19 inhibition: Unclear clinical significance

Documented bleeding events:

Evidence level: Multiple case reports but causality sometimes unclear (patients often on other anticoagulants).

Risk factors:

Recommendation:

Liquorice Root (Glycyrrhiza glabra): Pseudoaldosteronism

botanical drawing of Liquorice Root (Glycyrrhiza glabra)
Liquorice (Glycyrrhiza glabra)

Active constituent: Glycyrrhizin (glycyrrhizic acid)

Mechanism:

  1. Glycyrrhizin inhibits 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)
  2. This enzyme normally converts cortisol → cortisone (inactive) in kidney
  3. Inhibition → cortisol accumulates in kidney
  4. Cortisol activates mineralocorticoid receptors (normally respond to aldosterone)
  5. Result: Sodium retention, potassium loss, water retention, hypertension

Clinical syndrome: Pseudoaldosteronism

Drug interactions:

Dose-dependency:

Time course: Effects develop over days to weeks, resolve over days after stopping.

Recommendation: Avoid in hypertension, heart failure, kidney disease, concurrent diuretics. Monitor potassium if using therapeutically.

Medication-Specific Interaction Profiles

Warfarin: The Narrow Therapeutic Index Drug

Warfarin pharmacology:

Warfarin metabolism: Primarily CYP2C9 (90%), minor CYP3A4, CYP1A2.

Herb interactions affecting warfarin:

Pharmacokinetic:

  1. CYP2C9 induction: St John’s Wort → reduced warfarin levels → decreased INR → clotting risk
  2. CYP2C9 inhibition: Goldenseal (berberine) → increased warfarin levels → increased INR → bleeding risk (case reports limited)

Pharmacodynamic (additive anticoagulation):

  1. Anti-platelet herbs: Ginkgo, garlic, ginger, feverfew → additive bleeding risk
  2. Vitamin K-containing herbs: High-dose green tea, nettle, alfalfa → reduced warfarin effect (theoretical; requires very high doses)

Case report: Cranberry juice + warfarin:
Multiple case reports of increased INR, some resulting in fatal haemorrhage. Mechanism debated (possible CYP2C9 inhibition). FDA and UK MHRA issued warnings.

Clinical protocol for warfarin + herbs:

  1. Inform patient about ALL potential interactions
  2. Avoid herbs with known anti-platelet effects
  3. Monitor INR more frequently if any dietary change
  4. Maintain consistent intake (if consuming vitamin K-rich herbs, keep dose consistent)
  5. Stop herbal supplements 1-2 weeks before surgery

Statins: CYP3A4 Substrate Variability

Statin classes by metabolism:

High CYP3A4 metabolism (HIGH grapefruit interaction risk):

Low/no CYP3A4 metabolism (LOW grapefruit interaction risk):

Clinical significance: A patient on rosuvastatin can consume grapefruit safely. A patient on simvastatin should avoid grapefruit entirely.

Herb interactions with statins:

Antidepressants: The Serotonin Syndrome Risk

SSRIs (selective serotonin re-uptake inhibitors):

Herb interaction: St John’s Wort

Scenario 1: Adding St John’s Wort to stable SSRI

Scenario 2: Stopping SSRI and starting St John’s Wort

Documented serotonin syndrome cases: Multiple case reports of St John’s Wort + SSRI. Presentations range from mild (tremor, sweating) to severe (hyperthermia, seizures).

MAOIs (monoamine oxidase inhibitors):

Absolute contraindication: MAOIs + any serotonergic herb. Serotonin syndrome risk is extreme.

Other herbs affecting mood:

Clinical recommendation: Never combine antidepressants with St John’s Wort, SAMe, or 5-HTP.

Clinical Assessment and Risk Prediction

Evidence Hierarchy for Herb-Drug Interactions

Level 1: Established clinical interaction (highest confidence)

Level 2: Probable interaction

Level 3: Possible interaction (theoretical)

Level 4: Unlikely interaction

Critical point: Absence of clinical reports doesn’t mean absence of risk (publication bias, underreporting). Conservative approach warranted for narrow therapeutic index drugs.

