Zyrtecset Allergy 10mg is an antihistamine medicine containing cetirizine dihydrochloride. It is used to relieve symptoms associated with seasonal and year-round allergic rhinitis, including nasal and eye symptoms, and may also be used for symptoms of chronic urticaria (hives).

Suitable for adults and children from 6 years of age.

Benefits

• Helps relieve symptoms of seasonal allergic rhinitis

• Helps relieve year-round allergy symptoms

• Helps reduce allergic nasal and eye symptoms

• May help relieve symptoms associated with chronic urticaria

• Contains 10mg cetirizine dihydrochloride per tablet

• Suitable for adults and children from 6 years

Active Ingredient

Each film-coated tablet contains:

Cetirizine Dihydrochloride – 10mg

Directions

Adults and adolescents 12 years and older:
Take 1 tablet (10mg) once daily.

Children 6 to 12 years:
Take ½ tablet (5mg) twice daily.

For people with moderate kidney impairment, the recommended dose may be reduced to 5mg once daily.

If you or your child has severe kidney disease, consult a healthcare professional before use.

Precautions

Do not use if you are allergic to cetirizine, hydroxyzine, piperazine derivatives, or any of the other ingredients.

Consult a healthcare professional before use if you:

• Have kidney problems

• Have a history of epilepsy or seizures

• Are pregnant or breastfeeding

• Take medicines that may cause drowsiness or affect the central nervous system

Avoid alcohol while taking this medicine.

Cetirizine may cause drowsiness or reduced alertness in some people. Use caution when driving or operating machinery until you know how the medicine affects you.

Do not exceed the recommended dose.

Possible Side Effects

Possible side effects may include:

• Drowsiness

• Headache

• Dizziness

• Fatigue

• Dry mouth

• Nausea

• Diarrhea

• Rhinitis or sore throat

Rarely, allergic reactions may occur, including swelling of the face or throat. Seek medical attention if you experience a serious allergic reaction.

Refer to the package leaflet for the complete list of possible side effects and precautions.

Ingredients

Active Ingredient:
Cetirizine Dihydrochloride 10mg per film-coated tablet.

Other Ingredients:
Microcrystalline Cellulose, Lactose Monohydrate, Colloidal Anhydrous Silica, Magnesium Stearate, Opadry Y-1-7000 (Hydroxypropyl Methylcellulose [E464], Titanium Dioxide [E171], Macrogol 400).

Brand: Zyrtecset
Manufacturer: UCB
Strength: 10mg
Package Size: 7 Tablets
Product Type: Antihistamine Allergy Medicine
Age: Adults and children from 6 years
Barcode / EAN: 3400936461680

Please read the following full disclosure before taking or purchasing this product.

• for the treatment of nasal and ocular symptoms of seasonal and perennial allergic rhinitis;

• for the treatment of symptoms of chronic idiopathic urticaria.

Medical advice is recommended for chronic idiopathic urticaria.

4.2 Posology and method of administration

Posology

10 mg once daily (1 tablet).

Special populations

Elderly patients

No dose adjustment is required in elderly patients with normal renal function.

Renal impairment

Available data do not allow the benefit/risk ratio to be adequately documented in patients with renal impairment.

Because cetirizine is primarily eliminated by the kidneys, if no alternative treatment can be used, the interval between doses should be adjusted according to renal function.

Dosage should be adjusted as follows:

Hepatic impairment

No dose adjustment is necessary in patients with isolated hepatic impairment.

In patients with hepatic impairment associated with renal impairment, dose adjustment is recommended according to renal function.

Pediatric population

The tablet form should not be used in children under 6 years of age because it does not allow appropriate dose adjustment.

Children aged 6 to 12 years:
5 mg twice daily, corresponding to half a tablet twice daily.

Adolescents over 12 years:
10 mg once daily, corresponding to one tablet.

In children with renal impairment, the dose should be individually adjusted according to renal clearance, age, and body weight.

Method of administration

The tablets should be swallowed with a drink.

4.3 Contraindications

• Hypersensitivity to the active substance, any of the excipients listed in section 6.1, hydroxyzine, or piperazine derivatives.

