Download How to do an enquiry on interactions between complementary or

Good Practice Guide
How to do an enquiry on interactions between complementary or
alternative medicines and conventional medicines.
Date prepared: 29th May 2010
Background
Complementary and/or alternative medicines (CAMs) are increasingly being used by members of the
public to treat common ailments. Medicines Information centres may be asked by members of the
public or other healthcare professionals about the potential use of CAMs in combination with a
patient’s conventional (pharmaceutical) medication. This Q&A will look at the questions that need to
be asked when taking in an enquiry, what principles need to be considered when answering the
enquiry and the types of resources that may be used.
Answer
When a CAM drug interaction enquiry is received into the Medicines Information centre, the following
information should be requested from the enquirer:
 CAM details: brand name, generic name, manufacturer, ingredients, strength, route, dose,
frequency, course length.
 Indication for the CAM.
 Patient details: name/initials or identifier, age, past medical history and current conditions,
drug history and current pharmaceutical medicines (including over the counter preparations),
any drug allergies
 Has the patient already started the CAM or are they looking to start/purchase the CAM (i.e. is
the enquiry retrospective or prospective)?
 Has the CAM been selected as a result of self diagnosis or on advice (personal or
professional)?
 Has the patient spoken to their doctor?
It is important to distinguish whether the product is an herbal or a homoeopathic remedy. For example
arnica is toxic if taken internally except in suitable homoeopathic dilutions (1). If a homoeopathic
remedy is being used it is especially relevant to identify the strength (dilution) of the product, for
example, 30c, 2X, 1M as this will affect how the enquiry is handled. For further details on
homoeopathic remedies please refer to the Q&A ‘What are the basic principles of homoeopathy’ (2).
When investigating the likelihood of an interaction between CAMs and pharmaceutical medicines a
number of factors should be considered:
 CAMs can contain multiple ingredients which are pharmacologically active (3)
 Due to inadequate reporting, there is often a paucity of relevant clinical information in the
literature on potential interactions (3, 4).
 Causality is often not established (3) and reports may be inaccurate due to misidentification of
the CAM (4).
 Not all CAMs are regulated under the same strict criteria as for pharmaceutical medicines; the
product label for a CAM may not accurately reflect their contents; consideration should be
given to the potential risk of adulteration with pharmaceutical medicines, heavy metals (4) or
pesticides.
 It is important that the product is purchased from a reputable source and that the
manufacturer’s guidance is followed.
Each patient is different and therefore it is important to consider whether an interaction reported in the
literature is likely to be significant and could apply to your patient. Much of the data reported in the
literature is anecdotal or from uncontrolled studies or animal studies (5). As such, the evidence
presented may be biased and particularly critical. It is therefore important to judge the evidence based
on the information provided and to consider whether this information is corroborated elsewhere. It is
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important to be aware that unsubstantiated statements are often repeated in reviews and other
papers without verification. When looking for information care should be taken to ensure that you are
looking at the correct species and the correct part of the plant (e.g. root, leaf etc), as these will effect
the active constituents of the CAM. For example, milk thistle contains the active ingredient silymarin
proposed for its hepatoprotective effects, but this is only found in the fruit, though the leaf has been
used incorrectly for this purpose too (1). Also consider the route of administration or formulation being
used (e.g. tea, oral, topical, IV). Herbs are often used in complex combinations and the effects of
single herbs may not accurately reflect the activity of the mixture.
As with conventional pharmaceutical drug interactions, CAM-drug interactions may be
pharmacodynamic or pharmacokinetic (1,6):
Pharmacodynamic interactions
Pharmacodynamic interactions are usually predictable depending upon how much information is
available for a particular CAM (1). Synergistic therapeutic effects may complicate the management of
chronic diseases, for example an herb used for its glucose lowering effect may precipitate
hypoglycaemia in a patient taking conventional antidiabetic medicines (4). Some CAMS may
potentiate the effect of anticoagulants, for example garlic and dong quai both have antiplatelet
properties (6). This would be of concern should the patient be taking warfarin, but also if a patient was
due to undergo surgery. Such medicines would need to be discontinued two weeks prior to elective
surgery (7). Other CAMs may oppose or antagonise the effect of a patient’s current medicine, for
example products that naturally contain vitamin K (e.g. green tea, [8]) may antagonise the effects of
warfarin (5).
