SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Ultarin 10 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10 mg loratadine.

Each Ultarin 10 mg tablet contains 72.50 mg of lactose monohydrate (see section 4.4).

For a full list of excipients, see 6.1.

3 PHARMACEUTICAL FORM

Tablets

White coloured, circular, flat beveled uncoated tablets, with central breakline on one side and L on the other side.

The central break line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Ultarin 10 mg Tablets are indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria

4.2 Posology and method of administration

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

The tablet may be taken without regard to mealtime.

Children 2 to 12 years of age with:

Body weight more than 30 kg: 10 mg once daily (one tablet once daily).

The 10 mg strength tablet is not appropriate in children with a body weight less than 30 kg.

Efficacy and safety of Ultarin 10 mg Tablets in children under 2 years of age has not been established. The use is therefore not recommended in these patients.

Patients with severe liver impairment should be administered a lower initial dose because they may have reduced clearance of loratadine. An initial dose of 10 mg every other day is recommended for adults and children weighing more than 30 kg.

No dosage adjustments are required in the elderly or in patients with renal insufficiency.

4.3 Contraindications

Ultarin 10 mg Tablets are contraindicated in patients who are hypersensitive to the active substance or to any of the excipients in these formulations.

In children under 2 years (see section 4.2).

During pregnancy or lactation (see section 4.6)

4.4 Special warnings and precautions for use

Ultarin 10 mg Tablets should be administered with caution in patients with severe liver impairment (see Section 4.2).

The administration of Ultarin 10 mg Tablets should be discontinued at least 48 hours before skin tests since antihistamines may prevent or reduce otherwise positive reactions to dermal reactivity index.

These tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

There are no significant interactions between loratadine and food.

4.5 Interaction with other medicinal products and other forms of interaction

When administered concomitantly with alcohol, Ultarin 10 mg Tablets has no potentiating effects as measured by psychomotor performance studies.

Potential interaction may occur with all known inhibitors of CYP3A4 or CYP2D6 resulting in elevated levels of loratadine (see section 5.2), which may cause an increase in adverse events.

4.6 Fertility, pregnancy and lactation

Loratadine was not teratogenic in animal studies. The safe use of loratadine during pregnancy has not been established. The use of Ultarin 10 mg Tablets during pregnancy is therefore not recommended.

Loratadine is excreted in breast milk, therefore the use of loratadine is not recommended in breast-feeding women.

4.7 Effects on ability to drive and use machines

In clinical trials that assessed driving ability, no impairment occurred in patients receiving loratadine. However, patients should be informed that very rarely some people experience drowsiness, which may affect their ability to drive or use machines.

4.8 Undesirable effects

In clinical trials in a paediatric population children aged 2 through 12 years, common adverse reactions reported in excess of placebo were headache (2.7%), nervousness (2.3%), and fatigue (1%).

In clinical trials involving adults and adolescents in a range of indications including allergic rhinitis and chronic idiopathic urticaria, at the recommended dose of 10 mg daily, adverse reactions with loratadine were reported in 2% of patients in excess of those treated with placebo. The most frequent adverse reactions reported in excess of placebo were somnolence (1.2%), headache (0.6%), increased appetite (0.5%) and insomnia (0.1%). Other adverse reactions reported very rarely during the post marketing period are listed in the following table.

Immune system disorders

Nervous system disorders

Eye disorders

Cardiac disorders

Gastrointestinal disorders

Hepato-biliary disorders

Skin and subcutaneous tissue disorders

General disorders and administration site condition

4.9 Overdose

Overdosage with loratadine increased the occurrence of anticholinergic symptoms. Somnolence, tachycardia, and headache have been reported with overdoses.