• End-stage renal impairment with a glomerular filtration rate below 15 mL/min.

4.4 Special warnings and precautions for use

At therapeutic doses, no clinically significant interaction has been demonstrated with alcohol at blood alcohol concentrations up to 0.5 g/L. However, caution is recommended when alcohol is consumed at the same time.

Caution should be exercised in patients with factors predisposing them to urinary retention, such as spinal cord injury or prostatic hyperplasia, because cetirizine may increase the risk of urinary retention.

Cetirizine should be administered with caution in patients with epilepsy or those at risk of seizures.

Antihistamines inhibit responses to allergy skin testing. A treatment-free period of 3 days is required before such testing is performed.

Patients with galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption syndrome, which are rare hereditary disorders, should not take this medicine.

Itching and/or urticaria may occur after cetirizine is discontinued, even when these symptoms were not present before treatment began. In some cases, symptoms may be severe and may require treatment to be restarted. Symptoms should resolve when treatment is resumed.

Pediatric population

Use of the film-coated tablet is not recommended in children under 6 years because this formulation does not allow appropriate dosage adjustment for this age group.

A pediatric formulation of cetirizine is recommended instead.

4.5 Interaction with other medicinal products and other forms of interaction

Based on the pharmacokinetic, pharmacodynamic, and tolerability profile of cetirizine, no interactions are expected with this antihistamine.

To date, no significant pharmacodynamic or pharmacokinetic interactions have been reported in drug-interaction studies, particularly with pseudoephedrine or theophylline at 400 mg/day.

The extent of cetirizine absorption is not reduced by food, although the rate of absorption is slower.

Concomitant use of alcohol or other central nervous system depressants may impair alertness or performance in sensitive patients, although cetirizine does not potentiate the effects of alcohol at a blood concentration of 0.5 g/L.

4.6 Fertility, pregnancy and breastfeeding

Pregnancy

Prospective data collected on pregnancy outcomes following exposure to cetirizine do not suggest maternal or embryo-fetal toxicity greater than that observed in the general population.

Animal studies have shown no direct or indirect harmful effects on pregnancy, embryonic and fetal development, delivery, or postnatal development.

Caution is recommended when prescribing cetirizine during pregnancy.

Breastfeeding

Cetirizine passes into breast milk.

A risk of adverse effects in breastfed newborns cannot be excluded.

Cetirizine is excreted into human breast milk at concentrations ranging from approximately 25% to 90% of those measured in plasma, depending on the timing of sampling relative to administration.

Caution is therefore recommended when prescribing cetirizine to breastfeeding women.

Fertility

Human fertility data are limited, but no risk has been identified.

Animal data do not indicate a reproductive safety concern for humans.

4.7 Effects on ability to drive and use machines

Objective measurements of driving ability, sleep onset, and assembly-line performance have not demonstrated clinically relevant effects at the recommended dose of 10 mg.

However, patients who experience drowsiness should not drive, take part in potentially hazardous activities, or operate machinery.

They should not exceed the recommended dose and should take into account their individual response to the medicine.

4.8 Undesirable effects

Clinical trials

Summary

Mild adverse effects involving the central nervous system, including drowsiness, fatigue, dizziness, and headache, were observed during clinical trials using cetirizine at the recommended dose.

In some cases, a paradoxical stimulating effect on the central nervous system was observed.

Despite its selective antagonistic action on peripheral H1 receptors and relatively low anticholinergic activity, isolated cases of difficulty urinating, accommodation disorders, and dry mouth have been reported.

Abnormal liver function, including elevated liver enzymes associated with increased bilirubin, has also been reported. In most cases, these abnormalities resolved after cetirizine dihydrochloride was discontinued.

Adverse reactions reported during clinical trials

More than 3,200 subjects exposed to cetirizine were included in double-blind controlled clinical trials comparing cetirizine at the recommended dose of 10 mg/day with placebo or other antihistamines.

The following adverse reactions occurred with cetirizine 10 mg at an incidence of 1.0% or greater:

Drowsiness occurred significantly more often than with placebo, but in most cases it was mild to moderate.

