Complementary medicine interactions guide - Blackmores CMIG_FINAL 9th... · Complementary medicine interactions guide ... send a ‘blue card’ adverse reaction reporting form to

For healthcareprofessionals

Complementarymedicineinteractionsguide

9TH EDITION AUGUST 2016

Now available online. Visit www.blackmoresinstitute.org

Pg.2 Pg.3

K E Y

Theoreticalin vitro and/or

animal evidence with unclear implications

Unlikely evidence suggests this interaction can

occur, but is not likely

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 hospitalisation may

be 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

Likeli-hood

Level of evidence

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 advise. 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 manufacturers of both the complementary medicine and the medication.

ABOUT THIS GUIDE

Blackmores Institute has produced this comprehensive reference guide for healthcare professionals. It provides easy access to information about the evidence for interactions between complementary medicines and drugs.

For the most part, complementary medicines can be used alongside conventional treatments, however some complementary medicines may interact with certain medications to reduce, or sometimes increase, the effect of one or the other, or to cause potential harmful effects.

Severity, likelihood and level of evidence is provided to assist in assessment of risk and to support appropriate recommendations.

More than half of all Australians take complementary medicines and this number is increasing all the time. Hence it is critical that the natural healthcare industry is committed to providing the highest quality products, and to ensuring healthcare professionals have the support required to recommend complementary medicines safely and effectively.

Blackmores Institute

Blackmores Institute was established as a centre of excellence in the field of natural health research and education. Our mission is to improve public health outcomes through the quality use of complementary medicines. The Institute is a driver of research, evidence translation, education and healthcare advice and is dedicated to sharing this knowledge with the wider community of healthcare professionals, researchers, industry and consumers. We work with a wide range of thought-leaders and experts in complementary medicine practice and research and focus on furthering the application and relevance of natural health.

Research

Blackmores has a long association with supporting research into natural medicine within Australia either through financial support, supply of clinical trial materials or through holding research symposia.In following that established lead, Blackmores Institute works with some of Australia’s best education and research bodies and supports a wide range of complementary medicine research. Research is currently being conducted at such institutions as the Swinburne University, University of Sydney, Southern Cross University, Monash University and Western Sydney University. Blackmores Institute is also forging ties with universities in Asia.

Education

Blackmores Institute offers CPD-accredited, evidence-based education for health professionals. This education can be accessed by healthcare professionals after registering on the Blackmores Institute website. We believe that education is key in helping pharmacists, doctors and other health professionals translate evidence into practice, to integrate natural medicine into patient care. We have established partnerships with leading higher education providers to further this goal and have hosted our own highly successful symposia in Australia, Asia and NZ.

Subscribe at blackmoresinstitute.org

The Blackmores Institute website is designed to provide healthcare professionals with the latest news, opinion and research pieces online or via a weekly email update. This information is a user-friendly and valuable resource for health professionals looking to keep up-to-date with evidence-based research on natural medicines sourced from peer-reviewed, scientific, nutrition and medical journals.

Healthcare Professional Advisory Service

Our Healthcare Professional Advisory Service has been providing free quality support and trusted advice in complementary medicine for over 25 years, to help guide the safe and appropriate use of natural medicines. This service is provided by our team of qualified naturopaths, along with the support of a qualified pharmacist. Call our dedicated healthcare professional line on 1800 151 493 to use this service.

9th Edition

Pg.4 Pg.5

INGREDIENT MECHANISM LIKELIHOOD RECOMMENDATIONSDRUG/CLASS/ENZYME/TRANSPORTER

EVIDENCENATURE of INTERACTION

SEVERITY of

OUTCOMEINGREDIENT LIKELIHOOD RECOMMENDATIONS

SEVERITY of

OUTCOME

AndrographisAndrographis

paniculata

Alpha-lipoic acid(ALA)

Acidophilus

AstragalusAstragalus

membranaceus

Black cohoshCimicifuga racemosa

Calcium

Betacarotene

Anticoagulants and anti-platelet drugs

Increases drug effect


Additive effect to drug

Additive hypoglycaemic effect

Level DAnimal and in vitro study

Level DPreliminary animal studies

Level AClinical trials suggest ALA may

affect glucose-lowering effect of these medication

Level DAnimal and in vitro studies



Level DIn vitro study on mice breast

cancer cell line

Level CCase reports

Level CCase report and study in

patients with arrhythmia using i.v. calcium

Level BSmall human study. Calcium-rich food considered to be the major reason for reduced absorption

Level A (quinolones)Level B (bisphosphonates)Level C (tetracyclines, thyroid hormones)

