Lorine is indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

For Lorine tablet:

Adults and children 6 years of age and older with a body weight greater than 30 kg:

10mg once daily (one tablet once daily).

Patients with severe liver impairment should be administered a lower initial dose because they have reduced clearance of loratadine. An initial dose of 10 mg of tablet every other day is recommended for adults and children 6 years of age and older with a bodyweight greater than 30 kg.

The tablet may be taken without regard to mealtime.

For Lorine syrup:

Adults and children over 12 years:

2 x 5 ml spoonfuls 10ml (10mg) of the syrup once daily.

Children of 2 to 12 years who weigh more than 30 kg:

2 x 5ml spoonfuls 10ml (10mg) of the syrup once daily.

Children of 2 to 12 years who weigh 30kg or less:

1 x 5ml spoonful (5mg) of the syrup once daily.

Patients with severe liver impairment should be administered a lower initial dose because they have reduced clearance of loratadine. Adults and children with a body weight above 30 kg should take 2 x 5ml spoonfuls 10 ml (10 mg) of syrup once every two days. Adults and children with a body weight 30 kg or less should take 1 x 5ml spoonful (5mg) of syrup once every two days.

The syrup may be taken without regard to mealtime.

The 10mg strength tablet is not appropriate in children younger than 6 years or who weigh 30 kg or less.

Efficacy and safety of Lorine in children under 2 years of age has not been established. No dosage adjustments are required in the elderly or in patients with renal insufficiency.

Lorine Tablets should be administered with caution in patients with severe liver impairment (see section 4.2).

Lorine tablets contain lactose; thus patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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

When administered concomitantly with alcohol, Lorine Tablets have 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.

Loratadine was not teratogenic in animal studies. The safe use of loratadine during pregnancy has not been established. The use of Lorine 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.

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.

4.3  In clinical trials in a paediatric population, children aged 6 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 AR and CIU, at the recommended dose of 10mg daily, adverse reactions with loratadine were reported in 2% of patients in excess of those treated with placebo. The most frequent adverse events 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.

Overdosage with loratadine increased the occurrence of anticholinergic 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.

5.1  Pharmacotherapeutic group: antihistamines – H1 antagonist, ATC code: R06A X13.

Loratadine, the active ingredient in Lorine, 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.

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 the 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.

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.

·       Lorine tablets: maize starch, lactose, magnesium stearate.

·       Lorine syrup: citric acid monohydrate, peach flavour, glycerol, propylene glycol, sodium benzoate, sucrose granular and purified water.

Do not store above 30° C. Protect from excessive moisture.

Lorine tablets:

·  Blister Strip Transparent thermoforming PVDC/PVC 250 micron, Hard tempered aluminium foil 20 micron.

·     Carton: End opening unit carton with hot melt-glued flaps.

Lorine syrup:

·      Bottle: 100 ml amber glass bottle.

·      Cap: Child Resistant Cap (CRC).

·      Carton: End opening unit carton with reverse tuck flaps and locking slits.

None