Objective testing, supported by other studies, showed that normal daily activities were not affected in healthy young volunteers taking the recommended daily dose.

Pediatric population

The following adverse reactions were reported with an incidence of 1% or greater in children aged 6 months to 12 years participating in placebo-controlled clinical trials:

Adverse reactions reported after marketing

In addition to adverse reactions reported during clinical trials, the following reactions have been reported since the product was marketed.

Frequencies are defined as:

• 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

• Frequency not known: cannot be estimated from available data

Blood and lymphatic system disorders

Very rare: thrombocytopenia.

Immune system disorders

Rare: hypersensitivity.

Very rare: anaphylactic shock.

Metabolism and nutrition disorders

Frequency not known: increased appetite.

Psychiatric disorders

Uncommon: agitation.

Rare: aggression, confusion, depression, hallucinations, insomnia.

Very rare: tics.

Frequency not known: suicidal thoughts, nightmares.

Nervous system disorders

Uncommon: paresthesia.

Rare: seizures.

Very rare: dysgeusia, syncope, tremor, dystonia, dyskinesia.

Frequency not known: amnesia, memory impairment.

Eye disorders

Very rare: accommodation disorder, blurred vision, oculogyric crisis.

Ear and labyrinth disorders

Frequency not known: vertigo.

Cardiac disorders

Rare: tachycardia.

Gastrointestinal disorders

Uncommon: diarrhea.

Hepatobiliary disorders

Rare: abnormal liver function tests, including increased transaminases, alkaline phosphatase, gamma-GT, and bilirubin.

Frequency not known: hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: itching, rash.

Rare: urticaria.

Very rare: angioedema, fixed drug eruption.

Frequency not known: acute generalized exanthematous pustulosis.

Musculoskeletal and connective tissue disorders

Frequency not known: joint pain, muscle pain.

Renal and urinary disorders

Very rare: painful urination, bedwetting.

Frequency not known: urinary retention.

General disorders and administration site conditions

Uncommon: weakness, malaise.

Rare: edema.

Investigations

Rare: weight gain.

Description of selected adverse reactions

Cases of itching, including severe itching, and/or urticaria have been reported after stopping cetirizine.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important because it allows continuous monitoring of the benefit/risk balance.

Healthcare professionals should report suspected adverse reactions through the French national reporting system operated by the Agence nationale de sécurité du médicament et des produits de santé (ANSM) and the Regional Pharmacovigilance Centers.

4.9 Overdose

Symptoms

Symptoms observed following cetirizine overdose are mainly associated with central nervous system effects or effects suggesting anticholinergic activity.

Adverse effects reported after taking a dose at least five times greater than the recommended daily dose include:

• confusion

• diarrhea

• dizziness

• fatigue

• headache

• malaise

• dilated pupils

• itching

• agitation

• sedation

• drowsiness

• stupor

• tachycardia

• tremor

• urinary retention

Management

There is no known specific antidote for cetirizine.

In the event of overdose, symptomatic treatment and supportive measures are recommended.

Gastric lavage may be considered if ingestion occurred recently.

Cetirizine is not effectively removed by hemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihistamines for systemic use, piperazine derivatives.

ATC code: R06AE07.

Mechanism of action

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 receptors other than H1 receptors.

Pharmacodynamic effects

In addition to its anti-H1 effects, cetirizine has demonstrated antiallergic activity.

When administered 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 individuals subjected to allergen challenge testing.

Clinical efficacy and safety

Studies in healthy volunteers have shown that cetirizine at doses of 5 mg and 10 mg strongly inhibits wheal-and-flare reactions induced by very high concentrations of histamine in the skin.

However, a direct correlation between these observations and clinical effectiveness has not been established.

In a six-week placebo-controlled study involving 186 patients with allergic rhinitis and mild to moderate asthma, cetirizine 10 mg once daily improved rhinitis symptoms without affecting pulmonary function.

This study demonstrates the safe use of cetirizine in allergic patients with mild to moderate asthma.

In a placebo-controlled study, cetirizine administered at a high daily dose of 60 mg for 7 days did not cause a statistically significant prolongation of the QT interval.