Level A Clinical trials

Theoretical

Theoretical

Possible

Possible

Possible

Theoretical

Theoretical

Theoretical

Theoretical

Likely

Unlikely

Unlikely

High

Variable

Variable

Moderate

Moderate

Moderate

Moderate

Moderate

Moderate

Use with caution under supervision of a healthcare professional









Interaction can be avoided by separating dose of medication and calcium by at

least 2 hours

Interaction can be avoided by separating dose of medication and calcium by at

least 2 hours

Interaction can be avoided by separating dose of medication and betacarotene by at least 2 hours. Supplementation

recommended

CYP1A1, CYP1A2 and CYP2B substrates

Bisphosphonates, tetracycline or quinolone

antibiotics, thyroid hormones

Decreases drug effect







Increases drug side effects

Drug effect on nutrient

Conflicting

Immunosupressants

Immunosupressants

See ‘probiotics’

Hypoglycaemic drugs

Thyroxine

Low

Low

Low

Chemotherapeutic drugs

Atenolol, Sotolol

Thiazide diuretics

Calcium channel blockers

Calcium may increase the risk of hypercalcaemia with

these drugs

Orlistat, Plant sterols

Decreases blood levels of substrates

Opposing effect to drug

Betacarotene absorption may be decreased by

these drugs

Calcium may decrease absorption of atenolol

and sotalol

Calcium may decrease the hypotensive effect of

verapamil

Calcium may decrease the absorption and efficacy of

these drugs

Immunostimulant activity

Increased cytotoxicity of docetaxel and doxorubicinDecreased cytotoxicity of

cisplatin

Co-administration of thyroxine with ALA may decrease conversion to

active T3 form

CeleryApium

graveolens

Level CCase reports Unlikely Moderate

Use with caution under supervision of a healthcare professionalDecreases drug effectThyroxine Decrease blood levels of

drug

Pg.6 Pg.7



SEVERITY of

OUTCOME

Possible

Possible

Possible

Possible

Possible

Additive hypotensive effect

Level AClincial trial in leukaemia and

lymphoma patients

Level AConflicting data

Clinical trials

Level BClinical studies in

glaucoma patients


Clinical trial found no interaction.Case reports of changes to INR

Level ASeveral studies in patients with

hyperlipidaemia; statins decreased plasma CoQ10 levels (effect on

tissue levels not established)

Level ACoQ10 found to have migraine preventive activity. No additive effect with antimigraine drugs

investigated


Clinical trials show conflicting results. Systematic review

found inadequate evidence to recommend routine use with

statins

Level AMeta-analyses in patients taking

antihypertensive drugsLevel D

In vitro studies found beta blockers inhibited mitochondrial CoQ10

enzymes

Theoretical

Theoretical

Low

Low

Low

Low

Low

Low

Low No significant adverse effect expected Supplementation may be beneficial

Supplementation may be beneficial







Avoid, or consult with healthcare professional before concomitant use



Decreases drug side effects




Chemotherapeutic drugs (anthracyclines such as

daunorubcin, doxorubicin)

B-blocker adrenergic agents

Hypoglycaemic drugs

Migraine drugs

Warfarin

HMG-CoA reductase inhibitors (statins)


Ocular timolol (glaucoma medication)

Antihypertensive drugs Likely

Likely

CoQ10 levels may be decreased by these drugs

CoQ10 may decrease cardiovascular side effects

of these drugs

CoQ10 levels may be depleted by these drugs

CoQ10 may decrease myalgia associated with

statin use

CoQ10 may decrease cardiovascular side effects

of this medication but does not affect efficacy


CoQ10 may increase or decrease the anticoagulant

effect of warfarin

Additive antimigraine effect

Conflicting

Conflicting

Conflicting

Co-enzyme Q10 (CoQ10)

High

Moderate

ColeusColeus forskohlii Additive effect to drug


Level DAnimal studies

Level BAnimal and human studies using

i.v. extractsRelevance to oral doses unknown.

