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Adverse-Event Profile of Crataegus Spp.

A Systematic Review

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Abstract

Crataegus spp. (hawthorn) monopreparations are predominantly used for treating congestive heart failure. The effectiveness of hawthorn preparations (flowers with leaves; berries) is documented in a number of clinical studies, reviews and meta-analyses. The aim of this article is to assess the safety data of all available human studies on hawthorn monopreparations.

Systematic searches were conducted on MEDLINE, EMBASE, AMED, The Cochrane Library, the UK National Research Register and the US ClinicalTrials.gov (up to January 2005). Data were requested from the spontaneous reporting scheme of the WHO. Hand searches were also conducted in a sample of relevant medical journals, conference proceedings, reference lists of identified articles and our own files. Eight manufacturers of hawthorn-containing preparations were contacted and asked to supply any information on adverse events or drug interactions. Data from all clinical studies and reports were assessed. Only human studies on monopreparations were included. Data from hawthorn-containing combination preparations and homeopathic preparations were excluded. All studies were read and evaluated by one reviewer and independently verified by at least one additional reviewer.

Twenty-nine clinical studies were identified, of which 24 met our inclusion criteria. A total of 7311 patients were enrolled, and data from 5577 patients were available for analysis. The daily dose and duration of treatment with hawthorn monopreparations ranged from 160 to 1800mg and from 3 to 24 weeks, respectively. The extracts most used in the clinical trials were WS 1442 (extract of hawthorn standardised to 18.75% oligomeric procyanidins) and LI 132 (extract of hawthorn standardised to 2.25% flavonoids). Overall, 166 adverse events were reported. Most of these adverse events were, in general, mild to moderate; eight severe adverse events have been reported with the LI 132 extract. The most frequent adverse events were dizziness/vertigo (n = 15), gastrointestinal complaints (n = 24), headache (n = 9), migraine (n = 8) and palpitation (n = 11). The WHO spontaneous reporting scheme received 18 case reports. In the identified trials, the most frequent adverse events were dizziness (n = 6), nausea (n = 5), fall (n = 2), gastrointestinal haemorrhage (n = 2), circulation failure (n = 2) and erythematous rash (n = 2). There were no reports of drug interactions.

In conclusion, all data reviewed in this article seem to indicate that hawthorn is well tolerated even if some severe adverse events were reported; this suggests that further studies are needed to better assess the safety of hawthorn-containing preparations. Moreover, the unsupervised use of this drug can be associated with problems, especially if given with concomitant medications.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

The authors wish to thank Dr Antonella Di Sotto, Department of Pharmacology of Natural Substance and General Physiology, University of Rome, ‘La Sapienza’, Rome, Italy, for her support.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Human Physiology and Pharmacology of Natural Substance and General Physiology, University of Rome ‘La Sapienza’, P.le Aldo Moro 5, 00185, Rome, Italy

    Claudia Daniele & Gabriela Mazzanti

  2. Peninsula Medical School, Complementary Medicine, Universities of Exeter and Plymouth, Exeter, UK

    Max H. Pittler & Edzard Ernst

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  1. Claudia Daniele
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  2. Gabriela Mazzanti
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  3. Max H. Pittler
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  4. Edzard Ernst
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Correspondence to Claudia Daniele.

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Daniele, C., Mazzanti, G., Pittler, M.H. et al. Adverse-Event Profile of Crataegus Spp.. Drug-Safety 29, 523–535 (2006). https://doi.org/10.2165/00002018-200629060-00005

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