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Himalaya update
Volume 18 Number 8
I 2010
MEDICINE
UPDATE
Clinical study to evaluate the safety and
efficacy of Septilin tablets in respiratory
tract infection: An open clinical study
Authors
*Corresponding Author:
Dr. Kavitha Rajarathna MBBS., MD.,
Dr. D.Palaniyamma, M.D.
Lecturer, Department of pharmacology
Medical Advisor
Bangalore Medical College,
R&D Center
K.G.Halli, Bangalore
The Himalaya Drug Company
Makali, Bangalore, India
Dr. Suprabha Hegde MS (Ayu),
Research associate,
The Himalaya Drug company,
Makali, Bangalore, India
ABSTRACT
Respiratory tract infection includes both upper and lower respiratory tract which range from the common cold typically a mild,
self-limited, catarrhal syndrome of the nasopharynx to life threatening illnesses such as epiglottitis.
Aim: To evaluate the of role of septilin in the treatment of respiratory tract infection.
Materials and Methods: The present study comprised of 148 cases suffering from upper and lower respiratory tract infections.
Septilin tablet was given to all the patients at a dose of 2 tablets, twice daily for a period of 6 weeks. All the patients were evaluated
at intervals of 2 weeks for a period of 6 weeks for the presenting symptoms.
Results: The control of symptoms and gradual improvement noticed after 2 weeks of treatment which further improved with
continued treatment. Out of 148 patients treated only two patients experienced mild abdominal discomfort effects and all the
patients tolerated the drug well. None of the patients were withdrawn due to adverse effects.
Conclusion: This study showed that septilin tablets showed statistically significant improvement in the symptoms of upper and
lower respiratory tract infections and also Septilin was safe in the dose administered and well tolerated by the patients.
KEY WORDS: Respiratory tract infection, Septilin
INTRODUCTION
Respiratory tract infection includes infections of both upper
and lower respiratory tract. Upper respiratory tract infections
(URTIs) comprising tonsillitis, pharyngitis, laryngitis, sinusitis,
otitis media, and the common cold are frequent presenting
conditions in primary care. The majority of URTIs are of viral
origin, due to rhinovirus, parainfluenza virus, coronavirus,
adenovirus, Coxsackie virus, and influenza virus. However,
pharyngitis and the common cold have the greatest probability
of being of viral origin. Only 10% of URTIs has been attributable
to bacterial aetiology, with the three most common organisms
being Streptococcus pneumoniae, Haemophilus influenzae, and
Moraxella catarrhalis. Of these conditions, those that present with
sore throat (tonsillitis, pharyngitis, laryngitis) are responsible for
just over 50% of presentations, with otitis media adding another
25%.1 These conditions are frequently treated with antibiotics, and
rates of antibiotic prescribing have been increased.2 Transmission
of organisms causing URIs occurs by aerosol, droplet, or direct
hand-to-hand contact with infected secretions, with subsequent
passage to the nares or eyes. Thus, transmission occurs more
commonly in crowded conditions. Direct invasion of the respiratory
epithelium results in symptoms corresponding to the area(s)
involved. Lower respiratory tract infection includes pneumonia,
lung abscess, acute bronchitis, and emphysema. The two most
common infections are bronchitis and pneumonia. Influenza
affects both the upper and lower respiratory tracts. Symptoms
of Lower respiratory tract infection include shortness of breath,
weakness, high fever, coughing and fatigue.
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Respiratory tract infections are frequently treated with
antibiotics, and rates of antibiotic prescription have been increased.
Interview studies 3,4 have shown that general practitioners (GPs)
have a range of reasons why they prescribe antibiotics for sore
throats. These include the feeling that patients ‘want something
done’ or expect to receive a prescription; beliefs that, despite
the evidence, antibiotics may help some patients and could do
little harm; a concern to preserve and build relationships with
patients; and workload factors. Other studies have found that
GPs often feel uncomfortable about prescribing antibiotics5, and
that antibiotics are ten times more likely to be prescribed if the
doctor perceives that a patient expects them6. The development
of antimicrobial resistance has occurred predominantly among
Streptococcus pneumoniae, Haemophilus influuenzae, and
Moraxella catarrhalis.