Theoretical

Theoretical

High

Low


No significant adverse effects expected



Anticoagulants and antiplatelet drugs

Antihypertensive drugs

CranberryVaccinium

macrocarponLevel D Theoretical Variable N/AIncreases effect of

substratesCYP3A substrates

Increases blood levels of substrates (high-strength

preparations)

Pg.8 Pg.9



SEVERITY of

OUTCOME

Evening primrose oil

EchinaceaEchinacea

angustifolia Echinacea purpurea

FenugreekTrigonella

foenum-graecum

FeverfewTanacetum parthenium

Fish oil

Flaxseed oil

Level BAnimal studies, in vitro and

in vivo evidence of immunomodulatory effects

No case reports of interaction

Level BConflicting data

Human study found no interactionCase reports of seizures exist in

patients with schizophrenia


In vitro and in vivo studies found feverfew inhibits platelet

aggregationHuman study found no such effect


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

Unlikely

Unlikely(possible with high

doses)

Unlikely(possible with high

doses)

Likely

Likely

High

High

High

Moderate

Moderate






No significant adverse effect expected. Supplementation may be beneficial

Interaction unlikely at normal doses


Decreases drug effectImmunosupressants

Hypoglycaemic drugs

Phenothiazines


May lower seizure threshold

May have additive effect to drug

High doses of fish oil (>3 g/d omega-3 fatty acids)

may increase the risk of bleeding with these drugs

High doses (30-40g/d) of flaxseed oil may increase the risk of bleeding with

these drugs

May increase blood levels of drug


Conflicting

Conflicting

Conflicting

Conflicting

Possible

Dong quaiAngelica

polymorphaAdditive effect to drug


Level DSeveral case reports and animal study. No reports of abnormal

bleeding

Level DIn vitro study found low inhibitory

activity

Level AMeta-analyses in patients taking

anti hypertensive drugs

Level AConflicting dataHuman studies

Level AHuman studies and meta-analyses

confirm blood glucose-lowering effect in patients with

type 2 diabetes

High Use with caution under supervision of a healthcare professionalIncreases drug effect





Warfarin, Aspirin, Antiplatelet drugs




CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP3A4

substrates

Unlikely

Unlikely HighUse with caution under supervision of a

healthcare professionalMay increase blood

levels of drugConflicting


Clinical studies suggest no interaction

Case reports exist.In vitro studies suggest cranberry may affect warfarin metabolism

(CYP3A4 minor metaboliser)

WarfarinCranberryVaccinium

macrocarpon

Theoretical

Theoretical Low

Low

High

Pg.10 Pg.11



SEVERITY of

OUTCOME

Folic acid

GarlicAllium sativum

GingerZingiber officinale

GinkgoGinkgo biloba

Anticonvulsant drugs

Fluorouracil

Methotrexate

Intestinal ABCB1 and ABCC2 substrates

Co-trimoxazole, sulphazalazine, phenytoin, phenobarbital, primidone

and methotrexate


Anticoagulants and antiplatelet agents

CYP2E1 substrates


CYP2C19 enzyme substrates

Antihypertensive medication






Conflicting

Conflicting

Conflicting

Conflicting


Increases drug side effect

Folic acid may decrease the efficacy of phenytoin. Phenytoin and folic acid

should be commenced at the same time

May decrease efficacy of folic acid supplements

Folic acid may increase the toxicity of flourouracil

Increase blood levels of substrates

May increase the risk of bleeding with these

medications

May induce these enzymes and increase clearance of substrates


Increases risk of seizure

May increase the risk of bleeding with these

medications

May decrease blood levels of substrates via

upregulation of intestinal ABCB1 or ABCC2 activity

Folic acid may decrease the efficacy of

methotrexate for children with lymphoblastic

leukaemiaFolic acid may decrease

drug side effect in rheumatoid arthritis

Level BUncontrolled studies in patients with epilepsy

Level BIn vitro and human studies found

garlic decreases levels of the protease inhibitors saquinivir and

ritonavir


Human studies show conflicting results. Interaction more likely at high doses (>7 g). Case reports

exist

Level AHuman studies indicate

antihypertensive activity with aged garlic extract (480-960 mg/d)

Level BConflicting Data

Ginkgo decreased levels of omeprazole, but had no effect on

voriconazole

Level AConflicting Data

In vitro studies indicate ginger inhibits platelet aggregation

however normal doses ≤4 g/d are unlikely to cause platelet

dysfunction

Level DMultiple case reports

Level DCase reports

Level AClinical trials

Level C

Level BIn vitro and open studies using

chlorzoxazone

Possible

Possible

Possible

Possible

Possible

High

High

High

High

Start phenytoin and folic acid at the same time, under supervision of a treating

physician

Low

Low


Avoid high doses (>7 g) prior to surgery. Use with caution under supervision of a

healthcare professional

Do not use high doses (≥4 g) in patients with bleeding disorders or those taking

antiocagulant medication. Use with caution under supervision of a healthcare

professional






Unlikely

Unlikely

Unlikely

Unlikely

Moderate

ModerateLikely

Likely

Variable

Variable

Variable

N/A

N/A

Pg.12 Pg.13



SEVERITY of

OUTCOME

GinkgoGinkgo biloba

Ginseng (Korean) Panax ginseng

Ginseng (Siberian)

