10TH EDITION MARCH 2019
10TH EDITION MARCH 2019
Pg.2 Pg.3
NOTE: Blackmores has made every effort to ensure that the information in this guide is accurate and up-to-date but this does not guarantee that every possible interaction is included. Blackmores cannot be held responsible for any future changes that may occur in this constantly expanding area of study. The information in this guide is for informational purposes only and is not intended as a substitute for professional advice. Healthcare professionals who consult this document are cautioned that any medical or product-related decision is the sole responsibility of the healthcare professional. Blackmores advises that healthcare professionals should ask patients about both complementary medicine and drug use. Should an adverse event occur, send a ‘blue card’ adverse reaction reporting form to the TGA or go online to www.tga.gov. au/reporting-problems-0#medicine and inform the manufacturer of both the complementary medicine and the medication.
About this guide
This Complementary Medicine Interactions Guide is a concise and comprehensive reference resource designed to give healthcare professionals clinically relevant, evidence-based information about potential interactions between complementary medicines and pharmaceutical medications.
For the most part, complementary medicines can be used alongside conventional pharmaceutical drug treatments. However, some complementary medicines may interact with certain medications to reduce, or sometimes increase, their effect, or to cause potential adverse effects. In addition, some complementary medicines may have the ability to reduce drug side effects and also some common medications may adversely affect the nutritional status of individuals over time. Severity, likelihood and level of evidence is provided in this guide to assist in assessment of risk and to support appropriate recommendations.
Blackmores Institute is grateful to the University of Sydney School of Pharmacy for their role in reviewing the evidence and contribution to this updated guide.
Blackmores Institute
Blackmores Institute is the academic and professional arm of Blackmores Limited, established to support and drive an evidence-based approach to natural medicine. With a focus on research and education, our primary purpose is to improve the quality use of natural medicine by contributing to the evidence base and translating this knowledge into practical healthcare education and clinical resources. We partner with leading academic institutions and research bodies to investigate novel ingredient development, discovery and innovation, and legacy projects. We also proudly support the development of future leaders through academic and practice grants. Our team includes researchers, academics, healthcare professionals, educators and communicators, working together to evaluate natural health literacy through
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10th Edition
K E YTheoretical
in vitro and/or animal evidence with unclear implications, However, it cannot exclude the
possibility of occurring in humans
Possible Evidence suggests this
interaction might occur in some patients
Likely Evidence suggests this interaction is likely to occur in most patients
Variable Nature of interaction
may vary
Low Healthcare professional intervention unlikely to
be required
Moderate Intervention by a
healthcare professional may be required
High Clinical evaluation by a
healthcare professional is recommended to assess
the degree of intervention required
A - At least 1 good quality randomised,
placebo-controlled trial or meta-analysis or systematic review
B - Lower quality human study
D - in vitro or animal studies
C - Case reports
Severity of
interaction
Likelihood of
interaction
Level of evidence
• Research funding• Education programs• Healthcare professional advisory services• Research symposia and conferences• Interactions guidelines• News and research updates• Systematic reviews• Academic projects
Printed on FSC paper
Unlikely Evidence suggests this
interaction can occur, but is not likely to occur in
many patients
Pg.4 Pg.5
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
AndrographisAndrographis
paniculata
Alpha-lipoic acid
AstragalusAstragalus
membranaceus
Anticoagulants and antiplatelet agents
May increase drug effect
May increase or decrease drug effect
May have additive effect to drug
Antioxidants may decrease the activity of chemotherapy or make
chemotherapy more effective
Level DAnimal and in vitro study
Level DAnimal study
Level AClinical trials
Theoretical
Theoretical
Variable
Moderate
Moderate
Moderate
Use with caution under supervision of a healthcare professional and monitor
Avoid concomitant use
No significant adverse effect or reduction in the effectiveness of chemotherapy
identified in studies. Supplementation may reduce side effects
Herb effect on drug (May decrease drug
side effect)
Chemotherapeutic agents (Cisplatin and vinorelbine)
Chemotherapeutic agents
No direct interaction
Acidophilus See ‘Probiotics’
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
May increase drug effect
May have additive hypoglycaemic effect
Level AClinical trials suggest ALA may affect glucose-lowering effect of
these medications
Use with caution under supervision of a healthcare professional and monitor
Hypoglycaemic drugs
May decrease drug effect
Co-administration of levothyroxine with ALA
may decrease conversion to active T3 form
Level DPreliminary animal studies Theoretical
Use with caution under supervision of a healthcare professional and monitor
Levothyroxine
CYP450 enzyme substrates (CYP1A1, CYP1A2 and
CYP2B)
May increase or decrease drug effect
May increase or decrease blood levels of substrates
via inhibition of these enzyme activities
Level DAnimal and in vitro study Theoretical
Variable (depending
on drug and disease
state)
Use with caution under supervision of a healthcare professional and monitor
Immunosuppressants May decrease drug effect
May have opposing effect to drug
Level CCase report
Avoid concomitant use
AshwagandhaWithania somnifera
Benzodiazepines (Diazepam)
May increase drug effect
May have additive effect to drug due to GABAergic
activity
Level DAnimal study (Co-administration of extract of withania somnifera (50 mg/kg) and diazepam (0.5 mg/kg) increased the seizure threshold)
Theoretical Use with caution under supervision of a healthcare professional and monitor
Chemotherapeutic agents (Doxorubicin, cyclophospha-mide, epirubicin, fluorouracil)
Herb effect on drug (May improve che-motherapy-induced
fatigue)
Unknown mechanism of the interaction
Level BHuman study (Withania somnifera
6 g/d throughout 6 months chemotherapy in breast cancer
patients)
Low Use with caution under supervision of a healthcare professional and monitor
Psychotropic drugs (Olan-zapine, typical antipsychot-ics, antidepressants, mood
stabilisers, antianxiety, hypnotic)
Herb effect on drug (May improve nega-
tive, general and total symptoms and stress)
May improve neurotrans-mitter dysfunctions due
to GABAergic and NMDA potentiating activity of
withania
Level AClinical trials (Adjunctive treat-ment with extract of Withania somnifera 1000 mg/d improved
negative symptoms and stress in patients with recent exacerbation of schizophrenia. Another clinical
trial showed extract of Witha-nia somnifera 500 mg/d improved cognitive abilities without serious
adverse effects.)
Low
Use with caution under supervision of a healthcare professional and monitor. Mild
to moderate and transient side effects were reported such as somnolence, epigastric discomfort or loose stools
Low
Possible
Possible
Possible
Possible
Possible
Moderate - High
Moderate - High
Moderate - High
Moderate
Moderate - High
Moderate - High
Pg.6 Pg.7
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Bacopa See “Brahmi”
Black cohoshCimicifuga racemosa
Level BHuman study
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease drug effectCYP2D6 substrates
May increase or decrease blood levels of drug via
inhibition of this enzyme activity
Level Din vitro study on mouse breast
cancer cell lineTheoretical Avoid concomitant use
May increase or decrease drug effect
depending on chemotherapeutic
agents
Chemotherapeutic agents (Docetaxel, doxorubicin,
cisplatin)
May increase cytotoxicity of docetaxel and
doxorubicin or may decrease cytotoxicity
of cisplatin
Level DAnimal and in vitro study
Avoid concomitant useMay decrease drug effect
Immunosuppressants Astragalus may have immunostimulant activity Theoretical Moderate
- High
AstragalusAstragalus
membranaceus
Possible
Moderate -High
Variable (depending on drug and
disease state)
Betacarotene Level AClinical trials
Interaction may be minimised by separating dose of medication and betacarotene by at least 2 hours. Supplementation recommended
Drug effect on nutrient (May
decrease nutrient effect)
Orlistat, plant sterolsBetacarotene absorption
may be decreased by these drugs
LowLikely
Bilberry Vaccinium myrtillus
Level C Case report (Rectal bleeding after
taking warfarin with bilberry)
Use with caution under supervision of a healthcare professional and monitor
May increase risk of bleeding
Anticoagulants and antiplatelet agents
May have additive effect to drug
Moderate - High
Possible
Level AClinical trial (Drug-herb
interaction was not directly studied. The ingestion of bilberry
extract significantly decreased the incremental AUC for both
glucose and insulin compared to placebo)
Use with caution under supervision of a healthcare professional and monitor
May increase drug effectHypoglycaemic drugs
May have additive effect to drug
Theoretical
Variable (depending
on drug and disease
state)
TheoreticalLevel D
in vitro study Use with caution under supervision of a
healthcare professional and monitor
Herb effect on drug (The combination
may have an immunostimulatory
effect)
Antibiotics (Doxycycline and cephalosporins)
May improve the viability of thymocytes Moderate
Level Din vitro study (Drug-herb
interaction was not directly studied. A significant dose-de-
pendent inhibition of ACE activity was seen after incubation with
bilberry extract)
Use with caution under supervision of a healthcare professional and monitorMay increase drug
effect
Antihypertensive drugs (ACE inhibitors)
May have additive effect to drug
Theoretical Moderate - High
Level Din vitro study (Drug-herb
interaction was not directly studied. Bilberry extract in-
creased IC50 values of erlotinib)
Avoid concomitant useMay decrease drug effect
Anticancer agent (Erlotinib)Bilberry anthocyanins
may modulate the growth-inhibitory effect of
erlotinib
Theoretical Moderate - High
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
Pg.8 Pg.9
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
BromelainLevel A
Clinical trials (160 mg bromelain appreared to increase intra-
operative amoxicillin levels in tissue, serum and skin samples.
