COMPARATIVE ANALYSIS OF MONTELUKAST, LEVOCETIRIZINE ...
Transcript of COMPARATIVE ANALYSIS OF MONTELUKAST, LEVOCETIRIZINE ...
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1305
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
COMPARATIVE ANALYSIS OF MONTELUKAST,
LEVOCETIRIZINE, CETIRIZINE & FEXOFENADINE
Namia Mansoor*, Ramya Nadig, Rohan Munoth, Vasavi Reddy and Yadini Kamdi
Manipal Institute of Technology, Vishnu Institute of Pharmaceutical Education, Priyadarshini
Institute of Engineering and Technology.
ABSTRACTS
This article is an examination of the Comparative Analysis of
Fexofenadine, Levocetirizine, Cetirizine and Montelukast. The
scientific development and subsequent continues to influence
researchers all over the globe today. This article examines the research
done and published by researchers and scientists. Consideration of
current trends and data in scientific queries and demonstrates further
aspects of Comparative Analysis of Fexofenadine, Levocetirizine,
Cetirizine and Montelukast. Additionally, this article explores options
for therapeutic functions of the antihistamines while diving into
allergenic issues as well.
KEYWORDS: Montelukast, Cetirizine, Levocetirizine, Fexofenadine,
Allergy.
INTRODUCTION
Antihistamines are a class of drugs that are generally used to combat allergic reactions and
subsequent symptoms. These medications are used to treat conditions resulting in an
increased incidence of histamine, a chemical produced by the immune system. People who
are allergic to pollen and other allergens are the most active members of antihistamines.
They're also used to treat a host of other issues, including digestive issues, colds, and anxiety.
Antihistamine medications are among the most widely used drugs in pediatric medicine.
According to the International Medical Statistics (IMS), approximately 2 million
antihistamine units were sold in Spain (2006) for paediatric use. Of this first-generation or
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 10, Issue 4, 1305-1335 Research Article ISSN 2278 – 4357
*Corresponding Author
Namia Mansoor
Manipal Institute of
Technology, Vishnu
Institute of Pharmaceutical
Education, Priyadarshini
Institute of Engineering and
Technology.
Article Received on
11 Feb. 2021,
Revised on 03 March 2021,
Accepted on 23 March 2021
DOI: 10.20959/wjpps20214-18729
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1306
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
sedating antihistamines accounted for 34% of the total. When it comes to drug development
testing, the challenges are multiplied significantly when children are involved. Any drug used
in this age group must maintain the strictest safety regulations and provide the highest degree
of efficacy satisfaction. As a consequence, thorough knowledge of the best scientific
evidence available concerning these aspects is required. The first-generation antihistamines
have never been extensively tested in infants, even though they are still commonly used in
paediatric patients.
The paper provides a comparative investigation of four commonly used antihistamines such
as montelukast, levocetirizine, cetirizine and fexofenadine while weighing in factors such as
cardiological safety and pulmonary function.
METHODS
The study was conducted using four databases Gosogle Scholars SAGE, DOAJ and PubMed.
Selection of papers were done based on keywords and themes relevant to this review. Further
the published papers from these databases were arranged in systematic order with respect to
the year of publication.
RESULTS AND DISCUSSION
Montelukast
The efficiency of montelukast as a beta antagonist
Compared to the placebo, montelukast significantly improved asthma control during a 12-
week treatment period. With a sample size of 300 patients for the montelukast group and 200
patient’s placebo group, the study was designed to have 95% power to detect a mean
difference between treatment groups of 5.4 percentage points in forced expiratory flow in 1
second (FEV1) and 9.1% in daytime symptom score. Patient-reported endpoints, e.g.,
daytime asthma symptoms and as-needed β-agonist, were significantly compared with
placebo) improved by montelukast (Figure 1). Each asthma-specific quality-of-life domain
had notably higher scores for patients treated with montelukast during the 12week treatment
period (Figure 2). This clinical trial demonstrated that montelukast provides clinical benefits
during the 12-week treatment period as it had consistent and significant improvement of all
asthma control variables compared with placebo.
Tolerance can sometimes be a clinical problem with some therapies, including receptor
antagonists. Following the 12 weeks of treatment, montelukast removal did not cause
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1307
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
rebound worsening of asthma at any endpoint. Across patient pre-randomization
characteristics, the effect of montelukast was generally consistent. These characteristics
include demographic variables and baseline values for the endpoints (forced expiratory flow
in 1 second and daytime symptom score), indicating a similar clinical response to
montelukast across subgroups of the asthmatic population studied.
The 10 mg dosage given orally once daily at bedtime during a 12-week treatment period,
montelukast sodium, provided significant clinical benefit to patients with chronic asthma.
Effective, well-tolerated oral therapies may have a substantial impact on the management of
asthma.
Adverse skin effects due to montelukast
Asthma is a widely present long-term disease affecting nearly 300 million people, with 100
million more patients by 2025. Allergic rhinitis is a common disease; it affects 10 – 40% of
the United States population. In epidemiologic studies, evidence for the association between
allergic rhinitis and asthma has been reported frequently. Montelukast is a potent and specific
cysteinyl leukotriene receptor antagonist that possesses broncho-dilating and anti-
inflammatory properties and effectively treats both asthma and allergic rhinitis. Developed as
a treatment for asthma, montelukast treats allergic rhinitis. Adverse effects of asthma
treatment using montelukast includes headache, gastrointestinal disturbance, fatigue,
pharyngitis, upper-respiratory-tract infection, rash, worsening of asthma, cough, sore throat,
hallucinations, depression, suicidal ideation, and tremors. During studies with montelukast
treatment, a few sporadic cases of mild to moderate acute hepatitis were reported. Skin
reactions associated with montelukast include unspecified rash, with or without blistering,
hives, inflammation in blood vessels, swelling of the area beneath the skin, erythema
nodosum, ecchymosis, skin ulcers, and, rarely, skin nodules. The most severe complication is
Churg- Strauss syndrome, a vasculitis reported in people with asthma treated with leukotriene
receptor antagonists. Frequent skin problems of Churg-Strauss syndrome are palpable
purpura, hemorrhagic lesions, cutaneous and subcutaneous nodules, erythematous
maculopapular rarely, ulcers, infarcts, livedo-like eruption and facial oedema. It was thought
that the decreased corticosteroid dosage needed to control asthma symptoms in patients
receiving leukotriene receptor antagonists unmasked an underlying vasculitis that had been
controlled previously by the corticosteroids. The authors' patient was not receiving oral
corticosteroid. The beginning leukotriene receptor antagonists in asthmatic patients were not
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1308
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
treated with steroids. The American College of Rheumatology has proposed six criteria for
diagnosing Churg-Strauss syndrome: asthma, eosinophilia of greater than 10% in peripheral
blood, paranasal sinusitis, pulmonary infiltrates, histologic proof of vasculitis with
extravascular eosinophils, and mononeuritis multiplex or polyneuropathy.
Inhibition of cysteinyl leukotrienes by montelukast for whooping cough
Postinfectious cough is a commonly found symptom in primary care but has no guaranteed
treatments. Raised concentrations are observed in children with RSV bronchiolitis and virus-
induced wheeze. Cysteinyl leukotrienes are involved in developing a postinfectious cough
and whooping cough and potentiating the effects of inflammatory neuropeptides. Respiratory
viruses can sensitize airways to leukotrienes by increasing the production of interferon-γ,
eight, thereby increasing cysteinyl leukotriene type 1 receptor expression. The authors
investigated montelukast's effectiveness, a cysteinyl leukotriene receptor antagonist, to treat
postinfectious cough. For this randomized and placebo-controlled trial, health-care specialists
at 25 clinics in southwest England and Thames Valley recruited patients aged 16–49 years
with a postinfectious cough.
Between April 13, 2011, and September 21, 2012, the authors screened 339 patients, of
whom 276 were randomly allocated to receive placebo (n=139) or montelukast (n=137).
Seventy (25%) patients had positive lab tests for pertussis. In both groups, improvements in
cough-specific quality of life occurred after two weeks, but the difference between groups did
not match the minimum clinically significant difference of 1·3. After four weeks, significant
differences were not present between-group in cough-specific quality of life improvement or
adverse effect rates. However, 21 (15%) of 137 patients on montelukast reported one or more
adverse events: 31 (22%) of 139 on placebo.
Montelukast drug monitoring to ensure drug safety for asthma patients
The reporting odds ratio compares the rate of reporting a specific adverse effect in a drug
with reporting the same adverse effect in all other drugs. The division calculation for ROR is
as follows. The numerator is the number of patients who used montelukast. A specific ADR
was reported divided by the number of cases using montelukast in which the side effects were
not reported. The denominator is the number of adult and pediatric cases using other drugs,
reporting a specific adverse drug reaction divided by the number of cases using other drugs
without reporting that specific adverse drug reaction. For the global database VigiBase, the
study obtained numbers of reports and disproportionality per reported association, both in
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1309
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
adults and children, through VigiLyze, a search and analysis tool. Conclusion: The study
covers a detailed overview of the safety of montelukast in clinical practice. Results Of the
331 reports on adverse drug reactions after montelukast were present, of which 124 were
reported in men, and 203 in women were present in the Dutch spontaneous reporting
database, in almost a third, the reports concerned individuals aged between 0 and 18 years
and in 214 cases, adults aged 19 years and older. This is the first study at the time of
publication, highlighting both adverse drug reactions in adults and children extracted from
two large databases.