Eleutherococcus senticosus

Chlorpromazine and haloperidol

Warfarin, aspirin, antiplatelet drugs

Hypoglycaemic drugs

Digoxin

Hypoglycaemic drugs

MAO inhibitors(Phenelzine)

MAO inhibitors(Phenelzine)

AnticoagulantsWarfarin

Digoxin

Warfarin




Test interferance



Ginkgo may add to the beneficial effect of

halperidol, chlorpromazine and olanzapine in the

treatment of schizophrenia

Level AMeta-analysis and studies

Level BIn vitro, animal and human

ex vivo studies

Level AHuman studies in patients with

type 2 diabetes and healthy subjects

Level CCase reports

(ginseng type not specified)


Clinical studies suggest no interaction

Case reports exist.In vitro studies suggest interaction

Level DIn vivo study found anticoagulant activity for an isolated constituent.

Human study in athletes administered a preparation

of Siberian ginseng and andrographis found reduced

coagulation.

Level BIn vitro, animal and human ex vivo

studies

Level C2 case reports



Human trials find ginkgo does not have a significant effect on platelet function and does not interact with warfarin, aspirin

or clopidogrel.Lower quality evidence

(case reports) have suggested an interaction is possible.


Low

Low

Likely

Likely


Conflicting

Conflicting

Conflicting

Test interferance

Ginkgo may increase or decrease blood glucose

levels

Korean ginseng may falsely elevate assays for

blood digoxin

Korean ginseng may increase side effects

of phenelzine or other MAOIs


Korean ginseng may increase or decrease

anticoagulant/antiplatelet effects

Siberian ginseng may falsely elevate assays for

blood digoxin

Siberian ginseng may increase risk of bleeding with these medications

Siberian ginseng may increase side effects

of phenelzine or other MAOIs

Ginkgo may increase the risk of bleeding with

these medications

Unlikely

Unlikely

Unlikely

Unlikely









Use with caution under supervision of a HCP. If unusual bleeding or bruising

occurs, stop use immediately. Suspend use for 1 week prior to major surgery in

at-risk patients.

High

High

High

Possible

Possible

Possible

Moderate

Moderate

Moderate

Moderate

Moderate

Theoretical

Pg.14 Pg.15



SEVERITY of

OUTCOME

Ginseng (Siberian)

Eleutherococcus senticosus

Glucosamine

Iodine

Iron

Green-lipped mussel

HawthornCrataegus monogyna

Holy basilOcimum

tenuiflorum

HopsHumulus lupulus

Chemotherapeutic drugs

Hypoglycaemic drugs

Warfarin

Warfarin

Lithium carbonate

Thyroxine

Hypoglycaemic medications


CYP450 enzyme substrates 1A1, 1A2, 1B1, 2C8, 2C9,

2C19, 3A4

Bisphosphonates, tetracycline and quinolone

antibiotics, thyroid hormone, methyldopa,

carbidopa, levadopa and penicillamine


Conflicting









Siberian ginseng may increase tolerance for chemotherapy

and improve immune response

Glucosamine may affect blood glucose levels in

diabetics



Hops may increase blood levels of these

medications

Iodine at high doses may increase the hypothyroid

activity of lithium carbonate

Iodine (at very high doses) may precipitate or exacerbate hyper- or

hypothyroidism

Iron may decrease the absorption and efficacy

of these drugs. Dose separation of 2 hours is

recommended

Glucosamine may increase the risk of bleeding with

this medication

Green-lipped mussel may increase the risk of bleeding

with this medication

Level C2 case reports


Level CCase reports

Level AClinical trials suggest

hypotensive effect

Level DIn vitro studies

Level DCase reports and open study in

patients taking lithium

Level DCase report and studies in

euthyroid subjects - thyroid function inhibited

Level AClinical trial in patients with type 2 diabetes found Holy basil may

decrease blood glucose levels

Level AClinical trials indicate

no interactionLower-level studies report changes to glucose and

insulin levels


Several case reports of raised INRSmall human study found no

effect on platelet aggregation, prothrombin time, APTT,

fibrinogen or factor VII

Level BEvidence of chelation formation

with bisphosphonates, tetracyclines, quinolones

Studies in patients (thyroid hormone, carbidopa , levodopa,

methyldopa) and healthy subjects (penicillamine, tetracyclines,

quinolones)