The effect persisted 3 hours after surgery)
Use with caution under supervision of a healthcare professional and monitorMay increase drug
effectAmoxicillin
May increase levels of amoxicillin in tissue and blood by increasing the
absorption and enhancing its penetration into tissues
Level DAnimal and in vitro study (Oral bromelain retained substantial
proteolytic activity throughout the gastrointestinal tract when in com-
bination with antacids)
No evidence from human studies to support clinical recommendations
Drug effect on nutrient (May
increase nutrient effect)
Antacids
May increase retention of proteolytic effect
of bromelain when in combination with antacids
Theoretical Low
Brahmi Bacopa monnieri Level A
Clinical trialsUse with caution under supervision of a
healthcare professional and monitor
May increase effect of AChE inhibitor and
cholinergic drug. May decrease
effectiveness of anticholinergic drug
Acetylcholinesterase (AChE) inhibitor, anticholinergic drug, cholinergic drug
May increase acetylcholine levels due to inhibition of
acetylcholinesterase Moderate
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A2, CYP2C19, CYP2C9, CYP3A4)
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
Theoretical
Level DAnimal study
Use with caution under supervision of a healthcare professional and monitor
May increase drug effect
Thyroid hormone May have additive effect to drug
Theoretical Moderate
Boswellia Boswellia serrata
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A2, CYP2C9,
CYP2C19, CYP2D6 and CYP3A4)
May increase or decrease substrate blood levels via inhibition of these enzyme
activities
Theoretical
Level D in vitro study Avoid concomitant useMay decrease drug
effectImmunosuppressants
May have opposing effect to drug
Theoretical
Variable (depending on drug and
disease state)
Variable (depending on drug and
disease state)
Likely
Moderate
Level Din vitro study (Bromelain 25-50mg/
mL decreased IC50 value of cisplatin in malignant peritoneal
mesothelioma cells)
Use with caution under supervision of a healthcare professional and monitor
May increase drug effect Cisplatin Bromelain may increase
apoptosis and autophagy Theoretical
Moderate - High
Level CCase report (Ecchymosis devel-oped on forearms after taking
naproxen with bromelain)
Use with caution under supervision of a healthcare professional and monitor
May increase drug side effectNSAIDs (Naproxen) Mechanism unclear Possible
Moderate - High
Level B Human study (Drug-herb interaction was not directly studied. Bromelain
showed antiplatelet and anticoagulant effect)
Use with caution under supervision of a healthcare professional and monitor
May increase risk of bleeding
Anticoagulants and antiplatelet agents
May have additive effect to drug
Theoretical Moderate - High
Moderate -High
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
Possible
Pg.10 Pg.11
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Chromium
Multiple mechanisms pro-posed (addressing dietary
intake, skeletal muscle fat oxidation, and insulin signalling) with studies
ongoing
Level A Clinical trials (Evidence based
on sulfonylureas. Combination of glipizide and chromium improved
glycaemic control, increased insulin sensitivity and significantly
attenuated body weight gain induced by glipizide)
Use with caution under supervision of a healthcare professional and monitor
Nutrient effect on drug (May increase
drug effect but decrease associated
side effects)
Hypoglycaemic drugs Low
Chondroitin sulfate Level C
Case report (warfarin)
Possible Avoid concomitant useMay increase drug effect
Anticoagulant and antiplatelet agents
May have additive effect to drug. Chondroitin is a small component of a heparinoid and might
have weak anticoagulant activity
Moderate - High
Chaste Tree See “Vitex”
CeleryApium
graveolens
Level CCase report
Level DAnimal and in vitro study
Level C Case reports
Theoretical
Possible
Possible Moderate - High
Avoid concomitant use
Use with caution under supervision of a healthcare professional and monitor
Use with caution under supervision of a healthcare professional and monitor
Thyroid hormone
May increase or decrease drug effect
May decrease drug effect
May increase drug effect
CYP1A2 substrates
Venlafaxine
May increase or decrease blood levels of drug via
inhibition of this enzyme activity
Celery may increase blood levels of venlafaxine by
inhibition of CYP2D6
May decrease blood levels of drug
Moderate
Variable (depending on drug and
disease state)
Calcium
Level BSmall human study. Calcium-rich food considered to be the major reason for reduced absorption
PossibleInteraction may be minimised by
separating dose of medication and calcium by at least 2 hours
May decrease drug effect
ModerateBeta Blockers (Atenolol,
sotolol)
Calcium may decrease absorption of atenolol
sotalol
Level B Study in arrhythmic patients
using IV calcium and case report
Use with caution under supervision of a healthcare professional and monitor
Calcium channel blockers (verapamil)
May decrease drug effect
Calcium may decrease the hypotensive effect of
verapamilModeratePossible
Level CCase reports
Use with caution under supervision of a healthcare professional and monitor
May increase drug side effect
Thiazide diureticsCalcium may increase the
risk of hypercalcaemia with these drugs
ModeratePossible
Level A (quinolones)Level B (bisphosphonates)
Level C (tetracyclines, thyroid hormones)
Interaction may be minimised by separating dose of medication and
calcium by at least 2 hours
May decrease drug effect Moderate
Bisphosphonates, tetracycline or quinolone
antibiotics, thyroid hormones
Calcium may decrease the absorption and efficacy of
these drugsPossible
Level CCase reports
Avoid concomitant useMay increase drug side effect
Ceftriaxone
IV calcium and IV ceftriaxone may result
in precipitation of a ceftriaxone-calcium salt in
the lungs and kidneys
Possible High
Level AClinical trials
Avoid concomitant use. If indicated, interaction may be minimised by taking
2 hours before or 6 hours after taking calcium
May decrease drug effect
Antiretrovirals (Integrase inhibitors - dolutegravir, elvitegravir, raltegravir)
Calcium may reduce blood levels of dolutegravir,
elvitegravir and raltegravir through chelation
Possible Moderate - High
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
May decrease absorption of chromium by forming insoluble complex when pH is raised in gastroin-testinal tract by antacids
Level DAnimal study (Chromium levels
in blood were lower when in combination with antacids)
Use with caution under supervision of a healthcare professional and monitor
Drug effect on nutrient (May
decrease blood levels of nutrient)
Antacids (Aluminium hydroxide and magnesium
hydroxide)Theoretical Moderate
Possible
Pg.12 Pg.13
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Level AClinical trial in leukemia and
lymphoma patients
Level Din vitro studies found beta blockers
inhibited mitochondrial CoQ10 enzymes
Theoretical Low Assess nutrient status and supplement if indicated
Avoid concomitant use
Drug effect on nutrient (May
decrease nutrient effect)
Nutrient effect on drug (May decreases
drug side effect)
May increase or decrease drug effect
Chemotherapeutic agents (Anthracyclines such as
daunorubcin, doxorubicin)
Beta-blocker adrenergic agents
Anticoagulants and antiplatelet agents
CoQ10 levels may be decreased by these drugs
Despite the potential benefits of CoQ10 in
preventing cardiotoxicity, it is unknown if
CoQ10 diminishes the antineoplastic effect of
doxorubicin therapy
CoQ10 may have procoagulant or
anticoagulant effect
Co-enzyme Q10 (CoQ10)
Low
ColeusColeus forskohlii
May have additive effect to drug
Level DAnimal studies
TheoreticalModerate -
HighUse with caution under supervision of a
healthcare professional and monitorMay increase drug
effect
Anticoagulants and antiplatelet agents
May have additive effect to drug
Level BHuman and animal studies using
IV extractsRelevance to oral doses unknown
TheoreticalNo significant adverse effect expected. Use with caution uder supervision of a health care professional and monitor
May increase drug effect
Antihypertensive drugs Moderate - High
CoQ10 does not elicit its protective effect against doxorubicin-induced cardiotoxicity by reducing the drug levels in the blood or by inhibiting
the formation of doxorubicinol
Moderate - High
May have additive hypotensive effect
Level AMeta-analyses in patients taking
anti-hypertensive drugs
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May increase drug effectAntihypertensive drugs Likely
Possible
Level ASeveral studies in hyperlipidaemic patients; statins decreased plasma CoQ10 levels (effect on tissue levels
not established)
Low Assess nutrient status and supplement if indicated
Drug effect on nutrient (May
decrease nutrient effect)
HMG-CoA reductase inhibitors (statins) Likely
CoQ10 levels may be depleted by these drugs
Level AConflicting data
Clinical trial found no interaction.Multiple case reports of changes
to INR
Possible
Level AConflicting data
Clinical trials show conflicting results. Systematic review
found inadequate evidence to recommend routine use with
statins
LowInadequate evidence to support
supplementation in all patients taking statins
HMG-CoA reductase inhibitors (statins)
CoQ10 may decrease myalgia associated with
statin use
Nutrient effect on drug (May decrease
drug side effect)
PossibleLevel A
Conflicting dataClinical trials
Use with caution under supervision of a healthcare professional and monitor
Hypoglycaemic drugs May have additive hypoglycaemic effect
May increase drug effect
Moderate - High
Possible
Chromium May decrease blood
levels of drug by reducing absorption
Level BHuman study (Chromium picolinate significantly decreased the AUC of
serum thyroxine)
ModerateAvoid concomitant use. If chromium is
indicated, interaction may be minimized by separating the dose by 2 hours
May decrease drug effect
Levothyroxine Possible
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
May increase the absorp-tion of chromium
Level DAnimal studies (Chromium levels in blood, urine and tissues were
higher when in combination with aspirin or indomethacin)
ModerateUse with caution under supervision of a
healthcare professional and monitor
Drug effect on nutrient (May
increase blood levels of nutrient)
NSAIDs (Aspirin and indomethacin) Theoretical
Pg.14 Pg.15
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
EchinaceaEchinacea
angustifolia Echinacea purpurea
Evening primrose oil
Dong quaiAngelica
polymorpha
CranberryVaccinium
macrocarpon
Level BConflicting data
Human study found no interactionCase reports of seizures in
schizophrenic patients exist
High Use with caution under supervision of a healthcare professional and monitor
May increase drug side effect
Phenothiazine May lower seizure threshold
Unlikely
Level CCase report in patient using
lopinavir/ritonavir with evening primrose experiencing an increase
in blood levels of drugs
Moderate - High
Avoid concomitant useMay increase drug effect
Antiretrovirals (Lopinavir/ritonavir)
May increase blood levels of drug
Possible
Level BHuman studies
Variable (depending on drug and
disease state)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease drug effect
CYP3A4 substratesMay increase or decrease blood levels of drug via
induction of this enzyme activity
Possible
Level BAnimal studies, in vitro and in vivo
evidence of immunomodulatory effect.
No case report evidence
Moderate-High Avoid concomitant use
May increase drug side effectImmunosuppressants May have opposing effect
to drugPossible
Level BHuman studies
Variable (depending on drug and
disease state)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease drug effect
CYP1A2 and CYP2D6 substrates
May increase or decrease blood levels of drug
via inhibition of these enzyme activities
Possible
Level CCase report involving concurrent use of etoposide, cisplatin, and echinacea. Patient developed profound thrombocytopenia
Moderate - High Avoid concomitant useMay increase drug
effectChemotherapeutic agent
(Etoposide)
May increase blood levels of drug via inhibition of CYP1A2, CYP2C19,
CYP2C9, CYP3A4
Possible
Level CSeveral case reports and animal
studies
Moderate - High Avoid concomitant useMay increase drug
effect
Anticoagulant and antiplatelet agents
May have additive effect to drug Possible
Level AClinical trials
High Use with caution under supervision of a healthcare professional and monitor
May increase drug effect
Aspirin May have additive effect to drug Unlikely
Level CCase report
High Avoid concomitant useMay decrease drug effect
Tacrolimus May decrease blood levels of drug Possible
Level AConflicting data.