In Vitro vs. In Vivo Translation Challenge

Why in vitro data doesn’t always predict clinical interactions:

  1. Concentration mismatch: In vitro studies often use herb concentrations (μM range) far exceeding achievable plasma concentrations (nM range)
  2. Bioavailability: Many herb constituents have poor oral bioavailability (extensive first-pass metabolism, poor absorption)

Example: Milk thistle (silymarin)

  1. Metabolite effects: Parent compound may not be the active form. Gut microbiome metabolism can activate or deactivate compounds.

Implication: In vitro screening identifies potential interactions but requires clinical validation.

Preparing for Your Healthcare Appointments

Information to Share with Your Doctor or Pharmacist:

When discussing your health, it’s helpful to provide your healthcare team with complete information about everything you’re taking. Consider preparing a list that includes:

All prescription medications (name, dose, and how often you take them)

Symptoms Worth Mentioning:

Let your healthcare provider know if you’ve experienced any of these, especially after starting a new herb or supplement:

Unexpected changes in how well your medications seem to be working

Working with Your Healthcare Team

Your Pharmacist Can Help:
New Zealand community pharmacists provide free medicines information services. They can:

Check for potential interactions between your medications and herbal products

Your Doctor Can Help:
Your doctor can review all your medications and supplements together to:

Adjust doses if needed
Arrange appropriate monitoring (blood tests, efficacy checks)
Refer you to specialists if required

Being Your Own Advocate:*
You know your body best. If something feels different after starting an herbal product alongside your medications, trust that instinct and speak up. Your healthcare team needs your observations to provide the best care.

New Zealand-Specific Considerations

Regulatory Framework

Medsafe (New Zealand Medicines and Medical Devices Safety Authority):

Natural Health Products Bill: Proposed regulatory framework (not yet enacted as of 2024). Would create mandatory product notification, GMP requirements, adverse event reporting.

Current reality: Variable product quality, limited regulatory oversight for complementary medicines.

Complementary Medicine Usage Patterns in NZ

Prevalence:

Common herbs used in NZ:

Rongoā Māori and Traditional Māori Medicine

Rongoā Māori as Complete Pharmacological System:

Rongoā Māori represents centuries of systematic empirical observation regarding New Zealand native plants, including sophisticated understanding of plant interactions, preparation methods that affect bioavailability, and integration with Western medications when patients use both systems.

Traditional Knowledge of Plant Interactions:

Māori traditional practitioners (tohunga rongoā) developed expertise in:

Native NZ Plants with Potential Interactions:

Kawakawa (Macropiper excelsum):

leaves of kawakawa (Piper excelsum) plant
Kawakawa (Piper excelsum)

Manuka (Leptospermum scoparium):

leaves and flowers of mānuka (Leptospermum scoparium)
Mānuka (Leptospermum scoparium)

Horopito (Pseudowintera colorata):

leaves of horopito (pseudowintera colorata)
Horopito (Pseudowintera colorata)

Professional Boundaries and Collaborative Care:

Healthcare providers working in New Zealand should:

Acknowledge Limitations:

Referral Pathways:

Respect Cultural Protocols:

Clinical Assessment Framework:
When patients use both rongoā Māori and Western medications:

  1. Ask specifically about rongoā Māori use (patients may not volunteer this information)
  2. Document rongoā use in medical records
  3. Consult with rongoā practitioner when possible (with patient consent)
  4. Apply conservative interaction assessment when clinical data unavailable
  5. Monitor drug levels, efficacy markers, adverse effects more closely
  6. Respect patient autonomy in choosing healing modalities

Research Gaps:

Significant research needed on:

Resources for Healthcare Providers:

Critical Principle for Deep Dive Understanding:

This guide provides Western pharmacological and toxicological perspectives on herb-drug interactions. Rongoā Māori represents an equally sophisticated knowledge system with its own evidence base, diagnostic frameworks, therapeutic protocols, and safety knowledge developed over centuries. The two systems are complementary but not interchangeable.