Likely Moderate

Moderate

Moderate









Interaction can be avoided by separating dose of medication and iron

by at least 2 hours

Interaction unlikelyUnlikely

Unlikely

Unlikely

Low

Low

Low

Low

Low

Possible

Possible

Possible

Possible

Possible

High

High

Theoretical

Pg.16 Pg.17



SEVERITY of

OUTCOME

KelpFucus vesiculosus

Magnesium

LiquoriceGlycyrrhiza glabra

Thyroxine


Digoxin

Amphotericin-B

Antiarrythmic drugs

Loop and thiazide diuretics

Antihypertensive drugs (calcium channel blockers)

Potassium-depleting diuretics, laxatives

Corticosteroids(Prednisolone)

Anticoagulant/antiplatelet drugs

Increases or decreases drug effect

Increases or decreases drug effect



Increases drug effectConflicting (warfarin)





Increased blood levels of drug

Magnesium may have an additive antiarrhythmic

effect

Magnesium may have an additive hypotensive effect


Kelp (at very high doses) may precipitate or exacerbate hyper- or

hypothyroidism

Liquorice may increase the risk of digoxin

toxicity (possibly via hypokalaemia and/or

inhibition of P-gp)

Liquorice (at high doses - over 100 g/d)

may increase the risk of electrolyte disturbances, especially hypokalaemia, with these medications

Electrolyte distrubances, including low serum

magnesium levels, may occur with this medication. This has been associated with nephrotoxicity, and may necessitate stopping the

drug and giving intravenous electrolyte replacement

Loop diuretics and, to a lesser extent thiazide diuretics, interfere with

magnesium reabsorption in the kidneys, which

increases urinary losses and may reduce serum

magnesium levels

Additive effect to drug classes, however may

induce CYP3A4 and 2C9 (metabolisers of warfarin)

which may decrease blood levels of warfarin

Hypertensive effect (at high doses 50-200 g/d)

Level AClinical trial found T3 decreased,

TSH increasedCase reports of hyperthyroidism

and hypothyroidism

Level BOpen studies and case report

Level BOpen human studies

Level BIn vitro and in vivo studies

Level BHuman studies and case reports

Level AMeta-analysis

Level BMultiple studies and case reports

Level CIn vitro study, animal study and

case report

Level BOpen human studies (dosage 100-

200 g/d) and case reports

Level AClinical trial using

high dose of magnesium (3204 mg/d magnesium chloride)

Possible

Possible

Possible

Possible

Possible

Possible

Possible

Possible

Moderate

Moderate

Moderate

Moderate










Supplementation recommended when taking these drugs long term

Low

Low

Low

Unlikely High

High

Likely (with long term use)

Moderate

Pg.18 Pg.19



SEVERITY of

OUTCOME

Magnesium

L-methionine

Milk thistle/St Mary’s thistle

Silybum marianum

Oats Avena sativa

Para-aminobenzoic

acid (PABA)

Pau d’ArcoTabebuia

avellanedae

Pelargonium sidoides

PeppermintMentha x piperita

Nicotinic acid

Proton pump inhibitors

Warfarin

Levodopa

CYP3A4 substrates

P-gp substrates


Immunosuppressant drugs

CYP3A4 enzyme substrates

Sulphonamides and sulphones

Warfarin Aspirin,

Antiplatelet drugs

Chemotherapeutic agents(cisplatin, doxorubicin)




Conflicting

Conflicting




PPIs may decrease magnesium absorption

Magnesium may reduce the efficacy of warfarin

Increased or decreased drug effect

Increased or decreased drug effect



PABA may decrease the efficacy of these drugs

Additive anticoaguant effect (very high doses)

Peppermint oil may increase blood levels of these

medications






Methionine may decrease the efficacy of levodopa in

Parkinson’s disease

Milk thistle may have cardioprotective activity against doxorubicin and

nephroprotective activity against cisplatin

High dose nicotinic acid (1500 mg/d) may increase the

risk of rhabdomyolysis and myopathy with statins

Level BMultiple studies and case reports

Level DIn vitro study

Level DIn vitro and animal studies

Level DCase reports

Level BIn vitro studies and human study

Level BOpen study using

felodipine, simvastatin

Level DIn vitro studies find pelargonium has immune modulatory activity

Level BOpen study in patients with

Parkinson’s disease

Level AHuman studies suggest

interaction is unlikely to be clinically significant.