Clinical trials suggest no evidence of increasing drug affects with
cranberry juice. Case reports exist.in vitro studies suggest cranberry
effect warfarin metabolism (CYP3A4 minor metaboliser)
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May increase drug effect
Anticoagulant and antiplatelet agents
May increase blood levels of drug
Unlikely
Level CCase report
Variable (depending
on drug and disease
state)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease drug effect
CYP3A4 substrates
May increase or decrease blood levels of drug via
inhibition of this enzyme activity
Possible
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
Pg.16 Pg.17
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Flaxseed oil
Fish Oil
FeverfewTanacetum parthenium
FenugreekTrigonella
foenum-graecum
Likely Moderate - High
Use with caution under supervision of a healthcare professional and monitor
Hypoglycaemic drugs May have additive effect to drug
Level AHuman studies and meta-analyses
confirm blood glucose-lowering effect in patients with type-2
diabetes
May increase drug effect
Theoretical ModerateUse with caution under supervision of a
healthcare professional and monitorTheophylline May decrease blood levels
of drug
Level DAnimal study (oral administration
of theophylline 200 mg after fenugreek in male beagle dog)
May decrease drug effect
Possible Moderate - High
Avoid concomitant useAnticoagulant and antiplatelet agents
May have additive effect to drug
Level CCase report in patients with arrhythmia using fenugreek
capsule and warfarin
May increase drug effect
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
Folic acid
Level CCase report
Moderate - High
Avoid concomitant useMay cause compound resistance
May decrease drug effect
Chemotherapeutic agents (Cisplatin, oxaliplatin,
irinotecan)
Possible
Level AConflicting data.
Multiple clinical trials have found no increase in risk of bleeding
with antiplatelet or anticoagulant drugs, however there are
some studies that suggest an interaction, particularly at higher
doses
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
High doses of fish oil (>3 g/d omega-3 fatty acids) may increase the risk of
bleeding with these drugs
May increase drug effect depending on
fish oil dose
Anticoagulants and antiplatelet agents
Possible (depending on fish oil
dose)
Level AConflicting dataHuman studies
Moderate - High
Interaction unlikely at normal doses. Use with caution under supervision of a
healthcare professional and monitor
High doses (30-40 g/d) of flaxseed oil may increase the risk of bleeding with
these drugs
May increase drug effect
Anticoagulants and antiplatelet agents
Unlikely (possible with high
doses)
Level BConflicting data.
in vitro and in vivo studies found feverfew inhibits platelet
aggregation.Human study found no such effect
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Anticoagulant and antiplatelet agents
Possible Moderate - High
Level Din vitro study found low inhibitory
activity
No significant adverse effect expected. Use with caution under supervision of a
healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A2,
CYP2C8, CYP2C9, CYP2C19 and CYP3A4)
Theoretical
Variable (depending on drug and
disease state)
Level AMeta-analyses in patients taking
anti-hypertensive drugs
Blood pressure should be monitored when patient is on high dose of fish oil
May have additive hypotensive effect
depending on fish oil dose
May increase drug effect
Antihypertensive drugs Likely Moderate
Level A Clinical trials
Moderate - High
Blood pressure should be monitored when patient is on high dose of flaxseed
oil
May have additive hypotensive effect. Dose
dependent
May increase drug effect. Dose dependent
Antihypertensive drugs Likely
Level CMultiple case reports
Moderate - High
Assess and monitor nutrient status and supplement if indicated
May decrease folic acid levels
Drug effect on nutrient (May decrease blood
levels of nutrient)
Co-trimoxazole, sulphazalazine,
phenytoin, phenobarbital, primidone and methotrexate
Possible
Pg.18 Pg.19
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Folic acid
GarlicAllium sativum
Level CCase reports
Moderate - High
Avoid concomitant useFolic acid may increase the toxicity of fluorouracil and
capecitabine
May increase drug side effect
Fluorouracil and capecitabine Possible
Level AClinical trials
Moderate - High
Follow Australian Medicines Handbook’s recommendations for concurrent use of
folic acid and methotrexate
Folic acid may decrease the efficacy of
methotrexate for children with lymphoblastic
leukaemiaFolic acid may decrease
drug side effect in rheumatoid arthritis
May decrease drug effect
Methotrexate Likely
Level A Conflicting data
Human studies show conflicting results. Interaction more likely at higher doses (>7 g). Case reports
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May increase the risk of bleeding with these
medications
May increase drug effect depending on
formulation and dose
Anticoagulants and antiplatelet agents Possible
Level AClinical trials indicate
antihypertensive activity with aged garlic extract (480-960 mg/d)
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May have additive hypotensive effect to drug.
Dose dependent
May increase drug effect
Antihypertensive drugs Likely
Level Bin vitro and open studies using
chlorzoxazone
Variable (depending on drug and
disease state)
Use with caution under supervision of a healthcare professional and monitor
May increase blood levels of substrates via inhibition
of this enzyme activity
May increase drug effect
CYP2E1 substrates Possible
Level CCase report
Variable (depending on drug and
disease state)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of hepatic CYP3A4 enzyme activity
May increase or decrease drug effect
Hepatic CYP3A4 substrates
Possible
Level BHuman study
Variable (depending on drug and
disease state)
Use with caution under supervision of a healthcare professional and monitor
May decrease blood levels of drug via induction of
intestinal CYP3A4 enzyme activity
May decrease drug effect
Intestinal CYP3A4 substrates (Saquinavir)
Possible
Level Bin vitro and human studies found
garlic decreased levels of the protease inhibitors saquinivir and
ritonavir
Variable (depending on drug and
disease state)
Use with caution under supervision of a healthcare professional and monitor
May decrease blood levels of substrates via
upregulation of intestinal ABCB1 or ABCC2 activity
May decrease drug effect
Intestinal P-glycoprotein substrates Possible
Level BHuman study
Modeate - High
(depending on dose)
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycemic effect
May increase drug effect
Metformin Possible
INGREDIENTLIKELIHOOD
of INTERACTION
RECOMMENDATIONSEVERITY
of OUTCOME
MECHANISM of INTERACTION
DRUG, DRUG CLASS, ENZYME or TRANSPORTER
Level BUncontrolled studies in epileptic
patients
HighUse only under supervision of healthcare
professional and monitor phenytoin blood concentration
Folic acid may decrease the efficacy of phenytoin
May decrease drug effect
Phenytoin Likely
Pg.20 Pg.21
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
GingerZingiber officinale
Level AConflicting data.
Clinical trials indicate normal doses ≤4 g/d are unlikely to cause
platelet dysfunction.Human study with high dose
ginger (10 g) and in vitro studies showed inhibition of platelet
aggregation
Moderate - High
Do not use high doses (≥4 g/d) in patients with bleeding disorders or
those taking antiocagulant medication. Use with caution under supervision of a
healthcare professional and monitor
May increase the risk of bleeding with these
medications
May increase drug effect
Anticoagulants and antiplatelet agents Unlikely
Level DAnimal study
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May decrease blood level of drug
May decrease drug effect
Ciclosporin Theoretical
Level DAnimal study
ModerateUse with caution under supervision of a
healthcare professional and monitor May increase absorption
and plasma half lifeMay increase drug
effectMetronidazole Theoretical
Level DAnimal study
High Avoid concomitant useMay increase blood levels of drug via unknown
mechanism
May increase drug effect
Tacrolimus Theoretical
GinkgoGinkgo biloba
Level CCase reports
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May increase risk of seizure
May decrease drug effect
Anticonvulsants (Phenylbarbitone, sodium
valproate, phenytoin)Possible
Level AMeta-analysis and studies
Low No significant adverse effect expected
Ginkgo may add to the beneficial
effect of haloperidol, chlorpromazine and
olanzapine in the treatment of schizophrenia
Herb effect on drug (May increase drug
efficacy)
Chlorpromazine and haloperidol
Likely
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via weak inhibition of these
enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP 1A2,
CYP2C9, CYP3A)Theoretical
Level BConflicting data.
Human studies found ginkgo decreased levels of omeprazole,
but had no effect on voriconazole
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
induction of this enzyme activity
May increase or decrease drug effect
CYP2C19 substrates Possible
Level CCase report
Moderate - High
Avoid concomitant use
May increase blood levels of drug due to possible
induction of CYP3A4 and P-glycoprotein
May decrease drug effect
Efavirenz Possible
Level B Conflicting data.
Clinical trials and human studies found ginkgo had a variable effect
on drug activity. Animal and in vitro studies suggest ginkgo may
reduce insulin resistance
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
Ginkgo may increase or decrease blood glucose
levels
May increase or decrease drug effect
Hypoglycaemic drugsPossible
Level BHuman studies
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May increase blood level of drug
May increase drug effect
Nifedipine Possible
Variable (depending on drug and
disease state)
Variable (depending on drug and
disease state)
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Pg.22 Pg.23
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Ginseng (Korean) Panax ginseng
GinkgoGinkgo biloba
Level BHuman studies
Moderate - High
Avoid concomitant useMay increase blood level of drug
May increase drug effect
Raltegravir Possible
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level CCase report
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May have an effect on neurochemical system
May increase drug effect
Amitriptyline Possible
Level Bin vitro, animal and human ex vivo
studiesAvoid concomitant use
Korean ginseng may falsely elevate or decrease assays for blood digoxin
levels
May interfere with the accuracy of a range of tests measuring serum
digoxin
DigoxinPossible High
Level AConflicting data.
Clinical trials find ginkgo does not have a significant effect on platelet function and does not interact with
warfarin, aspirin or clopidogrel.Case reports suggest an interaction is possible
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
Ginkgo may increase risk of bleeding with these
medications
May increase drug effect
Anticoagulants and antiplatelet agents Unlikely
Level AClinical trials in NIDDM patients
and healthy subjects
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycaemic effect
May increase drug effect
Hypoglycaemic drugs Moderate - HighLikely
Level CCase reports (ginseng type not
specified)
Use with caution under supervision of a healthcare professional and monitor
Korean ginseng may increase the side effect of
phenelzine or other MAOIs
May increase drug side effect
Monoamine Oxidase Inhibitors (MAOI)
(Phenelzine)
ModerateUnlikely
Level AConflicting data.
Clinical trial results suggest no interaction.
