CLINICAL
RESPIRATORY CPD
maxillary sinusitis. Overall safety and a
very low incidence of side effects have
been confirmed.
TOXICOLOGY, ADVERSE
EFFECTS, PRECAUTIONS,
CONTRAINDICATIONS,
INTERACTIONS
The cytotoxicity of coumarins present
in the crude drug and/or extracts can
be considered negligible (Kayser, 1997;
Kolodziej et al, 1997; Kolodziej, 2002).
To date, there are no contraindications
or known drug interactions with the
root extract (EPs 7630).
Schulz (2008) and Conrad et al
(2007) summarised efficacy and
safety-related findings for Eps
7630. Controlled clinical trials all
demonstrated that EPs 7630 is well-
tolerated and safe. In studies with over
7000 adults and children suffering
from acute bronchitis, acute tonsillo-
pharyngitis, or acute maxillary sinusitis,
adverse events occurred in 1%-15%
of subjects. These events have been
reported as largely mild, consisting of
gastrointestinal complaints and skin
rashes. With regards to a potential
risk related to the coumarin content,
a NOEL value of more than 750mg/
kg body weight was established in
toxicological studies in dogs and rats.
A daily intake of 60mg (3°ø30 drops)
of extract would be equivalent to 4
and 1mg/kg bodyweight (15 kg for a
child or 60kg for an adult, respectively)
translating into a safety factor of more
than 100. No hepatotoxic activity could
be established for 7-hydroxycoumarin
derivatives (the only coumarins present
in EPs 7630) (Loew and Koch, 2008).
A theoretical risk of interactions
with anticoagulants and antiplatelet
drugs could not be confirmed as the
coumarins so far identified in EPs 7630
do not appear to possess anticoagulant
characteristics. Koch and Biber (2007)
administered EPs 7630 to rats and
observed changes in coagulation
parameters and interactions with
anti-coagulants of the coumarin type
(warfarin). After two weeks of oral
application of EPs 7630, no impact on
coagulation parameters was observed.
Treatment with warfarin, however,
resulted in a significant lowering of
coagu lation parameters. Cotreatment
with EPs 7630 and warfarin did not
show any effect of EPs 7630 over
the efficacy of warfarin, neither did
it influence the pharmacokinetics of
warfarin. A total of 34 case reports
of allergic (hypersensitivity) reactions
have been recorded through the
World Health Organization (WHO)
international pharmacovigilance
programme, which may be associated
with the use of Pelargonium extract (De
Boer et al, 2007).
The extract of Pelargonium sidoides
root (EPs 7630) is contraindicated
during pregnancy and lactation as
no specific data on its effect on
pregnant or lactating women is
available. Treatment of infections of
the upper respiratory tract, particularly
tonsillitis, often requires administration
of antibiotics. Roots et al (2004)
investigated a potential interaction
of a EPs 7630 with penicillin V in a
placebo-controlled, double-blind trial
with 28 healthy humans. EPs 7630 and
penicillin V were administered for 7 and
8 days, respectively. None of the target
parameters showed any statistically
significant difference between verum
and placebo. Adverse reactions linked
to the herbal extract were not recorded.
Schulz (2008) and Conrad et
al (2007) found that controlled
clinical trials all demonstrated that
Pelargonium root extract is well-
tolerated and safe. In studies with over
7000 adults and children suffering
from acute bronchitis, acute tonsillo-
pharyngitis, or acute maxillary sinusitis,
adverse events occurred in 1%-15%
of subjects. These events have been
reported as largely mild, consisting of
gastrointestinal complaints and skin
rashes. A total of 34 case reports of
allergic (hypersensitivity) reactions
have been recorded through the
World Health Organization (WHO)
international pharmacovigilance
programme, which may be associated
with the use of Pelargonium extract,
all originating from Germany (De Boer
et al, 2007)
CONCLUSION
The traditional uses of the roots of
Pelargonium myrrhifolium as tonic and
treatment for tuberculosis, as recorded
by Burman in 1759 (Scott and Hewett,
2008) is particularly noteworthy.
The underground parts of
Pelargonium sidoides are known to
contain a wealth of highly oxygenated
coumarins and numerous other
phenolic and polyphenolic compounds.
The study of Kolodziej (2007), excellent
and detailed as it may be, was based on
single samples of Pelargonium sidoides
and Pelargonium reniforme, so that
possible geographical, phenotypical
and genotypical patterns remain as
a challenge for future research. It
may also be interesting to extend the
study of coumarins and coumarin
derivates to other red-rooted species of
Pelargonium with a recorded history of
ethnomedicinal use. It is likely that the
efficacy in treating respiratory ailments
is due to the activities and interactions
of several components rather than that
of a single main constituent. EPs 7630,
a root extract of Pelargonium sidoides,
showed in vitro antibacterial, antiviral,
and immunomodulatory properties
in several studies. These activities
seem to account for its therapeutic
effect in patients suffering from acute
bronchitis, tonsillopharyngitis, sinusitis
and symptoms of the common cold.
