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BENADRYL ALLERGY LIQUID RELEASE 10MG CAPSULES

Active substance(s): CETIRIZINE DIHYDROCHLORIDE / CETIRIZINE DIHYDROCHLORIDE / CETIRIZINE DIHYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Benadryl Allergy Liquid Release 10 mg Capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each soft capsule contains 10 mg cetirizine dihydrochloride.
For the full list of excipients, see section 6.1. The product contains a
maximum of 19.3 mg sorbitol per capsule dose.

3

PHARMACEUTICAL FORM
Capsule, soft.
Each capsule has a colourless to slightly yellow, clear shell containing a clear,
colourless viscous fill. Each soft gel capsule has the logo "C10" printed with
black ink.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Benadryl Allergy Liquid Release 10mg Capsules is indicated in children aged
12 years and above, adolescents and adults:
o for the relief of nasal and ocular symptoms of seasonal and perennial
allergic rhinitis.
o for the relief of symptoms of chronic idiopathic urticaria.

4.2

Posology and method of administration
Adults and adolescents 12 years of age and over: 10mg once daily (1 capsule).
The capsules need to be swallowed with a glass of liquid.
Elderly subjects: data do not suggest that the dose needs to be reduced in
elderly subjects provided that the renal function is normal.
Patients with moderate to severe renal impairment: the dosing intervals must
be individualized according to renal function. Refer to the following table and
adjust the dose as indicated. To use this dosing table, an estimate of the
patient’s creatinine clearance (CLcr) in ml/min is needed. The CLcr (ml/min)
may be estimated from serum creatinine (mg/dl) determination using the
following formula:

CLcr =

[140 − age( years)] x weight (kg ) (x 0.85 for women )
72 x serum creatinine (mg / dl )

Dosing adjustments for adult patients with impaired renal function
Creatinine clearance
Group
Dosage and frequency
(ml/min)
Normal
≥ 80
10mg once daily
Mild
50 – 79
10mg once daily
Moderate
30 – 49
5mg once daily*
Severe
< 30
5mg once every 2 days*
End-stage renal disease < 10
Contra-indicated
Patients undergoing dialysis
*The product cannot be halved to give the required dose adjustment in renallyimpaired patients.
In paediatric patients suffering from renal impairment, the dose will have to be
adjusted on an individual basis taking into account the renal clearance of the
patient, and his body weight.
Patients with hepatic impairment: no dose adjustment is needed in patients
with solely hepatic impairment.
Patients with hepatic impairment and renal impairment: adjustment of the dose
is recommended (see Patients with renal impairment above).

4.3.

Contraindications
Hypersensitivity to cetirizine dihydrochloride, to hydroxyzine, to any piperazine
derivatives, to soya, peanut or to any of the excipients listed in section 6.1.
Patients with moderate to severe renal impairment at less than 50 ml/min creatinine
clearance (as the product cannot be halved to give the required dose adjustment).

4.4.

Special warnings and precautions for use
At therapeutic doses, no clinically significant interactions have been demonstrated
with alcohol (for a blood alcohol level of 0.5 g/L). Nevertheless, precaution is
recommended if alcohol is taken concomitantly.
Patients with both liver and kidney disease should consult a physician before use. The
physician should determine if a different dose is needed.
Caution should be taken in patients with predisposition factors of urinary retention
(e.g. spinal cord lesion, prostatic hyperplasia) as cetirizine may increase the risk of
urinary retention.
Caution in epileptic patients and patients at risk of convulsions is recommended.
Allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is
required before performing them.

This product contains sorbitol (E420). Patients with rare hereditary problems of
fructose intolerance should not take this medicine.
If symptoms persist or worsen, stop use and consult a physician.
Paediatric Population
The use of the capsule formulation is not recommended in children aged less than 12
years since this formulation does not allow for appropriate dose adaptation.