Case reports existin vitro studies suggest possible
interaction
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
Possible CYP450 enzymes interaction and Vitamin K
effect on ginseng
May increase or decrease drug effect
Anticoagulant and antiplatelet agents Possible
Level A Clinical trials
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood level of drugs via
inhibition of this enzyme activity
May increase or decrease drug effect
CYP2D6 substrates PossibleVariable
(depending on drug and
disease state)
Level Din vitro study Low No evidence from human studies to
support clinical recommendations
May enhance susceptibility of colon cancer cells to
docetaxel
Herb effect on drug (May increase drug
efficacy)
Docetaxel Theoretical
Level DAnimal study
Low No evidence from human studies to support clinical recommendations
May have a protective effect on doxorubicin-
induced toxicity
Herb effect on drug (May decrease drug
side effect)
Doxorubicin Theoretical
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
Korean ginseng may cause a phytoestrogenic effect
May increase or decrease drug effect Oestrogen
Theoretical Low - Moderate
Level A Clinical trials
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May decrease blood levels of drugs possibly due to
induction of CYP3A4
May decrease drug effect
Midazolam Possible
Level CCase report High Avoid concomitant use
May increase blood levels of drugs possibly due to
inhibition of CYP3A4
May increase drug side effect
Imatinib Possible
Pg.24 Pg.25
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Glucosamine
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Ginseng (Siberian)
Elutherococcus senticosus
Level B in vivo study found anticoagulant
activity for an isolated constituent.Human study in athletes
adminstered a preparation of Siberian ginseng and andrographis
found reduced coagulation
Avoid concomitant useSiberian ginseng may
increase risk of bleeding with this medication
May increase drug effect
Anticoagulant and antiplatelet agents
Level AHuman trials in women with
breast and ovarian cancer undergoing chemotherapy
treatment
Use with caution under supervision of a healthcare professional and monitor
Siberian ginseng may increase tolerance for
chemotherapy and improve immune response
Nutrient effect on drug (May decrease drug
side effect)
Chemotherapeutic agents
Level B Human studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP3A4 and CYP2D6 substrates
Level Bin vitro, animal and human ex vivo
studies
Avoid concomitant useSiberian ginseng may
falsely elevate or decrease assays for blood digoxin
levels
May interfere with the accuracy of a range of tests measuring serum
digoxin levels
Digoxin
Level A Clinical trials
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycaemic effect to
drug
May increase drug effect
Hypoglycaemic drugs
Level CTwo case reports (ginseng type
not specified)
Use with caution under supervision of a healthcare professional and monitor
Siberian ginseng may increase side effect of
phenelzine or other MAOIs
May increase drug side effect
Monoamine Oxidase Inhibitors (MAOI)
(Phenelzine)
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase blood level of drug via inhibition of P-gp
May increase drug effectP-glycoprotein substrates
Moderate - High
High
Moderate - High
Moderate - High
Grape seedVitis vinifera
Level Din vitro studies
Use with caution under supervision of a healthcare professional and monitor
May decrease platelet adhesion to fibrinogen
May increase risk of bleeding
Anticoagulants and antiplatelet agents
Theoretical Moderate - High
Variable (depending on drug and
disease state)
Variable (depending on drug and
disease state)
Moderate
LowLikely
Likely
Possible
Possible
Possible
Unlikely
Possible
Level CCase reports Avoid concomitant use
Glucosamine may increase risk of bleeding with this
medication
May increase drug effect
Anticoagulant and antiplatelet agents
Moderate - High
Possible
Level AClinical trials indicate no
interaction.Lower-level studies reports
changes to glucose and insulin levels
Interaction unlikely but use with caution under supervision of a healthcare
professional and monitor
Glucosamine may affect blood glucose levels in people with diabetes
May decrease drug effectHypoglycaemic drugs Unlikely
Level A Clinical trial (6 weeks treatment with both vitamin C 500 mg and grape seed polyphenol 1000 mg
daily increased blood pressure in hypertensive patients)
Avoid combination of vitamin C and grape seed in hypertensive pateintsUnknown mechanismMay have opposing
effect to drug Antihypertensive drugs +
vitamin CModerate -
HighPossible
Pg.26 Pg.27
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Grape seedVitis vinifera
HawthornCrataegus monogyna
Level Din vitro study (100 mg of grape seed extract inhibited CYP2C9
and intestinal CYP3A4 activity) in vitro and animal study (Wild grape
seed procyanidins diminished CYP2E1 expression in vitro
and downregulated the protein expression level of liver CYP2E1
in rats)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via inhibition
of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP2C9, CYP2E1, Intestinal
CYP3A4)
Theoretical
Variable (depending on drug and
disease state)
Level DAnimal study (1 week treatment
of grape seed extract (80 mg/kg) with the administration of
intravenous midazolam (10mg/kg) increased the effect of midazolam) Midazolam is bio-transformed to the active metabolite via hepatic
CYP3A4 enzyme
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
induction of hepatic CYP3A4 enzyme activity
May increase or decrease drug effect
Hepatic CYP3A4 substrates
Theoretical
Variable (depending on drug and
disease state)
Level DAnimal study (400 mg/kg of grape
seed extract showed protective effects on the testicular toxicity induced by cisplatin (10 mg/kg)
in rats)
No evidence from human studies to support clinical recommendations
Unclear mechanism. May suppress free radicals and rescue the down-regulated expression of testosterone
synthesis induced by cisplatin
Herb effect on drug (May reduce cisplatin-
induced oxidative/nitrative stress)
Cisplatin Theoretical Low
Level DAnimal study (100 mg/kg grape
seed extract showed cardio-protective effect without affecting
antitumor effects of 2mg/kg doxorubicin)
No evidence from human studies to support clinical recommendations
Unclear mechanism. May protect DNA from oxidative
damage
Herb effect on drug (May attenuate
doxorubicin-induced toxicity)
Doxorubicin Theoretical Low
Level BHuman study (300 mg of grape
seed did not significantly change metabolic rates of
dextromethorphan (CYP2D6 substrate) in healthy volunteers)
Level DIn vitro study (100 mg of grape seed extract inhibited CYP2D6
activity)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via inhibition of this
enzyme activity
May increase or decrease drug effect
CYP2D6 substrates
Variable (depending on drug and
disease state)
Unlikely
Level CCase report
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Anticoagulants and antiplatelet agents
Possible
Green-lipped mussel
Level BConflicting data.
Several case reports of raised INR.Small human study found no
effect on platelet aggregation, prothrombin time, APTT, fibrinogen or factor VII
Use with caution under supervision of a healthcare professional and monitor
Green-lipped mussel may increase the risk of bleeding with this
medication
May increase drug effect
Anticoagulant and antiplatelet agents
Theoretical Moderate - High
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Pg.28 Pg.29
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
HawthornCrataegus monogyna
Level DAnimal study
High Use with caution under supervision of a healthcare professional and monitor
May have additive vasodilation effect
May increase drug effect
Phosphodiesterase-5-Inhibitors
Theoretical
Holy basilOcimum
tenuiflorum
Level DAnimal study
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May inhibit platelet aggregation
May increase drug effect
Anticoagulant and antiplatelet agents
Theoretical
Level AClinical trial in NIDDM patients found holy basil may decrease
blood glucose levels
Moderate - High
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycaemic effect
May increase drug effect
Hypoglycaemic drugs
Level DAnimal study High Use with caution under supervision of a
healthcare professional and monitor
May potentiate phenobarbitone - induced
sleeping time
May increase drug effect
Phenobarbital Theoretical
HopsHumulus lupulus Level D
in vitro studiesUse with caution under supervision of a
healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A1,
CYP1A2, CYP1B1, CYP2C8, CYP2C9,
CYP2C19, CYP3A4)
Theoretical
Level Din vitro studies
Use with caution under supervision of a healthcare professional and monitor
May bind to estrogen receptor site
May decrease drug effectOestrogen Theoretical
HorsetailEquisetum
arvense
Level CCase reports (2 patients had
detectable viral loads)High Avoid concomitant use
May decrease blood levels of drug by increasing renal excretion of drug due to its diuretic properties or via flavonoids and phenols in horsetail that could induce
CYP450 enzyme activity
May decrease drug effect
Antiretrovirals (Lamivudine, zidovudine, emtricitabine, efavirenz,
tenofovir)
Level Din vitro study (Horsetail extract
from 800 mg of horsetail)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A2,
CYP2D6)Theoretical
Iodine Level CCase reports
ModerateUse with caution under supervision of a
healthcare professional and monitorMay increase blood levels
of iodine
May increase adverse effect on thyroid
function Amiodarone
Level Din vitro studies
Moderate Use with caution under supervision of a healthcare professional and monitor
Iodine may precipitate hypothyroidism
May increase drug effect
Antithyroid drugs Theoretical
Level CCase reports and open study in
patients taking lithiumModerate Use with caution under supervision of a
healthcare professional and monitor
Iodine at high doses may increase the hypothyroid
activity of lithium carbonate
May increase drug side effectLithium
Level BStudies in euthyroid subjects -
thyroid function inhibited Moderate
Use with caution under supervision of a healthcare professional and monitor
Iodine (at very high doses) may precipitate or exacerbate hyper or
hypothyroidism
May increase drug effect
Thyroid hormone
Variable (depending on drug and
disease state)
Variable (depending on drug and
disease state)
Low - Moderate
Level BHuman studies
Use with caution under supervision of a healthcare professional and monitor
May have additive vasodilation effect
May increase drug effect
Nitrate Possible
Possible
Possible
Possible
Possible
Possible
Level AClinical trials suggest hypotensive
effect
Use with caution under supervision of a healthcare professional and monitor
May have additive hypotensive effect
May increase drug effect Antihypertensive drugs Moderate -
HighLikely
Moderate - High
Pg.30 Pg.31
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Iron Level BHuman studies
Avoid concomitant use. If indicated, interaction may be minimised by taking
2 hours before or 6 hours after drug
May decrease the absorption of drug
May decrease drug effect Bisphosphonates
Level AClinical trials
Use with caution under supervision of a healthcare professional and
monitor. Avoid concomitant use. If iron is indicated, interaction may be reduced by taking 4-6 hour before or 2 hours after
drug
May decrease blood level of drug
May decrease drug effect
Captopril
Level AClinical trials
Avoid concomitant use. If iron is indicated, interaction may be minimised by taking 2 hours before or 6 hours after
drug
May decrease the absorption of drug
May decrease drug effect Dolutegravir
Level BStudies in patients (carbidopa,
levodopa, methyldopa) and healthy subjects (penicillamine)
Avoid concomitant use. If iron is indicated, interaction may be minimised by taking 2 hours before or 6 hours after
drug
May decrease the absorption of drug
May decrease drug effect
Methyldopa, levadopa, carbidopa and penicillamine
Level B Human studies
Avoid concomitant use. If iron is indicated, interaction may be minimised by taking 2 hours before or 6 hours after
drug
May decrease the absorption of drug
May decrease drug effect
Mycophenolate
Level B Human studies
Avoid concomitant use. If iron is indicated, interaction may be minimised by taking 2 hours before or 6 hours after
drug
May decrease the absorption of drug
May decrease drug effect
