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Table 1
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Evidence-based complementary medicine interactions8,11,13,14
This table shows complementary medicines with at least one 'major' interaction.
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Complementary medicine
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Interacting drug
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Possible outcome
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Severity and level of evidence*
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Proposed mechanisms/comment
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Black cohosh
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Cisplatin
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↓ cytotoxic effect
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Moderate, level D
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Animal data only
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Hepatotoxic drugs e.g. high-dose paracetamol, alcohol
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↑ risk of hepatotoxicity
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Moderate, level D
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Pharmacodynamic additive risk
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CYP2D6 substrates e.g. amitriptyline
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↑ substrate levels and drug effect
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Moderate, level B
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Moderate inhibitor of CYP2D6
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Calcium
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Quinolone antibiotics, sotalol, tetracycline, thyroxine
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↓ drug effect
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Moderate, level B
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Formation of insoluble salts and decreased absorption
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Celery seed
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Thyroxine
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↓ drug level and effect
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Moderate, level D
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Mechanism unknown but two case reports
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Chamomile (German)
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CYP1A2 and CYP3A4 substrates
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↑ drug levels
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Moderate, level D
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Theoretical
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CNS depressants
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↑ drug effect
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Moderate, level D
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Additive sedative effects
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Coenzyme Q10
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Chemotherapy (e.g. alkylating drugs)
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↓ cytotoxic effect
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Moderate, level B
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May counteract cytotoxic oxidative stress
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Antihypertensives
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↑ drug effect
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Moderate, level B
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Coenzyme Q10 has an antihypertensive effect
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Warfarin
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↓ drug effect
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Moderate, level D
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Coenzyme Q10 may have vitamin K-like effects
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Cranberry
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Warfarin
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↑ drug effect
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Moderate, level B
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Cranberry has variable effects on CYP3A4, CYP2C9, CYP1A2
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Echinacea
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CYP1A2 and CYP3A4 substrates e.g. clopidogrel (prodrug), olanzapine, warfarin
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↑ substrate levels
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Moderate, levels B and D respectively
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Inhibition of CYP1A2 and CYP3A4
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Evening primrose oil
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Antiplatelet drugs, warfarin
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↑ drug effect
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Major, level B
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Contains gamma-linolenic acid, probable anticoagulant
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Fenugreek
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Hypoglycaemic drugs
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↑ drug effect
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Moderate, level B
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Additive hypoglycaemic effect
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Antiplatelet drugs, warfarin
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↑ bleeding risk
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Moderate, level D
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Antiplatelet activity
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Fish oil
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Antihypertensive drugs
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Additive blood pressure lowering
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Moderate, level B
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Additive blood pressure-lowering effect found with some antihypertensives.
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Antiplatelet drugs, warfarin
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↑ bleeding risk
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Minor, level B
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Antiplatelet activity in high dose
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Contraceptives, oral
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↓ fish oil effects
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Moderate, level B
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May decrease triglyceride-lowering effects
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Garlic
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Contraceptives, oral
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↓ drug effect
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Moderate, level D
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Induces CYP3A4
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Saquinavir/non-nucleoside reverse transcriptase inhibitors
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↓ drug levels and effect
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Major, level B
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Induces CYP3A4
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Antiplatelet drugs, warfarin
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↑ bleeding risk
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Moderate, level D
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Theoretical antiplatelet activity
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Ginger
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Antiplatelet drugs, warfarin
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↑ bleeding risk
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Moderate, level B
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Antiplatelet activity
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Ginseng (Panax)
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Hypoglycaemic drugs
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↓ blood glucose
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Moderate, level B
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Hypoglycaemic effect. Conflicting evidence.
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Immunosuppressants e.g. azathioprine
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↓ drug effect
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Moderate level B
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Largely theoretical
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CYP2D6 substrates
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↑ substrate levels
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Moderate, level B
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CYP2D6 inhibitor but conflicting evidence
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Stimulants e.g. caffeine
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↑ drug effects
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Moderate, level B
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Additive pharmacodynamic effect
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Ginkgo
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Anticonvulsants
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↑ seizure risk
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Moderate, level D
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Large amounts of ginkgotoxin can cause neurotoxicity
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Warfarin, antiplatelet drugs
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↑ bleeding risk
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Major, level D
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Antiplatelet activity after several weeks
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CYP2C9 substrates e.g. glipizide, warfarin, celecoxib
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↑ substrate levels
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Moderate, level D
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Inhibits CYP2C9 activity
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CYP1A2, CYP2C19, CYP2D6 and CYP3A4 substrates
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↑ substrate levels
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Moderate, level B
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Potentially inhibits these enzymes
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Hypoglycaemic drugs
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↑ ↓ drug effect
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Moderate, level B
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Variably affects blood glucose concentrations
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Glucosamine
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Warfarin
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↑ bleeding risk
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Major, level D
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Several case reports of increased INR
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Hawthorn
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Calcium channel blockers, nitrates, phosphodiesterase inhibitors
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↑ drug effect
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Major, level D
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Additive vasodilator effects
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Digoxin, beta blockers
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↑ drug effect
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Major, level D
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Additive effects on heart rate and/or blood pressure. Hawthorn has cardiotonic effects.
