This information is intended for use by health professionals

1. Name of the medicinal product

Benadryl One A Day Relief

Benadryl Allergy One A Day 10mg Tablets

2. Qualitative and quantitative composition

One film-coated tablet contains 10 mg cetirizine dihydrochloride

Excipients with known effect: one film-coated tablet contains 66.40 mg lactose-monohydrate

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Film-coated tablets.

White, oblong, film-coated tablet, with breakline and Y-Y logo

4. Clinical particulars
4.1 Therapeutic indications

Benadryl Allergy One a Day 10mg Tablets are indicated in children aged 12 years and above, adolescents and adults:

- for the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.

- for the relief of symptoms of chronic idiopathic urticaria.

4.2 Posology and method of administration

Adults and adolescents over 12 years of age: 10 mg once daily (1 tablet).

The tablets 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: there are no data to document the efficacy/safety ratio in patients with renal impairment. Since cetirizine is mainly excreted via renal route (see section 5.2), in cases no alternative treatment can be used, 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:

Dosing adjustments for adult patients with impaired renal function

Group

Creatinine clearance (ml/min)

Dosage and frequency

Normal

≥80

10 mg once daily

Mild

50 – 79

10 mg once daily

Moderate

30 – 49

5 mg once daily

Severe

< 30

5 mg once every 2 days

End-stage renal disease - Patients undergoing dialysis

< 10

Contra-indicated

In pediatric 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, his age 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: dose adjustment is recommended (see Patients with moderate to severe renal impairment above).

4.3 Contraindications

Hypersensitivity to cetirizine dihydrochloride, to hydroxyzine, to any piperazine derivatives, or to any of the excipients listed in section 6.1.

Patients with severe renal impairment at less than 10 ml/min creatinine clearance.

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 kidney disease are instructed to consult a physician before use. The physician should determine if a different dose is needed (see section 4.2).

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.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicine.

Paediatric Population

The use of the film-coated tablet formulation is not recommended in children aged less than 12 years.

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 (400 mg/day).

In sensitive patients, concurrent use with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance (see section 4.7).

The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.

4.6 Fertility, pregnancy and lactation

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.

Breast-feeding

Cetirizine is excreted in human milk at concentrations representing 25% to 90% of 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.

However, patients who experience somnolence should refrain from driving, engaging in potentially hazardous activities or operating machinery, they 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 (see section 4.5).

4.8 Undesirable effects

Clinical studies have shown that cetirizine at the recommended dosage has minor undesirable 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 treatment with cetirizine dihydrochloride.

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

(WHO-ART)

Cetirizine 10 mg

(n= 3260)

Placebo

(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

(WHO-ART)

Cetirizine

(n=1656)

Placebo

(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 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, syncope, tremor, dystonia, dyskinesia

Not known: amnesia, memory impairment

Eye disorders:

Very rare: accommodation disorder, blurred vision, oculogyration

Not known: Eye pain

Ear and labyrinth disorders:

Not known: vertigo

Cardiac disorders:

Rare: tachycardia

Gastro-intestinal disorders:

Uncommon: diarrhoea

Hepatobiliary disorders:

Rare: hepatic function abnormal (increased transaminases, alkaline phosphatase, γ-GT 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

Reproductive system and breast disorders:

Not known: erectile dysfunction

General disorders and administration site conditions:

Uncommon: asthenia, malaise

Rare: oedema

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 10 mg 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 10 mg 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 10 mg 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 60 mg 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 300 ng/ml and is achieved within 1.0 ± 0.5 h. No accumulation is observed for cetirizine following daily doses of 10 mg 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 60 mg.

Special populations

Elderly: Following a single 10 mg 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 40 ml/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 hemodialysis (creatinine clearance less than 7 ml/min) given a single oral 10 mg dose of cetirizine had a 3-fold increase in half-life and a 70 % decrease in clearance compared to normals. 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 20 mg 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

Microcrystalline cellulose

Lactose

Colloidal anhydrous silica

Magnesium stearate

Opadry Y-1-7000

- Hydroxypropylmethylcellulose (E464)

- Titanium dioxide (E171)

- Macrogol 400

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

5 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Thermoformed transparent, colorless, physiologically inert PVC blister strip thermosealed by an aluminium foil covered by suitable lac; in a carton box.

Boxes of 7, 14 or 30 tablets.

Not all the packs may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements for disposal

Administrative Data

7. Marketing authorisation holder

McNeil Products Limited

Foundation Park

Roxborough Way

Berkshire SL6 3UG

United Kingdom

8. Marketing authorisation number(s)

PL 15513/0118

9. Date of first authorisation/renewal of the authorisation

27/11/2008

10. Date of revision of the text

18 May 2018