4.5

Interaction with other medicinal products and other forms of interaction
Due to the pharmacokinetic, pharmacodynamic and tolerance profile of
cetirizine, no interactions are expected with this antihistamine. Actually,
neither pharmacodynamic nor significant pharmacokinetic interaction was
reported in drug-drug interactions studies performed, notably with
pseudoephedrine or theophylline (400mg/day).
The extent of absorption of cetirizine is not reduced with food, although the
rate of absorption is decreased.

4.6.

Fertility, pregnancy and lactation
This product should not be used during pregnancy or breastfeeding unless the
potential benefit of treatment to the mother outweighs the possible risks to the
developing fetus or nursing infant.
Pregnancy
For cetirizine very rare clinical data on exposed pregnancies are available. Animal
studies do not indicate direct or indirect harmful effects with respect to pregnancy,
embryonal/fetal development, parturition or postnatal development. Caution should
be exercised when prescribing to pregnant women.
Lactation
Cetirizine is excreted in human milk at concentrations representing 25% to 90% those
measured in plasma, depending on sampling time after administration. Therefore,
caution should be exercised when prescribing cetirizine to lactating women.

4.7.

Effects on ability to drive and use machines
Objective measurements of driving ability, sleep latency and assembly line
performance have not demonstrated any clinically relevant effects at the
recommended dose of 10 mg.
Patients intending to drive, engaging in potentially hazardous activities or operating
machinery should not exceed the recommended dose and should take their response
to the medicinal product into account. In sensitive patients, concurrent use with

alcohol or other CNS depressants may cause additional reductions in alertness and
impairment of performance.
Caution should be used when driving a motor vehicle or operating machinery.

4.8.

Undesirable effects
Clinical studies have shown that cetirizine at the recommended dosage has minor
adverse effects on the CNS, including somnolence, fatigue, dizziness and headache.
In some cases, paradoxical CNS stimulation has been reported.
Although cetirizine is a selective antagonist of peripheral H1-receptors and is
relatively free of anticholinergic activity, isolated cases of micturition difficulty, eye
accommodation disorders and dry mouth have been reported.
Instances of abnormal hepatic function with elevated hepatic enzymes accompanied
by elevated bilirubin have been reported. Mostly this resolves upon discontinuation
of the drug.
Clinical trials
Double blind controlled clinical trials comparing cetirizine to placebo or other
antihistamines at the recommended dosage (10 mg daily for cetirizine), of which
quantified safety data are available, included more than 3200 subjects exposed to
cetirizine.
From this pooling, the following adverse events were reported for cetirizine 10 mg in
the placebo-controlled trials at rates of 1.0 % or greater:

Adverse event

Cetirizine 10 mg

Placebo

(WHO-ART)

(n= 3260)

(n = 3061)

Body as a whole – general disorders
Fatigue

1.63 %

0.95 %

Central and peripheral nervous system disorders
Dizziness
Headache

1.10 %
7.42 %

0.98 %
8.07 %

Gastro-intestinal system disorders
Abdominal pain
Dry mouth
Nausea

0.98 %
2.09 %
1.07 %

1.08 %
0.82 %
1.14 %

Psychiatric disorders
Somnolence

9.63 %

5.00 %

Respiratory system disorders
Pharyngitis

1.29 %

1.34 %

Although statistically more common than under placebo, somnolence was mild to
moderate in the majority of cases. Objective tests as demonstrated by other studies
have demonstrated that usual daily activities are unaffected at the recommended daily
dose in healthy young volunteers.
Adverse drug reactions at rates of 1 % or greater in children aged from 6 months to
12 years, included in placebo-controlled clinical trials are:

Adverse drug reactions

Cetirizine

Placebo

(WHO-ART)

(n=1656)

(n =1294)

