Reviewed: Fazio S, Pouso J, Dolinsky D, et al. Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicenter postmarketing study in 9657 patients. Phytomed. 2009;16(1):17-24.
Ivy (Hedera helix, Araliaceae) leaf extract has secretolytic and bronchodilating effects linked to its constituent saponins, notably alpha hederin. Clinical trials on ivy extracts have shown safety and efficacy in the treatment of respiratory illnesses, but their study designs and objectives vary. Since 1988 the German Commission E has approved the use of ivy leaf extracts for “Catarrhs of the respiratory passages [and] symptomatic treatment of chronic inflammatory bronchial conditions.”1 This uncontrolled, multicenter, post-marketing study was designed to investigate the efficacy and tolerance of ivy extract (Prospan®; Engelhard Arzneimittel GmbH & Co.; Niederdorfelden, Germany) in the treatment of bronchitis-related symptoms.
The patients had physician-diagnosed bronchitis, defined as an acute or chronic bronchial inflammatory disease with symptoms including the hypersecretion of mucus and a productive cough. They were recruited at outpatient clinics throughout Latin America. All patients received Prospan, a syrup containing an extract of dried ivy leaves (drug-to-extract ratio 5-7.5:1, extraction solvent: ethanol 30% w/w). The main purported active chemical constituents of Prospan are triterpene saponins, including a standardized content of 30 mg/g hederacoside C in the dried leaves used to make the extract. For 7 days, the patients received Prospan syrup containing 700 mg ivy extract at the manufacturer’s recommended doses for each age group: 2.5 ml/3 times daily for 0-5 years, 5 ml/3 times daily for 6-12 years, and 5-7.5 ml/3 times daily for those patients over 12 years of age. The patients’ physicians filled out a questionnaire on adverse effects (AEs), discontinuation of therapy, and efficacy and tolerance. The researchers evaluated the overall change in the following symptoms: cough, expectoration, dyspnea (shortness of breath), and respiratory chest pain.
The patients (n=9,657) were recruited from 11 Latin American countries between January 2003 and November 2004. The predominant populations were from Argentina, Mexico, Venezuela, and Peru. The study group included 5,181 children aged 014 years and 4,476 adults aged 15-98 years. The patients suffered from cough (100%), expectoration (74.5%), dyspnea (22.0%), and respiratory-related chest pain (21.9%). The average duration of symptoms was 4 days, and the average duration of treatment was 7 days. About 60% of patients received concomitant conventional drugs, including antibiotics.
In 96.6% of the patients, the tolerance of Prospan was rated as good or very good (no AEs). For 0.8% of patients, tolerance was rated as poor (presence of AEs that caused discontinuation of therapy). There were AEs reported by 2.1% of the patients (95%
CI: 1.8-2.4%), including 112 AEs reported in children. The AEs were mild and transient, and most were gastrointestinal complaints (n=149). They included diarrhea (n=75), abdominal and epigastric pain (n=38), nausea and vomiting (n=26), and dry mouth and thirst (n=6). Other reported AEs included skin or other allergies (n=10), anxiety, restlessness or tremor (n=5), headache (n=6), and drowsiness (n=4). There were 46 patients (0.5%) who discontinued therapy due to AEs. A further 1.9% discontinued due to improvement or disappearance of symptoms, while 0.9% discontinued due to therapeutic failure.
After treatment with Prospan syrup, 95.1% of patients (n=9,183, 95% CI: 94.6-95.5%) experienced improvement or disappearance of their symptoms, 3.3% (n=318, 95% CI: 2.9-3.7%) experienced no change, and 0.6% (n=62, 95% CI: 0.5-0.8) reported worsening of their symptoms. The authors judge that the efficacy of the Prospan syrup alone was comparable to the efficacy of the syrup plus prescribed conventional drugs. The relative risk (RR) of adverse events was lower in the group receiving Prospan, compared to patients taking Prospan plus antibiotics (RR: 1.26, 95% CI: 0.86-1.84). Similarly, the RR was lower for patients taking Prospan alone, when compared to patients taking concomitant non-antibiotic medication (RR: 2.34, 95% CI: 1.66-3.28).
The results of this study indicate primarily that Prospan syrup is safe and is well-tolerated with few AEs when taken alone. The authors also conclude that it is an effective treatment in patients with bronchitis. It should be noted, however, that uncomplicated acute bronchitis generally resolves after 3-5 days, and the average duration of treatment in this study was 7 days. Thus, it is possible that the amelioration of symptoms that have been attributed to the action of the ivy leaf extract may be due to the time period at which the results were measured. The authors recommend further studies in order to determine the effects of Prospan in special patient groups, as well as in patients from different age groups, those taking concomitant therapies, and those with different baseline conditions.
—Marissa Oppel, MS
1. Blumenthal M, Busse W, Goldberg A, Gruenwald J, Hall T, Riggins CW , Klein S, Rister RS, trans. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council;1998.