When working with Māori patients or patients using rongoā Māori:

Kawakawa Clinical Summary for Prescribers:

Given kawakawa’s increasing use and limited interaction data:

Resources Available in NZ

National Poisons Centre: 0800 764 766 (24/7)

Medsafe: www.medsafe.govt.nz

Pharmacist consultation:

Medical herbalists:

Evidence Levels and Research Limitations

The Evidence Gap

Current state:

Publication bias:

Challenges in Herb-Drug Interaction Research

Herb variability:

Example: Ginseng studies show conflicting results partly because “ginseng” refers to multiple species, parts, and preparations with different ginsenoside profiles.

Methodological issues:

  1. Dose: Clinical studies often use arbitrarily chosen doses, not reflecting real-world usage
  2. Duration: Short-term studies may miss delayed effects (enzyme induction takes days)
  3. Healthy volunteer bias: Interaction magnitude may differ in patient populations
  4. Outcome measures: Surrogate markers (drug levels) vs. clinical outcomes (bleeding events)

Interpreting Contradictory Evidence

When studies conflict:

Example: Milk thistle + cyclosporine

Factors explaining discrepancies:

  1. Herb preparation differences
  2. Patient genetics (CYP polymorphisms)
  3. Study power (small studies miss small effects)
  4. Timing of sampling

Conservative approach: For narrow therapeutic index drugs, err on side of caution even with conflicting evidence.

Future Directions

Needed research:

  1. Population pharmacokinetic studies (account for individual variability)
  2. Long-term safety monitoring (post-market surveillance)
  3. Genetic factors (CYP polymorphisms, transporter polymorphisms)
  4. Herb-herb-drug interactions (poly-herbal formulas)
  5. Food-herb-drug interactions
  6. Microbiome effects on herb and drug metabolism

Emerging tools:

Conclusion: Practical Integration

The Core Principles

  1. Communication is paramount: Patients must disclose all herb use; providers must ask non-judgmentally.
  2. Risk stratification matters: Not all herb-drug combinations are equally risky. Narrow therapeutic index drugs require intensive screening.
  3. Evidence-based but cautious: Use available evidence, but recognise its limitations. Conservative approach for high-stakes situations.
  4. Individual variability: Genetics, age, disease state, and concurrent medications all affect interaction risk.
  5. Timing matters (sometimes): Some interactions can be mitigated by separating administration times; others cannot.

Clinical Decision Framework

For each patient taking medications + herbs:

Step 1: Inventory

Step 2: Risk Assessment

Step 3: Mechanism Analysis

Step 4: Evidence Review

Step 5: Management Plan

Step 6: Follow-up

The Balanced Perspective

Herbs are not inherently dangerous, but they are not inherently safe either. They contain bioactive compounds that interact with the body—and therefore can interact with medications.

The goal is not herb avoidance, but informed, safe co-administration when appropriate.

Most interactions are manageable with:

Final thought: Herb-drug interactions are a clinical reality requiring evidence-based assessment, not fear-based prohibition. With proper knowledge and communication, the vast majority of patients can safely integrate herbal and pharmaceutical medicine.

