Herb - Drug Interactions

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HERB DRUG INTERACTIONS

• Dr. RODDA HARISH CHANDRA
• M.Pharm., Ph.D.
• ASSOCIATE PROFESSOR
• Head Department of Pharmacognosy and
  Phytochemistry
• Vaagdevi College of Pharmacy
• Hanamkonda, Warangal

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A Review of Herbal/Traditional Medicine

• POPULAR HERBS AND PLANTS

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Safety herbal medicines
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Facts about interactions

• Drug interactions - 4th 6th Cause of death
• At least 100 preoperative fatalities due to herb
  -drug/surgery interactions
• gt70 80 Herbs - Increase risk of bleeding
• gt30 40 Herbs possibility of causing hepatic
  failure
• Ephedra 54 deaths , 1600 Adverse events
• Aloe vera injection 4 Deaths
• Pennyroyal tea 2 infants Multiorgan Dysfunction
• Aristolochic Acid Death of 100 Belgian Women

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Interactions between Immunomodulatory herbs and
drugs
Herb Drug/ Class of drugs Mechanism of Herb Drug Interaction
Astragalus (ASTRAGALUS MEMBRANACEUS) Azathioprine Cyclosporine Methotrexate Antagonism
Borage (BORAGO OFFICINALIS) Hypnotics Potentiation
Echinacea (ECHINACEA PURPUREA) Acetaminophen Potentiation of Hepatotoxicity
Echinacea (ECHINACEA PURPUREA) Corticosteroids Cyclosporine Antagonism
Echinacea (ECHINACEA PURPUREA) Fexofenadine Itraconazole Lovastatin Inhibition of CYP3A4 leading to increase in drug concentration
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Interactions between herbs used for
cardiovascular disorders and drugs

• GARLIC
• Antihyperglycemic effect when it was co
  administered with chlorpropamide
• Decreases bioavailabilty of saquinavir
  induction of P- glycoprotein (P gP)
• GUM GUGGULU (COMMIPHORA MUKUL)
• It may produce an additive effect with
  anticoagulants
• It is believed to act as a thyroid stimulating
  agent avoid the co administration with
  thyroid drugs
• Guggul - predicted to decrease the absorption of
  beta blockers and calcium-channel blockers