Tetracycline and quinolone
Level B Human studies
Avoid concomitant use. If iron is indicated, interaction may be minimised by taking 2 hours before or 6 hours after
drug
May decrease the absorption of drug
May decrease drug effect
Thyroid hormone
KelpFucus vesiculosus
Level CCase reports
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood level of drug
May increase or decrease drug effectLithium
Level AClinical trial found T3 decreased
and TSH increased.Case reports of hyperthyroidism
and hypothyroidism
Use with caution under supervision of a healthcare professional and monitor
Taking kelp may precipitate or exacerbate hyper or hypothyroidism
May increase or decrease drug effect
Thyroid hormone
LiquoriceGlycyrrhiza glabra Level A
in vitro and in vivo studies and systematic review
Use with caution under supervision of a healthcare professional and monitor
Additive effect to drug classes, however may induce CYP3A4 and
CYP2C9 (metabolisers of warfarin) which may decrease blood levels of
warfarin
May increase or decrease drug effect
Anticoagulants and antiplatelet agents
Level BOpen studies and case report
Use with caution under supervision of a healthcare professional and monitor
May have hypertensive effect (at high doses 50-
200 g/d)
May have opposing effect to drug
Antihypertensive drugs
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May decrease blood level of drug
May decrease drug effect
Cisplatin Theoretical
High
Moderate - High
High
Moderate - High
Moderate - High
Moderate - High
Moderate - High
Moderate - High
Moderate
Moderate
Moderate
Moderate
Possible
Possible
Possible
Possible
Possible
Likely
Likely
Likely
Likely
Possible
Possible
Pg.32 Pg.33
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LiquoriceGlycyrrhiza glabra
Level BOpen human studies
Use with caution under supervision of a healthcare professional and monitor
May increase blood levels of drug
May increase drug effect
Corticosteroids (Prednisolone)
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level B Human studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition or induction of this enzyme activity
May increase or decrease drug effectCYP3A4 substrates
Level Din vitro studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP2C9, CYP2C19, CYP2B6,
CYP2C8)
Theoretical
Level CCase report, in vitro study and
animal studyAvoid concomitant use
Liquorice may increase the risk of digoxin toxicity (possibly via hypokalaemia and/or inhibition of P-gp)
May increase drug side effectDigoxin
Level BOpen human studies (dosage 100-
200 g/d) and case reportsUse with caution under supervision of a
healthcare professional and monitor
Liquorice (at high doses - over 100 g/d) may increase
the risk of electrolyte disturbances, especially
hypokalaemia, with these medications
May increase drug side effect
Potassium-depleting diuretics, laxatives
LuteinLevel D
Animal study (Co-administration of Lutein 0.5 mg/kg and cisplatin
5mg/kg in rats)
No evidence from human studies to support clinical recommendations
May have antioxidant and anti-inflammatory effects
Nutrient effect on drug (May prevent cisplatin-
induced retinal damage)
Cisplatin Theoretical
Level Din vitro studies showed dose-dependent effects. (Lutein (5-
100mg/L) had inhibitory effects on CYP3A4. Lutein (2.8 mg/L) did not
inhibit CYP3A4 activity)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of this enzyme activity
May increase or decrease drug effect
CYP3A4 substrates Theoretical
Level Din vitro study study showed enhanced cytotoxic effect in
breast cancer cells. Another in vitro and animal study showed
that the combination of lutein and doxorubicin reduced sarcoma cell proliferation and tumour growth.
No evidence from human studies to support clinical recommendations
May have additive effect to drug on reactive
oxygen species-mediated apoptosis. May reduce doxorubicin-induced
inflammatory response via inhibition of NF-kB
expression
Nutrient effect on drug (May enhance
cytotoxicity and reduce cancer
resistance)
Doxorubicin Theoretical
Level DAnimal study (Co-administration of lutein 0.5 mg/kg, ethambutol
50 mg/kg and isoniazid 50 mg/kg in rats)
No evidence from human studies to support clinical recommendations
May have antioxidant and anti-inflammatory effects
Nutrient effect on drug (May prevent
isoniazid-induced toxic optic neuropathy)
Ethambutol + isoniazid Theoretical
High
Moderate - High
Variable (depending on drug and
disease state)
Variable (depending on drug and
disease state)
Moderate
Moderate
Variable (depending on drug and
disease state)
Low
Low
Possible
Possible
Possible
Possible
MagnesiumLevel C
Case reportAvoid concomitant use
May have additive inhibitory effects on
presynaptic acetylcholine release
May increase drug side effect such as muscle weakness
Aminoglycosides Moderate - HighPossible
Pg.34 Pg.35
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level BHuman studies Avoid concomitant use
Proguanil may form complexes with
magnesium
May decrease drug effect Proguanil HighPossible
Level Bin vitro study and human
study based on IV route of administration
Avoid concomitant useMagnesium may reduce the efficacy of warfarin
May decrease drug effect
Anticoagulant and antiplatelet agents
Moderate - High
Possible
Magnesium
Level BHuman studies and case reports
Assess nutrient status and supplement if indicated
Electrolyte disturbances, including low serum
magnesium levels, may occur with this medication. This has been association with nephrotoxicity, and
may necessitate stopping the drug and giving
intravenous electrolyte replacement
Drug effect on nutrient (May decrease blood
levels of nutrient)Amphotericin-B Possible Moderate
Level AClinical trial using high dose of
magnium (3204 mg/d magnesium chloride)
Use with caution under supervision of a healthcare professional and monitor
Magnesium may have additive antiarrythmic
effect
Nutrient effect on drug (May increase drug
efficacy)
Antiarrythmic drugs LowPossible
Level AMeta-analysis
Use with caution under supervision of a healthcare professional and monitor
Magnesium may have additive hypotensive effect
May increase drug effect
Antihypertensive drugs (calcium channel blockers)
Moderate - HighPossible
Level AClinical trial using IV
administration
Use with caution under supervision of a healthcare professional and monitor
May have additive inhibitory effects on acetylcholine release
May increase drug effect
Rocuronium ModeratePossible
Level BMultiple case reports, case series,
reviews Assess nutrient status and supplement
if indicated
Proton pump inhibitors may cause
hypomagnesaemia if taken long-term (usually >1 year)
Drug effect on nutrient (May decrease blood
levels of nutrient)Proton pump inhibitors Moderate
Likely (with long term use)
Level AClinical trials Avoid concomitant use
Bisphosphonates may form complexes with
multivalent cations such as magnesium
May decrease drug effect Bisphosphonates ModerateLikely
Level A (tetracycline and quinolone antibiotics)
Level B (chlorpromazine)Level B (penicillamine)
Level D (digoxin)Level D (nitrofurantoin)
Interaction may be minimised by separating the administration of
medication and magnesium by at least 2 hours
Magnesium may decrease the absorption and efficacy
of these drugsMay decrease drug
effect
Digoxin, chlorpromazine, penicillamine, tetracycline,
nitrofurantoin and quinolone antibiotics
LowPossible
Level BHuman studies Avoid concomitant use
May decrease blood level of drug
May decrease drug effect Gabapentin
Level BMultiple studies and case reports Assess nutrient status and supplement
if indicated
Loop diuretics and, to a lesser extent, thiazide
diuretics, interfere with magnesium reabsorption
in the kidneys, which increase urinary losses and may reduce serum
magnesium levels
Drug effect on nutrient (May decrease blood
levels of nutrient)
Loop and thiazide diuretics
Moderate - High
Moderate
Possible
Likely (with long term use)
Pg.36 Pg.37
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Milk thistle/St Mary’s thistle
Silybum marianum
Level A Clinical trials
No significant adverse effect expected. Use with caution uder supervision of a health care professional and monitor
Milk thistle may have cardioprotective activity against doxorubicin and nephroprotective activity
against cisplatin
Herb effect on drug (May decrease drug
side effect)
Chemotherapeutic agents(Cisplatin, doxorubicin)
Level AClinical trials
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of substrate
via inhibition or induction of this enzyme activity
May increase or decrease drug effect
CYP3A4 substrates
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May inhibit or induce P-gp activity
May increase or decrease drug effect
P-glycoprotein substrates Theoretical
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase blood levels of drug by inhibiting
glucuronidation of drug
May increase drug effect
Raloxifene Theoretical
Level BHuman studies
Avoid concomitant useMay decrease drug hepatic clearance
May increase drug effect
Sirolimus
Level BHuman studies
Avoid concomitant use depending on severity of disease state
May increase blood level of drug via inhibition of
CYP2CP, CYP3A4 and P-gp activity
May increase or decrease drug effect
Tamoxifen
Nicotinic acidLevel C
Case reports (Warfarin)Avoid concomitant useMay have additive effect
to drug May increase drug
effectAnticoagulant and antiplatelet agents
Level BHuman studies
Use with caution under supervision of a healthcare professional and monitor
May reduce the clearance of niacin by competing for
glycine conjugation
Drug effect on nutrient (May increase or
decrease niacin side effect)
Aspirin
Oats (Avena sativa)
Level AClinical trials find oats decrease blood pressure. In one trial, 73% of patients were able to stop or
reduce their medication
Use with caution under supervision of a healthcare professional and monitor
May have additive hypotensive effect
May increase drug effect
Antihypertensive drugs
High
High
Moderate - High
Moderate - High
Variable (depending on drug and
disease state)
Variable (depending on drug and
disease state)
Moderate
Low
Unlikely
Possible
Possible
Possible
Possible
Possible
Level C Case report
Use with caution under supervision of a healthcare professional and monitor
Mechanism unknownMay increase drug side effect
Bile acid sequestrants
Level C Case report
Use with caution under supervision of a healthcare professional and monitor
May increase risk of myopathy
May increase drug side effect
Gemfibrozil
Level C Case report
Use with caution under supervision of a healthcare professional and monitor
High dose nicotinic acid (1500 mg/d) may increase the risk of rhabdomyolysis and myopathy with statins
May increase drug side effect
HMG-CoA reductase inhibitors (statins)
Moderate
Moderate
Low - Moderate
Possible
Possible
Possible
Level A Clinical trials
Use with caution under supervision of a healthcare professional and monitor
May decrease blood levels of drug
May decrease drug effect Thyroid hormone
Level CCase reports
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to nutrient
Drug effect on nutrient (May increase nutrient
side effect)Transdermal nicotine
Moderate
Low - Moderate
Possible
Possible
Likely
L-methionineLevel B
Open study in patients with Parkinson’s disease
Use with caution under supervision of a healthcare professional and monitor
Methionine may decrease the efficacy of levodopa in
Parkinson’s disease
May decrease drug effect
Levodopa LowPossible
Moderate - High
Pg.38 Pg.39
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Oats (Avena sativa)
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May reduce intestinal absorption of atorvastatin
May decrease drug effect
Atorvastatin Theoretical
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level BHuman study
Use with caution under supervision of a healthcare professional and monitor
May decrease metabolism of cortisone
May increase drug effect
Intramuscular cortisonePara-aminobenzoic acid (PABA)
Level Bin vitro studies and human study Avoid concomitant useMay inhibit antimicrobial
activities of drugMay decrease drug
effect
Sulphonamides and sulphones (Dapsone)
Level BOne uncontrolled study found very high dose of isolated constitutent
prolonged prothrombin time
Use with caution under supervision of a healthcare professional and monitor
May have additive anticoagulant effect (at
very high doses)
May increase drug effect
