Reviewed: Schapowal A. Treating Intermittent Allergic Rhinitis: A Prospective, Randomized, Placebo and Antihistamine-controlled Study of Butterbur Extract Ze 339. Phytotherapy Research 2005;19(6):530-537.
This clinical trial demonstrates the safety and efficacy of a special extract of butterbur leaf for treating intermittent allergic rhinitis (IAR), commonly referred to as hay fever.
In the largest clinical trial to date on butterbur leaf, the randomized, double-blind, placebo- and reference-controlled, three-arm, multi-center trial was based on 330 out-patients in 11 centers in Switzerland and Germany. (A reference-controlled trial compares a medication directly against a medication known to be active, in this case, the antihistamine fexofenadine, serving as an active control.) The trial was conducted according to US Food and Drug Administration Guidance for Industry on clinical trials for allergic rhinitis.
Study medications were a special carbon dioxide extract of butterbur leaf (Ze 339, aka Tesalin®, produced by Max Zeller Söne AG of Romanshorn, Switzerland) and fexofenadine (Telfast® 180 aka Allegra®, Aventis), a conventional antihistamine drug. Daily dosages used in the trial were 3 tablets of Ze 339 (standardized to 8 mg petasine each) versus one tablet of fexofenadine (180 mg), or placebo, using a double dummy technique for complete blinding.
All patients were 18 years of age or older and had a history of seasonal allergic rhinitis for at least two seasons in consecutive years. The primary measurement was a change in IAR symptoms during the day. These symptoms include sneezing, watery eyes, itching eyes and nose, and nasal congestion. Researchers also measured changes experienced in the evening and at night, based on the physicians' assessments and the rates of patients' responses.
Patients were randomized to the butterbur (n = 110), fexofenadine (n = 113), or placebo (n = 107) group. Based on changes in the total symptom score and other measurements, the trial results concluded that both the special butterbur leaf extract and the antihistamine drug were equally and significantly superior to the placebo (P < 0.001) in reducing IAR symptoms. The phytomedicine and the conventional drug demonstrated about equal efficacy (P = 0.037). Superiority of both treatments to placebo was demonstrated during the evening/night (P < 0.001), according to the attending physicians' own assessment and by patient responder rates.
Although both the butterbur preparation and the fexofenadine were both well tolerated, the butterbur showed a predictably safer profile than the conventional drug as butterbur did not produce the sleepy, drowsy effect that is characteristic of antihistamine medications. There were few adverse events reported in any of the groups, although symptoms related to sedation accounted for three-quarters of all events reported in patients on fexofenadine and just over one-third of all events in the butterbur and placebo groups. There was no evidence suggesting an adverse event that might be associated with generic butterbur preparations (e.g., potential liver problems associated with pyrrolizidine alkaloids [PAs]), as liver enzyme levels were monitored and did not show an increase.
The research team was led by principal investigator Dr. Andreas Schapowal of the Allergy Clinic in Landquart, Switzerland. Dr. Schapowal has previously published clinical trials on Ze 339, demonstrating its efficacy compared to placebo in a dose-ranging trial1 and in another trial favorably comparing it to the conventional pharmaceutical IAR drug, cetirizine (Zyrtec®, Pfizer).2
Butterbur (Petasites hybridus [L.] P. Gaertn. et al., Asteraceae) is native to Europe. All parts of the plant are known to contain potentially hepatotoxic PAs, although the PAs are found in higher concentrations in the root than in the leaves and other aerial parts. Ze 339 is made from specially grown butterbur plants that have been bred to produce a low amount of PAs in the leaves, with the PAs then removed to virtually almost undetectable levels by a special carbon dioxide-based extraction process.
Note: A significantly different butterbur preparation, a standardized extract made from butterbur roots, called Petadolex® (Weber & Weber GmbH & Co, KG, Germany, imported by Weber & Weber International, Windermere, FL) has recently shown potential benefit for treating asthma in a non-controlled observational study3 as well as some evidence for treating migraine headaches in recently published clinical trials.4,5
1. Schapowal A. Butterbur Ze339 for the treatment of intermittent allergic rhinitis: dose-dependent efficacy in a prospective, randomized, double-blind, placebo-controlled study. Arch Otolaryngol Head Neck Surg. December 2004;130(12):1381-1386.
2. Schapowal A. Randomized controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ. January 2002;19;324(7330):144-146.
3. Danesch U. Petasites hybridus (Butterbur root) extract in the treatment of asthma—an open trial. Altern Med Rev. 2004;9(1):54-62.
4. Lipton RB, Gobel H, Einhaupl KM, Wilks K, Mauskop A. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240?2244.
5. Pothmann R, Danesh U. Migraine prevention in children and adolescents: Results of an open trial with a special butterbur root extract. Headache 2005;45:1-8.