Gastro-intestinal system disorders
Diarrhoea

1.0 %

0.6 %

Psychiatric disorders
Somnolence

1.8 %

1. 4 %

Respiratory system disorders
Rhinitis

1.4 %

1.1 %

Body as a whole – general disorders
Fatigue

1.0 %

0.3 %

Post-marketing experience
In addition to the adverse reactions reported during clinical studies and listed above,
the following undesirable effects have been reported in post-marketing experience.
Undesirable effects are described according to MedDRA System Organ Class and by
estimated frequency based on the post-marketing experience.
Frequencies are defined as follows: Very common (≥1/10); common (≥1/100 to
<1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare
(<1/10,000), not known (cannot be estimated from the available data)
Blood and lymphatic disorders:
Very rare: thrombocytopenia
Immune system disorders:
Rare: hypersensitivity
Very rare: anaphylactic shock
Metabolism and nutrition disorders:
Not known: increased appetite
Psychiatric disorders:
Uncommon: agitation
Rare: aggression, confusion, depression, hallucination, insomnia
Very rare: tics
Not known: suicidal ideation
Nervous system disorders:
Uncommon: paraesthesia

Rare: convulsions
Very rare: dysgeusia, dystonia, dyskinesia, syncope, tremor
Not known: amnesia, memory impairment
Eye disorders:
Very rare: accommodation disorder, blurred vision, oculogyration, eye swelling
Ear and labyrinth disorders
Not known: vertigo
Cardiac disorders:
Rare: tachycardia
Respiratory, thoracic and mediastinal disorders:
Very rare: Cough
Gastro-intestinal disorders:
Uncommon: diarrhoea
Very rare: Nausea
Hepatobiliary disorders:
Rare: hepatic function abnormal (increased transaminases, alkaline phosphatase, γGT and bilirubin)
Skin and subcutaneous tissue disorders:
Uncommon: pruritus, rash
Rare: urticaria
Very rare: angioneurotic oedema, fixed drug eruption
Renal and urinary disorders:
Very rare: dysuria, enuresis
Not known: urinary retention
General disorders and administration site conditions:
Uncommon: asthenia, malaise
Rare: oedema
Very rare: Feeling abnormal
Investigations:
Rare: weight increased
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard

4.9

Overdose
Symptoms
Symptoms observed after an overdose of cetirizine are mainly associated with
CNS effects or with effects that could suggest an anticholinergic effect.

Adverse events reported after an intake of at least 5 times the recommended
daily dose are: confusion, diarrhoea, dizziness, fatigue, headache, malaise,
mydriasis, pruritus, restlessness, sedation, somnolence, stupor, tachycardia,
tremor, and urinary retention.
Management
There is no known specific antidote to cetirizine.
Should overdose occur, symptomatic or supportive treatment is recommended.
Gastric lavage should be considered following ingestion of a short occurrence.
Cetirizine is not effectively removed by dialysis.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Piperazine derivatives, ATC code: R06A E07
Cetirizine, a human metabolite of hydroxyzine, is a potent and selective
antagonist of peripheral H1-receptors. In vitro receptor binding studies have
shown no measurable affinity for other than H1-receptors.
In addition to its anti-H1 effect, cetirizine was shown to display anti-allergic
activities: at a dose of 10mg once or twice daily, it inhibits the late phase
recruitment of eosinophils, in the skin and conjunctiva of atopic subjects
submitted to allergen challenge.
Studies in healthy volunteers show that cetirizine, at doses of 5 and 10mg
strongly inhibits the wheal and flare reactions induced by very high
concentrations of histamine into the skin, but the correlation with efficacy is
not established.
In a 35-day study in children aged 5 to 12, no tolerance to the antihistaminic
effect (suppression of wheal and flare) of cetirizine was found. When a
treatment with cetirizine is stopped after repeated administration, the skin
recovers its normal reactivity to histamine within 3 days.
In a six-week, placebo-controlled study of 186 patients with allergic rhinitis
and concomitant mild to moderate asthma, cetirizine 10mg once daily
improved rhinitis symptoms and did not alter pulmonary function. This study
supports the safety of administering cetirizine to allergic patients with mild to
moderate asthma.
In a placebo-controlled study, cetirizine given at the high daily dose of 60mg
for seven days did not cause statistically significant prolongation of QT
interval.
At the recommended dosage, cetirizine has demonstrated that it improves the
quality of life of patients with perennial and seasonal allergic rhinitis.