Anticoagulants and antiplatelet agents Theoretical
Pau d’Arco
Pelargonium Pelargonium
sidoides
PeppermintMentha x piperita
Level AClinical trials and systematic
reviews
No significant adverse effect expected. Use with caution uder supervision of a health care professional and monitor
May have additive LDL-c lowering effect
May increase drug effect
Lipid-lowering agents (Statins and ezetimibe)
Phytosterols / Plant sterols
Level CMultiple case reports
Avoid concomitant usePotassium may increase
the risk of hyperkalaemiaMay increase drug
side effect
ACE inhibitors, angiotensin receptor
blockers and potassium-sparing diuretics
Potassium
Level A Multiple trials in adults and children taking antibiotics
No significant adverse effects expected. Supplementation may be beneficial
May restore gut flora and reduce diarrhoea
secondary to antibiotic therapy
Nutrient effect on drug (May decrease
drug side effect)Antibiotics
Probiotics
Level AClinical trial in women with
vulvovaginal candidiasis
No significant adverse effects expected. Supplementation may be beneficial
Combination therapy may improve clinical outcome
Nutrient effect on drug (May increase drug
efficacy)Fluconazole
Lactobacillus species including:
L. acidophilusL. reuteri
Level CCase report
Avoid concomitant use in critically ill and immunocompromised patients
May predispose opportunistic infection due
to immunosuppression
May predispose opportunistic infection
ImmunosuppressantsL.Rhamnosus
GR-1L. Reuteri RC-14
Moderate - High
Level Din vitro studies find pelargonium has immune modulatory activity
Avoid concomitant useMay have opposing effect to drug
May decrease drug effectImmunosuppressants
Theoretical Moderate - High
Level DAnimal study suggests interaction
unlikely
Use with caution under supervision of a healthcare professional and monitor
Pelargonium contains coumarin which
may reduce platelet aggregation, additive
effect to drug
May increase drug effect
Anticoagulant and antiplatelet agents
TheoreticalModerate -
High
Level D Animal study Avoid concomitant use
May increase blood levels of drug
May increase drug effect
Ciclosporin Theoretical High
Moderate - High
Moderate - High
Moderate
Moderate
Low - Moderate
Low - Moderate
Low
Low
Possible
Possible
Level BOpen study using felodipine,
simvastatin (CYP3A4 substrates) Level D
Animal study (CYP1A2, CYP2C0 and CYP2C19 substrates)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via inhibition of CYP1A2, CYP2C9 and CYP2C19 enzyme activities and induction of intestinal
CYP3A4 enzyme activity
May increase or decrease drug effect
CYP450 enzyme substrates (CYP3A4,
CYP1A2, CYP2C9, CYP2C19)
Variable (depending on drug and
disease state)
Possible
Likely
Likely (dose-
dependant)
Likely
Likely
Possible (depending on disease
state)
Pg.40 Pg.41
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Level AClinical trial
Use with caution under supervision of a healthcare professional and monitor
Psyllium may decrease post-prandial blood
glucose levels
May increase drug effect
Hypoglycaemic drugsPsyllium husk
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level BHuman studies
Interaction may be minimised by separating dose of medication and
psyllium by at least 2 hours
Psyllium may decrease the absorption of oral
drugs if doses are taken comcommitantly
May decrease drug effect
Oral drugs and nutritional supplements
Quercetin
Level D Animal study and in vitro study
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Anticoagulant and antiplatelet agents Theoretical Red clover/
IsoflavonesTrifolium pratense
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A2, CYP2C9,CYP2C19,
CYP3A4)
Theoretical
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May decrease drug metabolism due to
decrease in glutathione cellular concentration
May increase drug side effect Daunorubicin Theoretical
Level D in vitro study Avoid concomitant use
May increase blood levels of drug via inhibition of
P-gp expression
May increase drug effectDigoxin Theoretical
Moderate - High
Moderate - High
Moderate - High
Moderate - High
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Possible
Possible
Level AClinical trial found quercetin
supplementation reduced systolic, diastolic and mean arterial
pressure in stage 1 hypertensive subjectsLevel D
in vivo study found increased bioavailability for diltiazem but
mechanism is unknown
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Antihypertensive drugs (Calcium channel
blockers)
Moderate - High Possible
Level BHuman, animal and in vitro
studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of enzyme
substrates via inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP1A1,
CYP1A2, CYP2C8, CYP3A4, CYP2C9,
CYP2D6)
Level B Human studies
Use with caution under supervision of a healthcare professional and monitor
Quercetin may inhibit OATP1B1-mediated
transport
May increase drug effect
Organic anion transporting polypeptide
(OATP) substrates (OATP1B1)
Level B Human studies
Use with caution under supervision of a healthcare professional and monitor
Quercetin may inhibit P-gp pump efflux
May increase drug effect
P-glycoprotein substrates
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Level D in vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase blood level of drug by displacing warfarin from human
serum albumin binding site and CYP2C9 inhibition
May increase drug effect
Anticoagulant and antiplatelet agents Theoretical
Moderate - High
Possible
Possible
Possible
Pg.42 Pg.43
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
Red clover binds to estrogen receptors and is capable of acting as both agonists and antagonists
May increase or decrease drug effect
Oestrogen Theoretical
Red clover/ Isoflavones
Trifolium pratense
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycaemic effect to
drug
May increase drug effect
Hypoglycaemic drugs Theoretical
Level AClinical trials
Use with caution under supervision of a healthcare professional and monitor
May have additive lipid-lowering effect to drug
May increase drug effect
Lipid-lowering drugs
Level CCase report Avoid concomitant useMechanism unknownMay increase drug
side effect Methotrexate
Level BHuman studies Avoid concomitant use
Red clover may have oestrogenic activity and
may theoretically interfere with tamoxifen efficacy
May increase drug effect
Tamoxifen
Level Din vitro study
Avoid concomitant useMay increase blood levels of drug via inhibition of
P-gp expression
May increase drug effect
Vinblastine Theoretical
Saw palmetto Serenoa repens
Level BHuman study (Study with 12
volunteers showed interaction with CYP1A2, 3A4, 2E1, 2D6 is
unlikely) Level D
in vitro study (Saw palmetto extract showed potent inhibition of CY3A4, CYP2D6 and CYP2C9)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood level of drugs via
inhibition of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates
(CYP1A2,3A4,2E1,2D6)
Level AClinical trials
Use with caution under supervision of a healthcare professional and monitor
May have additive hypotensive effect to drug
May increase drug effectAntihypertensive drugs
Soy/isoflavonesGlycine max
Moderate - High
Moderate - High
High
Moderate - High
Moderate - High
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Low - Moderate
Level Din vitro study (Drug-herb
interaction was not directly studied. Saw palmetto extract showed an inhibitory effect on
5-alpha reductase activity)
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug due to inhibitory
effect on 5-alpha reductase
May increase drug effect
5-alpha reductase inhibitors
Theoretical
Level Din vitro study (Drug-herb
interaction was not directly studied. Saw palmetto decreased
the androgen-sensitive LNCaP human prostate cancer cell number in the presence of testosterone or
dihydrotestosterone)
Use with caution under supervision of a healthcare professional and monitor
May have inhibtory effect on 5-alpha reductase
May decrease drug effect
Androgen (Testosterone and dihydrotestosterone) Theoretical
Moderate
Moderate
Possible
Possible
Possible
Possible
Unlikely
Level CCase report (Drug-herb interaction
was not directly studied. Saw palmetto can lead to prolonged
bleeding time)
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Anticoagulants and antiplatelet agents
Theoretical Moderate - High
Pg.44 Pg.45
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Soy/isoflavonesGlycine max
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level BHuman studies (CYP2C9 and 3A4)
Level Din vitro studies (CYP1A2) and
animal study (CYP2E1)
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition of CYP1A2 and CYP2E1 enzyme activities and induction of CYP2C9
and CYP3A4 enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP2C9,
CYP2E1, CYP3A4)
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May have additive diuretic effect to drug
May increase drug effect
Diuretic drugs Theoretical
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May increase blood levels of drug
May increase drug side effect
Gemfibrozil Theoretical
Level AClinical trials
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycemic effect to
drug
May increase drug effect
Hypoglycaemic drugs
Level D Animal study Avoid concomitant use
Soy may have estrogenic activity and may
theoretically interfere with tamoxifen activity
May decrease drug effectTamoxifen
Level B Human study and case report
Use with caution under supervision of a healthcare professional and monitor
Soy may decrease blood levels of drug
May decrease drug effect
Thyroid hormone
Level AMultiple studies with oral
contraceptives, warfarin, protease inhibitors, reverse transcriptase
inhibitors, simvastatin, atorvastatin, verapamil, irinotecan, imatinib, methadone, cyclosporin,
tacrolimus, fexofenadine, nifedipine, midazolam,
omeprazole, voriconazole
Avoid or consult with healthcare professional before concomitant us
May increase or decrease blood levels of drug via
induction of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP2C19,
CYP3A4)
St John’s wortHypericum perforatum
Level Din vitro study
Avoid High doses (>7 g) prior to surgery. Use with caution under supervision of a
healthcare professional and monitorMechanism unknownMay increase drug
effect Chemotherapeutic agents Theoretical
Moderate - High
Moderate - High
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Moderate
Moderate
Possible
Possible
Possible
Level Din vitro studies (fermented soy
products contain tyramine)
Use with caution under supervision of a healthcare professional and monitor
Tyramine in fermented soy products may cause additive blood pressure
effect
May increase drug effect
Monoamine Oxidase Inhibitors (MAOI) Theoretical
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase blood level of drug via inhibition of P-gp
May increase drug effect
P-glycoprotein substrates (daunorubicin)
Theoretical
Level AClinical trials
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug side effect Progesterone
Variable (depending
on drug and disease
state)
Moderate Possible
Likely
Level BHuman study and case report
(Warfarin)Avoid concomitant use
Soy protein may decrease the anticoagulant effect of
warfarin
May decrease drug effect
Anticoagulant and antiplatelet agents
Moderate - High Possible
Moderate - High
Moderate - High
Moderate
Possible
Level AClinical trials
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
HMG-CoA reductase inhibitors
(Atorvastatin, simvastatin)
Low - ModeratePossible
Pg.46 Pg.47
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level B Human study of the various CYP
enzymes
Avoid or consult with healthcare professional before concomitant use
May increase or decrease blood levels of drug via
induction of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP2B6,
CYP2C9, CYP2E1 and CYP 1A2)
St John’s wortHypericum perforatum
Level AClinical trials Avoid concomitant use
St John’s wort may decrease blood levels of
this medication
May decrease drug effectDigoxin
Level Din vitro and animal studies Avoid concomitant use
May have additive serotonergic effect
May increase drug side effect
Pethidine and dextromethorphan
Theoretical
Level AClinical trials - interaction seen at
doses over 2 g/d (dried herb)
Avoid or consult with healthcare professional before concomitant use
St John’s wort may decrease blood levels of these medications via induction of P-gp
expression
May decrease drug effectP-glycoprotein substrates
Level CCase study of aminolevulinic acid.