In the United States, the respiratory tract infection accounts for
75 to 100 million physician visits annually at a conservative cost
estimate of $7.7 billion per year. Americans spend $2.9 billion on
over-the-counter drugs and another $400 million on prescription
medicines for symptomatic relief.7,8 More than one-third of patients
who saw a doctor received an antibiotic prescription, which has
implications for antibiotic resistance from overuse of such drugs.8
An estimated 22 to 189 million school days are missed annually
due to a cold. As a result, parents missed 126 million workdays to
stay home to care for their children. When added to the 150 million
workdays missed by employees suffering from a cold, the total
economic impact of cold-related work loss exceeds $20 billion
per year.7,8 This accounts for 40% of time lost from work.9
Patients with recurrent upper respiratory tract infections receive
various combinations of potent antibacterial agents, which are not
only expensive but also potentially toxic, producing unwanted
adverse effects and hence not safe for frequent long term use.
Indiscriminate use of an antibiotic also produces drug-resistance,
creating problem for further use in future when such use may be
genuinely life saving. Septilin, reported to have effective antibacterial and anti-inflammatory properties in the management of
acute and or recurrent upper and lower respiratory tract infections
based on the extensive clinical trials conducted on this herbal
medicine. It is an economical and safe drug, free from side-effects
when used for a longer period. This prompted us to try Septilin
in our cases of respiratory tract infections. The principal herbs
of Septilin include Tinospora cordifolia, Emblica officinalis,
Glycyrrhiza glabra, Moringa pterygosperma, Balsamodendron
mukul and Rubia cordifolia.
Aim: To evaluate the efficacy and safety of Septilin tablets in
upper and lower respiratory tract infection.
MATERIALS AND METHODS
Study design
An open clinical evaluation was conducted on 148 cases presenting
with signs and symptoms of upper and lower respiratory tract
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Table 1. Demographic data
Total number of patients
148
Mean age in years (Mean ± SD)
40.20 ± 8.60
Mean weight in kgs (Mean ± SD)
57.30 ± 2.80
Sex ratio (M:F)
78:70
infection who attended the Outpatient Department of Medicine,
Bangalore Medical College, Bangalore, Karnataka, India.
Inclusion criteria
Adult patients presenting with upper and lower respiratory tract
infections of either sex aged between 18-50 years, were included
in the study.
Exclusion criteria
Patients with severe infections like pneumonia, tuberculosis, status
asthamaticus, severe bronchospasm were not included in the study.
Patients with evidence of pregnancy, lactation, any patients with
severe psychiatric/cardiac, metabolic, gastrointestinal disorders
or metabolic disorders were excluded from the study.
Study procedure
The present study comprised of 148 cases suffering from upper
and lower respiratory tract infections. At entry demographic details
are listed in table 1. Detailed history of the duration, frequency,
severity of the infection and history of smoking, allergic/atopic
details and occupation related risks of the illness were elicited. A
thorough examination of ear, nose, throat, and chest examination,
physical examination and vitals including respiratory rate were
also conducted and recorded in case report form. Patients entered
into the study after signing the voluntary informed consent form.
Septilin tablets were given to all the patients at a dose of 2 tablets
twice daily for a period of 6 weeks. Adverse effects if any were
noted down. The protocol of the study was as per the ICH-GCP
guidelines and the patients were free to withdraw from the study
Table 2. Break-up of respiratory tract infection
Indication
No. of patients
Duration of
illness (days)
Respiratory tract
infections
148
-
Upper respiratory
tract infection
112
-
Tonsillitis
28
5.26±2.5
Pharyngitis
24
7.23±4.4
Laryngitis
08
7.58±5.1
Sinusitis
20
5.3±1.26
Rhinitis
32
7.47±3.22
Lower respiratory
tract infection
36
Bronchitis
36
9.42±3.41
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Himalaya update
if they so desired. No other medication was allowed for these
patients.
