Issue: 63 Page: 17-19
Extract of Pelargonium sidoides: South African Herbal Remedy Successfully Treats Acute Bronchitis and Tonsillopharyngitis
by Donald J. Brown
HerbalGram. 2004; 63:17-19 American Botanical Council
Extract of Pelargonium sidoides: South African Herbal Remedy Successfully Treats Acute Bronchitis and Tonsillopharyngitis
Although antibiotics continue to be used for the treatment
of acute bronchitis and tonsillopharyngitis, there is a growing consensus among
medical professionals worldwide that the preferred course of therapy for both
conditions is to treat the symptoms without resorting to antibiotics. With the
exception of acute tonsillopharyngitis due to group A beta-hemolytic
streptococcus (GABHS), recent clinical guidelines recommend that patients with
GABHS-negative tonsillopharyngitis be told about the self-limiting nature of
the illness and treated with supportive care only.1,2 Although acute
bronchitis is predominantly caused by viral infections, some reports have
placed the use of antibiotics in clinical practice at as high as 70%.3
Overuse of antibiotics may lead to gastrointestinal disorders, allergic
reactions, and the development of resistant organisms.
While there are many
traditional herbal remedies used for acute bronchitis and tonsillopharyngitis,
few clinical trials have been performed to support their efficacy. One
exception has been the development of an extract of pelargonium (Pelargonium
sidoides DC, Geraniaceae) roots, referred to as EPs® 7630
(Umckaloabo®, manufactured by Dr. Willmar Schwabe Pharmaceuticals,
Karlsruhe, Germany, and registered by ISO Pharmaceuticals, Ettlingen, Germany).
In recent years, the ethanolic root extract (1:9-11) has become a popular
herbal medicine in Germany, approved for the treatment of acute bronchitis,
acute tonsillopharyngitis, as well as acute sinusitis. Clinical trials support
its efficacy.
Pelargonium sidoides is
native to the coastal regions of South Africa.4 The plant is notable
for its narrow, deep red flowers and its large, heart-shaped leaves. Along with
the closely related P. reniforme Curt,
the root has been used for centuries by the Zulu to treat coughs, upper
respiratory tract irritations, tuberculosis, and gastrointestinal complaints.5
In the late nineteenth century, a product made from the root gained some
popularity in England as a cure for tuberculosis.
Active Constituents and Pharmacology
The primary constituents of the root of P. sidoides include coumarins, tannins of the proanthocyanidin
type, and simple phenolic compounds.6 Although the mechanism of
action of the root extract is somewhat unclear, in vitro studies suggest that
it may be related to antimicrobial7 and immunomodulatory8,9
properties that have been demonstrated for the tannins (e.g., catechin,
gallocatechin, and gallic acid) and coumarins (e.g., umckalin). The
immunomodulatory actions are mediated by the release of tumor necrosis factor
alpha and nitric oxide as well as the stimulation of interferon and an increase
of natural killer cells.10
Clinical Overview
The subject of 9 randomized trials conducted on a total of
1,477 patients (680 of them children ages 6 to 12 years) to date, EPs 7630 has
been shown to safely and effectively shorten the severity and duration of acute
bronchitis and tonsillopharyngitis.6 Perhaps most notable has been
the rapid recovery noted for children with GABHS-negative
tonsillopharyngitis—the clinical trial reviewed below demonstrated a clinically
significant effect by the second day of treatment. On a practical note, the
product used in these trials is palatable and easy to deliver to young
children. Results from trials with adults and children support the introduction
of this product made from a traditional herb with a long history of use. The
product offers health care professionals an alternative to antibiotics for the
acute treatment of these conditions. New research is also focusing on the use
of the product in acute maxillary sinusitis.