Pharmacokinetic interactions
Pharmacokinetic interactions may be less predictable (1) and may affect a number of key processes:
 CAMs can interfere with the absorption of pharmaceutical medicines e.g. aloe leaf and guar
gum have laxative properties which decrease intestinal transit time (6). St John’s Wort
induces intestinal P-glycoprotein, potentially decreasing the absorption of P-glycoprotein
substrates such as digoxin (6).
 In general interactions involving changes in volume of distribution are less significant (6).
Displacement of a medicine from protein binding sites would be more of an issue for products
that have saturable metabolism or where increased drug excretion is compromised due to
liver or renal disease.
 CAMs may affect the metabolism of a pharmaceutical medicine through induction or inhibition
of cytochrome P450 isoenzymes. One of the best studied is St John’s Wort, which is a potent
inducer of CYP3A4 (6). In 2000 the Medicines and Healthcare Products Regulatory Agency
(MHRA) issued guidance to healthcare professionals on the management of interactions
between St John’s Wort and pharmaceutical medicines (9).
 There have been many in vitro studies of cytochrome P450 activity of herbal extracts but
clinical relevance is not always described.
 Toxic herbs may impair hepatic or renal function, reducing drug excretion (6).
 The excretion of lithium may be reduced in patients taking CAMs with diuretic properties e.g.
dandelion (6) and artichoke (10).
Resources
Taking into consideration the above mechanisms by which an interaction can occur, the following
resources may be useful when attempting to answer the enquiry:
Books (paper/electronic):
 Aromatherapy Science: A guide for healthcare professionals (Lis-Balchin M) (subscription/fee)
 Dietary Supplements (Mason P) (subscription/fee)
 Herbal Medicines (Barnes J, Anderson LA, Phillipson JD) (subscription/fee)
 Homeopathic Pharmacy: Theory and Practice (Kayne SB) (fee)
 Martindale (Sweetman SC) (subscription/fee)
 Nutraceuticals (Lockwood B) (subscription/fee)
 Stockley’s Herbal Medicines Interactions (subscription/fee)
Databases/electronic resources:
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AltMedex (subscription)
Herbmed (fee charged)
Lexi Natural (subscription)
Longwood Herbal Taskforce
Memorial Sloan-Kettering Cancer Centre
Medscape drug interaction checker (free registration)
Natural Medicines Comprehensive Database (subscription)
Natural Standard (subscription)
National Centre for Complementary and Alternative Medicine (NCCAM)
UKMi Q&As on NeLM
AltMed/Embase/Medline/IOWA (subscription)
Other resources
By April 2011 all manufactured herbal medicines will be required to have either a traditional herbal
registration (THR) or a Marketing Authorisation (MA). Products will therefore be required to meet
specific standards of safety and quality (8). However this only applies where products come within the
definition of a medicinal product. Many herbal products will continue to be available as food
supplements.
In the meantime the MHRA are currently preparing information sheets on herbs that have been
assessed for THR product registration which can be accessed via:
http://www.mhra.gov.uk/Howweregulate/Medicines/Herbalmedicines/Herbalsafetyadvice/Herbalinform
ationsheets/index.htm
Overall, the risks of interaction are of most concern in individuals receiving medicines with a narrow
therapeutic window such as warfarin, phenytoin and digoxin. Other patients at risk are those with
poor drug clearance such as patients with kidney or liver impairment, the old and very young (5). In
such patients or in those whose therapy is deemed critical e.g. patients receiving chemotherapy, it
may be prudent to avoid use of a particular CAM if there is limited evidence of safety data.
It is often difficult to truly assess whether a CAM will interact with a conventional medicine. In this
situation it may be prudent to advise against using them together. In most cases this is not because
there is evidence of an interaction but because there is a lack of evidence to assess risk. Individuals
using a CAM should be advised to be consistent with the brand, dose and frequency of administration
of the product being used. They should also inform their doctor that they are taking the CAM so that
the clinician can monitor the patient accordingly. In addition there may be a risk to the patient if by
seeking alternative therapies their condition is not treated promptly and appropriately.
Summary
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There is often limited clinically relevant information available regarding interactions between
CAMs and conventional medicines.
Many publications report theoretical interactions based on chemistry of plants or in vitro
studies of plant extracts.
Interactions may be pharmacokinetic or pharmacodynamic.
Pharmacodynamic interactions may be predictable based on what is known about the
mechanism of action of the CAM.
