Ucerax Tablets 25 mg.

Hydroxyzine hydrochloride 25 mg.

For excipients, see 6.1.

Film-coated tablets.

Ucerax is indicated to assist in the management of anxiety.

Ucerax is indicated to assist in the management of pruritus associated with acute and chronic urticaria, including cholinergic and physical types, and in atopic and contact dermatosis in adults and children.

Adults:

Anxiety.

50 mg/day in 3 separate administrations of 12.5-12.5-25mg. In more severe cases, doses up to 300mg/day can be used.

Pruritus.

Starting dose of 25 mg at night, increasing as necessary to 25 mg three or four times daily.

The maximum single dose in adults should not exceed 200mg whereas the maximum daily doses should not exceed 300mg.

Children:

Children aged from 12 months to 6 years: 1mg/kg/day up to 2.5mg/kg/day in divided doses.

Children aged over 6 years:1mg/kg/day up to 2mg/kg/day in divided doses.

The dosage should be adjusted according to the patient's response to therapy.

In the elderly, it is advised to start with half the recommended dose due to the prolonged action.

In patients with hepatic dysfunction, it is recommended to reduce the daily dose by 33%.

Dosage should be reduced in patients with moderate or severe renal impairment due to decreased excretion of its metabolite cetirizine.

Ucerax is contra-indicated in patients with a history of hypersensitivity to any of its constituents, to cetirizine, to other piperazine derivatives, to aminophylline, or to ethylenediamine.

Ucerax is contra-indicated during pregnancy and lactation.

Ucerax is contra-indicated in patients with porphyria.

Ucerax should be administered cautiously in patients with increased potential for convulsions.

Young children are more susceptible to develop adverse events related to the central nervous system (see section 4.8). In children, convulsions have been more frequently reported than in adults.

Because of its potential anticholinergic effects, Ucerax should be used cautiously in patients suffering from glaucoma, bladder outflow obstruction, decreased gastro-intestinal motility, myasthenia gravis, or dementia.

Dosage adjustments may be required if Ucerax is used simultaneously with other central nervous system depressant drugs or with drugs having anticholinergic properties (see section 4.5).

The concomitant use of alcohol and Ucerax should be avoided (see section 4.5).

Caution is needed in patients who have a known predisposing factor to cardiac arrhythmia, or who are concomitantly treated with a potentially arrhythmogenic drug. In patients with pre-existing prolonged QT intervals use of alternative treatments is to be considered.

In the elderly, it is advised to start with half the recommended dose due to a prolonged action.

Ucerax dosage should be reduced in patients with hepatic dysfunction and in patients with moderate or severe renal impairment (see section 4.2).

The treatment should be stopped at least 5 days before allergy testing or methacholine bronchial challenge, to avoid effects on the test results.

Due to the presence of lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Patients should be informed that Ucerax may potentiate the effects of barbiturates, other CNS depressants or drugs having anticholinergic properties.

Alcohol also potentiates the effects of Ucerax.

Ucerax antagonizes the effects of betahistine, and of anticholinesterase drugs.

The treatment should be stopped at least 5 days before allergy testing or methacholine bronchial challenge, to avoid effects on the test results.

Simultaneous administration of Ucerax with monoamine oxidase inhibitors should be avoided.

Ucerax counteracts the epinephrine pressor action.

In rats, hydroxyzine antagonised the anticonvulsant action of phenytoin.

Cimetidine 600 mg bid has been shown to increase the serum concentrations of hydroxyzine by 36% and to decrease peak concentrations of the metabolite cetirizine by 20%.

Ucerax is an inhibitor of cytochrome P450 2D6 (Ki: 3.9 µM ; 1.7 µg/ml) and may cause at high doses drug-drug interactions with CYP2D6 substrates.

Ucerax has no inhibitory effect at 100 µM on UDP-glucuronyl transferase isoforms 1A1 and 1A6 in human liver microsomes. It inhibits cytochrome P₄₅₀ 2C9/C10, 2C19 and 3A4 isoforms at concentrations (IC₅₀ : 19 to 140 µM ; 7 to 52 µg/ml) well above peak plasma concentrations. The metabolite cetirizine at 100 µM has no inhibitory effect on human liver cytochrome P₄₅₀ (1A2, 2A6, 2C9/C10, 2C19, 2D6, 2E1 and 3A4) and UDP-glucuronyl transferase isoforms. Therefore, Ucerax is unlikely to impair the metabolism of drugs which are substrates for these enzymes.

As hydroxyzine is metabolized in the liver, an increase in hydroxyzine blood concentrations may be expected when hydroxyzine is co-administered with other drugs known to be potent inhibitors of liver enzymes.

Animal studies have shown reproductive toxicity.

Hydroxyzine crosses the placental barrier leading to higher fetal than maternal concentrations.

To date, no relevant epidemiological data are available relating to exposure to Ucerax during pregnancy.