5.2

Pharmacokinetic properties
The steady-state peak plasma concentrations is approximately 300ng/ml and is
achieved within 1.0 ± 0.5 h. No accumulation is observed for cetirizine
following daily doses of 10mg for 10 days. The distribution of

pharmacokinetic parameters such as peak plasma concentration (Cmax) and
area under curve (AUC) is unimodal in human volunteers.
The extent of absorption of cetirizine is not reduced with food, although the
rate of absorption is decreased. The extent of bioavailability is similar when
cetirizine is given as solutions, capsules or tablets.
The apparent volume of distribution is 0.50 l/kg. Plasma protein binding of
cetirizine is 93 ± 0.3%. Cetirizine does not modify the protein binding of
warfarin.
Cetirizine does not undergo extensive first pass metabolism. About two third
of the dose are excreted unchanged in urine. The terminal half-life is
approximately 10 hours.
Cetirizine exhibits linear kinetics over the range of 5 to 60mg.
Special populations
Elderly: Following a single 10mg oral dose, half-life increased by about 50%
and clearance decreased by 40% in 16 elderly subjects compared to the normal
subjects. The decrease in cetirizine clearance in these elderly volunteers
appeared to be related to their decreased renal function.
Children, infants and toddlers: The half-life of cetirizine was about 6 hours in
children of 6-12 years and 5 hours in children 2-6 years. In infants and
toddlers aged 6 to 24 months, it is reduced to 3.1 hours
Renally impaired patients: The pharmacokinetics of the drug were similar in
patients with mild impairment (creatinine clearance higher than 40ml/min) and
healthy volunteers. Patients with moderate renal impairment had a 3-fold
increase in half-life and 70% decrease in clearance compared to healthy
volunteers.
Patients on haemodialysis (creatinine clearance less than 7ml/min) given a
single oral 10mg dose of cetirizine had a 3-fold increase in half-life and a 70%
decrease in clearance compared to normal. Cetirizine was poorly cleared by
haemodialysis. Dosing adjustment is necessary in patients with moderate or
severe renal impairment (see section 4.2).
Hepatically impaired patients: Patients with chronic liver diseases
(hepatocellular, cholestatic, and biliary cirrhosis) given 10 or 20mg of
cetirizine as a single dose had a 50% increase in half-life along with a 40%
decrease in clearance compared to healthy subjects.
Dosing adjustment is only necessary in hepatically impaired patients if
concomitant renal impairment is present.

5.3

Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional
studies of safety pharmacology, repeated dose toxicity, genotoxicity,
carcinogenic potential, toxicity to reproduction.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Capsule contents
Macrogol 600
Potassium Hydroxide 43% w/w
Povidone K30
Purified water
Capsule shell
Gelatin
Sorbitol (E420)
Glycerol
Purified Water
Lecithin
Medium chain triglycerides
Black ink
Components of black printing ink
Propylene Glycol
Black iron oxide (E172)
Polyvinyl Acetate Phthalate
Macrogol 400
Ammonium Hydroxide

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
36 months

6.4

Special precautions for storage
Store below 30ºC.

6.5

Nature and contents of container
PVC/PE/PVdC blisters of 7 capsules sealed with aluminium lidding foil,
packed into cardboard cartons.

6.6.

Special precautions for disposal
No special requirements for disposal.

7

MARKETING AUTHORISATION HOLDER
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire
United Kingdom
SL6 3UG

8

MARKETING AUTHORISATION NUMBER(S)
PL 15513/0378

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
20/04/2011

10

DATE OF REVISION OF THE TEXT
02/02/2017

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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