Table 1: Adverse drug reactions (ADRs) after montelukast reported to the Netherlands
Pharmacovigilance Center Lareb and deemed serious, for example, leading to death,
hospitalization, or life threatening condition.
Adverse drug reaction Comments Relation with montelukast
according to the Naranjo
score (Naranjo et al. 1981)
Death 20‐year‐old woman with
pulmonary embolism
Woman of unknown age with
renal failure.
Allergic granulomatous
angiitis
Angioedema 4‐year‐old girl with
concomitant use of pulmicort
and foradil. Patient was
treated with tavergil and
prednisone. Montelukast was
discontinued. Angioedema
disappeared.
Possible
Malaise 45‐year‐old woman with
concomitant use of 8 other
medicines. Montelukast was
discontinued and she
recovered.
Possible
Epilepsy 9‐year‐old boy with no
concomitant use of other
medicines. Montelukast was
discontinued and he
recovered.
Possible
Chest pain Man of unknown age with
concomitant use of seretide.
Montelukast was
discontinued and he
recovered.
Possible
Hallucination 13‐year‐old boy with no Possible
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1310
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
concomitant use of
medicines. Montelukast was
discontinued and he
recovered.
Myalgia 47‐year‐old man with
concomitant use of 5 other
medicines. Montelukast was
discontinued and he
recovered.
Possible
Eosinophilia 66‐year‐old woman with
concomitant use of seretide.
Montelukast was
discontinued and she
recovered slowly.
Possible
Nightmare/somnambulism 72‐year‐old woman with
concomitant use of 9 other
medicines. Montelukast was
discontinued and she
recovered.
Possible
Chest discomfort Woman of unknown age with
concomitant use of 5 other
medicines. Further
information unknown
Woman of unknown age with
concomitant use of 3 other
medicines. Further
information unknown.
Possible
Anaphylactic reaction 13‐year‐old boy with
concomitant use of 4 other
medicines. Montelukast was
discontinued and he
recovered.
Possible
Table 2: Characteristics of six patients hospitalized with allergic granulomatous angiitis
reported to the Netherlands Pharmacovigilance Center Lareb.
Description Latency Concomitant medicine
use
Action and
outcome
Relation with
Montelukast
33‐year‐old
woman with a
history of
asthma
6 months Doxycycline, prednisone,
flixonase
Patient was
treated with
high dose oral
prednisone;
not yet
recovered at
the time of
reporting.
Possible
53‐year‐old
man with an
unknown
history
5 years Flixonase, seretide Montelukast
has been
Withdrawn;
patient has
Doubtful
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1311
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
not recovered
at the time of
reporting.
55‐year‐old
woman with a
history of
asthma
8 months Cetirizine, seretide,
flixonase
Montelukast
has been
withdrawn;
patient
recovered
after
treatment with
prednisone.
Possible
75‐year‐old
woman with a
history of
asthma
7 days Phenprocoumon,
furosemide, digoxine,
isosorbide mononitrate,
carvedilol, ramipril,
omeprazole, tiotropium
Montelukast
has been
withdrawn;
patient was
treated with
prednisone
and is
recovering.
Possible
59‐year‐old
woman with a
history of
asthma,
rhinitis, and
bronchiectasis
3 months Mometasone, tiotropium,
ciclesonide,
beclometasone/formoterol
Montelukast
has been
withdrawn,
and the
patient is
treated with
prednisone.
She is
recovering.
Probable
75‐year‐old
woman with a
history of
asthma
Unknown Phenprocoumon,
omeprazole, calcium
carbonate, digoxine,
furosemide, ramipril,
isosorbide mononitrate,
beclometasone/formoterol,
tiotropium, carvedilol
Montelukast
has been
withdrawn;
patient
recovered.
Possible
Montelukast and Potential skin hypersensitivity
Although a montelukast is a relatively safe drug, there is a probability of skin bruising and
skin rashes. The reappearance of rashes after montelukast introduction and complete
resolution of the skin rashes after discontinuing it confirms montelukast as an offending drug.
Results The authors presented a case report of a 64-year-old chronic asthmatic female patient
with widespread erythematous rashes with mild bruising and generalized pruritus, mainly
affecting her lower abdomen and upper extremities 28 days after the introduction of
montelukast as add-on therapy to budesonide. The researchers confirmed the relation between
the drug and skin rashes through a de-challenge followed by a montelukast's rechallenge.
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1312
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
After 28 days of montelukast introduction, the rash's appearance showed the adverse drug
reaction was a type of delayed hypersensitivity. The certainty of definite association with
montelukast was confirmed with a rechallenge with montelukast during the desensitization
procedure. The disappearance of skin rashes after discontinuing montelukast favours the
montelukast being the cause of these adverse effects. Although montelukast packaging lists
skin bruising as one of the AEs, not much has been mentioned in the existing literature. We
emphasize the need for monitoring and reporting even the mild AEs of montelukast through
the present case report.
Levocetirizine
Levocetirizine as an antihistamine
Levocetirizine is classified as a second generation Antihistamine. Levocetirizine is available
for the treatment such as Allergic Rhinitis and chronic idiopathic utricularia. Levocetirizine
,the R-isomer of the racemic mixture cetirizine hydrochloride. Levocetirizine has a high
affinity and selective antagonistic activity against histamine H1 receptors and exerts an
inhibitory effect on eosinophil chemotaxis. Allergic rhinitis and chronic urticarial are highly
burden some diseases, which are increasing in prevalence, especially in the pediatric
population. Despite the availability of a large number of medications for treatment of AR and
CIU symptoms in children.
The H1 antihistamines are associated with marked adverse effects such as sedation,
sleepiness as well as difficulties in learning and cognitive processing; thus, they are
recommended for limited or discontinued use in children with AR or CIU.Levocetirizine is an
over-the counter non sedating antihistamine agent commonly used to treat allergic diseases.
Clinically significant acute liver injury has been very rarely associated with its use .Only 2
cases of acute liver injury associated with levocetirizine have been reported in the literature.
Previous clinical studies and preclinical studies have shown that levocetirizine was rapidly
and extensively absorbed. Levocetirizine does not inhibit cytochrome P450, 2C9, 2C19, 2D6,
2E1 and 3A4 and does not induce uridine at concentrations near the clinical dose, which
produces peak plasma concentrations. Evidence suggests that children do not generally
respond to medications in the same way as adults, primarily due to differences in the
metabolism, renal clearance and other drug disposition mechanisms associated with
anatomical, physiological and developmental differences. As pediatric formulations,
especially for children under 6 years of age, are usually in a liquid form, special knowledge
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1313
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
and skills are necessary to make them stable, sterile, pleasant tasting, long lasting and with
favorable pharmacokinetic as well as pharmacodynamics properties.
The effects of histamine are exerted through three well defined classical G Protein coupled
histamine receptor subtypes termed H1R, H2R and H3R and the more recently described
H4R.Histamine signaling through H1R is responsible for the majority of the immediate
manifestations of allergic disease. The parent compound cetirizine, a once daily 10 mg
formulation, is also an effective treatment for allergic disease being the most –widely used
second generation antihistamine worldwide. Orally disintegrating tablets are used widely in
drug therapy and are clinically attractive because they are suitable for use in patients with
dysphagia, improve adherence, increase the likelihood of achieving the desired therapeutic
effect, and are convenient to take without water. Anti allergic, drugs, particularly the
antihistamines and intranasal steroids, are among the most commonly prescribed medications
in children as allergic rhinitis is currently one of the most common chronic disorder in the
pediatric populations.
The study consisted of 2 parts: part 1compared the bioavailability of levocetirizine ODT and
levocetirizine IRT taken with water in the fasted state, part 2 compared the bioavailability of
levocetirizine ODT without water and levocetirizine IRT with water in the fasted state.BE
between levocetirizine ODT and levocetirizine IRT was evaluated in 48 healthy Japanese
male subjects in the first study. Because BE was not demonstrated in part 2 of the initial
study, an add on subject study was conducted in 24 subjects using the same methodology as
used in the initial study of part 2 in accordance with the Japanese guideline for
bioequivalence studies in generic products issued by evaluation and licensing division. The
key inclusion criteria were age 20-55 years, body mass index of 18-24.9 kg/m2 and good
general health as determined by medical history, clinical examinations, 12-lead ECG and
clinical laboratory tests.
Treatment of AR in children involves the use of a variety of medications together with
allergen and irritant avoidance measures, and can often be achieved in primary care for most
patients. Pharmacologic management encompasses the use of both over the counter and
prescription drugs including oral and intranasal H1-antihistamines, intranasal steroids,
decongestant, cromons, anti-leukotrienes of which the antihistamines and INS are most
frequently used as first-line treatment, depending on the severity of symptoms of
AR.presently only three H1 –antihistamines have been investigated for long term safety in the
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1314
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
pediatric populations. The study of loratadine collected safety information over a period of 12
months in similarly aged pediatric populations.