Some in vivo and in vitro studies suggest milk thistle may affect

CYP isoforms

Level BOpen study found milk thistle

may decrease blood levels, however animal and in vitro

studies suggest increased blood levels

Level AClinical trials find oats decreases blood pressure. In one trial, 73% were able to stop or reduce their

medication.

Level B1 uncontrolled study found very

high dose of isolated constitutent prolonged prothrombin time

Likely (with long term use)

Moderate

Moderate

Moderate

Moderate

Moderate

Supplementation recommended when taking PPIs long term

High

High

Theoretical

Theoretical

Theoretical

Theoretical

Theoretical

Theoretical










Avoid concomitant use

No significant adverse effects expected. Possible beneficial effect

Possible

Possible

Possible

Possible

Low

Low

Low

Variable

Variable

Likely

Pg.20 Pg.21



SEVERITY of

OUTCOME

Phytosterols / Plant sterols

Statins(pravastatin)

Antibiotics

Fluconazole

Oral drugs

Hypoglycaemic drugs

Calcium channel blockers

Tamoxifen

Warfarin

Thyroxine

Tamoxifen

CYP450 enzyme substrates (1A1, 1A2, 2C8, 3A4)

ACE inhibitors, angiotensin receptor blockers and

potassium-sparing diuretics





Conflicting

May decrease drug effect

Conflicting

May decrease drug effect

ConflictingMay decrease

drug effect

ConflictingMay reduce drug effect





Additive LDL-c lowering effects

Potassium may increase the risk of hyperkalaemia

May restore gut flora and reduce diarrhoea secondary

to antibiotic therapy

Psyllium may decrease the absorption of oral

drugs if doses are taken concomitantly

Psyllium may decrease post-prandial insulin and

blood glucose levels

Quercetin may inhibit these enzymes and increase levels

of enzyme substrates

Soy protein may decrease the anticoagulant effect

of this medication

Soy may decrease blood levels of drug (decreased

absorption)

Soy may have oestrogenic activity and may

theoretically interfere with tamoxifen efficacy

Red clover may have oestrogenic activity and may

theoretically interfere with tamoxifen efficacy

Combination therapy may improve clinical outcome

Quercetin may increase activity of these drugs

Level AClinical trials and

systematic reviews

Level CMultiple case reports

Level AClinical trial in women with

vulvovaginal candidiasis

Level BHuman studies

Level DIn vivo study found increased

bioavailability for diltiazem

Level AClinical trial

level BHuman, animal and

in vitro studies

Level BCase report and

uncontrolled study

Level CCase reports

Level DConflicting data

In vitro and animal studies with soy and isolated isoflavones

Level DConflicting data

In vitro and animal studies with soy and isolated isoflavones

Level A Multiple trials in adults and children taking antibiotics

Likely

Likely

Likely

Low

Low

Low

No significant adverse effects expected. Supplementation may be beneficial

No significant adverse effects expected. Supplementation may be beneficial

Interaction can be avoided by separating dose of medication and psyllium by at

least 2 hours


Consult a healthcare professional before use if taking potasium-sparing diuretics or

ACE inhibitorsPotassium

Probiotics

Psyllium huskPlantago ovata

Quercetin

Lactobacillus species including:

L. acidophilusL. reuteri

L.Rhamnosus GR-1

L. Reuteri RC-14

Red clover/ Isoflavones

Trifolium pratense

Soy/IsoflavonesGlycine max

Possible (dose-

dependant)

Possible

Possible

Possible

Possible

Possible

High

High

Variable

Variable

Moderate

Moderate

Moderate

Moderate

Moderate







Interaction can be avoided by separating dose of medication and soy by at least 2

hours

Theoretical

Theoretical

Theoretical

Pg.22 Pg.23



SEVERITY of

OUTCOME

Digoxin

P-gp substrates

Orlistat

Migraine drugs

Desferrioxamine

Protease inhibitors (Indinavir)

Aluminium-containing antacids

Prescription antidepressants -

tricyclics, SSRIs and SNRIs

Warfarinaspirin, antiplatelet drugs



Variable







St John’s wort may decrease blood levels

of this medication

St John’s wort may decrease blood levels of

these medications

Additive effect to drug (antiplatelet effect) at high

doses (over 15 g/d)

Vitamin B2 found to have migraine preventive

activity. No additive effect with antimigraine drugs

investigated

Vitamin A absorption may be decreased by Orlistat

Vitamin C increases aluminium absorption

Decrease blood levels of drug

Vitamin C may cause transient deterioration

of cardiac function with desferrioxamine

St John’s wort may cause serotonergic

syndrome with SSRIsSt John’s wort may

decrease blood levels of tricyclic antidepressants



Level BHuman studies

Level BCase reports and human study

Level CCase reports

Level BOpen study

Level DIn vitro studies found

antiplatelet effect

Level AClinical trials - interaction seen at

doses over 2 g/d (dried herb)