References

Comprehensive bibliography of herb-drug interaction research:

Foundational Reviews and Textbooks:

Williamson, E. M., Driver, S., & Baxter, K. (Eds.). (2013). Stockley’s Herbal Medicines Interactions (2nd ed.). Pharmaceutical Press, London.
[Definitive professional reference—comprehensive interaction monographs]

Bone, K., & Mills, S. (2013). Principles and Practice of Phytotherapy: Modern Herbal Medicine (2nd ed.). Churchill Livingstone, Edinburgh.
[Comprehensive herbal pharmacology including drug interactions and clinical applications]

Izzo, A. A., & Ernst, E. (2009). Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs, 69(13), 1777-1798. https://doi.org/10.2165/11317010-000000000-00000
[Systematic review of clinical evidence for herb-drug interactions]

St John’s Wort—CYP450 Induction:

Zhou, S., Chan, E., Pan, S. Q., Huang, M., & Lee, E. J. (2004). Pharmacokinetic interactions of drugs with St John’s wort. Journal of Psychopharmacology, 18(2), 262-276. https://doi.org/10.1177/0269881104042632
[Comprehensive review of St John’s Wort CYP3A4 induction mechanisms and clinical consequences]

Henderson, L., Yue, Q. Y., Bergquist, C., Gerden, B., & Arlett, P. (2002). St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology, 54(4), 349-356. https://doi.org/10.1046/j.1365-2125.2002.01683.x
[Clinical case reports of St John’s Wort interactions with cyclosporine, oral contraceptives, others]

Wang, L. S., Zhou, G., Zhu, B., et al. (2004). St John’s wort induces both cytochrome P450 3A4-catalysed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clinical Pharmacology & Therapeutics, 75(3), 191-197. https://doi.org/10.1016/j.clpt.2003.11.011
[CYP3A4 and CYP2C19 induction by St John’s Wort]

Grapefruit—CYP3A4 Inhibition:

Bailey, D. G., Dresser, G., & Arnold, J. M. (2013). Grapefruit-medication interactions: forbidden fruit or avoidable consequences? Canadian Medical Association Journal, 185(4), 309-316. https://doi.org/10.1503/cmaj.120951
[Comprehensive review of grapefruit furanocoumarin mechanism-based CYP3A4 inhibition]

Bailey, D. G., Malcolm, J., Arnold, O., & Spence, J. D. (1998). Grapefruit juice-drug interactions. British Journal of Clinical Pharmacology, 46(2), 101-110. https://doi.org/10.1046/j.1365-2125.1998.00764.x
[Classic paper establishing grapefruit-drug interaction mechanisms]

Anticoagulant/Antiplatelet Interactions:

Ulbricht, C., Chao, W., Costa, D., et al. (2008). Clinical evidence of herb-drug interactions: a systematic review by the Natural Standard Research Collaboration. Current Drug Metabolism, 9(10), 1063-1120. https://doi.org/10.2174/138920008786485074
[Systematic review including anticoagulant herb interactions—ginger, garlic, ginkgo, feverfew]

Jiang, X., Williams, K. M., Liauw, W. S., et al. (2005). Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. British Journal of Clinical Pharmacology, 59(4), 425-432. https://doi.org/10.1111/j.1365-2125.2005.02322.x
[Clinical trial showing no significant warfarin interaction at tested doses]

P-glycoprotein Interactions:

Zhou, S., Lim, L. Y., & Chowbay, B. (2004). Herbal modulation of P-glycoprotein. Drug Metabolism Reviews, 36(1), 57-104. https://doi.org/10.1081/DMR-120028427
[Comprehensive review of P-glycoprotein herb interactions including St John’s Wort]

Pharmacodynamic Interactions:

Ang-Lee, M. K., Moss, J., & Yuan, C. S. (2001). Herbal medicines and perioperative care. JAMA, 286(2), 208-216. https://doi.org/10.1001/jama.286.2.208
[Clinical review of herb-anaesthesia interactions and perioperative herb management]

Evidence Quality and Research Methods:

Chen, X. W., Sneed, K. B., Pan, S. Y., et al. (2012). Herb-drug interactions and mechanistic and clinical considerations. Current Drug Metabolism, 13(5), 640-651. https://doi.org/10.2174/1389200211209050640
[Review of interaction mechanisms, research methodologies, evidence quality assessment]