At the recommended dose, improved quality of life has been demonstrated in patients with perennial and seasonal allergic rhinitis treated with cetirizine.

Pediatric population

In a 35-day study in children aged 5 to 12 years, no reduction in the antihistamine effect of cetirizine was observed.

After discontinuation following repeated administration, skin reactivity to histamine returned within 3 days.

5.2 Pharmacokinetic properties

Absorption

At steady state, peak plasma concentrations are approximately 300 ng/mL and are reached after approximately 1.0 ± 0.5 hours.

The distribution of measured pharmacokinetic parameters, including peak plasma concentration and area under the curve, is unimodal.

The bioavailability of cetirizine is not altered by food, although the rate of absorption is reduced.

Cetirizine bioavailability is equivalent when administered as a solution, capsule, or tablet.

Distribution

The apparent volume of distribution is 0.50 L/kg.

Plasma protein binding of cetirizine is 93 ± 0.3%.

Cetirizine does not alter the protein binding of warfarin.

Biotransformation

Cetirizine does not undergo significant first-pass hepatic metabolism.

Elimination

The terminal plasma half-life of cetirizine is approximately 10 hours.

No accumulation of cetirizine occurs after daily administration of 10 mg for 10 days.

Approximately two-thirds of the administered dose is excreted unchanged in the urine.

Linearity / non-linearity

Cetirizine pharmacokinetics are linear over the dose range of 5 to 60 mg.

Renal impairment

Cetirizine pharmacokinetics were similar in patients with mild renal impairment, defined as creatinine clearance greater than 40 mL/min, and in healthy volunteers.

In patients with moderate renal impairment, the half-life was increased threefold and clearance was reduced by 70% compared with healthy volunteers.

In hemodialysis patients with creatinine clearance below 7 mL/min, the half-life was increased threefold and clearance was reduced by 70% after a single oral 10 mg dose.

Cetirizine was only minimally removed by hemodialysis.

Dose adjustment is required in patients with moderate or severe renal impairment.

Hepatic impairment

In patients with chronic liver disease, including hepatocellular, cholestatic, and biliary cirrhosis, receiving a single dose of 10 or 20 mg of cetirizine, the half-life increased by approximately 50% and clearance decreased by approximately 40% compared with healthy subjects.

Dose adjustment is required in patients with hepatic impairment only when renal impairment is also present.

Elderly patients

After a single oral dose of 10 mg cetirizine in 16 elderly subjects, the half-life increased by approximately 50% and clearance decreased by approximately 40% compared with younger subjects.

The reduction in cetirizine clearance in these elderly volunteers appears to be related to impaired renal function.

Pediatric population

The cetirizine half-life is approximately:

• 6 hours in children aged 6 to 12 years

• 5 hours in children aged 2 to 6 years

• 3.1 hours in infants and young children aged 6 to 24 months

5.3 Preclinical safety data

Non-clinical data from conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenicity, and reproductive and developmental toxicity revealed no particular hazard for humans.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

• Microcrystalline cellulose

• Lactose monohydrate

• Colloidal anhydrous silica

• Magnesium stearate

• Opadry Y-1-7000, composed of:

  • Hydroxypropyl methylcellulose (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

PVC/aluminum blister packs.

Boxes containing 7 tablets.

6.6 Special precautions for disposal and other handling

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with applicable regulations.

7. MARKETING AUTHORIZATION HOLDER

UCB PHARMA

Tour Emblem
7 Allée de l’Arche
92400 Courbevoie
France

8. MARKETING AUTHORIZATION NUMBER

34009 364 616 8 0

7 scored film-coated tablets in a PVC/aluminum blister pack.

9. DATE OF FIRST AUTHORIZATION / RENEWAL OF AUTHORIZATION

To be completed subsequently by the marketing authorization holder.

10. DATE OF REVISION OF THE TEXT

To be completed subsequently by the marketing authorization holder.

11. DOSIMETRY

Not applicable.

12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

Not applicable.

CONDITIONS OF PRESCRIPTION AND SUPPLY

Medicinal product not subject to medical prescription.