Elsevier

Phytomedicine

Volume 18, Issue 6, 15 April 2011, Pages 433-436
Phytomedicine

Short communication
Observational study on the tolerability and safety of film-coated tablets containing ivy extract (Prospan® Cough Tablets) in the treatment of colds accompanied by coughing

https://doi.org/10.1016/j.phymed.2010.11.009Get rights and content

Abstract

The only saponin drug currently prescribed in any significant amount in monotherapy medicines is ivy. This post-marketing surveillance study (PMSS) aimed at investigating the tolerability and safety of film-coated tablets containing ivy leaves dry extract (extracting medium: ethanol 30%, DER 5–7.5:1 [Prospan® Cough Tablets]) under practice conditions. Adults and children aged 11–85 years of both genders were included. A total of 330 patients suffering from colds accompanied by coughing or from chronic, inflammatory bronchial diseases were scheduled to undergo treatment for a period of at least seven days. The tolerability of the tablets was rated by means of questionnaires.

The results of this PMSS reflect the good to very good tolerability of the tablets in the global assessment by both, the practitioner (98.5%) and by the patient (96.4%). This is one of the reasons for the high acceptance and compliance (rated as ‘good’ in 98.8% of all cases). The safety not only regarding the administration form but also regarding the active substance is thus underlined once again.

Introduction

Hedera helix Linné (L.) or ivy is an evergreen cirrus belonging to the family of Araliaceae. It is the only saponin-containing herbal drug which is considerably used in monotherapy due to expectorant and bronchospasmolytic effects. A number of controlled clinical studies have demonstrated its respective therapeutic effectiveness using a dry extract of ivy leaves for human use prepared from an aqueous-ethanolic extract (extracting medium: ethanol 30%, Drug-Extract Ratio (DER) 5–7.5:1) (Meyer-Wegener et al., 1993, Lässig et al., 1996, Hecker, 1997, Mansfeld et al., 1997, Mansfeld et al., 1998). Thus ivy belongs to a group of particularly well researched phytopharmaceuticals (Schulz and Hänsel, 2004, Stauss-Grabo et al., 2008). Aqueous extraction of its juvenile leaves has been used since the 19th century in traditional medicine for the treatment of respiratory disorders. Today various formulations of medicinal products containing ivy leaves dry extract such as syrup, effervescent tablets, drops, tablets and suppositories are available.

Recently the efficacy of this extract has been reviewed (Guo et al., 2006, Hofmann et al., 2003, Landgrebe et al., 1999). Besides catarrh of the upper respiratory tract, the Commission E monograph “Ivy leaves”, the ESCOP and the HMPC monograph consequently also name the symptomatic treatment of chronic-inflammatory bronchial diseases with the accompanying symptom of cough as therapeutic indications (Kommission, 1988, ESCOP, 2003, EMA, 2009). Based on this well documented and verified clinical and pharmacological efficacy the ‘Study Group History of the Development of Medicinal Botany’ of the University of Würzburg, Germany, selected ivy as the ‘medicinal plant of the year’ 2010, a nomination provided annually in Germany (Czygan et al. 2010).

The tolerance of different ivy extract-containing preparations with exception of the film-coated tablets has likewise been tested many times in various studies (Hecker et al., 2002, Bolbot et al., 2004, Fazio et al., 2006).

For a long time it was assumed, that saponins generally would be absorbed by the gastrointestinal tract only to a very small extent, if at all, and thus no systemic effects were to be expected following oral administration. In the year 2004, α-hederin, a triterpenesaponin from therapeutically used ivy leaf dry extract, was identified as the central molecule responsible for the therapeutic effect (Hegener et al., 2004, Runkel et al., 2005). This was confirmed by recent in vitro studies showing that the mucolytic and expectorant action of ivy is based on indirect β2-adrenergic effects and that this is due to the saponins α-hederin and Hederacoside C, the latter of which is metabolised to α-hederin in the organism (Sieben et al. 2009). Under stimulating conditions α-hederin inhibits the intracellular uptake of β2-receptors and leads to an increased β2-adrenergic response of the cell. The description of α-hederin as the primary effective ingredient at a molecular level offered for the first time a plausible in vitro explanatory model for the pulmonary effects of ivy leaf dry extract observed in numerous clinical trials and therapeutically used in humans.

Section snippets

Study drug

The study was performed with film-coated tablets each containing 25 mg of ivy leaves dry extract (extracting medium: ethanol 30%, DER 5–7.5:1 [Prospan® Cough Tablets]). In order to specify the content of ivy leaves dry extract used for the preparation of the study drug, the saponin Hederacoside C is used as the primary reference substance following the requirements of the European Pharmacopoeia (content of Hederacoside C used for the HPLC-quantitative analysis calculated via HPLC against ivy

Demographic and disease data

A total of 331 patients was included, 330 patients (206 female and 124 male) were evaluable. One female patient was excluded from the evaluation because she admitted not to have taken any dose of the study medication. Deviating from the study plan, an 11-year old girl was included and evaluated as well. Thus, patients included were between 11 and 85 years old (mean/median: 42/43 years). Fig. 1 shows that most of these patients were between 20 and 60 years old. The treatment was mainly initiated

Discussion

This observational study fulfilled the ‘guideline on population exposure’ (CPMP 1995) with a minimum requirement of 301 patients to detect (very) frequent ADRs with an incidence of at least 1%. In this study 330 patients were evaluated after a treatment with film-coated tablets containing ivy leaves dry extract (extracting medium: ethanol 30%, DER 5–7.5:1 [Prospan® Cough Tablets]). 310 of 330 evaluable patients received an at least 7-day treatment.

Both patients (96.4%) and attending

Acknowledgment

The authors thank Karl Ludwig Rost for his help in editing this manuscript.

References (22)

  • D. Hofmann et al.

    Efficacy of dry extract of ivy leaves in children with bronchial asthma – a review of randomized controlled trials

    Phytomedicine

    (2003)
  • Y.U. Bolbot et al.

    Comparing the efficacy and safety of high-concentrate (5–7.5:1) ivy leaves extract and Acetylcysteine for treatment of children with acute bronchitis

    Drugs of Ukraine

    (2004)
  • CPMP

    Extent of Population Exposure to Assess Clinical Safety – CPMP/ICH/375/95 (ICH E1A)

    (1995)
  • F.C. Czygan et al.

    Efeu ist die Arzneipflanze des Jahres 2010

    Zeitschrift für Phytotherapie

    (2010)
  • EMA/HMPC/289432/2009. Hedera Helix folium...
  • ESCOP Monograph Ivy Leaf

    (2003)
  • S. Fazio et al.

    Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicentre postmarketing study in 9657 patients

    Phytomedicine

    (2006)
  • R. Guo et al.

    Herbal medicines for the treatment of COPD: a systematic review

    European Respiratory Journal

    (2006)
  • M. Hecker

    Hustentropfen mit Ethanol deutlich bessere Wirksamkeit. Verschiedene Zubereitungen von Efeublättertrockenextrakt: Dosisanpassung erforderlich

    T&E Pädiatrie

    (1997)
  • M. Hecker et al.

    Behandlung chronischer Bronchitis mit einem Spezialextrakt aus Efeublättern – multizentrische Anwendungsbeobachtung mit 1350 Patienten

    Forsch. Komplementärmed. u. Klassische Naturheilkunde

    (2002)
  • O. Hegener et al.

    Dynamics of beta2-adrenergic receptor-ligand complexes on living cells

    Biochemistry

    (2004)
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