Gurley, B. J., Gardner, S. F., Hubbard, M. A., et al. (2005). In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clinical Pharmacology & Therapeutics, 77(5), 415-426. https://doi.org/10.1016/j.clpt.2005.01.009
[Clinical phenotyping study of herb CYP effects]

Immunosuppressant Interactions:

Piscitelli, S. C., Formentini, E., Burstein, A. H., Alfaro, R., Jagannatha, S., & Falloon, J. (2002). Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy, 22(5), 551-556. https://doi.org/10.1592/phco.22.7.551.33666
[Clinical trial showing no indinavir interaction with milk thistle]

NZ-Specific and Rongoā Māori:

Brooker, S. G., Cambie, R. C., & Cooper, R. C. (1987). New Zealand Medicinal Plants. Heinemann, Auckland.
[Ethnobotanical documentation of rongoā Māori and European settler plant medicine—historical reference]

Riley, M. (1994). Māori Healing and Herbal: New Zealand Ethnobotanical Sourcebook. Viking Sevenseas NZ Ltd.
[Scholarly compilation of traditional Māori plant knowledge]

Pledger, M., Cumming, J., & Burnette, M. (2010). Health service use amongst users of complementary and alternative medicine. New Zealand Medical Journal, 123(1312), 26-35.
[NZ-specific data on complementary medicine usage patterns]

Clinical Guidelines:

Natural Medicines Database. TRC Healthcare. Available at: https://naturalmedicines.therapeuticresearch.com
[Subscription database—frequently updated herb-drug interaction monographs]

Micromedex. IBM Watson Health. Available at: http://www.micromedexsolutions.com
[Clinical interaction database used by healthcare providers]

New Zealand Formulary (NZF). Available at: https://nzformulary.org/
[NZ medication reference including some herb-drug interaction information]

Disclaimer: This guide is for educational and professional reference purposes only. It provides evidence-based information on herb-drug interactions but does not constitute medical advice, clinical guidelines, or standard of care. Individual patient management requires clinical judgment considering specific medications, doses, co-morbidities, pharmacogenomic factors, and patient-specific variables. Always consult with qualified healthcare professionals for personalised clinical recommendations.

This guide covers herb-drug interactions from Western pharmacological perspectives and is not a substitute for traditional indigenous knowledge systems including rongoā Māori. Rongoā Māori has its own frameworks for understanding plant interactions and safe integration with Western medications. For rongoā Māori approaches, refer to qualified rongoā practitioners (tohunga rongoā). Western healthcare providers should not assume rongoā Māori preparations have identical interaction profiles to Western herbal supplements.

The interaction information represents current scientific understanding based on available research, but significant evidence gaps exist. Individual responses to herb-drug combinations vary due to genetic polymorphisms (CYP450 variants, transporter polymorphisms), disease states, age, sex, and concurrent medications. Not all herb-drug combinations have been studied—absence of published interaction data does not indicate safety. For narrow therapeutic index drugs and critical medications (immunosuppressants, anticoagulants, chemotherapy, transplant drugs), apply conservative precautionary principle even when interaction data are limited.

Healthcare providers should maintain appropriate professional indemnity insurance, follow all Medsafe regulations, report serious adverse reactions to CARM (Centre for Adverse Reactions Monitoring), and work within their scope of practice. This guide does not establish standard of care and should not replace clinical guidelines, poison control consultation (National Poisons Centre: 0800 764 766), specialist advice, or medication package inserts. Children under 2 years should not receive herbal preparations without specialist paediatric guidance.

The authors and publisher assume no liability for adverse reactions, drug interactions, clinical decisions, misidentifications, or treatment complications arising from use of this information. Herb-drug interaction assessment requires integration of multiple data sources, clinical experience, and patient-specific factors. When in doubt, consult the National Poisons Centre (0800 764 766), pharmacist, or specialist.

The Public Herbarium is built on a foundation of scientific integrity, transparency, and care. Research sources are referenced throughout the site wherever possible. Content creation is assisted by AI tools and carefully reviewed for accuracy.