Lorahist Syrup is indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria in adults and children over the age of 2 years

Adults and children over 12 years of age

10ml (10mg) of the syrup once daily

Paediatric population

Children 2 to 12 years of age are dosed by weight

Body weight more than 30kg : 10ml (10mg) of the syrup once daily

Body weight 30kg or less: 5ml (5mg) of the syrup once daily

The safety and efficacy of Lorahist Syrup in children under 2 years of age has not been established. No data are available

Patients with hepatic impairment

Patients with severe liver impairment should be administered a lower initial dose because they may have reduced clearance of loratadine. An initial dose of 10mg every other day is recommended for adults and children weighing more than 30kg and for children weighing 30kg or less, 5ml (5mg) every other day is recommended

Patients with renal impairment

No dosage adjustments are required in patients with renal insufficiency

Elderly

No dosage adjustments are required in the elderly

Method of administration

Oral use. The syrup may be taken without regard to meal time

Lorahist Syrup should be administered with caution in patients with severe liver impairment (see section 4.2). This medicinal product contains sucrose; thus patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrose isomaltase insufficiency should not take this medicine. The administration of Lorahist Syrup 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, Lorahist Syrup 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

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

Pregnancy

A large amount of data on pregnant women (more than 1000 exposed outcomes) indicate no malformative nor feto/ neonatal toxicity of loratadine Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Lorahist Syrup during pregnancy

Breast-feeding

Loratadine is excreted in breast milk. Therefore, the use of Lorahist Syrup is not recommended in breast-feeding women

Fertility

There are no data available on male and female fertility

In clinical trials that assessed driving ability, no impairment was observed in patients receiving loratadine. Lorahist Syrup has no or negligible influence on the ability to drive and use machines. However, patients should be informed that very rarely some people experience drowsiness, which may affect their ability to drive or use machines

Summary of the safety profile

In clinical trials involving adults and adolescents in a range of indications including allergic rhinitis (AR) and chronic idiopathic urticarial (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 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)

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness

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

( National Pharmacovigilance and Drug Safety Center (NPC

• Fax: +966-11-205-7662
• To contact national Pharmacovigilance management: +966-11-2038222 ext.: 2353 – 2356 – 2317 – 2354 – 2334 – 2340
• Toll-free: 8002490000
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc

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

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

Mechanism of action

Loratadine, the active ingredient in Lorahist Syrup, 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 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

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

Absorption

Loratadine is rapidly and well-absorbed. Concomitant ingestion of food can delay slightly the absorption of loratadine but without influencing the clinical effect. The bioavailability parameters of loratadine and of the active metabolite are dose proportional

Distribution

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

Biotransformation

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

Elimination

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 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

Renal impairment

In patients with chronic renal impairment, both the AUC and peak plasma levels (C_max) increased for loratadine and its active metabolite as compared to the AUCs and peak plasma levels (C_max) of patients with normal renal function. The mean elimination half-lives of loratadine and its active 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

Hepatic impairment

In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (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 active metabolite were 24 hours and 37 hours, respectively, and increased with increasing severity of liver disease

Elderly

The pharmacokinetic profile of loratadine and its active metabolite is comparable in healthy adult volunteers and in healthy geriatric volunteers

Non-clinical data reveal no special hazard for humans 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

Sucrose

Sodium Benzoate

Propylene glycol

Glycerol

Citric Acid Monohydrate

Strawberry Flavour

Purified Water

None Known

Do not store above 30°C

Keep in the original container to protect from light

Once the pack has been opened, the content should be used within 28 days

100ml Amber glass bottle with 28mm white plastic cap

Keep all medicine out of reach and sight of children