in vitro study
Use with caution under supervision of a healthcare professional and monitor
Hypericin content of St John’s wort may
increase the possibility of photosensitivity reactions
May increase drug side effect
Photosensitising drugs
Level BMultiple case reports of
serotonergic syndrome. Human study in patients taking
amitriptyline. Case report of monoxidase activity
Avoid concomitant use
St John’s wort has additive serotonergic effects that
can lead to serotonin toxicity when taking the
respective antidepressants concomitantly
May increase drug effect
Prescription antidepressants -
tricyclics, SSRIs and SNRIs, MAOIs
Level C Case report
Avoid concomitant useMay have additive serotonergic effect
May increase drug effect
Triptans
Level Din vitro and animal studies (Drug-herb interaction was not directly studied. 10 mg/kg of lyophilized aqueous extract of tribulus fruit decreased ACE activity in rats)
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Antihypertensive drugs (ACE inhibitors)
Theoretical
Tribulus Tribulus terrestris
Moderate - High
Moderate - High
Moderate - High
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Moderate
Moderate
Moderate
Level DAnimal study (Tribulus dry extract ameliorated the damage induced
by cyclophosphamide in mice testes)
No evidence from human studies to support clinical recommendations
May have antioxidative effect
Herb effect on drug (May improve
reproductive damage induced by cyclophosphamide)
Cyclophosphamide Theoretical Low
Level DAnimal study (Tribulus fruit
extract at dose 100, 300 and 500 mg/kg body weight provided
protection against the cisplatin induced renal toxicity in mice)
No evidence from human studies to support clinical recommendations
May decrease cisplatin accumulation in kidney via diuretic effect of tribulus
Herb effect on drug (May decrease renal
side effects induced by cisplatin)
Cisplatin Theoretical Low
Possible
Possible
Possible
Possible
Likely
Possible
Level AClinical trials (Drug-herb
interaction was not directly studied. Tribulus terrestris showed a significant blood
glucose-lowering effect in diabetic women compared to placebo.)
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Hypoglycaemic drugs Theoretical Moderate - High
Pg.48 Pg.49
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level DConflicting data in vitro study Avoid concomitant use
Antioxidant effect of curcumin may inhibit
apoptosis
May increase or decrease drug effect
Chemotherapeutic agents Theoretical
TurmericCurcuma longa
Level Din vitro and animal studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease substrate blood levels via inhibition of this enzyme
activity
May increase or decrease drug effect
CYP1A1 substrates Theoretical
Level BHuman studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease substrate blood levels via inhibition of this enzyme
activity
May increase or decrease drug effectCYP1A2 substrates
Level BHuman studies
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease substrate blood levels via induction of this enzyme
activity
May increase or decrease drug effect
CYP2A6 substrates
Level CCase report on tacrolimus
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease substrate blood levels via inhibition of this enzyme
activity
May increase or decrease drug effectCYP3A4 substrates
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
May compete with estrogen binding sites
(dose dependent)
May increase or decrease drug effectOestrogen Theoretical
Level BHuman study (for glibenclamide)
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycaemic effect
May increase drug effect
Hypoglycaemic drugs
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May increase blood levels of drug
May increase drug effect
Norfloxacin Theoretical
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May increase drug blood levels via inhibition of P-gp
May increase drug effect
P-glycoprotein substrates Theoretical
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May increase drug blood levels due to increased
bioavailability
May increase drug effect
Paclitaxel Theoretical
Level BHuman studies
Avoid concomitant useMay increase drug blood levels
May increase drug effect
Sulfasalazine
Level CCase report (Case of patient
self-medicating with valerian and passion flower while on 2 mg
lorazepam)
Avoid concomitant useMay have additive effect to drug by binding to the
GABA receptors
May increase inhibitory activitiy of drug and drug side
effect
Benzodiazepines (Lorazepam, alprazolam)
ValerianValeriana officinalis
Moderate - High
Moderate - High
Moderate - High
Moderate - High
Level Din vitro studies find antiplatelet
effect
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug (antiplatelet effect) at high doses (o ver 15 g/d)
May increase drug effect
Anticoagulants and antiplatelet agents
TheoreticalModerate -
High
Moderate - High
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Moderate
Variable (depending
on drug and disease
state)
Possible
Possible
Possible
Possible
Possible
Possible
Pg.50 Pg.51
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
Level AClinical trial (1000 mg of valerian tablet daily did not significantly
change CYP3A4 and CYP2D6 activities)Level D
in vitro studies showed moderate to potent CYP3A4 inhibitory
effects by valerian. Another in vitro study showed an induction of CYP3A4 and CYP2D6 activities
by valerian
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
inhibition or induction of these enzyme activities
May increase or decrease drug effect
CYP450 enzyme substrates (CYP3A4,
CYP2D6)
ValerianValeriana officinalis
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level AClinical trial (4 weeks treatment
of valerian 530 mg at night 1 hour before sleep improved
neuropsychiatric adverse effects of efavirenz such as anxiety and
insomnia)
Use with caution under supervision of a healthcare professional and monitor
May act on GABA-A receptor and boost melatonin release
Herb effect on drug (May prevent efavirenz-induced neuropsychiatric adverse effects)
Efavirenz
Level Din vitro study (Inhibitory effects
of valerian on the glucuronidation of paracetamol, estradiol and
morphine)
Use with caution under supervision of a healthcare professional and monitor
May have inhibitory effects on glucuronidation
May decrease excretion of drug
UGT substrates (UGT1A1, UGT2B7) (Paracetamol,
estradiol, morphine)Theoretical
Level AClinical trials
Assess nutrient status and supplement if indicated. Interaction may be minimised
by separating dose of medication and vitamin A by at least 2 hours
Vitamin A absorption may be decreased by orlistat
Drug effect on nutrient (May decrease nutrient
effect)
OrlistatVitamin A
Level A Systematic review
Avoid concomitant useMay have additive effect to drug
May increase drug side effectRetinoids
Level DVitamin A and tetracycline are in the list of medications that may
produce intracranial hypertension
Avoid concomitant useMay have additive effect to drug
May increase risk of benign intracranial
hypertensionTetracycline
Level BHuman studies
Supplementation may be beneficial
Vitamin B2 found to have migraine preventive
activity. No additive effect with antimigraine drugs
investigated
Nutrient effect on drug (May increase drug
effect)
Migraine drugs Theoretical
Vitamin B2
Level BCase reports and human study
Avoid concomitant useVitamin C chelates
alumium and may increase aluminium absorption
May increase drug side effect (especially
in renal failure patients)
Aluminium-containing antacids
Vitamin C
Level AClinical trial (6 weeks treatment with both vitamin C 500 mg and grape seed polyphenol 1000 mg
daily increased blood pressure in hypertensive patients)
Avoid combination of vitamin C and grape seed in hypertensive patients
Unknown mechanism of the interaction
May have opposing effect to drug
Antihypertensive drugs + Grape seed
High
High
Moderate - High
Moderate - High
Variable (depending
on drug and disease
state)
Variable (depending
on drug and disease
state)
Low
Low
Low
Unlikely
Possible
Likely
Likely
Possible
Possible
Possible
Pg.52 Pg.53
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Vitamin C
Level CCase reports
Avoid concomitant use
Vitamin C may cause transient deterioration of cardiac function with
desferrioxamine
May have opposing effect to drug
Desferrioxamine
Level B Human studies
Use with caution under supervision of a healthcare professional and monitor
May increase blood levels of drug
May increase drug effect
Oestrogen
Level B Human studies
Use with caution under supervision of a healthcare professional and monitor
High doses of vitamin C (>3 g) may decrease the elimination rate of
paracetamol
May increase drug effect
Paracetamol
Level BOpen study Avoid concomitant use
May decrease blood levels of drug
May decrease drug effect
Protease inhibitors (Indinavir)
Level D Animal study
Use with caution under supervision of a healthcare professional and monitor
May increase drug absorption
May increase drug effect Aluminium TheoreticalVitamin D3
No significant adverse effect expected. Assess nutrient status and supplement
if indicated
Vitamin D3 improves bone mineral density and
decreases the risk of bone-related side effect
Nutrient effect on drug (May decrease
drug side effect)
Anticonvulsants Level A Clinical trials
No significant adverse effect expected in humans. Assess nutrient status and
supplement if indicated
Vitamin D3 decreases the risk of bone mineral
density loss with the initiation of antiviral
agents
Nutrient effect on drug (May decrease
drug side effect)
Antiretrovirals (Efavirenz, emtricitabine
and tenofovir) Level A
Clinical trials
Use with caution under supervision of a healthcare professional and monitor
May decrease blood level of drugs via induction of
CYP3A4 Nutrient effect on drugAtorvastatin
Level B Human studies
No significant adverse effect expected in humans. Use with caution under
supervision of a healthcare professional and monitor
Combination therapy may improve clinical outcome
Nutrient effect on drug (May increase drug
efficacy)Budesonide (oral) Level A
Clinical trials
Avoid concomitant use
May have opposing effect to drug. Decrease drug effect by causing
hypercalcemia with high doses of vitamin D3
May decrease drug effect (Dose
dependent)
Calcium channel blockers (Diltiazem and verapamil)
Level C Case report
Assess nutrient status and supplement if indicated
Mechanism unknownDrug effect on nutrient
(May decrease nutrient effect)
Chemotherapeutic agentsLevel B
Human study
Level Din vitro study
Avoid concomitant use
Antioxidants like vitamin C may reduce the activity of chemotherapeutic drugs or may make chemotherapy
more effective by reducing oxidative stress
May increase or decrease drug effect
Chemotherapeutic agents TheoreticalModerate -
High
Level Din vitro study
Assess nutrient status and supplement if indicated
Calcium channel blockers may inhibit uptake of
vitamin C by intestinal cells
Drug effect on nutrient (May decrease nutrient effect)
Calcium channel blockers (Nifedipine) Theoretical Moderate -
High
High
Moderate - High
Moderate - High
Moderate - High
Moderate - High
Moderate
Moderate
Low
Low
Low
Low - Moderate
Possible
Possible
Possible
Possible
Possible
Possible
Possible
Possible
Possible
Possible
Pg.54 Pg.55
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level B Human study
Assess nutrient status and supplement if indicated
Cimetidine inhibits an enzyme involved in
conversion of vitamin D to its active form in the
liver and affect vitamin D metabolism in men
Drug effect on nutrient (May decrease nutrient effect)
Cimetidine
Vitamin D3
Use with caution under supervision of a healthcare professional and monitor
May increase drug effect via inhibition of P-gp
May increase drug side effect
Digoxin Level B
Human study suggests no significant interaction
Assess nutrient status and supplement if indicated
Heparin and LMWH decrease the metabolism of vitamin D to its active
form
Drug effect on nutrient (May decrease nutrient effect)
Heparin and low-molecular-weight heparin
(LMWH)
Level B Human studies
Assess nutrient status and supplement if indicated. Interaction may be minimised
by separating dose of medication and vitamin D by at least 2 hours
Vitamin D absorption may be decreased by orlistat
Drug effect on nutrient (May decrease nutrient effect)
OrlistatLevel A
Clinical trials
Avoid concomitant useMay increase the
metabolism of sirolimusMay decrease drug
effectSirolimus
TheoreticalLevel B
Human study
Use with caution under supervision of a healthcare professional and monitor
Vitamin D3 may increase the risk of hypercalcaemia
if taken with calcium supplements and/or
thiazide diuretics
May increase drug side effect
Thiazide diuretics
Level AMultiple case reports.