Acute Non-GABHS Tonsillopharyngitis
In a randomized, double-blind, placebo-controlled trial, 143
children ages 6-10 years, with non-GABHS tonsillopharyngitis received either P.
sidoides root extract (EPs 7630) or a
placebo at a dose of 20 drops (1 mL) 3 times per day for 6 days.11
Children enrolled in the study were diagnosed less than 48 hours prior to
starting the trial with a negative rapid test for GABHS and a
Tonsillopharyngitis Severity Score (TSS) ? 8 points. In the case of fever
(? 38.5° C), acetaminophen suppositories (500mg) were allowed from day 0
to day 4. The main outcome measure was change in TSS from baseline (day 0) to
day 4. TSS measures two subjective features of acute tonsillopharyngitis—sore
throat and functional impairment (difficulty swallowing). It also objectively
measures symptoms of inflammation—pharyngeal erythema and fever. Each symptom
was assessed by an investigator using a 4-point rating scale ranging from 0 to
3 (0 = absent; 1 = mild; 2 = moderate; 3 = severe). Secondary outcome criteria
included: (1) response criteria based on the TSS; (2) change of individual
symptoms and further complaints including headache; (3) treatment outcomes
according to the Integrative Medicine Outcome Scale (IMOS; complete recovery,
major improvement, slight to moderate improvement, no change, deterioration);
and (4) patient activity level. Following the enrollment day (day 0),
controlled examinations occurred on days 2, 4, and 6. At each visit the
investigator recorded clinical status, reviewed the patient’s diary, documented
the consumption of acetaminophen, and recorded information about adverse
events.
There was a statistically significant decrease in the
primary outcome criteria (change in TSS from day 0 to day 4) in the EPs 7630
group compared with the placebo group. The decrease of TSS from baseline (day
0) to day 4 was 7.0 ± 2.4 points in the EPs 7630 group and 2.9 ± 2.4 points in
the placebo group (p < 0.0001). On day 2, TSS decreased from 10.3 ± 1.2 to
6.8 ± 2.2 in the EPs 7630 group compared to 9.7 ± 1.4 to 8.2 ± 2.8 in the
placebo group (p < 0.0001)—suggesting an early response in the EPS 7630
group.
A TSS of < 5 points on
day 4 was seen in 76.7% of patients in the EPs 7630 group compared with 34.3%
of subjects in the placebo group (p < 0.0001). A decrease of at least 5
points by day 4 was seen in 91.8% in the EPs 7630 group compared with 35.7% in
the placebo group. Rapid recovery, defined as fulfillment of secondary response
criteria 1 and 2, was observed in 75.3% in the EPs 7630 group and 32.9% in the
placebo group (p < 0.0001). There was also an improvement seen in the
activity level of subjects in the EPs 7630 group, but not in the placebo group.
By day 6, the number of patients returning to school was 80.8% in the EPs 7630
group compared with 21.4% in the placebo group (p < 0.0001). Subjects in the
EPs 7630 group consumed less acetaminophen than did subjects in the
placebo group. No serious adverse events were reported.
Acute Bronchitis
To determine the efficacy of EPs7630 for treating acute bronchitis,
468 adult male and female subjects (age > 18 years) diagnosed with acute bronchitis < 48 hours and having a Bronchitis Severity Score (BSS) > 5 points were recruited for a randomized, double-blind, placebo-controlled trial.12
Patients received either EPs 7630 or a placebo at a dose of 30 drops (1.5 mL)
3 times per day for 7 days. In the case of fever (> 39° C), acetaminophen tablets (500mg) were allowed.