Pharmacokinetic interactions may be harder to distinguish due to lack of data.
Herbs are often used in combination and the effects of single herbs may not reflect the activity
of the formula.
Occasionally herbal products may be contaminated with other active substances, including
other medicines which could also interact with any conventional medicines the patient is
taking.
Interactions are of particular concern when the patient is taking conventional medicines that
have a narrow therapeutic window; where the patient is more likely to experience drug
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interactions due to impaired organ function and/or where any compromise to treatment would
be deemed clinically important.
Being consistent with the brand, dose and frequency of administration is recommended.
Patients should be encouraged to tell their clinicians if they are taking a CAM.
Patients may put themselves at risk due to an undiagnosed illness remaining untreated by
conventional methods.
Limitations
The examples of drug interactions and resources included in this Q&A are not exhaustive. Readers
should contact their Regional Medicines Information Centre should they require any further advice.
Disclaimer
 Medicines Q&As are intended for healthcare professionals and reflect UK practice.
 Each Q&A relates only to the clinical scenario described.
 Q&As are believed to accurately reflect the medical literature at the time of writing.
 The authors of Medicines Q&As are not responsible for the content of external websites and
links are made available solely to indicate their potential usefulness to users of NeLM. You
must use your judgement to determine the accuracy and relevance of the information they
contain.
 See NeLM for full disclaimer.
References
(1) Barnes JA, Anderson LA, Phillipson JD. Herbal Medicines. Pharmaceutical Press (electronic
version). Accessed via: http://www.medicinescomplete.com/mc/ on 26/4/10
(2) UKMi Q&A 11.3. What are the basic principles of homoeopathy? Accessed via:
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/What-are-the-basicprinciples-of-homoeopathy/?query=homoeopathy&rank=100 on 17/5/10
(3) Fugh-Berman A and Ernst E. Herb-drug interactions: Review and assessment of report
reliability. Br J Clin Pharmacol. 2001; 52: 587-95
(4) Fugh-Berman A. Herb-drug interactions. Lancet. 2000; 355:134-38
(5) Stockley’s Herbal Medicines Interactions. Pharmaceutical Press (electronic version).
Accessed via: http://www.medicinescomplete.com/mc/ on 26/4/10
(6) Nicholas Scott G and Elmer GW. Update on natural product-drug interactions. Am J HealthSyst Pharm. 2002; 59: 339-47
(7) Hodges PJ and Kam PCA. The peri-operative implications of herbal medicines. Anaesthesia.
2002;57:889-99
(8) Boullata JI and Nace AM. Safety issues with herbal medicine. Pharmacother. 2000; 20: 25769
(9) Medicines and Healthcare Products Regulatory Agency. Factsheet for healthcare
professionals. Accessed via: http://www.mhra.gov.uk/home/groups/commsic/documents/websiteresources/con019564.pdf on 17/5/10
(10)Jellin JM (Ed). Artichoke monograph. Natural Medicines Comprehensive Database.
Pharmacist’s Letter/Prescriber’s Letter. Natural Medicines Comprehensive Database.
Stockton, CA:Therapeutic Research Faculty. Accessed via http://www.naturaldatabase.com
on 17/5/10.
Quality Assurance
Prepared by
Gail Woodland, Senior Information Pharmacist, Welsh Medicines Information Centre.
Date Prepared
29th May 2010
Checked by
Fiona Woods, Director, Welsh Medicines Information Centre.
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Date of check
9th August 2010
Search strategy
AMED (exp Plants medicinal/ or exp Herbal drugs/ or exp Drugs Chinese herbal/ or exp Traditional
medicine/ or exp Plant extracts/ or Homeopathy/ or exp Homeopathic drugs AND exp Drug
Interactions).
Embase (exp herbal medicine/ or exp Chinese drug/ or exp plant extract/ or exp diet supplementation/ or exp
alternative medicine/ AND *drug interaction/).
Medline (exp Dietary Supplements/ or exp Herbal Medicine/ or exp Drugs, Chinese Herbal/ or exp
Plants, Medicinal/ AND *Drug Interactions/).
IOWA online (Drug(s): ("herbal medicines 92510000" ) or ("chinese herbal medicines 92510129") or
("homeopathic preparations 92000210") and Descriptors: ("drug interaction 50" or "dietary interaction
75" ) and "review adult 6").
In-house database/ resources.
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