Clinical trial in hypoparathyroid patients taking vitamin D and
thiazide diuretics
Level Din vitro study
Avoid concomitant useAntioxidant effects may reduce activity of drug
May decrease drug effect
Chemotherapeutic agents Theoretical
Vitamin E
Level AClinical trials in patients taking
vitamin E and cisplatin
Use with caution under supervision of a healthcare professional and monitor
Vitamin E may decrease the incidence and severity of neurotoxicity caused by
cisplatin
Nutrient effect on drug (May decrease drug
side effect)Cisplatin
Level Din vitro study
Use with caution under supervision of a healthcare professional and monitor
May increase or decrease blood levels of drug via
induction of this enzyme activity
May increase or decrease drug effect
CYP3A4 substrates Theoretical
Level AClinical trial
Use with caution under supervision of a healthcare professional and monitor
Vitamin E may prevent nitrate tolerance when given concurrently with
transdermal nitroglycerin
Nutrient effect on drug (May decrease drug
side effect)
Nitroglycerine
Level AClinical trial
Assess nutrient status and supplement if indicated. Interaction may be minimised
by separating dose of medication and vitamin E by at least 2 hours
Vitamin E absorption may be decreased by orlistat
Drug effect on nutrient (May decrease nutrient effect)
Orlistat
Moderate - High
Moderate - High
High
Moderate
Moderate
Low
Low
Low
Low
Variable (depending
on drug and disease
state)
Possible
Possible
Possible
Possible
Level AConflicting data.
Clinical studies have found no interaction with warfarin or
aspirin, or inhibition of platelet aggregation.
Case reports of interaction with warfarin and reduced clotting exist
Use with caution under supervision of a healthcare professional and monitor
Vitamin E may increase risk of bleeding
May increase drug effect
Anticoagulants and antiplatelet agents
Moderate - High
Unlikely
Likely
Likely
Likely
Likely
Moderate - High
Pg.56 Pg.57
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Vitamin K
Level Din vitro study (Drug-herb
interaction was not directly studied)
Use with caution under supervision of a healthcare professional and monitor
Binding to dopamine-2 receptor and suppresses prolactin release due to
dopamine agonistic effects of vitex
May increase or decrease drug effect
Dopamine receptor antagonist and agonist Theoretical
Vitex Vitex agnus-
castus
Level Din vitro and animal studies
(Drug-herb interaction was not directly studied. Vitex may exhibit estrogen receptor binding effects and induce progesterone receptor
expression)
Use with caution under supervision of a healthcare professional and monitor
Via hormone modulating activity
May increase or decrease drug effect
Oestrogen, contraceptive drugs
Theoretical
Level C Case report
Use with caution under supervision of a healthcare professional and monitor
May have additive adverse effect to drug as willow contains salicin, a plant
salicylate which may increase unbound plasma
level of acetazolamide
May increase drug side effect
Acetazolamide
Willow Salix alba
Level BCohort study reported increased
self-reported bleeding when taken with warfarin.
Clinical trial using herb alone found a mild antiplatelet effect
Avoid concomitant useMay have additive effect
to drug as willow contains salicin, a plant salicylate
May increase drug effect
Anticoagulants and antiplatelet agents
Level D Animal study (Co-administration of extract of withania coagulans
Dunal dried fruit (1000 mg/kg) and glipizide (1 mg/kg or 2.5 mg/kg) for
4 weeks in rats)
Use with caution under supervision of a healthcare professional and monitor
May have additive effect to drug
May increase drug effect
Hypoglycaemic drugs (Glipizide)
Theoretical
WithaniaWithania coagulans
Level AClinical trials
Assess nutrient status and supplement if indicated
Urinary zinc excretion may be increased with long-term use of these drugs
Drug effect on nutrient (May decrease nutrient effect)
ACE inhibitors, angiotensin receptor
blockers, thiazide diuretics
Zinc
Level DHuman study that suggests higher intake of vitamin K1 is associated with increased insulin sensitivity and reduced postprandial glucose
levels in adults but no direct study between vitamin K and
hypoglycaemic drugs
Use with caution under supervision of a healthcare professional and monitor
May have additive hypoglycaemic effect
May increase drug effect
Hypoglycaemic drugs Theoretical Moderate - High
Moderate - High
Moderate - High
Moderate
Moderate
Moderate
Low
Level AClinical trials and meta-analyses Avoid concomitant use
Vitamin K may decrease activity of warfarin and
other coumarin (oral) anticoagulants. Avoid changes in vitamin K
intake whilst taking these drugs
May decrease drug effect
Anticoagulant and antiplatelet agents
Moderate - High
Likely
Possible
Possible
Possible
WithaniaWithania somnifera
See “Ashwagandha”
Pg.58 Pg.59
INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER
EVIDENCENATURE of INTERACTION
SEVERITY of
OUTCOME
LIKELIHOOD of
INTERACTIONRECOMMENDATION
SEVERITY of
OUTCOMEINGREDIENT MECHANISM of
INTERACTIONDRUG, DRUG CLASS,
ENZYME or TRANSPORTER
Level B Human study
Interaction may be minimised by separating dose of zinc at least 3 hours
after taking cephalexin
Zinc may decrease absorption of drug by chelating with drug
May decrease drug effect
CephalexinZinc
Level AClinical trials
Assess nutrient status and supplement if indicated. Monitor blood glucose level and alter drug dose if required under the supervision of a healthcare professional
Low zinc status is common in diabetic patients. Zinc
supplementation and normalisation of zinc
levels has been shown to improve glycaemic control
Nutrient effect on drug (May increase drug
efficacy)
Hypoglycaemic drugs
Level A Systematic review Avoid concomitant use
May decrease blood level of drug by chelating with
drug
May decrease drug effect Integrase inhibitors
Level AClinical trial
Interaction may be minimised by separating dose of medication and zinc
by at least 2 hours
Zinc may decrease the activity of penacillamine
May decrease drug effect
Penicillamine
Level BMultiple studies
Interaction may be minimised by taking tetracycline at least 2 hours before, or
4-6 hours after zinc supplement
Zinc may decrease the absorption and blood levels of these drugs
May decrease drug effect
Tetracycline or quinolone antibiotics (not
doxycycline)
High
High
Moderate
Moderate
Low
Possible
Possible
Likely
Possible
Possible
Pg.60 Pg.61
INDEX
EchinaceaEchinacea purpureaEvening primrose oil
FFenugreek Trigonella foenum-graecum Feverfew Tanacetum partheniumFish oilFlaxseed oilFolic acid
GGarlicAllium sativumGingerZingiber officinaleGinkgoGinkgo bilobaGinseng (Korean) Panax ginsengGinseng (Siberian) Elutherococcus senticosusGlucosamineGreen-lipped musselGrape seedVitis vinifera
HHawthornCrataegus monogyna Holy basilOcimum tenuiflorumHopsHumulus lupulusHorsetailEquisetum arvense
IIodineIron
K Kelp Fucus vesiculosus
AAcidophilusSee “Probiotics”Alpha-lipoic acid (ALA)AndrographisAndorgraphis paniculataAshwagandha Withania somniferaAstragalusAstragalus membranaceus
BBacopaSee “Brahmi”BetacaroteneBilberry Vaccinium myrtillusBlack cohoshCimicifuga racemosaBoswellia Boswellia serrataBrahmi Bacopa monnieriBromelain
CCalciumCelery Apium graveolens) Chaste TreeSee “Vitex”Chondroitin sulfateChromium Co-enzyme Q10 (CoQ10)ColeusColeus forskohlii CranberryVaccinium macrocarpon
D Dong quai Angelica polymorpha
E EchinaceaEchinacea angustifolia
INDEX
L Liquorice Glycyrrhiza glabra Lutein
MMagnesiumL-methionineMilk thistle/St Mary’s thistle Silybum marianum
N Nicotinic acid
O Oats (Avena sativa)
PPara-aminobenzoic acid (PABA)Pau d’Arco Tabebuia avellanedaePelargonium Pelargonium sidoidesPeppermint Mentha x piperitaPhytosterols / Plant sterolsPotassiumProbioticsLactobacillus species including:L. acidophilusL. reuteriL.Rhamnosus GR-1L. Reuteri RC-14Psyllium husk
Q Quercetin
R Red clover/Isoflavones Trifolium pratense
SSaw palmetto Serenoa repensSoy/isoflavonesGlycine maxSt John’s wortHypericum perforatum
T Tribulus Tribulus terrestrisTurmericCurcuma longa
V ValerianValeriana officinalisVitamin AVitamin B2Vitamin CVitamin D3Vitamin E Vitamin KVitex Vitex agnus-castus
W Willow Salix albaWithania Withania somniferaSee “Ashwagandha”WithaniaWithania coagulans
Z Zinc
Pg.62
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