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Kava
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CNS depressants
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↑ drug effect
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Major, level A
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Additive somnolence
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CYP1A2, CYP2D6, CYP2C9, CYP2E1, CYP3A4 substrates
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↑ substrate levels
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Moderate, level B
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Kava potentially inhibits these enzymes
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P-glycoprotein substrates
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↑ substrate levels
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Moderate, level D
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Lactobacillus acidophilus
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Immunosuppressants
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↑ risk of infection
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Moderate, level D
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Antibiotics
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↓ drug effect
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Moderate, level D
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Milk thistle
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CYP2C9 substrates e.g. amitriptyline, phenytoin, warfarin
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↑ drug effect
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Moderate, level B
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Inhibits CYP2C9, glucuronidase and organic anion transporting polypeptide 1B1. Conflicting evidence.
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Noni juice
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Warfarin
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↓ drug effect
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Moderate, level D
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Contains vitamin K
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Olive leaf
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Antihypertensive drugs
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↑ drug effect
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Moderate, level B
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Additive antihypertensive effects
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Hypoglycaemic drugs
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↑ drug effect
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Moderate, level B
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Additive hypoglycaemic effects
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Psyllium
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Carbamazepine, lithium
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↓ drug effect
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Moderate, level D
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Decreases gastrointestinal absorption of other drugs
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Hypoglycaemic drugs
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↑ drug effect
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Moderate, level B
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Additive hypoglycaemic effects
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Selenium
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Antiplatelet drugs, warfarin
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↑ drug effect
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Moderate, level D
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Selenium dose of 10 microgram/kg/day can increase bleeding time
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Statins, niacin
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↓ drug effect
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Moderate, level A
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Selenium plus beta carotene, vitamins C and E decreased the lipid-lowering effect
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Senna
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Digoxin, diuretics
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↑ drug effect
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Moderate, level D
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Additive potassium loss with long-term use or high doses of senna
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St John's wort
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Alprazolam
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↓ drug levels & effect
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Major, level B
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Increased clearance; half-life reduced by 50%
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Amitriptyline
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↑ drug effect
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Major, level B
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Increased risk of serotonin syndrome
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Antidepressants, tramadol
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↑ drug effect
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Major, level D
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Pethidine
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↑ drug effect
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Major, level D
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Triptans
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↑ drug effect
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Moderate, level D
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Clopidogrel
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↑ bleeding risk
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Moderate, level B
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Increased conversion to active metabolite
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CYP1A2, CYP2C9, CYP3A4 substrates e.g. imatinib, indinavir, tacrolimus, carbamazepine, phenytoin
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↓ drug levels & effect
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CYP3A4 =Major, level B CYP1A2, CYP2C9 = Moderate, level B
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Induces CYP enzymes
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Non-nucleoside reverse transcriptase inhibitors, protease inhibitors
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↓ drug levels & effect
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Major, level B
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Induces CYP3A4
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Oral contraceptives
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↓ drug levels
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Major, level B
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Risk of breakthrough bleeding/contraceptive failure
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P-glycoprotein substrates e.g. digoxin, fexofenadine, irinotecan
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↓ drug levels & effect
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Major, level B
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Induces intestinal P-glycoprotein
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Simvastatin
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↓ drug levels
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Moderate, level B
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Statin levels reduced by up to 28%
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Warfarin
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↓ drug effect
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Major, level B
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Induces CYP1A2, CYP2C9 and CYP3A4
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Valerian
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Alprazolam
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↑ drug levels
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Major, level B
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CYP3A4 inhibitor. Alprazolam increased by 19% in one study.
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CNS depressants
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↑ drug effect
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Major, level D
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Pharmacodynamic effect
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CYP3A4 substrates
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↑ substrate effect
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Moderate, level D
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Vitamin E
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Antiplatelet ,warfarin
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↑ bleeding risk
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Moderate, level B
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Antiplatelet activity
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Chemotherapy
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↓ drug effect
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Moderate, level D
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Possible antagonism of oxidative stress
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CYP INR CNS
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cytochrome P450 international normalised ratio central nervous system
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* Interaction rating adapted from Natural Medicines Comprehensive Database.11 The level of severity (major, moderate, minor) has been calculated using the evidence and probability of harm. This rating is linked with a generic recommendation for management.
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Major
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Strongly discourage patients from using this combination as a serious adverse outcome could occur. If used, patient should be monitored closely for potential adverse outcomes.
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Moderate
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Use cautiously or avoid combination as a significant adverse outcome could occur. If used, monitor for potentialadverse outcomes.
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Minor
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Be aware that there is a chance of an interaction. Advise patients of symptoms that may occur and an action planto follow.
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Level of evidence ratings: AHigh-quality randomised controlled trial or meta-analysis BNon-randomised clinical trial, literature review, clinical cohort or case-control study, historical control or epidemiologic study CConsensus or expert opinion DAnecdotal evidence; in vitro or animal study or theoretical based on pharmacology
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