Fifteen patients with refractory CSU were given oral levocetirizine at a dose of 15 mg once
daily for 7 days, and treatment efficiency was determined using the utricularia activity score
and by evaluating wheal and erythema reactions and itching. The serum concentrations of IP3
at specific time points was determined by enzyme –linked immunosorbent assay. All 15
patients were enrolled from outpatients clinics and met the following inclusion criteria.[1]
diagnosis of CSU[2]
repeated use of loratadine, mizolastine or other antihistamine and
complementary medicines such as ruin and vitamin C[3]
UAS2a score calculated by adding
the UAS on the first treatment day to the score on the day prior to treatment initiation; and[4]
no glucose-corticoid treatment within the previous month and no history of other underlying
diseases or family history of other underlying diseases or family history of genetic disease.
In this, hDPCs were cultured in Dulbecco’s modified eagle medium containing different
concentrations of levocetrizine hydrochloride for 48 hrs. The growth of hDPCs was observed
by immunofluorescence staining, and the cell proliferation was detected by MTT assay. After
the hDPCs were cultured in DMEM containing 1, 10, 100, 1000, and 10000 ng/ml
levocetirizine hydrochloride for 48 hrs., the mRNA expressions of cyclooxygenase 2,
prostaglandin D2 synthase, prostaglandin and glycogen synthase kinase were determined by
real time fluorescence –based quantitative polymerase chain reaction and the protein
expressions of PTGDS, phosphorylated protein kinase B and phosphorylated glycogen
synthase kinase were detected by western blotting. After the hDPCs were cultured in DMEM
containing 1, 10, 100, 1000, and 10000 ng/ml levocetirizine hydrochloride for 24 hrs., The
secretion levels of prostaglandin D2 and PGD2 receptor in the culture supernatant were
determined by enzyme linked immunosorbent assay .one way analysis of variance was
performed using SPSS 17.0 software and the LSD_T test was used for pairwise comparisons.
0f the38 and 44 healthy Japanese male subjects screened in the initial study and add on
subject study, respectively , 24 subjects each were randomized and received at least 1 dose of
the investigational products .All subjects expect 1 who were randomized in the initial study
completed the study .One subject was withdrawn from the initial study after receiving the
ODT dose in period 1.He experienced a moderate AE during the washout period , and his
dosing scheduled for period 2 was postponed ;however he withdrew his consent because his
schedule did not suit the new study schedule did not suit the new study schedule for the in-
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1315
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
clinic stay. The safety profiles were generally similar between levocetirizine ODT and
levocetirizine IRT with no serious adverse events, deaths or adverse events leading to
withdrawal reported during the study.
Cetirizine
[ETAC]
Levocetirizine
[EPAA]
Somnolence 2.3% 0%
Nervousness 1.3% 0.4%
Insomnia 8.8% 1.2%
Fatigue 3.3% 0%
The mean serum concentration of IP3 was 43.54+-41.97 pg./ml prior to treatment , 18.40+-
17.53 pg./ml after treatment, and 1.31+-0.92 pg./ml in a healthy control group. The mean
concentration of IP3 was significantly higher before treatment was significantly higher than
that in the control group. High dose levocetirizine was shown to be effective in the treatment
of CSU. The level of serum IP3 was positively correlated with CSU activity, indicating that
IP3 may play an important role in the pathogenesis of this condition.
Immunofluorescence staining showed that hDPCs in the 100 ng/ml group grew well, with
over 90% confluence .Methyl thiazolyl tetra method showed that the proliferation rate of
hDPCs significantly differed between different levocetirizine hydrochloride groups and blank
control group ,while proliferation rate was significantly higher tin the 100ng/ml than in the
blank control group .The relative mRNA expressions of COX-2, PGF2a,PTGDs,GPR44
showed significant difference in different levocetirizine hydrochloride groups, whereas the
mRNA expressions of PGF2 and GSK3 showed no significant difference. The mRNA
expressions of COX-2, PTGDS and GPR44 in the 100 ng/ml group were significantly lower
than those in the blank control group. There were significant differences in the levels of
PTGDs, PGD2 and PGD2R proteins between the different levocetirizine hydrochloride
groups. The proteins expressions of PTGDS,PGD2 and PGD2R in the 100 ng /ml group were
significantly lower than those in the blank control group, whereas the protein expressions of
Akt AND Gsk3 in the 100 ng/ml group. Levocetirizine hydrochloride may promote the
growth and proliferation of Hdpc in vitro by inhibiting the PGD2-GPR44 pathway and
activating the AKT signaling pathway.
Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The
safety and tolerability of levocetrizine were confirmed following single oral administrations
of levocetrizine IRT 5 mg and ODT 5 mg administered with water or without water. Thus, a
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1316
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
5 mg levocetirizine ODT tablet can be used as a replacement for a 5 mg levocetirizine IR
tablet at the clinical site. The observed exposures were slightly higher after the administration
of levocetrizine IRT 5 mg with water and without water.
Children appear to be more affected than ever before and suffer from both persistent and
severe symptoms. The use of the first generation H1 antihistamines should undoubtedly be
limited or discontinued in children suffering from AR or CIU and physicians should,
whenever possible, prescribe only the new second generation H1 antihistamines to children
.In view of the data currently available for pharmacokinetics, clinical, efficacy, and general
preference for levocetirizine by both parents and physicians, levocetirizine seems suitable
treatment option for AR and chronic urticaria in children aged 6 months to 12 months.
Cetirizine
Year of
Publishing
Title of the paper Title of the review paper
December
1990 Urticaria: Clinical efficacy of cetirizine in
comparison with hydroxyzine and placebo
Comparison between cetirizine,
hydroxyzine and placebo
1 December
1993
A reappraisal of its Pharmacological
Properties and Therapeutic use in Selected
Allergic Disorders
Pharmacological and Therapeutic use
of Cetirizine
May 1995 Cetirizine in patients with seasonal rhinitis
and concomitant asthma: prospective,
randomized, placebo-controlled trial
Effects of Cetirizine on patients with
seasonal rhinitis and concomitant
asthma
August 1996 Improvement of quality of life by treatment
with cetirizine in patients with perennial
allergic
rhinitis as determined by a French version of
the SF-36 questionnaire
Impact of Cetirizine on Life
March 2011 A comparative analysis of cetirizine,
gabapentin and their combination in the
relief of post-burn pruritus
Comparison between cetirizine and
gabapentin
12 Sept 2012 A review of its use in Allergic Disorders Uses of Cetirizine in allergic disorder
17 Nov 2012 A review of its pharmacological
properties and clinical potential in Allergic
Rhinitis, Pollen induced Asthma and chronic
urticaria
Pharmacological properties of
Cetirizine
Sept 2013 The clinical Use of cetirizine in treatment of
allergic rhinitis
Treatment of Rhinitis with cetirizine
6 December
2019
Focus on the cetirizine use in a clinical
practice: a reappraisal 30 years later
Use of Cetirizine in clinical practices
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1317
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
Steady urticaria is an issue for both specialist and patient. With the ultimate objective to
avoid the risks related to corticosteroid treatment, some unique H1-receptor adversaries have
been endeavoured and found to incite terrible levels of sedation when given in totals
satisfactory to control urticaria. Cetirizine, a pharmacologically powerful oxidized metabolite
of hydroxyzine, was made to give specific H1-receptor impediment without wretchedness of
the central tangible framework. In a 4-week, multicenter, twofold outwardly hindered,
counterfeit treatment controlled security and practicality study, cetirizine, in a once-a-day
divide (5 to 20 mg), was similar insufficiency to hydroxyzine in disconnected measurements
(25 to 75 mg/day). The pace of drowsiness in the cetirizine pack was not inside and out not
exactly equivalent to that of the phoney treatment gathering. Regardless, in the hydroxyzine
assembling, the recurrence of dormancy was, by and large, higher than that in the phoney
treatment gathering (p=0.001). The outcomes of this assessment show that cetirizine has a
more noticeable security edge over the more prepared parent drug hydroxyzine. Cetirizine,
the carboxylated metabolite of hydroxyzine, is a specific and long-acting histamine H1-
receptor foe. It has checked antiallergic properties and limits eosinophil chemotaxis during
the touchy response. Clinical primer results show that cetirizine is a practical and particularly
suffered treatment for incidental/never-ending excessively touchy rhinitis and tenacious
idiopathic urticaria in adults, and infrequent/enduring vulnerable rhinitis in young people.