In the event of overdosage, general symptomatic and supportive measures are to be instituted and maintained for as long as necessary. Administration of activated charcoal as a slurry with water may be attempted. Gastric lavage may be considered. Loratadine is not removed by haemodialysis and it is not known if loratadine is removed by peritoneal dialysis. Medical monitoring of the patient is to be continued after emergency treatment.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Other antihistamines for systemic use ATC code: R06A X13

Loratadine is a tricyclic antihistamine with selective, peripheral H1 -receptor activity.

Loratadine has no clinically significant sedative or anticholinergic properties in the majority of the population and when used at the recommended dosage.

During long-term treatment there were no clinically significant changes in vital signs, laboratory test values, physical examinations or electrocardiograms.

Loratadine has no significant H2 -receptor activity. It does not inhibit norepinephrine uptake and has practically no influence on cardiovascular function or on intrinsic cardiac pacemaker activity.

5.2 Pharmacokinetic properties

After oral administration, loratadine is rapidly and well absorbed and undergoes an extensive first pass metabolism, mainly by CYP3A4 and CYP2D6. The major metabolite-desloratadine (DL) - is pharmacologically active and responsible for a large part of the clinical effect. Loratadine and DL achieve maximum plasma concentrations (Tmax) between 1-1.5 hours and 1.5-3.7 hours after administration, respectively.

Increase in plasma concentrations of loratadine has been reported after concomitant use with ketoconazole, erythromycin, and cimetidine in controlled trials, but without clinically significant changes (including electrocardiographic).

Loratadine is highly bound (97% to 99%) and its active metabolite moderately bound (73% to 76%) to plasma proteins.

In healthy subjects, plasma distribution half-lives of loratadine and its active metabolite are approximately 1 and 2 hours, respectively. The mean elimination half lives in healthy adult subjects were 8.4 hours (range = 3 to 20 hours) for loratadine and 28 hours (range = 8.8 to 92 hours) for the major active metabolite.

Approximately 40% of the dose is excreted in the urine and 42% in the faeces over a 10 day period and mainly in the form of conjugated metabolites. Approximately 27% of the dose is eliminated in the urine during the first 24 hours. Less than 1% of the active substance is excreted unchanged in active form, as loratadine or DL.

The bioavailability parameters of loratadine and of the active metabolite are dose proportional.

The pharmacokinetic profile of loratadine and its metabolites is comparable in healthy adult volunteers and in healthy geriatric volunteers.

Concomitant ingestion of food can delay slightly the absorption of loratadine but without influencing the clinical effect.

In patients with chronic renal impairment, both the AUC and peak plasma levels (Cmax) increased for loratadine and its metabolite as compared to the AUCs and peak plasma levels

(Cmax) of patients with normal renal function. The mean elimination half-lives of loratadine and its metabolite were not significantly different from that observed in normal subjects. Haemodialysis does not have an effect on the pharmacokinetics of loratadine or its active metabolite in subjects with chronic renal impairment.

In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (Cmax) of loratadine were double while the pharmacokinetic profile of the active metabolite was not significantly changed from that in patients with normal liver function. The elimination half-lives for loratadine and its metabolite were 24 hours and 37 hours, respectively, and increased with increasing severity of liver disease.

Loratadine and its active metabolite are excreted in the breast milk of lactating women.

5.3 Preclinical safety data

Preclinical data reveal no special hazard based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproductive toxicity studies, no teratogenic effects were observed. However, prolonged parturition and reduced viability of offspring were observed in rats a plasma levels (AUC) 10 times higher than those achieved with clinical doses

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate

Maize starch

Silica, colloidal anhydrous Croscarmellose sodium Talc

Magnesium stearate

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

Store in the original package.

6.5 Nature and contents of container

Blister strips comprising of clear PVC film with aluminium backing (with VMCH coating) containing 7, 14 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

APTIL Pharma Limited 9th Floor, CP House 97 - 107 Uxbridge Road Ealing, London W5 5TL

8    MARKETING AUTHORISATION NUMBER(S)

PL 40378/0160

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/02/2013

10    DATE OF REVISION OF THE TEXT

01/02/2013