The primary outcome measure was the change in the BSS on day
7 in relation to the baseline score. BSS measures the following features of
acute bronchitis—cough, sputum, rales/rhonchi, chest pain during coughing, and
dyspnea. (Note: rales refers to an abnormal or pathological respiratory sound
heard on auscultation [i.e., listening to the sounds of internal organs as a
diagnostic method]; rhonchi refers to a coarse rattling sound usually caused by
a secretion in the bronchial tubes.) Each symptom was scored by an investigator
using a 5-point rating scale ranging from 0 to 4 (0 = absent; 1 = mild; 2 =
moderate; 3 = severe; 4 = very severe). Secondary outcome measures included:
(1) prospective defined response criteria based on the BSS (A: BSS < 3
points; B: decrease of BSS ? 7 points; C: A+B); (2) treatment outcome
according to the Integrative Medicine Outcome Scale (IMOS); (3) onset of
treatment effect; (4) consumption of paracetamol (acetaminophen); (5) change of
individual symptoms of BSS and further symptoms; (6) patients’ health status
using the health-related quality of life questionnaires (SF-12 Health Survey,
EQ-5D); and (7) questions about the complaints and satisfaction with treatment
using the Integrative Medicine Patient Satisfaction Scale (IMPSS). Safety was
assessed with respect to frequency, nature, and severity of adverse events. Tolerability
of treatment was also assessed by investigators and patients, as well as by
laboratory tests. Following enrollment (day 0), controlled examinations
occurred on day 3, 4, or 5, and on day 7. At each visit the investigator
recorded clinical status, reviewed the patient’s diary, documented the
consumption of acetaminophen, and recorded the number of adverse events. On day
7, there was a final assessment, which included laboratory tests and sputum
analysis.
On day 7, BSS had decreased by 5.9 ± 2.9 in the EPs 7630
group and by 3.2 ± 4.1 in the placebo group compared to baseline. The 95%
confidence interval (CI) for the difference of effects between the two
treatment groups (EPs 7630 minus placebo) was calculated as [–3.359; –2.060],
showing a significant superiority of EPs 7630 over the placebo by day 7 (p <
0.0001). This statistically significant difference was observed as early as the first follow-up visit (day 3, 4, and 5) with a BSS score of 4.8 ± 2.3 points in the EPs 7630 group compared with 6.2 ± 3.0 in the placebo group (p < 0.0001).* In patients with the highest BSS at baseline (defined as a BSS ?
8 points), there was a statistically significant decrease in the BSS in the EPs
7630 group (6.8 ± 2.7) compared with the placebo group (4.5 ± 4.2) at day 7 (p
< 0.0001). A BSS of < 3 points (response criteria A) was observed in 64%
of patients in the EPs 7630 group compared with 37.9% in the placebo group (p
< 0.0001). A decrease of BSS of at least 7 points (response criteria B) was
observed in 43.3% of patients in the EPs 7630 group compared with 23.0% of
patients treated with the placebo at day 7 (p < 0.0001). Rapid recovery
(defined as response criteria C) was observed in 34.3% of EPs 7630 patients
compared with 20.4% receiving the placebo (p < 0.0001). There was a
statistically significant improvement in the individual symptoms of
rales/rhonchi and chest pain during coughing in the EPs 7630 group compared
with the placebo group (p < 0.0001). In the EPs 7630 group, cough
disappeared or improved in 89.2% of patients compared with 56.6% of patients in
the placebo group (p < 0.0001), and sputum disappeared or improved in 66% of
patients in the EPs 7630 group compared with 47.7% of those in the placebo
group (p < 0.0002). On day 7, fever had disappeared in 96.9% of patients in
the EPs 7630 group compared with 58.4% of those in the placebo group (p <
0.0001). Patients in the EPs 7630 group were able to return to work nearly two
days earlier than the placebo-treated group (p < 0.0001). Adverse events
were mild and similar in both groups—8.6% in the EPs 7630 group and 6.8% in the
placebo group. These events included ear-nose-throat (ENT) and respiratory
complaints (likely due to the existing condition), as well as mild
gastrointestinal upset.
Recommended Use and Safety
To date, acute bronchitis and acute non-GABHS
tonsillopharyngitis have been the primary conditions studied in controlled
clinical trials. The recommended dose of EPs 7630 for adults and children over
the age of 12 years is 30 drops (1.5 mL) 3 times per day for 7 days. Children
ages 6 to 12 years may take 20 drops (1.0 mL) 3 times per day. Unpublished
observational studies have suggested that children under the age of 6 years may
take 0.5 mL 3 times per day.6 Dosage and duration of treatment for
persons suffering from acute maxillary sinusitis should become clearer with the
results of a recently completed clinical trial awaiting publication.