Cetirizine 10 mg/day radiates an impression of being pretty much as amazing as conventional
estimations of other set up antihistamines, for instance, astemizole, hydroxyzine, ketotifen,
loratadine or terfenadine in reducing signs of these issues, and is connected with a lower pace
of sedation than hydroxyzine. Nevertheless, when sedation was uniquely studied, cetirizine
appeared to be more steadying than counterfeit treatment, loratadine or terfenadine in some
clinical starters. This differentiation was not found in a couple of other twofold outwardly
impeded assessments. Alternately, when reviewed fair-mindedly in pharmacodynamic
assessments, cetirizine was rarely more calming than counterfeit treatment or other second-
period histamine H1- receptor foes. Cetirizine may similarly have some work in the treatment
of explicit sorts of genuine urticaria, atopic dermatitis and reactions to mosquito snack.
Besides, it is being pursued for the treatment of overly sensitive asthma in adults and
children. The pharmacokinetic profile and dominatingly renal release of cetirizine suggest
that this expert may have a lessened potential for ominous prescription coordinated efforts
including hepatic impetus systems differentiated and other histamine H1-receptor foes which
are comprehensively prepared. Thus, cetirizine, with its speedy start and long length of
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1318
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
movement, appears to give a supportive alternative as opposed to the antihistamine experts in
clinical use.
This assessment researched the security and adequacy of cetirizine for the treatment of
excessively sensitive rhinitis and asthma. Daily treatment for about a month and a half with
cetirizine 10 mg was isolated and counterfeit treatment in a randomized, twofold blocked
similar appraisal of patients with conversely weak rhinitis and asthma. This multicenter study
was started not well before the start of the fall dust season. Rhinitis and asthma signs were
focused twofold consistently; spirometry was performed weekly. Placebo-treated patients
experienced a falling to pieces of rhinitis results from measure all through the examination, at
any rate, cetirizine-treated patients had a fundamental improvement in rhinitis signs at week
1, which was kept up in the wake of the start of the development season. Asthma signs in the
cetirizine pack improved from the plan at week 1; results were throughout better showed up
contrastingly corresponding to in the phoney treatment bunch for 5 of about a month and a
fragment of the appraisal. Pneumonic limits didn't decay in patients taking cetirizine or
phoney treatment; there were no partitions between arrangements as composed by
spirometry. Albuterol use was less steady in the cetirizine-treated patients for the whole
evaluation, yet isolates didn't show up at significance. Pseudoephedrine use was close in the
two parties. More cetirizine- treated patients completed the fundamental than faked treatment
treated patients. The two medications were especially determined forward.
Enduring overly sensitive rhinitis upsets public action, anyway it isn't known whether
individual fulfilment may be improved when patients are treated with an H1-blocker. A
randomized, twofold outwardly debilitated, counterfeit treatment controlled examination was
finished with cetirizine to assess the effect of this drug on close to home fulfilment. Methods:
Two hundred 74 patients with ceaseless overly sensitive rhinitis were attempted. Individual
fulfilment was assessed using the Medical Outcome Study Short-Form Health survey.
Following a 2-week spat period, cetirizine, 10 mg once daily, or counterfeit treatment was
given for the accompanying month and a half. The SF-36 survey was overseen after the fight
time frame and following 1 and a month and a portion of treatment. Result remedy scores
were assessed step by step during the study. After the disagreement period, there were no
basic differentiations between the cetirizine and phoney treatment bundles to the extent that
signs or individual fulfilment scores. Following a month and a portion of treatment, the level
of days without rhinitis or with simply delicate rhinitis appearances was more important in
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1319
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
the cetirizine bundle in assessment with the phoney treatment gathering. The whole of the
nine individual fulfilment estimations was in a general sense improved after 1 and a month
and a portion of cetirizine treatment differentiated and counterfeit treatment. There was no
improvement in the phoney treatment gathering. Post-devour pruritus is an upsetting result
having a reported recurrence someplace in the scope of 80 and 100%. The mainstay of the
heads of post-devour shivers has been with antihistamines and emollients yet the treatment is
deficient in an amazingly immense degree of patients. With the affirmation of an undeniable
shiver express neuronal pathway, which has an astounding coordinated effort with torture
pathway, another approach to manage shiver the board has surfaced with the usage of
gabapentin. Gabapentin is an antiepileptic drug which has been adequately used to supervise
neuropathic torture and is offering an explanation to be productive in the organization of a
wide range of shiver. With a shortage of randomized starters surveying the work of
gabapentin in post-burn-through shiver the board the current examination was embraced to
only evaluate gabapentin, cetirizine and their mix in relieving shiver. Twenty patients were
indiscriminately enrolled in all of the three social affairs and dealt with the specific drug in
doses constrained by starting VAS (visual basic scale) scores. There was no enormous
qualification taking everything together with the three get-togethers concerning mean age,
sex movement, mean degree of TBSA burn through and mean VAS score on day 0. VAS
scores were surveyed over the next 28 days, and no emollients were supported for the
assessment period. The hidden mean VAS score reduced 95% in the gabapentin bundle
appeared differently in relation to 52% for the cetirizine gathering, which was significantly
colossal. There was a 94% decline in mean VAS score in the mix pack which was identical to
the mitigation saw with gabapentin alone. Even the start of action with gabapentin was
snappier than the cetirizine pack as evident from the mean VAS scores on day 3, which
reduced 74% in gabapentin bundle appeared differently in relation to 32% in cetirizine
gathering. While all patients tolerating gabapentin showed up at a shiver free status by day 28
only 3/20 patients showed up at this level with cetirizine alone. It is exceptionally obvious
from this assessment that gabapentin is in a general sense better contrasted with cetirizine as
monotherapy in facilitating post-burn-through shiver and it in like manner has a faster action.
The hypothetical blend of a halfway acting medicine with a by chance acting expert didn't
achieve any better control of post-devour shiver than monotherapy with gabapentin. No
outcomes were represented with gabapentin association anyway all patients tolerating
cetirizine declared sedation. There is presently a need to relook at the antipruritic shows to
devour the board. Cetirizine, a piperazine subordinate and carboxylated metabolite of
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1320
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
hydroxyzine, is an immeasurable histamine H1-receptor enemy with antiallergic properties. It
has checked love for outskirts histamine H1-receptors and, at the standard section of 10mg
reliably, comes up short on the CNS depressant impacts of standard antihistamines. In like
way, it upsets histamine transport and eosinophil chemotaxis during the accomplice time of
the forebodingly feeble reaction. Results from controlled clinical starters show that cetirizine
is persuasive and all around endured treatment of unpredictable and suffering frail rhinitis
and constant idiopathic urticaria. Cetirizine radiates an impression of being on an
exceptionally fundamental level essentially as profitable as standard assessments of
terfenadine, chlorpheniramine and hydroxyzine in decreasing appearances related to these
issues and makes an amazingly lower speed of sedation than chlorpheniramine, hydroxyzine
a couple of other standard antihistamines. Hence, cetirizine seems to give an enormous option
instead of other 'nonsedating' antihistamines; cetirizine may moreover have a future part in
the treatment of inimically weak asthma and express sorts of authentic urticaria. Cetirizine,
a piperazine subordinate and carboxylated metabolite of hydroxyzine, is an unimaginable
histamine H1-receptor enemy with antiallergic properties. It has checked love for fringe
histamine H1-receptors and, at the standard section of 10mg reliably, comes up short on the
CNS depressant impacts of standard antihistamines. In like way, it upsets histamine transport
and eosinophil chemotaxis during the associate season of the forebodingly weak reaction.
Results from controlled clinical starters show that cetirizine is persuading and all around
endured treatment of intermittent and suffering horrendously feeble rhinitis and persistent
idiopathic urticaria. Cetirizine emanates an impression of being fundamentally pretty much as
productive as traditional assessments of terfenadine, chlorpheniramine and hydroxyzine in
decreasing appearances related to these issues and makes an amazingly lower speed of
sedation than chlorpheniramine, hydroxyzine several other standard antihistamines.
Consequently, cetirizine seems to give a huge option instead of other 'nonsedating'
antihistamines; cetirizine may also have a future part in the treatment of adversely
defenceless asthma and explicit sorts of real urticaria.
Cetirizine is among the fundamental second-age H1 antihistamines (SGAHs) made to give
explicit H1 receptor limitation without focal unmistakable structure horror. The motivation
behind this audit is, to sum up, the extent of information gathered from more than 25 years of
clinical utilization of cetirizine and distinction this and information open for other SGAHs in
the association of patients with effortlessly influenced rhinitis (AR). A serious forming look
for scatterings identifying with cetirizine was performed utilizing the Pubmed instructive file,
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1321
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
and huge papers passed on in English were picked for a particular audit. Differentiated and by
far most of other SGAHs, cetirizine was everything considered appeared to have a more
phenomenal pharmacological profile, to be especially endured, be at any rate equivalently or
more convincing in stifling/checking nasal and visual signs and to improve the individual
satisfaction in AR patients. Most clinical starters investigating the impact of SGAHs in AR
patients further displayed that cetirizine was regularly utilized as the pivotal comparator
dynamic medication. Considering the affirmation that cetirizine is a for the most part utilized
dynamic comparator drug in AR, it is unassuming to suggest that cetirizine might be a
reasonable benchmark in the progress of novel pharmacotherapies for AR. Antihistamines
are correct now potentially the most ordinarily oversaw classes of meds. They are used to
treat results that are assistant to histamine release, which is ordinary of certain extremely
touchy conditions, including rhinitis, conjunctivitis, asthma, urticaria, and excessive
touchiness. Cetirizine has a spot with the second-age family, consequently, it is explicit for
peripheral H1 receptors, is exceptional and quickly quiets signs, applies additional foe of
horribly defenceless/ alleviating impacts, and is commonly especially persevered. It was
exhibited 30 years back. In these years, an uncommon assortment of evidence has been
developed. The current study gives a sensible update on the usage of cetirizine in clinical
practice.
