How to do an enquiry on adverse effects of complementary or alternative medicines.

Date prepared: 5thJune 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 adverse drug reactions (ADRs) associated with CAMs. 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 ADR enquiry is received into the Medicines Information centre, the following information should be requested from the enquirer:

  • CAMdetails: brand name, generic name, manufacturer, ingredients, strength, route, dose, frequency.
  • When did they start taking the CAM? Are they still taking it?
  • 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).
  • Has the patient any history of ADRs and/or allergies?
  • When did the reaction begin? Have the symptoms resolved?
  • What are/were the signs and symptoms of the suspected reaction, how severe are/were they?
  • Was the CAMselected 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. Side effects are unlikely to occur where the homoeopathic remedy is used in high dilutions but lower dilutions may contain active ingredients and the principles for handling an herbal enquiry would then apply. For further details on homoeopathic remedies please refer to the Q&A ‘What are the basic principles of homoeopathy’ (2). Depending upon how the homoeopathic product is formulated, reactions may also occur in patients with lactose intolerance (3).

Consideration should be given to the following when handling an ADR CAM enquiry:

  • Patients may be exposed to potentially toxic substances either from the herbal ingredients themselves or as a result of exposure to contaminants present in the herbal product e.g. through adulteration (pharmaceutical products) or contamination (heavy metals, pesticides etc) (1)
  • There may be weak or missing information about the safe use of the product (e.g. patient has taken too much as the dosage guidance was missing or unclear, the ingredients are labelled incorrectly) (4)
  • Despite widespread traditional use of herbal medicines, there is an overall lack of long term safety data, in addition little is known about rarer side effects
  • Where case reports are available, causality is often not established and reports may be inaccurate due to misidentification of the CAM
  • It is important to consider any co-morbidities the patient may have and to be particularly careful when advising for patients who may be more predisposed to suffering an adverse event. Caution should be taken when using herbal medicines in pregnant women, breastfeeding mothers, children or older people and in anyone with a history of liver or kidney problems or any other serious health condition (5).
  • It is unlikely that a culinary herb used in the amounts usually acceptable during food preparation will represent a particular health hazard (1)
  • High potency dietary supplements may increase the risk of toxicity (6)
  • Self administration of any therapy in preference to conventional treatment may delay a patient seeking qualified advice, or abandonment of conventional treatment without first seeking medical advice (1), which in itself is associated with an increased risk to the patient.

Much of the data reported in the literature is anecdotal or from uncontrolled studies or animal studies (7). 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 important to be aware that unsubstantiated claims 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, cyanogenetic glycosides are found in the kernels of a number of fruits e.g. apricot, pear and plum. Oral ingestion of these results in the release of hydrogen cyanide which can lead to respiratory failure (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.

ADR CAM enquiries should be handled in the same way as ADR enquiries with conventional medicines. Consideration should be given to the following:

  • Timing of exposure
  • Recovery – did the patient continue on the CAM or was this stopped, how soon after stopping did the symptoms resolve?
  • Independent evidence – has the patient had a rechallenge of the suspected CAM and if so did the symptoms recur? Were any additional tests performed? Have other potential causes been ruled out (conventional medicines/contaminants etc)?
  • Predictability – do these symptoms match the characteristics of the suspected CAM?

Resources

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, AndersonLA, Phillipson JD) (subscription/fee)
  • Homeopathic Pharmacy: Theory and Practice (Kayne SB) (fee)
  • Martindale (SweetmanSC) (subscription/fee)
  • Meyler’s Side Effects of Drugs (Dukes MNG, Aronson JK) (subscription/fee)
  • Adverse Drug Reactions (Lee A) (fee)
  • Nutraceuticals (Lockwood B) (subscription/fee)

Databases/electronic resources:

  • 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)
  • 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:

If an ADR to a CAM is suspected this should be reported via the Yellow Card Scheme (9).

Summary

  • ADR CAM enquiries should be handled in the same way as ADR enquiries with conventional medicines, using TRIP: timing, recovery, independent evidence, predictability.
  • There is often limited information available regarding ADRs associated with CAMs.
  • Occasionally herbal products may be contaminated with other active substances, which may cause an ADR.
  • Despite widespread traditional use of herbal medicines, there is an overall lack of safety data on long term use and little is known about rarer side effects.
  • It is important to consider any co-morbidities the patient may have and to be particularly careful when advising for patients who may be more predisposed to suffering an adverse event.
  • Patients who choose a CAM instead of a conventional medicine may put themselves at further risk due to an undiagnosed illness remaining untreated by conventional methods.
  • If an ADR to a CAM is suspected this should be reported to the Yellow Card Scheme.

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 arenot responsible for the content of external websites and linksaremade 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, AndersonLA, Phillipson JD. Herbal Medicines. Pharmaceutical Press (electronic version). Accessed via: on 31/5/10

(2)UKMi Q&A 11.3. What are the basic principles of homoeopathy? Accessed via: on 31/5/10

(3)RPSGB. Homeopathic and Herbal Products Advice for Pharmacists. Accessed via: on 5/6/10

(4)Medicines and Healthcare Products Regulatory Agency. Public Health Risk with Herbal Medicines: An Overview. Accessed via: on 5/6/10

(5)Medicines and Healthcare Products Regulatory Agency.Advice to Consumers. Accessed via: on 5/6/10

(6)Mason P. Dietary Supplements. Pharmaceutical Press (electronic version). Accessed via: on 5/6/10

(7)Stockley’s Herbal Medicines interactions. Pharmaceutical Press (electronic version). Accessed via: on 26/4/10

(8)Medicines and Healthcare Products Regulatory Agency. Herbal Medicines Regulation and Safety. Accessed via: 5/6/10

(9)Medicines and Healthcare Products Regulatory Agency. Yellow card Scheme. Accessed via: on 5/6/10

Quality Assurance

Prepared by

Gail Woodland, Senior Information Pharmacist, Welsh Medicines Information Centre.

Date Prepared

9th August 2010

Checked by
Fiona Woods, Director, Welsh Medicines Information Centre.

Date of check

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 Adverse effects; limit: review)

Embase (exp herbal medicine/ or exp Chinese drug/ or exp plant extract/ or exp diet supplementation/ or exp alternative medicine/ AND *adverse drug reaction/)

Medline (exp Dietary Supplements/ or exp Herbal Medicine/ or exp Drugs, Chinese Herbal/ or exp Plants, Medicinal/ AND adverse drug reaction.mp or Drug Toxicity; limit humans and yr=2000-current)

IOWA online (Drug(s): ("herbal medicines 92510000") or ("chinese herbal medicines 92510129") or ("homeopathic preparations 92000210") and Descriptors: ("side ef adverse reaction 46" and "review adult 6")

In-house database/ resources

Medicines and Healthcare Products Regulatory Agency website

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