Efficacy has been proved in numerous
clinical trials. The demonstrated
pharmacological activities including
moderate direct antibacterial potencies
and notable immunomodulatory
capabilities provide strong evidence
for the efficacy of EPss 7630 in
the treatment of respiratory tract
infections. Conspicuously, infected cells
showed augmented activation of host
defence mechanisms.
This apparent selectivity in the
immune response, in contrast to
random macrophage activation, may
be of special benefit, reflecting effective
immunoregulatory activity
in infectious conditions, e.g., when
needed. Since respiratory tract
infections are frequently caused by
viruses, the modulatory potential of
this herbal medicine on the IFN system
that may contribute to an improved
antiviral protection deserves to be
explicitly mentioned. Owing to known
antiviral potencies of tannins, a closer
look onto polyphenols present in this
herbal medicine for this particular
biological activity may also be
worthwhile. Despite considerable
efforts, the remedial effects cannot
yet be related to a chemically defined
principle. Further studies are needed
towards a better understanding of the
mode of actions and the responsible
underlying biological principles.
One study compared an extract
of P. sidoides, Eps 7630, against
conventional non-antibiotic
treatment (acetylcysteine); the other
five studies tested Eps 7630 against
placebo. All RCTs reported findings
suggesting the effectiveness of P.
sidoides in treating acute bronchitis.
Meta-analysis of the four placebo-
controlled RCTs suggested that Eps
7630 significantly reduced bronchitis
symptom scores in patients with
acute bronchitis by day 7. No serious
adverse events were reported.
There is encouraging evidence from
currently available data that
P. sidoides is effective compared
to placebo for patients with acute
bronchitis.
PELARGONIUM SIDOIDES AND THE COMMON COLD
The common cold is a viral infection with symptoms
such as sneezing, sore throat, and running nose. It is
one of the most prevalent illnesses in the world, and
although commonly caused by rhinoviruses, antibiotics
are often prescribed unnecessarily.
Therefore, it is of utmost importance to evaluate
alternative treatments such as herbal medications,
whose efficacy and safety is proven by pharmacological
and clinical studies. The aim of the present study was to
evaluate the efficacy of a liquid herbal drug preparation
from the roots of Pelargonium sidoides compared with
placebo in adult patients with the common cold.
Design: The study was designed as a multicentre,
prospective, randomised, double blind, parallel group,
placebo-controlled phase III clinical trial with an
adaptive group-sequential design.
Setting: The study took place in eight outpatient
departments affiliated with hospitals.
Patients: One hundred three male and female adult
patients with at least two major and one minor or with
one major and three minor cold symptoms (maximum
symptom scor e of 40 points), present for 24 to 48
hours, and who gave provision of informed consent
were randomised to receive either 30 drops (1.5mL) of
the liquid herbal drug preparation EPs or placebo three
times a day.
Intervention: Patients received randomised treatment
for a maximum period of 10 days.
Measurements: The primary outcome criterion was
the sum of symptom intensity differences (SSID) of
the cold intensity score (CIS) from day one to day five.
The CIS consists of the following 10 cold symptoms:
nasal drainage, sore throat, nasal congestion, sneezing,
scratchy throat, hoarseness, cough, headache, muscle
aches, and fever.
Results: From baseline to day five, the mean SSID
improved by 14.6 +- 5.3 points in the EPs group
compared with 7.6 +- 7.5 points in the placebo group.
This difference was statistically significant
(P < 0.0001). The mean CIS decreased by 10.4 +- 3.0
points and 5.6 +- 4.3 points in EPs and placebo-treated
patients, respectively. After 10 days, 78.8% versus
31.4% in the EPs vs. placebo group were clinically cured
(CIS equals zero points or complete resolution of all
but a maximum of one cold symptom; P <0.0001). The
mean duration of inability to work was significantly
lower in the EPs treatment group (6.9+-1.8 days) than
in the placebo group (8.2 +- 2.1 days; P = 0.0003).
Treatment outcome (rates of complete recovery or
major improvement from disease [integrative medicine
outcomes scale]) was assessed better in the EPs
treatment group than in the placebo group by both the
investigator and the patient on day five (P <0.0001).
Adverse events occurred in three of
103 patients (2.9%), with two of 52 (3.8%) and
one of 51 (2.0%) patients in the EPs and placebo group,
respectively. All adverse events were assessed as
nonserious. At the end of treatment, all patients (100%)
in the active treatment group judged the subjective
tolerability of Eps as good or very good.
Conclusions: EPs represents an effective treatment
of the common cold. It significantly reduces the severity
of symptoms and shortens the duration of the common
cold compared with placebo. The herbal drug is
well tolerated.
CPD questionnaire on pg 58. Complete online: www.medicalchronicle.co.za/medicinal-use-of-pelargonium-sidoides/
MEDICAL CHRONICLE | MAY 2017 53