The break-up of respiratory tract infection and the duration of
the illness are listed in table 2. Out of the 148 patients suffering
from Respiratory tract infections, 112 patients suffered from upper
respiratory tract infection presenting with tonsillitis, pharyngitis,
rhinitis, laryngitis and sinusitis and remaining 36 cases suffered
from bronchitis.
Follow up and assessment
All the patients were evaluated at intervals of 2 weeks at the
end of 2nd week, 4th week and 6th week for the presence of the
symptoms.
Primary and secondary outcome measure
The primary outcome measures were clinical recovery from
the presenting symptoms of upper and lower respiratory tract
infections. Secondary end points were clinical safety and toxicity
profile of Septilin tablets.
Adverse events
All adverse events reported or observed by patients were recorded
with information about severity, date of onset, duration and action
taken regarding the study drug. Relation of adverse events to
study medication was predefined as “Unrelated” (a reaction
that does not follow a reasonable temporal sequence from the
administration of the drug), “Possible” (follows a known response
pattern to the suspected drug, but could have been produced by
the patient’s clinical state or other modes of therapy administered
to the patient), “Probable” (follows a known response pattern
to the suspected drug that could not be reasonably explained
by the known characteristics of the patient’s clinical state) and
“Certain” (the adverse events must have definitive relationship to
the study drug, which cannot be explained by concurrent disease
or any other agent).
Patients were allowed to voluntarily withdraw from the study
if they had experienced serious discomfort during the study or
sustained serious clinical events requiring specific treatment. For
patients withdrawing from the study, efforts were made to ascertain
the reason for dropout. Non-compliance (defined as failure to take
less than 80% of the medication) was not regarded as treatment
failure, and reasons for non-compliance were noted.
Statistical analysis
Statistical analysis was carried out using Fisher’s Exact Test using
GraphPad Prism, Version 4.03 for windows, Graphpad Software,
San Diego, California, USA. for presence or absence of various
signs and symptoms.
RESULTS
The effect of septilin treatment in respiratory tract infection is
shown in table 3. All the cases responded by 2 weeks of treatment
and continued to respond with further treatment. Among the 28
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Table. 3 Effect of Septilin tablets on respiratory tract
infection
Parameters
At entry
2 weeks
4 weeks
6 weeks
Tonsillitis
28
17
8*
03
Pharyngitis
24
8*
2**
00
Laryngitis
08
00
00
00
Sinusitis
20
12
07*
02**
Rhinitis
32
2**
00
00
Bronchitis
36
20
11*
04**
*p<0.01 compared to at entry values
** p<0.001 compared to at entry values
cases suffering from tonsillitis, at the end of 2 weeks only 17
cases and at the end of 4 weeks 8 cases (p<0.01 ) and at the end
of 6 weeks only 3 cases (p<0.001) presented with tonsillitis. The
3 cases who didn’t respond were further treated with antibiotics.
Twenty four patients with pharyngitis treated with septilin were
additionally advised salt water gargling 2-3 times daily. Patients
showed a significant response by 2 weeks of treatment where only
8 patients (p<0.01) and at 4 weeks only 2 patients presented with
pharyngitis. At the end of 6 weeks of treatment all the patients
responded to the treatment ( p<0.001). Of the 8 laryngitis cases
treated with septilin, all the cases responded by 2 weeks of
treatment but is not considered as statistically significant because
of the small sample size. Among the 20 patients with sinusitis,
patients treated with septilin additional steam inhalation was
advised. At the end of 2 weeks only 12 cases, at 4 weeks 07 cases
(p<0.01), and at the end of 6 weeks only 2 patients (p<0.001)
had symptoms of sinusitis. Of the thirty two patients of rhinitis,
patients were treated with septilin along with steam inhalation and
symptoms reduced significantly by 2 weeks with a significance
of p<0.001 and by 4 weeks all the patients responded.
