Antihistamines (sedating).

Hydroxyzine - allergy

Hydroxyzine hydrochloride 25 mg.

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.

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 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. 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.

The concomitant use of alcohol and Ucerax should be avoided.

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 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.

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. Pregnancy and lactation: 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.

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

UCB Pharma

(POM)

27 March 2009