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Interactions between herbs used for central
nervous system disorders and drugs
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CNS Stimulants
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CNS Depressants
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Herb Drug/Class of drugs Mechanism of Herb Drug Interaction
Areca (ARECA CATECHU) Procyclidine Antagonistic effect on drug leading to extra pyramidal syndrome
Capsicum (CAPSICUM FRUTESCENCE, CAPSICUM ANNUM) ACE inhibitors Increased risk of developing cough
Capsicum (CAPSICUM FRUTESCENCE, CAPSICUM ANNUM) Theophylline Enhanced bioavailability can lead to theophylline toxicity
Chasteberry (VITEX AGNUS CASTUS) Dopamine receptor antagonists Interferes with the activity of drugs
Feverfew (TANACETUM PARTHENIUM) Antimigraine Drugs Potentiation of drug effect
Feverfew (TANACETUM PARTHENIUM) Warfarin Additive antiplatelet effect due to inhibition of platelet aggregation
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Ginkgo (GINKGO BILOBA) Aspirin Clopidogrel Ticlopidine Increased risk of bleeding
Ginkgo (GINKGO BILOBA) Digoxin Increased bioavailability of digoxin
Ginkgo (GINKGO BILOBA) Diltiazem Increased bioavailability of drug
Ginkgo (GINKGO BILOBA) Ibuprofen Intracerebral mass bleeding due to inhibition of platelet aggregation
Ginkgo (GINKGO BILOBA) Nicardipine Induction of CYP 3A4 leading to decreased activity of drug
Ginkgo (GINKGO BILOBA) Omeprazole Induction of CYP2C9
Ginkgo (GINKGO BILOBA) Thiazide diuretics Increase in blood pressure
Ginkgo (GINKGO BILOBA) Trazodone Induction of CYP3A4
Ginkgo (GINKGO BILOBA) Warfarin Increased risk of bleeding
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Green tea (CAMELIA SINENSIS) Warfarin Increased risk of bleeding Increased risk of bleeding
Guarana(PAULLINIA CUPANA) Caffeine/ Respiratory stimulants Potentiation of activity Potentiation of activity
Kava (PIPER METHYSTICUM) Alprazolam Potentiation of sedation Potentiation of sedation
Kava (PIPER METHYSTICUM) Anesthetics Prolongation of anesthesia Prolongation of anesthesia
Kava (PIPER METHYSTICUM) Levodopa Antagonism Antagonism
Lemon balm (MELISSA OFFICINALIS) CNS depressants Additive CNS effects
Lemon balm (MELISSA OFFICINALIS) Thyroid hormones Inhibits binding of thyroid hormones to TSH receptors
Sage (SALVIA MITILIORRHIZA) Warfarin Increased risk of bleeding Increased risk of bleeding
Sage (SALVIA MITILIORRHIZA) Diazepam Induction of enzymes Induction of enzymes
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St.Johns wort
St.Johns wort
St.Johns wort
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Failure of contraception
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St.Johns wort (HYPERICUM PERFORATUM) Methadone Induction of CYP 3A4, 2C8 and CYP 2D6 leading to decrease in drug concentration
St.Johns wort (HYPERICUM PERFORATUM) Oral Contraceptives Failure of contraception due to induction of CYP3A4
St.Johns wort (HYPERICUM PERFORATUM) Piroxicam Photosensitizing drugs Increased risk of phototoxicity
St.Johns wort (HYPERICUM PERFORATUM) Quazepam Induction of CYP 3A4
St.Johns wort (HYPERICUM PERFORATUM) Sertraline Inhibits vesicular uptake of monoamines leading to serotonergic syndrome
St.Johns wort (HYPERICUM PERFORATUM) Simvastatin Induction of CYP3A4
St.Johns wort (HYPERICUM PERFORATUM) Tacrolimus Immuno graft rejection due to induction of CYP enzymes
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St.Johns wort (HYPERICUM PERFORATUM) Amitryptyline Induction of CYP3A4
St.Johns wort (HYPERICUM PERFORATUM) Cyclosporine Induction of CYP3A4 and P - gP leading to decrease in drug concentration and rejection of transplanted organ
St.Johns wort (HYPERICUM PERFORATUM) Digoxin Induction of P gP
St.Johns wort (HYPERICUM PERFORATUM) Fexofenadine Inhibition of P - gP
St.Johns wort (HYPERICUM PERFORATUM) Indinavir, Saquinavir Induction of CYP 3A4
St.Johns wort (HYPERICUM PERFORATUM) Loperamide Acute delirium mechanism unknown
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St.Johns wort (HYPERICUM PERFORATUM) Theophylline Induction of CYP1A2 leading to decreased concentration of drug
St.Johns wort (HYPERICUM PERFORATUM) Thyroid stimulating hormone Elevation of TSH levels
St.Johns wort (HYPERICUM PERFORATUM) Venlaxafine Serotonin syndrome Inhibition of serotonin reuptake and MAO Inhibition
St.Johns wort (HYPERICUM PERFORATUM) Verapamil Induction of CYP3A4, leading to decreased bioavailabilty
St.Johns wort (HYPERICUM PERFORATUM) Warfarin Induction of CYP3A4 and CYP2C9
Valerian (VALERIANA OFFICINALIS) Barbiturates Additive sedation
Yohimbine (PAUSINYSTALIA YOHIMBE) Clomipramine Increased blood pressure
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HERB DRUG INTERACTIONS DUE TO ALTERATION OF
CYTOCHROME P450 ENZYMES IN IN - VITRO MODELS
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Herb CYP Enzyme In vitro model
ANGELICA DAHURICA Inhibits CYP3A4 Inhibtis multidrug-resistant and methicillin-resistant strains of Staphylococcus aureus Liver microsomes
Devils Claw (HARPOGOPHYTUM PROCUMBENS) CYP2C8,CYP2C19, CYP3A4,CYP1A2, CYP2D6 Human kidney (HK-2) proximal tubule cell line
Echinacea (ECHINACEA PURPUREA) Inhibits CYP2C19, CYP2D6 Baculovirus expressed CYP enzymes
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Herb CYP Enzyme In vitro model
Garlic ( ALLIUM SATIVUM) Inhibits CYP2C9, CYP2C19, Inhibits CYP3A4 Inhibits CYP2E1 Human liver microsomes CYP 3A4 Substrates (7-Benzyloxyresorufin and 7-ethoxy-3 cyanocoumarin Rat iver microsomal cytochrome P450 fractions
Ginseng (PANAX GINSENG) Inhibits CYP1A2, CYP2B1, CYP2C9,CYP3A4 c-DNA-expressed cytochrome P450 enzyme catalytic activity
Goldenseal (HYDRASTIS CANADENSIS) CYP2D6, CYP3A4, CYP3A5 Caco 2 cell lines
Kava (PIPER METHYSTICUM) Inhibits CYP3A4, CYP1A2, CYP2C9, CYP2C19,CYP2D6 Human liver microsomes
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Herb CYP Enzyme In vitro model
Liquorice (GLYCYRRHIZA GLABRA) CYP3A4, CYP2C9 Human recombinant enzymes
Schizandra (SCHIZANDRA CHINENSIS) Inhibits CYP3A4 Liver microsomes
Silymarin (SILYBUM MARIANUM) Inhibits CYP3A4 CYP2C9 Human hepatocytes/ Human recombinant enzymes
Valerian (VALERIANA OFFICINALIS) Inhibits CYP3A4, CYP2C9 and CYP2C19 Cytochrome P450 CYP3A4 supersomes
Vinca (CATHARANTHUS ROSEUS) Inhibits CYP2D6 Human Liver Microsomes
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Interactions between herbs and drugs acting on
blood
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Herbs used by women