Level BMultiple case reports of serotonergic syndrome

Human study in patients taking amitriptyline

Possible

Possible

Possible

Possible

Possible

Possible

Moderate

Moderate







Interaction can be avoided by separating dose of medication and vitamin A

by at least 2 hours. Supplementation recommended

Interaction can be avoided by separating dose of medication and vitamin C by at

least 2 hours

Variable

Variable

TurmericCurcuma longa

Vitamin A

Vitamin B2

Vitamin C

High

High

Theoretical

Theoretical

Likely Low

Low

Low

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

CYP450 enzyme substrates (2C19, 3A4)


St John’s wort increases activity of the these

enzyme systems and decreases levels

of enzyme substrates

LikelySt John’s wort

Hypericum perforatum

High Avoid, or consult with healthcare professional before concomitant use


Pg.24 Pg.25



SEVERITY of

OUTCOME

Vitamin E

Vitamin K

Willow Salix alba

Chemotherapy drugs (cisplatin)



Warfarin

Nitroglycerin

Orlistat







Vitamin E may prevent nitrate tolerance when

given concurrently with transdermal

nitroglycerin

Vitamin E (at doses over 400 IU/d) may increase

the risk of bleeding with these drugs


Vitamin K may decrease activity of warfarin and other coumarin (oral) anticoagulants. Avoid changes in vitamin K intake whilst taking

these drugs

Vitamin E absorption may be decreased by

Orlistat

Vitamin E may decrease the incidence and severity of neurotoxicity caused by

cisplatin

Level AClinical trials in patients taking

vitamin E and cisplatin


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

Level BCohort study reported increased

self-reported bleeding when taken with warfarin

Clinical trial using herb alone found a mild antiplatelet effect



Level AClinical trials and meta-analyses

Likely

Likely

Low

Low

Low

Supplementation under supervision of a healthcare professional may be beneficial

Interaction can be avoided by separating dose of medication and vitamin E by at

least 2 hours

Avoid, or consult with healthcare professional before concomitant use

Use with caution under supervision of healthcare professional. Doses of

400 IU or unlikely to cause serious adverse effects

Supplementation may be beneficialPossible

Possible

Possible

Unlikely High

High

Moderate


Thiazide diuretics Increases drug side effects

Vitamin D3 may increase the risk of hypercalcaemia if taken

with calcium supplements and/or thiazide diuretics

(note cod liver oil contains 85 IU vitamin D per 1 g)

Level AMultiple case reports

Clinical trial in patients with hypoparathyroidism taking vit D

and thiazide diuretic

ModerateConsult a healthcare professional before

use if taking a thiazide diureticLikely


Orlistat


Drug effect on nutrient Vitamin D absorption may be decreased by orlistat

Carbamazepine, phenytoin and phenobarbitone may decrease vitamin

D levels. Vitamin D3 supplementation reverses

depletion


Level BHuman studies and case reports Possible

Interaction can be avoided by separating dose of medication and vitamin D by

at least 2 hours. Supplementation recommended

Supplementation recommendedVitamin D3

Likely

Low

Low

Pg.26 Pg.27



SEVERITY of

OUTCOME

ACE inhibitors, angiotensin receptor blockers, thiazide

diuretics Drug effect on nutrient

Urinary zinc excretion is increased with long-term use of these drugs


Possible Supplementation recommended

Tetracycline or quinolone antibiotics (not

doxycycline) Decreases drug effect

Zinc may decrease the absorption and blood levels of these drugs

Level BMultiple studies

PossibleInteraction can be avoided by

separating dose of medication and zinc by at least 2 hours

Penacillamine Decreases drug effect

Zinc may decrease the activity of

penacillamine. Dose separation by at least 2 hours is recommended

Level AHuman studies

PossibleInteraction can be avoided by

separating dose of medication and zinc by at least 2 hours

Zinc Hypoglycaemic drugs Increases drug effect

Low zinc status is common in diabetic

patients. Zinc supplementation and normalisation of zinc

levels has been shown to improve glycaemic control


Low

Low

PossibleSupplementation may be beneficial

however alteration of medication dosage may be required

Low

Low

Pg.28 Pg.29

INDEX

FFenugreek (Trigonella foenum-graecum) Feverfew (Tanacetum parthenium)Fish oilFlaxseed oilFolic acid