Fexofenadine
Assessment of effects of rifampin on pharmacokinetics of fexofenadine and influence of
Age and Sex
The study was conducted to assess the effects of rifampin on the pharmacokinetics of
fexofenadine and to assess its influence of the advanced age and sex age.
Twelve young candidates and twelve elderly candidates out of which 6 were males and 6
were female in each group were selected for the study. They received a 60mg oral dose of
fexofenadine before and 600mg oral dose of rifampin afterwards for 6 days. Blood and urine
samples were collected 48 hours and assayed for fexofenadine, azacyclonol and rifampin by
HPLC with either mass spectrometry or fluorescence detection.
All of the groups had a significant increase in the oral clearance of fexofenadine after
rifampin treatment. The peak serum concentration of fexofenadine was also significantly
reduced by rifampin treatment, time to maximum concentration, renal clearance and fraction
unbound of fexofenadine showed no significant difference between control and treatment.
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1322
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
The amount of azacyclonol, a CYP3A4 mediated metabolite of fexofenadine, eliminated on
average 2‐fold after rifampin dosing; however, this pathway accounted for less than 0.5% of
the dose. No effect of age or sex on fexofenadine disposition or serum trough rifampin
concentration (0.2 μg/mL to 1.8 μg/mL) was observed before or after rifampin treatment.
It was found that the rifampin significantly increased fexofenadine oral clearance and was
independent of the age and sex. It can be concluded that the increased oral clearance is due to
the reduced bioavailability caused by induction of intestinal P-glycoprotein.
Fexofenadine is an antihistamine that does not cause any sedation and it is used for the
treatment against the symptoms of allergic rhinitis. Almost 95% of fexofenadine is obtained
through urine and feces as it is but, it interacts with cytochrome P450 (CYP) 3A inhibitors
erythromycin or ketoconazole if administered together and hence, results in increase in serum
concentration. Rifampin is an inducer of CYP3A enzyme that causes an upregulation of P-
glycoprotein in cultured human colon carcinoma cells. Fexofenadine is a good probe because
it is found to be the substrate of P-glycoprotein in vivo and is not having any pharmacologic
or toxic effects that require close monitoring. The study was designed to examine the
hypothesis that sex and age modulates P-glycoprotein activity or the responsiveness of P-
glycoprotein expression to rifampin.
The study was carried out with 24 participants out of which 6 were healthy young women, 6
were healthy young men, 6 were healthy older men and 6 healthy older women. All were in
between the age group of 18 to 65. There were no significant health issues in the participants.
The drug quantification of fexofenadine in serum and urine was done by using solid phase
extraction and HPLC with fluorescence detection by doing the modification in the method.
Pharmacokinetic parameters were estimated by noncompartmental analysis with the use of
WinNONlin (Pharsight Corp, Mountain View, Calif). The terminal elimination rate constant
(β) was determined by log-linear regression. The terminal elimination half-life (t1⁄2) was
determined by the following relationship: t1⁄2 = 0.693/β. The effects of sex, age, and rifampin
treatment were analyzed with repeated-measures ANOVA with the use of the PC-SAS
statistical package (SAS Institute, Cary, NC). The primary endpoints were oral clearance and
half-life.
The mean serum concentration-time curve was used to determine the effect of rifampin
treatment on disposition of fexofenadine in young men, young women, elderly men and
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1323
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
elderly women. The average percentages of the fexofenadine dose eliminated unchanged in
the urine were 3.7% ± 1.52%, 5.8% ± 1.77%, 5.4% ± 0.80%, and 4.4% ± 0.95%, respectively,
for young men, young women, elderly men, and elderly women. These percentages decreased
non significantly to 2.4% ± 0.89%, 5.2% ± 0.61%, 2.7% ± 0.79%, and 1.9% ± 0.42%,
respectively, after rifampin treatment. After rifampin treatment, urinary excretion of
azacyclonol increased significantly by approximately 2-fold in men but not in women.
The rifampin pretreatment causes a substantial increase in the oral clearance of fexofenadine.
This observation shows that there is upregulation of P-glycoprotein expression on the apical
surface of the small intestine. The advanced age and sex did not have significant effect on the
induction. The fexofenadine was found to be the relatively inert probe drug.
Finding the efficacy and safety levels of fexofenadine compared to other antihistamines
The study was conducted to find the efficacy and safety levels of fexofenadine compared to
other antihistamines and also the effect of fexofenadine over the driving abilities and
cardiovascular health at high doses. A study was reviewed in which the efficacy of
fexofenadine was compared to loratadine through the rhinoconjunctivitis quality of life
questionnaire (RQLQ) which is commonly used to evaluate the treatment effects of drugs in
patients with allergic rhinitis. It was found that fexofenadine was more effective than the
loratadine. In another study, the incidence of drowsiness and fatigue in patients consuming
fexofenadine and cetirizine was compared where cetirizine was found to cause more fatigue
and drowsiness than fexofenadine.
Previously used antihistamines were found to interrupt the central nervous system
functioning and caused sedation which includes a group of symptoms like lack of
concentration, drowsiness, fatigue, etc. The recently used antihistamines to be precise
fexofenadine does not cross the blood-brain barrier and does not affect the central nervous
system. Positron emission tomography was used for the study to determine whether the
central H1-receptor distribution of C-doxepin in the human brain could be altered by single
oral doses of antihistamines. Fexofenadine has no effect while carrying out a skilled task
which includes machine work or public service vehicles thus recommended to use. The
studies regarding drug interaction indicated cardiovascular safety of the drug. The
pharmacokinetics of fexofenadine are similar to that of healthy subjects to that of impaired
liver function. Fexofenadine shows antihistaminergic effects along with its ability to attenuate
inflammatory mediator release which might contribute to its pharmacological properties.
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1324
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
In a trial including 688 people with SAR it was found that the primary efficacy measure was
24hr reflective Total Symptom Score (TSS) by adding an individual score of each symptom
with a maximum possible TSS of 16. There was no significant difference in the overall TSS
of fexofenadine and loratadine but the symptoms were treated well with fexofenadine
compared to loratadine.
The older antihistamines were demonstrating sedative and anticholinergic effects however,
several studies exhibited the fexofenadine did not exhibit significant sedation or the effect on
the central nervous system. Positron emission tomography was used to determine whether the
central H1-receptor distribution of C-doxepin in the human brain could be altered by single
oral doses of antihistamines.
It was found that previously used older generation antihistamines had reported some
cardiovascular events in rare cases but they were fatal forms of ventricular arrhythmia
characterised by prolonged QT intervals and twisting of QRS complexes. The drug
interaction studies conducted demonstrated the cardiovascular safety of fexofenadine with no
adverse effects. Along with this antiallergic effects were also studied which shows the
efficacy of fexofenadine in treating symptoms of running, itchy nose, watery eyes, nasal
congestion, etc.
Fexofenadine was found useful in treating the allergic symptoms with no significant adverse
effects. The cardiovascular safety of fexofenadine was found to be efficient. There is no
crossing of the blood-brain barrier and hence the sedative effects are not seen.
A comparison between fexofenadine and the second generation antihistamine for cough
reflex sensitivity and pulmonary function.
Most of the patients in the United States complain about coughs commonly towards the
medical practitioner. It is found that the most common cause of chronic cough is rhinitis/post
nasal drip syndrome (PNDS). The first generation antihistamines are found to be more
effective than the newer generation antihistamines for the treatment of chronic cough caused
by PNDS. As the antitussive activity of second generation antihistamine, fexofenadine is not
yet found, the effect of fexofenadine on capsaicin induced cough in healthy volunteers and in
patients with acute viral upper respiratory tract syndrome was studied.
Participants of the study were selected by considering 12 healthy volunteers with no
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1325
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
symptoms of cough and 12 otherwise healthy volunteers with symptoms of acute viral URI. It
was made sure that the patients were nonsmokers and had no history of pulmonary disease
and gastroesophageal reflux. The doses of fexofenadine and placebo in randomized double
blind fashion were given and then after two hours of ingestion of the study drug, the
spirometry test and capsaicin cough challenge testing was performed to correlate with high
plasma levels of fexofenadine.