In lower respiratory tract infection, 36 bronchitis cases treated
with septilin, by 2 weeks 20 cases, by 4 weeks 11 cases (p<0.01)
and at the end of 6 weeks 4 cases presented with symptoms who
required additional medications.
Out of 148 patients treated only two patients experienced mild
abdominal discomfort effects and all the patients tolerated the drug
well. None of the patients were withdrawn due to adverse effects.
In 3 patients suffering from tonsillitis, 2 patients suffering from
sinusitis and 4 patients suffering from bronchitis, there was no
improvement in symptoms as well as signs. They were advised
further treatment specific to the disease.
DISCUSSION
Upper respiratory tract infection represents the most common acute
illness evaluated in the outpatient setting. The upper respiratory
tract affects the sinuses, nasal passages, pharynx, and larynx,
which serve as gateways to the trachea, bronchi, and pulmonary
alveolar spaces and presents as rhinitis, pharyngitis, sinusitis,
epiglottitis, laryngitis, tracheitis and bronchitis.
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Management of certain chronic and recurrent infections is often
unsatisfactory and frustrating to the patient and physician alike.
This study demonstrates the efficacy of Septilin in the treatment
of such infections. Septilin has immunomodulatory, antioxidant,
anti-inflammatory, anti-allergic, antimicrobial actions. Septilin has
short and long term safety. Septilin is a multi-herbal preparation
and the effect of the formulation is due to synergistic action of
the ingredients.
Tinospora cordifolia has potent immunomodulatory and
immunostimulatory actions, which increases the levels of
antibodies and activate macrophages.10-13 Tinospora cordifolia
improves the phagocytic and intracellular bactericidal capacities
of neutrophils.14 Emblica officinalis enhances cell survival,
increases phagocytosis and γ-IFN production.15 Glycyrrhizin from
Glycyrrhiza glabra potentiates the reticuloendothelial system,16
enhances immunostimulation,17 and acts on macrophage function
in vitro, leading to stimulation of macrophages de novo,18 Betaglycyrrhetinic acid from Glycyrrhiza glabra is a potent inhibitor
of the classical complement pathway19 and antiviral activity.20
Emblica officinalis has antibacterial properties, especially
against Escherichia coli, Klebsiella pneumoniae, Klebsiella
ozaenae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella
typhi, Salmonella paratyphi A & B, and Serratia marcescens21
Rubia cordifolia22 has antibacterial properties.
Moringa pterygosperma possesses antibacterial and antiviral
properties, and inhibits the growth of gram-positive and gramnegative bacteria like Escherichia coli, Salmonella typhi,
Salmonella paratyphi etc.23 Tinospora cordifolia24 and Emblica
officinalis25 possess antipyretic properties.
Balsamodendron mukul,26-29 Rubia cordifolia30, Emblica
officinalis31, Glycyrrhiza glabra32, and Moringa pterygosperma33
have potent antioxidant actions. Balsamodendron mukul 34 have
strong anti-inflammatory potential. Glycyrrhiza glabra35 and
Moringa pterygosperma36 have also been reported for its antiinflammatory properties.
SUMMARY AND CONCLUSION
This study demonstrated that septilin tablets used in patients
suffering from upper and lower respiratory tract infection
showed significant improvement in the presenting symptoms. All
the symptoms started improving by 2nd week of treatment and
further improved with continued treatment. Out of 148 patients
treated only two patients experienced mild abdominal discomfort
effects and all the patients tolerated the drug well. None of the
patients were withdrawn due to adverse effects. Septilin is not
only cheap but a safe drug, well tolerated by the patients and can
be used over long-periods without any side-effects. Septilin, a
multiherbal formula, provides immunomodulatory activity that
enhances natural immunity. Therefore, it may be concluded that
Septilin is effective and safe in the treatment of respiratory tract
infections.
Himalaya update
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