• Studies reveal Chamomile administration with
  opioids leads to increased CNS depression
• Dandelion (Taraxacum officinalis) if co
  administered with diuretic drugs can potentiate
  the diuretic effect
• Dong quai (Angelica dahurica) is reported to
  increase the Cmax and AUC of diazepam along with
  an increase in t1/2 of tolbutamide

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Weight loss Herbs X Drugs

• Ephedra
• Germander
• Hoodia gordonii

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PREDICTED HERB DRUG INTERACTIONS

• Bearberry (ARCTOSTAPHYLOUS UVA URSI)
• Estrogens/Oral contraceptives - May ? response
  to estrogen
• Lipid lowering drugs Possibility of additive
  effect
• Black Cohosh (CIMIFUGA RACEMOSA)
• Lipid lowering drugs - Possibility of additive
  effect
• Bladderwrack (FUCUS VESICULOSUS)
• Hypoglycemic drugs - Possibility of additive
  effect
• Blue Cohosh (CAULOPHYLLUM THALICTROIDES)
• Nitrates and Calcium channel blockers - May
  antagonize the hypertensive effect

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• Chamomile (MATRICARIA RECUTITA) - Iron - May
  inhibit iron absorption
• Chaste tree berry (VITEX AGNUS CASTUS) -
  Dopamine receptor antagonists (Phenothiazines) -
  May antagonize drug effect
• Devils claw (HARPAGOPHYTUM PROCUMBENS) -
  Antiarrhythmic drugs - May interfere with drug
  activity
• Echinacea (ECHINACEA PURPUREA) Corticosteroids/
  Cyclosporine May nullify the effect of drug

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• Guarana (PAULLINIA CUPANA)
• Adenosine - May lower response
• Benzodiazepine - Drugs may be less effective
• Hawthorn (CRATAEGUS LAEVIGATA, C. MONOGYNA, C.
  PINNATIFIDA, C.OXYCANTHA)
• Anesthetics - May enhance hypotension

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Herbs to be avoided prior to surgery

• Ephedrine 24 hrs
• Garlic/Garlic products 7 days
• Ginkgo 36 hrs
• Ginseng 7 days
• Kava 24 hrs
• St.Johns Wort 5 days
• Valerian weeks before surgery by tapering

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Miscellaneous herb drug Interactions

• Artemesinin
• Artemisinin, - decreases omeprazole
  bioavailability - induction of CYP2C19 activity
  (Svensson et al., 1998).
• Foeniculum vulgare
• Decrease the rate of absorption of ciprofloxacin
  - chelation of the drug (Zhu et al., 1999).

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• Liquorice
• Antihypertensive drugs - synergistic effect
  (Cumming et al., 2003)
• Hydrocortisone - pseudoaldosteronism (Beate et
  al., 1999)
• Oral contraceptives - hypertension, edema and
  hyperkalemia (Gerty et al., 1997).

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• Silymarin
• potentiate the effects of antiarrhythmic drugs
  (Gyonos et al., 2001)
• Increases - pharmacological activity of cisplatin
  (Scambia et al., 1996),
• Decreases the blood concentrations of
• indinavir (Piscitelli et al., 2002)
• losartan (Han et al., 2009) and
• metronidazole (Chon et al., 2005)

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THE OTHER SIDE OF HERB DRUG INTERACTIONS

• Aromatic herbs such as ginger can be used to
  prevent drug-induced nausea
• Milk thistle can be used to prevent the liver
  toxicity associated with drugs
• Capsaicin reduces gastric mucosal damage induced
  by aspirin
• Combination of aqueous extract of Chinese
  medicinal plant Tripterygium wilfordi and
  cyclosporine significantly increases the heart
  and kidney allograft survival compared to
  cyclosporine alone

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• Garlic prevents the formation of toxic
  metabolites of paracetamol
• Co administration of Ginkgo with
  antipsychotics (haloperidol) in chronic
  schizophrenic patients reduces extra pyramidal
  side effects associated with haloperidol
• Centella asiatica can also be used as an
  adjunctive medication for patients with epilepsy
  due to its additive anticonvulsant activity
• Momordica charantia is reported to augment the
  hypoglycemic effect of rosiglitazone
• used to reduce the dose of rosiglitazone to
  achieve enhance therapeutic effect with minimum
  side effects

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• Piperine - bioavailability enhancer
• Enhances the bioavailability of propranolol
• Ginseng is considered to be potent adjuvant -
  delivery of vaccines
• proven to induce higher or similar antibody
  titres than vaccines adjuvanted with aluminium
  hydroxide

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• Rosemary (Rosmarinus officinalis) has
  chemopreventive effect as it increases efflux and
  intracellular accumulation of doxorubicin and
  vinblastine
• Silybinin enhances the antitumour activity of
  cisplatin

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Areas of research on Herb Drug Interactions

• Antiplatelet Drugs Herbs
• Antiviral Drugs Herbs
• Anticancer Drugs Herbs
• Antidiabetic Drugs Herbs
• Herbal teas Drugs
• Herbal health drinks Drugs

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