In neonates whose mothers received Ucerax during late pregnancy and/or labour, the following events were observed immediately or only a few hours after birth : hypotonia, movement disorders including extrapyramidal disorders, clonic movements, CNS depression, neonatal hypoxic conditions, or urinary retention.

Therefore, Ucerax should not be used during pregnancy.

Ucerax is contra-indicated during lactation. Breast-feeding should be stopped if Ucerax therapy is needed.

Alertness or reaction time may be impaired by Ucerax therefore patients' driving capacity or ability to use machines may be reduced. Concomitant use of Ucerax with alcohol or other sedative drugs should be avoided as it aggravates these effects.

Undesirable effects are mainly related to CNS depressant or paradoxical CNS stimulation effects, to anticholinergic activity, or to hypersensitivity reactions. The following adverse reactions, in MedDRA terms, have been spontaneously reported :

Cardiac disorders :

Tachycardia NOS

Eye disorders :

Accommodation disorder, vision blurred

Gastrointestinal disorders :

Constipation, dry mouth, nausea, vomiting NOS

General disorders and administration site conditions :

Fatigue, malaise, pyrexia

Immune system disorders :

Anaphylactic shock, hypersensitivity NOS

Investigations :

Liver function tests NOS abnormal

Nervous system disorders :

Convulsions NOS, dizziness, dyskinesia NEC, headache NOS, insomnia NEC, sedation, somnolence, tremor NEC

Psychiatric disorders :

Agitation, confusion, disorientation, hallucination NOS

Renal and urinary disorders :

Urinary retention

Respiratory, thoracic and mediastinal disorders :

Bronchospasm NOS

Skin and subcutaneous tissue disorders :

Angioneurotic oedema, dermatitis NOS, pruritus NOS, rash erythematous, rash maculo-papular, sweating increased, urticaria NOS

Vascular disorders :

Hypotension NOS

Symptoms observed after an important overdose are mainly associated with excessive anticholinergic load, CNS depression or CNS paradoxical stimulation. They include nausea, vomiting, tachycardia, pyrexia, somnolence, impaired pupillary reflex, tremor, confusion, or hallucination. This may be followed by depressed level of consciousness, respiratory depression, convulsions, hypotension, or cardiac arrhythmia. Deepening coma and cardiorespiratory collapse may ensue.

Airway, breathing and circulatory status must be closely monitored with continuous ECG recording and an adequate oxygen supply should be available. Cardiac and blood pressure monitoring should be maintained until the patient is free of symptoms for 24 hours. Patients with altered mental status should be checked for simultaneous intake of other drugs or alcohol and should be given oxygen, naloxone, glucose, and thiamine if deemed necessary.

Norepinephrine or metaraminol should be used if vasopressor is needed. Epinephrine should not be used.

Syrup of ipecac should not be administered in symptomatic patients or those who could rapidly become obtunded, comatose or convulsing, as this could lead to aspiration pneumonitis. Gastric lavage with prior endotracheal intubation may be performed if a clinically significant ingestion has occurred. Activated charcoal may be left in the stomach but there are scant data to support its efficacy.

It is doubtful that hemodialysis or hemoperfusion would be of any value.

There is no specific antidote.

Literature data indicate that, in the presence of severe, life-threatening, intractable anticholinergic effects unresponsive to other agents, a therapeutic trial dose of physostigmine may be useful. Physostigmine should not be used just to keep the patient awake. If cyclic antidepressants have been coingested, use of physostigmine may precipitate seizures and intractable cardiac arrest. Also avoid physostigmine in patients with cardiac conduction defects.

Hydroxyzine is an anxiolytic compound with a rapid onset of action and a wide margin of safety. It is unrelated chemically to the phenothiazines, reserpine, meprobamate or benzodiazepines.

Its action may be due to a suppression of activity in certain key regions of the subcortical area of the CNS.

Hydroxyzine also has potent antihistaminic properties.

In man a mean maximum hydroxyzine plasma concentration of about 30 to 80 ng/ml occurs about 2 to 5 hours after single oral doses of 25 to 100 mg. The drug and its metabolites are widely distributed in the tissues. Hydroxyzine crosses the blood - brain barrier and the placental barrier. Elimination is biphasic with a terminal half-life of about 20 hours.

There is no pre-clinical data of relevance to the subscriber additional to that noted in other sections of this SPC.

Lactose monohydrate.

Microcrystalline cellulose

Magnesium stearate

Anhydrous colloidal silica

Purified water

Opadry® Y-1-7000 containing:

Titanium dioxide

Hydroxypropylmethylcellulose 2910 5cP

Macrogol 400.

None.

5 years.

Keep container in the outer pack.

Aluminium foil / PVC blister packs containing 25, 30, 50 or 60 tablets.

Not applicable.

UCB Pharma Limited

208 Bath Road

Slough

Berkshire

SL1 3WE

PL 00039/0538

16 August 2001

January 2010