SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Loratadine 10mg tablets

Vantage Allergy Relief 10 mg tablets

Tesco one a day Hayfever & Allergy 10mg tablets

Haylief Hayfever & Allergy 10mg tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10mg loratadine.

For excipients see 6.1.

3    PHARMACEUTICAL FORM

Tablet.

Appearance: white, round, flat tablets with a scoreline.

4 CLINICAL PARTICULARS

Therapeutic indications

Loratadine 10 mg Tablets is indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

4.2 Posology and method of administration

Adults, including the elderly, and children 12 years of age and over:

One 10 mg tablet once daily

Children 2 to 12 years of age with:

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

Body weight 30 kg or less: 5 ml (5 mg) of the syrup once daily. The 10 mg strength tablet is not appropriate in children with a body weight less than 30 kg.

Efficacy and safety of Loratadine 10 mg Tablets in children under 2 years of age has not been established in this age group.

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, and for children weighing 30 kg or less, 5 ml (5 mg) every other day is recommended.

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

4.3 Contraindications

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

4.4 Special warnings and precautions for use

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

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

The administration of Loratadine 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.

4.5 Interaction with other medicinal products and other forms of interaction

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

Due to the wide therapeutic index of loratadine no clinically relevant interactions are expected and none were observed in the conducted clinical trials (see 5.2).

Loratadine is metabolised by hepatic CYP3A4 and CYP2D6 isoenzymes. 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).

Paediatric population

Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation

Pregnancy

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

Breast-feeding

Physico-chemical data suggest excretion of loratadine/metabolites in human milk. A risk to the newborns/infants cannot be excluded. Loratadine should not be used during breast-feeding.

Fertility

There are no data available on male and female fertility.

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 rarely experience drowsiness, which may affect their ability to drive or use machines.

4.8 Undesirable effects

In clinical trials involving adults and adolescents in a range of indications including AR and CIU, 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%).

Tabulated list of adverse reactions

The following adverse reactions reported during the post-marketing period are listed in the following table by System Organ Class. 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) and not known (cannot be estimated from the available data).

System organ class	Frequency	Adverse Experience Term
Immune disorders	Very rare	Anaphylaxis
Nervous system disorders	Very rare	Dizziness
Cardiac disorders	Very rare	Tachycardia, palpitation
Gastrointestinal disorders	Very rare	Nausea, dry mouth, gastritis
Hepato-biliary disorders	Very rare	Abnormal hepatic function

Skin and subcutaneous tissue disorders	Very rare	Rash, alopecia
General disorders and administration site conditions	Very rare	Fatigue

Paediatric population

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%).

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, website www.mhra.gov.uk/yellowcard.

4.9 Overdose

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

In the event of overdose, 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: antihistamines - H1 antagonist, ATC code R06A X13

Mechanism of action

Loratadine the active ingredient in Loratadine 10 mg Tablets is a tricyclic antihistamine with selective, peripheral H1 receptor activity.

Pharmacodynamic effects

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 of electrocardiograms.

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

Human histamine skin wheal studies following a single 10 mg dose has shown that the antihistamine effects are seen within 1-3 hours reaching a peak at 8-12 hours and lasting in excess of 24 hours. There was no evidence of tolerance to this effect after 28 days of dosing with loratadine.

Clinical efficacy and safety

Over 10,000 subjects (12 years and older) have been treated with loratadine 10 mg tablets in controlled clinical trials. Loratadine 10 mg tablets once daily was superior to placebo and similar to clemastine in improving the effects on nasal and non-nasal symptoms of AR. In these studies somnolence occurred less frequently with loratadine than with clemastine and about the same frequency as terfenadine and placebo.

Among these subjects (12 years and older), 1000 subjects with CIU were enrolled in placebo controlled studies. A once daily 10 mg dose of loratadine was superior to placebo in the management of CIU as demonstrated by the reduction of associated itching, erythema and hives. In these studies the incidence of somnolence with loratadine was similar to placebo.

Paediatric population

Approximately 200 paediatric subjects (6 to 12 years of age) with seasonal allergic rhinitis received doses of loratadine syrup up to 10 mg once daily in controlled clinical trials. In another study, 60 paediatric subjects (2 to 5 years of age) received 5 mg of loratadine syrup once daily. No unexpected adverse events were observed.

The paediatric efficacy was similar to the efficacy observed in adults.

5.2 Pharmacokinetic properties

After oral administration, loratadine is rapidly and well and undergoes an extensive first pass metabolism, mainly by CYP 3A4 and CYP 2D6. The major metabolite -desloratadine (DL) - is pharmacologically active and responsible for a large part of clinical effect. Loratadine and DL achieve maximum plasma concentrations (T_max) 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 electrocardiography).

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

In healthy subjects, plasma distribution half-lives for loratadine and its active metabolite are approximately 1 and 2 hours, respectively. The mean elimination halflives 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 (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 healthy geriatric volunteers.

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

In patients with chronic renal impairment, both the AUC and the peak plasma levels (Cmax) increased for loratadine and its metabolite as compared with the AUCs and C_max 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 pharmacokinetic profile of loratadine or its active metabolite in subjects with chronic renal impairment.

In patients with chronic alcoholic liver disease, the AUC and C_max 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 at plasma levels (AUC) 10 times higher than those achieved with clinical doses.

No evidence of mucous membrane irritation was observed after daily administration of up to 12 tablets (120 mg) of oral lyophilisates into the hamster cheek pouch for five days.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose monohydrate Microcrystalline cellulose Maize starch Magnesium stearate

6.2    Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

None

6.5 Nature and contents of container

Packages with 7, 10, 14, 20, 30, 50, 60 and 100 tablets in (PVC/aluminium)

6.6 Special precautions for disposal

No special instructions

7    MARKETING AUTHORISATION HOLDER

Relonchem Limited, Cheshire House, Gorsey lane, Widnes,

Cheshire,

WA8 0RP,

UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 20395/0072

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22^nd August 2002

DATE OF REVISION OF THE TEXT

14/04/2015