GGarlic (Allium sativum)Ginger(Zingiber officinale)Ginkgo (Ginkgo biloba)Ginseng (Korean)(Panax ginseng)Ginseng (Siberian)(Eleutherococcus senticosus)GlucosamineGreen-lipped mussel

HHawthorn (Crataegus monogyna)Holy basil (Ocimum tenuiflorum)Hops (Humulus lupulus)

IIodineIron

AAcidophilusAlpha-lipoic acidAndrographis (Andrographis paniculata)Astragalus(Astragalus membranaceus)

BBetacaroteneBlack cohosh (Cimicifuga racemosa)

CCalciumCelery (Apium graveolens)Co-enzyme Q10 (CoQ10)Coleus(Coleus forskohlii)Cranberry (Vaccinium macrocarpon)

D Dong quai (Angelica polymorpha)

E Echinacea (Echinacea angustifolia, Echinacea purpurea) Evening primrose oil

INDEX

K Kelp (Fucus vesiculosus)

L Liquorice (Glycyrrhiza glabra)

MMagnesiumL-methionineMilk thistle/St Mary’s thistle (Silybum marianum)

N Nicotinic acid

O Oats (Avena sativa)

PPara-aminobenzoic acid (PABA)Pau d’Arco (Tabebuia avellanedae)Pelargonium sidoidesPeppermint (Mentha x piperita)Phytosterols / Plant sterolsPotassium

Probiotics Lactobacillus species including: L. acidophilus L. reuteri L.Rhamnosus GR-1 L. Reuteri RC-14Psyllium husk(Plantago ovata)

Q Quercetin

R Red clover/Isoflavones (Trifolium pratense)

SSoy/Isoflavones (Glycine max)St John’s wort (Hypericum perforatum)

T Turmeric (Curcuma longa)

V Vitamin AVitamin B2Vitamin CVitamin D3Vitamin E Vitamin K

W Willow (Salix alba)

Z Zinc

Pg.30 Pg.31

Blackmores Institute Education

In conjunction with Griffith University, presented by the School of Pharmacy’s Associate Professor Evelin Tiralongo and Adjunct Associate Professor Greg Mapp.

Short Course in Integrative Medicine

Are you well equipped to answer patient queries about complementary medicine?

Blackmores Institute has been established with the purpose of becoming a centre of excellence in the field of natural health research and education. It brings together the best minds, knowledge and evidence, and is dedicated to sharing this knowledge with the wider community of healthcare professionals, researchers, industry and consumers.

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TEN ONLINE MODULESIntroduction to Integrative Medicine (CX160029)

Cancer (CX160077)

Cardiovascular diseases (CX160017)

Central Nervous System disorders (CX160082)

Endocrine disorders and men’s health (CX160078)

Gastrointestinal diseases (CX160081)

Pain (CX160079)

Respiratory disorders (CX160083)

Women’s health 1 - Infertility, PCOD, PMS (CX160080)

Women’s health 2 - Menopause, UTI, Pregnancy (CX160117)

Each module has been accredited for 1 hour of Group 1 CPD (or 1 CPD credit) suitable for inclusion in an individual pharmacist’s CPD plan which can be converted to 1 hour of Group 2 CPD (or 2 CPD credits) upon successful completion of relevant assessment activities. Pharmacist Competencies 1.3, 1.4, 5.1, 6.1, 6.2, 6.3, 7.1, 8.1

Register at www.blackmoresinstitute.org to access our education modules and upcoming events

LEARNING OBJECTIVES:On completion of these modules you should be able to

� Describe the mechanism of action, indications and use of a range of evidence-based complementary medicines (CMs) in key health conditions

� List key counselling points, including dosing directions, adverse effects, contraindications and/or interactions for a range of evidence-based CMs

� Provide appropriate co-prescribing of CMs with prescribed medications

Other CPD-accredited online modules include: � A natural, evidence-based approach to the management of acute bronchitis and acute sinusitis

� Eye health: nutritional supplementation for the prevention and management of macular degeneration

� Omega-3s for cardiovascular health

� Oat betaglucan and cardiovascular health

� Oral nicotinamide and skin health

Healthcare Professional Events � Symposia, Webinars and Scientific Meetings

This ten module program has been approved for 20 Category 2 RACGP CPD points. Activity ID number 33834.

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Complementary medicine interactions guide - Blackmores CMIG_FINAL 9th... · Complementary medicine interactions guide ... send a ‘blue card’ adverse reaction reporting form to