As for the subjects with URI the, no significant differences in cough reflex sensitivity and
pulmonary were found after the induction of five or more coughs in participants. In
participants with no symptoms of URI, no differences in cough sensitivity were noticed. It
was found that the second generation antihistamines and fexofenadine had no effect over the
cough reflex sensitivity in both healthy as well as participants with URI. The first generation
antihistamines with the combination of decongestants are recommended for chronic cough
with PNDS. A bronchodilator activity was observed in participants with no URI rather than
the participants with URI which was quite surprising but this finding was very little and of
least clinical significance. There needs to be a further investigation done in this direction
Bioequivalence of fexofenadine and pharmacokinetics in the form of oral suspension
This study was conducted for studying the bioequivalence of fexofenadine in oral suspension
and solid formulations of fexofenadine, pharmacokinetics of fexofenadine and the effect of
fruit juices on the absorption of fexofenadine. Fexofenadine interacts with lots of drugs at p-
glycoproteins and anion transporter polypeptides. The fexofenadine affects the working of
certain inflammatory mediators which can affect the inflammatory response of acute
inflammatory response to certain anti-allergic reactions.
Fexofenadine is widely used as a selective H1 antagonist and also found to have anti-
inflammatory properties. Several studies were reviewed which included administration of
fexofenadine by either solid tablet formulations or by oral suspension, equivalent area under
the curve and mean maximum plasma concentration were found in people with various age
groups.
The pharmacokinetics studies were also reviewed and it was found that if fexofenadine was
consumed alone, it had no side effects as such but when consumed with some other drugs
there was an increased risk of adverse effects. It did not react with P450 CYP 3A4 but
interacted with other drugs at P- glycoprotein and the organic anion transporter polypeptide.
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1326
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
It was found from various studies that the fexofenadine should not be consumed along with
grape juice or apple juice as the bioavailability is reduced. Fexofenadine reduces the immune
activities during the allergic reaction due to which the inflammatory responses to certain
allergens has seen to be increased which suggests for a better activity of selective H1
antagonist to be formulated further.
Administration of fexofenadine did not generate any adverse effects other than rare cardiac or
rash problems in some patients, it was found to be effective for allergic rhinitis and chronic
idiopathic urticaria and can be useful for patients with asthma. In conclusion fexofenadine is
useful as a selective antihistamine H1 antagonist but it can cause certain adverse effects if
interacted with other drugs through P-glycoprotein and organic anion transporter peptides.
The subjects tolerated fexofenadine well and the safety profiles of fexofenadine were found
to be clear. The antihistamine effects of fexofenadine were found to be useful and the
cardiovascular safety was also found. Anti Inflammatory and anti allergic treatment of
fexofenadine was also found to be effective. It was found to have less bioequivalence in the
presence of certain foods like grape juice.
Antihistamine effects and safety of fexofenadine: a systematic review and Meta-analysis
of randomized controlled trials
This study was aimed to determine the antihistamine effects and safety of fexofenadine
compared to the other antihistamines and drugs. An electronic literature survey was
conducted using some tools like Embase, Pubmed and Cochrane from 2018 for randomized
controlled trials (RTC) for antihistamine effects of fexofenadine compared to placebo and
other antihistamine drugs in healthy subjects.
It was found that amongst 51 studies and 14551 participants met the required criteria.
Randomized controlled trials (RCT) were conducted to compare the antihistamine effects of
either fexofenadine or the other antihistamines or placebo. A systematic literature mining was
conducted from softwares like Embase, Cochrane and Pubmed. The outcomes were measured
using various parameters like wheal flare, AE frequency, changes in cognitive/psychomotor
function score. Data analysis was performed using Revman 5.3 program and comparative
meta analysis V2.
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1327
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
As compared to the first generation antihistamine fexofenadine produced significantly lower
side effects such as drowsiness, loss of motor ability or psychomotor functions. The
comparison with second generation antihistamines demonstrated least sedative effects and
almost no change in cognitive or psychomotor functions. Fexofenadine has significantly more
antihistamine properties than placebo. The first generation antihistamines that were used
before exhibited cardiotoxicity. Some second generation antihistamines also exhibit
cardiotoxicity and hence are rarely used. Fexofenadine on the other hand is a new generation
antihistamine and an active metabolite of terfenadine- a highly selective H1 antagonist, it has
a positive antihistamine effect. Fexofenadine has no cardiotoxicity and minimal toxic effects
on the liver as only 5% of the total dosage is metabolized by the liver. The meta-analysis
conducted demonstrated that fexofenadine has better safety profiles compared to second
generation antihistamines. It was also found that subjects that consumed fexofenadine had
better information processing ability compared to the other ones who consumed second
CONCLUSION
This research review’s purpose is to help the reader understand different aspects posed by the
research on the Montelukast, Levocetirizine, Cetirizine & Fexofenadine. This is significant
because it gives insights about commonly used antihistamines and its effects on multiple .
There has been much research and discussion conducted on these opinions of montelukast,
levocetirizine, cetirizine and fexofenadine. Most of the research found was on the details of
levocetirizine, cetirizine, montelukast, fexofenadine, rhinitis and seasonal allergies. More
research and testing is required to gain better understanding for a comparative evaluation.
ACKNOWLEDGEMENT
We would like to thank our supervisor/guide Bharat Kwatra, from Invenzion Labs Inc. whose
expertise was invaluable in formulating the research questions, methodology and drawing
conclusions. His insightful feedback and guidance pushed us to sharpen our thinking and
brought our work to a higher level.
Ethics Approval and Consent to participate
Not applicable.
Human and Animal rights
No Animals/Humans were used for studies that are the basis of this research.
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1328
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
Consent for publication
Not applicable.
Availability of Data and Materials
The author confirms that the data supporting the findings of this research are available within
the article.
Funding Acknowledgement and Conflict of interest
The authors whose names are listed immediately above certify that they have NO affiliations
with or involvement in any organization or entity with any financial interest (such as
honoraria; educational grants; participation in speakers’ bureaus; membership, employment,
consultancies, stock ownership, or other equity interest; and expert testimony or patent-
licensing arrangements), or non-financial interest (such as personal or professional
relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed
in this manuscript.
REFERENCES
1. Ahuja, R. B., Gupta, R., Gupta, G., & Shrivastava, P. A comparative analysis of
cetirizine, gabapentin and their combination in the relief of post-burn pruritus. Burns,
2011; 37(2). https://doi.org/10.1016/j.burns.2010.06.004
2. Annunziata, G., Mayuko, I., & Barbara, M. Idiosyncratic Liver Injury Due to
Levocetirizine. ACG Case Reports Journal, 2019; 6(8):
https://doi.org/10.14309/crj.0000000000000191
3. Axelrod, D., & Bielory, L. Fexofenadine hydrochloride in the treatment of allergic
disease: A review. In Journal of Asthma and Allergy, 2008; 1.
https://doi.org/10.2147/jaa.s3092
4. Aypak, C., Türedi, Ö., Solmaz, N., Yikilkan, H., & Görpelioǧlu, S. A rare adverse effect
of montelukast treatment: Ecchymosis. Respiratory Care, 2013; 58(9).
https://doi.org/10.4187/respcare.02298
5. Bapputty, R., Talahalli, R., Zarini, S., Samuels, I., Murphy, R., & Gubitosi-Klug, R.
Montelukast prevents early diabetic retinopathy in mice. Diabetes, 2019; 68(10).
https://doi.org/10.2337/db19-0026
6. Bousquet, J., Duchateau, J., Pignat, J. C., Fayol, C., Marquis, P., Mariz, S., Ware, J. E.,
Valentin, B., & Burtin, B. Improvement of quality of life by treatment with cetirizine in
patients with perennial allergic rhinitis as determined by a French version of the SF-36
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1329
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
questionnaire. Journal of Allergy and Clinical Immunology, 1996; 98(2).
https://doi.org/10.1016/S0091-6749(96)70155-0
7. Campoli-Richards, D. M., Buckley, M. M. T., & Fitton, A. Cetirizine: A Review of its
Pharmacological Properties and Clinical Potential in Allergic Rhinitis, Pollen-Induced
Asthma, and Chronic Urticaria. Drugs, 1990; 40(5). https://doi.org/10.2165/00003495-
199040050-00009
8. Compalati, E., Baena-Cagnani, R., Penagos, M., Badellino, H., Braido, F., Gómez, R. M.,
Canonica, G. W., & Baena-Cagnani, C. E. Systematic review on the efficacy of
fexofenadine in seasonal allergic rhinitis: A meta-analysis of randomized, double-blind,
placebo-controlled clinical trials. In International Archives of Allergy and Immunology,
2011; 156: 1. https://doi.org/10.1159/000321896
9. Corsico, A. C., Leonardi, S., Licari, A., Marseglia, G., Miraglia del Giudice, M., Peroni,
D. G., Salpietro, C., & Ciprandi, G. Focus on the cetirizine use in clinical practice: a
reappraisal 30 years later. Multidisciplinary Respiratory Medicine, 2019; 14.
https://doi.org/10.4081/mrm.2019.487
10. Curran, M. P., Scott, L. J., & Perry, C. M. Cetirizine: A review of its use in allergic
disorders. In Drugs, 2004; 64: 5. https://doi.org/10.2165/00003495-200464050-00008
11. Davis, B. E., Illamperuma, C., Gauvreau, G. M., Watson, R. M., O’Byrne, P. M.,
Deschesnes, F., Boulet, L. P., & Cockcroft, D. W. Single-dose desloratadine and
montelukast and allergen-induced late airway responses. European Respiratory Journal,
2009; 33(6). https://doi.org/10.1183/09031936.00169008
12. Dicpinigaitis, P. V., & Gayle, Y. E. Effect of the second-generation antihistamine,
fexofenadine, on cough reflex sensitivity and pulmonary function. British Journal of
Clinical Pharmacology, 2003; 56(5). https://doi.org/10.1046/j.1365-2125.2003.01902.x
13. Grant, J. A., Nicodemus, C. F., Findlay, S. R., Glovsky, M. M., Grossman, J., Kaiser, H.,
Meltzer, E. O., Mitchell, D. Q., Pearlman, D., Selner, J., Settipane, G., & Silvers, W.