Controlled clinical
trials such as the two reviewed above demonstrate that EPs 7630 is
well-tolerated and safe for the short-term treatment of acute bronchitis and
tonsillopharyngitis. Open-label, observational studies with over 2,500 adults
and children suffering from acute bronchitis, acute tonsillopharyngitis, or
acute maxillary sinusitis have found adverse events occurring in 1.2% to 15.5%
of subjects.6 In only 1.6% of these cases was there a probable or
possible connection made to EPs 7630. Adverse events have been largely mild,
consisting of gastrointestinal complaints and skin rash.
The extract of P. sidoides root (EPs 7630) is contraindicated during pregnancy and lactation as
no specific data on pregnant or lactating women are available. To date, there
are no other contraindications or known drug interactions with the root
extract.
*Editor’s note: The hard copy version of HerbalGram 63 contained an error in this sentence. This online version of HerbalGram 63 contains the corrected sentence.
References:
1. Snow V, Mottur-Pilson C, Cooper RJ, Hoffman JR. (For the
American College of Physicians - American Society of Internal Medicine).
Principles of appropriate antibiotic use for acute pharyngitis in adults. Ann
Intern Med. 2001;134(6):506-–508.
2. Thomas
M, Del Mar C, Glasziou P. How effective are treatments other than antibiotics
for acute sore throat? Br J Gen Pract. 2000;50(459):817–820.
3. Bent
B, Saint S, Vittinghoff E, Grady D. Antibiotics in acute bronchitis: a
meta-analysis. Am J Med. 1999;107:62–67.
4. Van der Walt JJA, Vorster PJ. Pelargoniums
of Southern Africa, Vol. 3. National Botanic Gardens: Kirstenbosch; 1988.
5. Kolodziej H, Kayser O. Pelargonium sidoides DC.: Latest findings
towards understanding the phytotherapeutic preparation Umckaloabo. Zeitschrift
Phytotherapie. 1998;19:141–151.
6. Kolodziej
H, Schulz V. Umckaloabo: From traditional application to modern phytodrug. Deutsche
Apotheker Zeitung. 2003;143:55–64.
7. Kayser
O, Kolodziej H. Antibacterial activity of extracts and constituents of Pelargonium
sidoides and Pelargonium reniforme.
Planta Med. 1997;63(6):508–510.
8. Kayser
O, Kolodziej H, Kiderlen AF. Immunomodulatory principles of Pelargonium
sidoides. Phytotherapy Res. 2001;15(2):122-–126.
9. Kolodziej
H, Kayser O, Radtke OA, et al. Pharmacological profile of extracts of Pelargonium
sidoides and their constituents. Phytomedicine.
2003;10(Suppl 4):18–24.
10. Koch E,
Lanzendörfer-Goossens H, Wohn C. Stimulation of interferon (INF)-b-synthesis
and natural killer (NK) cell activity by an aqueous-ethanolic extract from
roots of Pelargonium sidoides (Umckaloabo).
Naunyn-Schmeideberg Arch Pharmacol. 2002;365(Suppl
1):R75 (Abstract 288).
11. Bereznoy
V, Riley D, Wassmer G, Heger M. Efficacy of extract of Pelargonium sidoides in children with acute non-group a beta-hemolytic
streptococcus tonsillopharyngitis: a randomized, double-blind,
placebo-controlled trial. Altern Ther Health Med. 2003;9(5):68–79.
12. Matthys
H, Eisebitt T, Seith B, Heger M. Efficacy and safety of an extract of Pelargonium
sidoides (EPs 7630) in adults with
acute bronchitis. Phytomedicine.
2003;10(Suppl 4):7–17.
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