Cetirizine in patients with seasonal rhinitis and concomitant asthma: prospective,
randomized, placebo-controlled trial. The Journal of Allergy and Clinical Immunology,
1995; 95(5). https://doi.org/10.1016/S0091-6749(95)70090-0
14. Haarman, M. G., van Hunsel, F., & de Vries, T. W. Adverse drug reactions of
montelukast in children and adults. Pharmacology Research and Perspectives, 2017;
5(5). https://doi.org/10.1002/prp2.341
15. Hamman, M. A., Bruce, M. A., Haehner-Daniels, B. D., & Hall, S. D. The effect of
rifampin administration on the disposition of fexofenadine. Clinical Pharmacology and
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1330
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
Therapeutics, 2001; 69(3). https://doi.org/10.1067/mcp.2001.113697
16. Huang, C. Z., Jiang, Z. H., Wang, J., Luo, Y., & Peng, H. Antihistamine effects and
safety of fexofenadine: A systematic review and Meta-analysis of randomized controlled
trials. BMC Pharmacology and Toxicology, 2019; 20(1). https://doi.org/10.1186/s40360-
019-0363-1
17. Huang, X., Li, Z., & Sun, R. High-dose levocetirizine for the treatment of refractory
chronic spontaneous urticaria and the effect on the serum inositol triphosphate level.
Journal of International Medical Research, 2019; 47(9).
https://doi.org/10.1177/0300060519857768
18. Inder, D., Manak, S., Akram, F., & Kumar, P. Skin rash and mild bruising: Is montelukast
a safe drug? Indian Journal of Respiratory Care, 2018; 7(2).
https://doi.org/10.4103/ijrc.ijrc_3_18
19. Ino, H., Shiramoto, M., Eto, T., Haranaka, M., Irie, S., Terao, T., Ogura, H., Wakamatsu,
A., Hoyano, K., & Nakano, A. Levocetirizine Oral Disintegrating Tablet: A Randomized
Open-Label Crossover Bioequivalence Study in Healthy Japanese Volunteers. Clinical
Pharmacology in Drug Development, 2020; 9(7). https://doi.org/10.1002/cpdd.791
20. Kalivas, J., Breneman, D., Tharp, M., Bruce, S., Bigby, M., & nine other investigators.
Urticaria: Clinical efficacy of cetirizine in comparison with hydroxyzine and placebo. The
Journal of Allergy and Clinical Immunology, 1990; 86(6,2).
https://doi.org/10.1016/S0091-6749(05)80246-5
21. Knorr, B., Holland, S., Rogers, J. D., Nguyen, H. H., & Reiss, T. F. Montelulkast adult
(10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections. Journal
of Allergy and Clinical Immunology, 2000; 106(3).
https://doi.org/10.1067/mai.2000.109424
22. Kusuhara, H., Miura, M., Yasui-Furukori, N., Yoshida, K., Akamine, Y., Yokochi, M.,
Fukizawa, S., Ikejiri, K., Kanamitsu, K., Uno, T., & Sugiyama, Y. Effect of
coadministration of single and multiple doses of rifampicin on the pharmacokinetics of
fexofenadine enantiomers in healthy subjects. Drug Metabolism and Disposition, 2013;
41(1). https://doi.org/10.1124/dmd.112.048330
23. Kwatra, B. HACKING THE BLOOD-BRAIN BARRIER. European Journal of Biology
and Medical Science Research, 2017; 5(4): 10–13.
https://www.eajournals.org/journals/european-journal-of-biology-and-medical-science-
research-ejbmsr/vol-5-issue-4-june-2017/hacking-blood-brain-barrier/.
24. Kwatra, B. LOCATOR THEORY FOR ELE-MENTS IN PERIODIC TABLE “LEPT.”
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1331
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
Global Journal of Pure and Applied Chemistry Research, 2017; 5(1): 9–10.
https://www.eajournals.org/journals/global-journal-of-pure-and-applied-chemistry-
research-gjpacr/vol-5-issue-1-march-2017/locator-theory-ele-ments-periodic-table-lept/
25. Kwatra, B. Tinospora Crispa As A Future Cure For Obesity/Cholesterol.
INTERNATIONAL JOURNAL OF SCIENTIFIC & TECHNOLOGY RESEARCH, 2017;
6(7), 340–341. https://www.ijstr.org/final-print/july2017/Tinospora-Crispa-As-A-Future-
Cure-For-Obesitycholesterol.pdf
26. Kwatra, B. A REVIEW ON POTENTIAL PROPERTIES AND THERAPEUTIC
APPLICATIONS OF BROMELAIN. Www.Wjpps.Com, 2019; 8(11): 488–500.
https://doi.org/10.20959/wjpps201911-14941
27. Kwatra, B. A Review on Potential Properties and Therapeutic Applications of DHA and
EPA. Ijppr.Humanjournals, 2019; 16(4): 140–176.
https://www.researchgate.net/publication/337745268_A_Review_on_Potential_Properties
_and_Therapeutic_Applications_of_DHA_and_EPA
28. Kwatra, B. Allicin-An After Digestion Antimicrobial Agent. ACTA SCIENTIFIC
MICROBIOLOGY, 2019; 2(5): 48–51. https://actascientific.com/ASMI/pdf/ASMI-02-
0213.pdf
29. Kwatra, B. Bioactive-Compounds: alternative to control Candida spp. International
Journal of Scientific Research and Reviews, 2019; 8(3): 221–223.
https://www.ijsrr.org/down_83045.php
30. Kwatra, B. Effects of Mineral Separation by Time and Enteric Coating Mechanism for
Calcium and Iron Absorption in Mammalia. International Journal of Science and
Research, 2019; 8(12): 1265–1270. https://doi.org/10.21275/13121901
31. Kwatra, B. EXPRESSION AND CHARACTERIZATION IN PICHIA PASTORIS BY
CLONING OF DELTA 4 DESATURASE FROM ISOCHRYSIS GALBANA. Indian
Journal of Applied Research, 2019; 9(5): 1–2. https://doi.org/DOI : 10.36106/ijar
32. Kwatra, B. Holothuroidea (Sea Cucumber): Key to Anti-Aging. International Journal of
Science and Research, 2019; 8(6): 884. https://doi.org/10.21275/6061901
33. Kwatra, B. HYDROQUINONE: A novel growth inhibitor and apoptosis inducer in U-251
MG CELLS. International Journal of Medical and Biomedical Studies, 2019; 3(6):
15–16. https://doi.org/10.32553/ijmbs.v3i6.284
34. Kwatra, B. MECHANISMS OF PATTERN FORMATION OF FBP17 IN MAST
CELLS. International Journal of Advanced Research, 2019; 7(4): 413–414.
https://doi.org/10.21474/IJAR01/8832
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1332
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
35. Kwatra, B. Procuring Natural Dye for Solar Cell Using Leaf Waste. International Journal
of Scientific and Engineering Research, 2019; 7(5): 46–47.
https://www.ijser.in/archives/v7i5/21051905.pdf
36. Kwatra, B. THE SIMVASTATIN AND DMXAA ON THE CO-CULTURE OF B16.F10
MELANOMA CELLS AND MACROPHAGES SHOWS ANTITUMOR ACTIVITY.
World Journal of Pharmaceutical Research, 2019; 8(9): 1318–1319.
https://doi.org/10.20959/wjpr20199-15539
37. Kwatra, B. A REVIEW ON POTENTIAL PROPERTIES AND THERAPEUTIC
APPLICATIONS OF BRANCHED CHAIN AMINO. WORLD JOURNAL OF
PHARMACY AND PHARMACEUTICAL SCIENCES, 2020; 9(5): 561–588.
https://doi.org/10.20959/wjpps20205-16075
38. Kwatra, B. A REVIEW ON POTENTIAL PROPERTIES AND THERAPEUTIC
APPLICATIONS OF GRAPE SEED EXTRACT. World Journal of Pharmaceutical
Research, 2020; 9(5): 2519–2540.
https://www.researchgate.net/publication/341134392_A_REVIEW_ON_POTENTIAL_P
ROPERTIES_AND_THERAPEUTIC_APPLICATIONS_OF_GRAPE_SEED_EXTRAC
T
39. Kwatra, B. A REVIEW ON POTENTIAL PROPERTIES AND THERAPEUTIC
APPLICATIONS OF LYCOPENE. International Journal of Medical and Biomedical
Studies, 2020; 4(4), 33–44. https://doi.org/10.32553/ijmbs.v4i4.1081
40. Kwatra, B. A Review on Potential Properties and Therapeutic Applications of Vitamin D.
International Journal of Science and Research, 2020; 9(4): 682–691.
https://doi.org/10.21275/SR20410125311
41. Kwatra, B. Candidate genes of OCD interacts with human retrovirus to form new link in
inflammatory hypothesis. International Journal of Sciences & Applied Research, 2020;
7(5): 1–2.
https://www.researchgate.net/publication/341180827_Candidate_genes_of_OCD_interact
s_with_human_retrovirus_to_form_new_link_in_inflammatory_hypothesis
42. Kwatra, B. COLLAGEN SUPPLEMENTATION : THERAPY FOR SKIN
DISORDERS : A REVIEW. World Journal of Pharmaceutical Research, 2020; 9(5):
2504–2518. https://doi.org/10.20959/wjpr20205-17513
43. Kwatra, B. COLLAGEN SUPPLEMENTATION : THERAPY FOR THE PREVENTION
AND TREATMENT OF OSTEOPOROSIS AND OSTEOARTHRITIS : A REVIEW.
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, 2020; 9(5):
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1333
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
589–604. https://doi.org/10.20959/wjpps20205-16076
44. Kwatra, B. Maprovit 3, 6, 9: Perfect Companion of your Immune System to Fight Corona
Virus Hit. International Journal of Science and Research, 2020; 9(4): 241.
https://doi.org/10.21275/SR20406111953
45. Kwatra, B. Studies on People Employed in High Risk Workplace : Between Genetic
Polymorphism for Tumor Necrosis Factor ( TNF- Α ) and Blood Pressure.
INTERNATIONAL JOURNAL OF INNOVATIVE RESEARCH IN TECHNOLOGY, 2020;
6(12), 268–270.
https://www.researchgate.net/publication/341180645_Studies_on_People_Employed_in_
High_Risk_Workplace_Between_Genetic_Polymorphism_for_Tumor_Necrosis_Factor_
TNF-A_and_Blood_Pressure
46. Meeves, S. G., & Appajosyula, S. Efficacy and safety profile of fexofenadine HCl: A
unique therapeutic option in H1-receptor antagonist treatment. Journal of Allergy and
Clinical Immunology, 2003; 112(4). https://doi.org/10.1016/S0091-6749(03)01879-7
47. Mösges, R., König, V., & Köberlein, J. The effectiveness of levocetirizine in comparison
with loratadine in treatment of allergic rhinitis-a meta-analysis. Allergology International,
2011; 60(4). https://doi.org/10.2332/allergolint.10-OA-0300
48. Nelson, H. S., Reynolds, R., & Mason, J. Fexofenadine HCl is safe and effective for
treatment of chronic idiopathic urticaria. Annals of Allergy, Asthma and Immunology,
2000; 84(5). https://doi.org/10.1016/S1081-1206(10)62515-X
49. No Title. (n.d.).
50. Pampura, A. N., Papadopoulos, N. G., Špičák, V., & Kurzawa, R. Evidence for clinical
safety, efficacy, and parent and physician perceptions of levocetirizine for the treatment
of children with allergic disease. International Archives of Allergy and Immunology,
2011; 155(4). https://doi.org/10.1159/000321181
51. Pratt, C. M., Mason, J., Russell, T., Reynolds, R., & Ahlbrandt, R. Cardiovascular safety
of fexofenadine HCl. American Journal of Cardiology, 1999; 83(10).
https://doi.org/10.1016/S0002-9149(99)00124-1
52. Reiss, T. F., Chervinsky, P., Dockhorn, R. J., Shingo, S., Seidenberg, B., & Edwards, T.
B. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic
asthma: A multicenter, randomized, double-blind trial. Archives of Internal Medicine,
1998; 158(11). https://doi.org/10.1001/archinte.158.11.1213
53. Robertson, C. F., Price, D., Henry, R., Mellis, C., Glasgow, N., Fitzgerald, D., Lee, A. J.,
Turner, J., & Sant, M. Short-course montelukast for intermittent asthma in children a
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1334
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
randomized controlled trial. American Journal of Respiratory and Critical Care
Medicine, 2007; 175(4). https://doi.org/10.1164/rccm.200510-1546OC
54. Russell, T., Stoltz, M., & Weir, S. Pharmacokinetics, pharmacodynamics, and tolerance
of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers.
Clinical Pharmacology and Therapeutics, 1998; 64(6). https://doi.org/10.1016/S0009-
9236(98)90052-2
55. Scaparrotta, A., Di Pillo, S., Attanasi, M., Rapino, D., Cingolani, A., Consilvio, N. Pietro,
Verini, M., & Chiarelli, F. Montelukast versus inhaled corticosteroids in the management
of pediatric mild persistent asthma. In Multidisciplinary Respiratory Medicine, 2012; 7: 2.
https://doi.org/10.1186/2049-6958-7-13
56. Simons, F. E. R., Bergman, J. N., Watson, W. T. A., & Simons, K. J. The clinical
pharmacology of fexofenadine in children. Journal of Allergy and Clinical Immunology,
1996; 98(6 I). https://doi.org/10.1016/S0091-6749(96)80192-8
57. Singh, R. M., Saini, P. K., Mathur, S. C., Singh, G. N., & Lal, B. Development and
validation of a RP-HPLC method for estimation of montelukast sodium in bulk and in
tablet dosage form. Indian Journal of Pharmaceutical Sciences, 2010; 72(2).
https://doi.org/10.4103/0250-474X.65023
58. Spencer, C. M., Faulds, D., & Peters, D. H. Cetirizine: A Reappraisal of its
Pharmacological Properties and Therapeutic Use in Selected Allergic Disorders. Drugs,
1993; 46(6). https://doi.org/10.2165/00003495-199346060-00008
59. Virchow, J. C., & Bachert, C. Efficacy and safety of montelukast in adults with asthma
and allergic rhinitis. Respiratory Medicine, 2006; 100(11).
https://doi.org/10.1016/j.rmed.2006.02.026
60. Walsh, G. M. The anti-inflammatory effects of levocetirizine - are they clinically relevant
or just an interesting additional effect? Allergy, Asthma & Clinical Immunology, 2009;
5(1). https://doi.org/10.1186/1710-1492-5-14
61. Wang, K., Birring, S. S., Taylor, K., Fry, N. K., Hay, A. D., Moore, M., Jin, J., Perera, R.,
Farmer, A., Little, P., Harrison, T. G., Mant, D., & Harnden, A. Montelukast for
postinfectious cough in adults: A double-blind randomised placebo-controlled trial. The
Lancet Respiratory Medicine, 2014; 2(1). https://doi.org/10.1016/S2213-2600(13)70245-
5
62. Wen, S., Wei, J., Bao, J., Guo, T., Zheng, W., Zhuang, X., & Lin, Y. Effect of
levocetirizine hydrochloride on the growth of human dermal papilla cells: A preliminary
study. Annals of Cardiothoracic Surgery, 2020; 9(2).
www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │
1335
Mansoor et al. World Journal of Pharmacy and Pharmaceutical Sciences
https://doi.org/10.21037/apm.2020.01.15
63. Zhang, L., Cheng, L., & Hong, J. The clinical use of cetirizine in the treatment of allergic
rhinitis. In Pharmacology, 2013; 92: 1–2. https://doi.org/10.1159/000351843
64. (Ahuja et al., 2011; Annunziata et al., 2019; Axelrod & Bielory, 2008; Aypak et al., 2013;
Bapputty et al., 2019; Bousquet et al., 1996; Campoli-Richards et al., 1990; Compalati et
al., 2011; Corsico et al., 2019; Curran et al., 2004; Davis et al., 2009; Dicpinigaitis &
Gayle, 2003; Grant et al., 1995; Haarman et al., 2017; Hamman et al., 2001; C. Z. Huang
et al., 2019; X. Huang et al., 2019; Inder et al., 2018; Ino et al., 2020; Kalivas et al., 1990;
Knorr et al., 2000; Kusuhara et al., 2013; Kwatra, 2017b, 2017c, 2017a, 2019h, 2019a,
2019d, 2019b, 2019e, 2019f, 2019g, 2019i, 2019j, 2019k, 2019c, 2020h, 2020d, 2020b,
2020a, 2020e, 2020g, 2020c, 2020i, 2020f; Meeves & Appajosyula, 2003; Mösges et al.,
2011; Nelson et al., 2000; No Title, n.d.; Pampura et al., 2011; Pratt et al., 1999; Reiss et
al., 1998; Robertson et al., 2007; Russell et al., 1998; Scaparrotta et al., 2012; Simons et
al., 1996; Singh et al., 2010; Spencer et al., 1993; Virchow & Bachert, 2006; Walsh,
2009; Wang et al., 2014; Wen et al., 2020; Zhang et al., 2013.