Loratadine 10mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Loratadine 10mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 10 mg loratadine.
Excipient with known effect: each tablet contains 84.5 mg lactose monohydrate.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet.
White, round, biconvex film-coated tablets scored on one side and marked “LR 10” on the other side.
The tablet can be divided into equal doses.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Loratadine Tablets are indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria in adults and children over the age of 2 years with a body weight more than 30 kg.
4.2 Posology and method of administration
Posology
Adults and children over 12 years of age:
10 mg once daily (one film-coated tablet once daily).
Paediatric population
Children 2 to 12 years of age are dosed by weight:
Body weight more than 30 kg: 10mg once daily (one film-coated tablet once daily).
Body weight 30 kg or less: The 10 mg strength film-coated tablet is not appropriate in children with a body weight less than 30 kg.
Safety and efficacy of loratadine 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 10 mg every other day is recommended for adults and children weighing more than 30 kg.
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
For oral use. The tablet may be taken without regard to mealtime.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Loratadine should be administered with caution in patients with severe liver impairment (see section 4.2).
Loratadine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The administration of loratadine 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 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.
4.6 Fertility, pregnancy and lactation
Pregnancy
A large amount of data on pregnant women (more than 1000 exposed outcomes) indicate no malformative nor foeto/ 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 loratadine during pregnancy.
Breast-feeding
Loratadine is excreted in breast milk. A risk to the newborns/infants cannot be excluded. The use of loratadine is not recommended in breast-feeding women.
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 experience drowsiness, which may affect their ability to drive or use machines.
4.8 Undesirable effects
Summary of the safety profile
In clinical trials involving adults and adolescents in a range of indications including allergic rhinitis (AR) and chronic idiopathic urticaria (CIU), at the recommended dose of 10 mg daily, adverse reactions with loratadine were reported in 2% of patients in excess of those 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 by System Organ Class.
Tabulated list of adverse reactions
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.
|
System Organ Classes |
Common |
Uncommon |
Rare |
Very Rare |
|
Immune system disorders |
Hypersensitivity reactions (including angioedema and anaphylaxis) | |||
|
Nervous system disorders |
Dizziness, convulsion | |||
|
Cardiac disorders |
Tachycardia, palpitation | |||
|
Gastrointestinal disorders |
Nausea, dry mouth, gastritis | |||
|
Hepatobiliary disorders |
Abnormal hepatic function | |||
|
Skin and subcutaneous tissue disorders |
Rash, alopecia | |||
|
General disorders and administration site conditions |
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 [to be completed nationally].
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 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 Pharmacodynamic properties
Pharmacotherapeutic group: antihistamines for systemic use, ATC code: R06AX13. Mechanism of action
Loratadine, the active ingredient in Loratadine 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 or electrocardiograms.
Loratadine has no significant H2-receptor activity. It does not inhibit norepinephrine uptake and has practically no influence on cardiovascular function or no 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
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% - 99 %) and its active major metabolite desloratadine (DL) moderately bound (73% - 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 the 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 (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.
Hepatic impairment
In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (Cmax) of loratadine were doubled while the pharmacokinetic profile of the active metabolite was not significantly changed from that in patients with normal liver function. The elimination halflives for loratadine and its 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 volunteers and in healthy geriatric volunteers.
5.3 Preclinical safety data
Non-clinical 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.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core Lactose monohydrate Cellulose, microcrystalline Maize starch Starch, pregelatinised Silica colloidal hydrated Magnesium stearate
Film-coat Hypromellose Macrogol 400 and 6000 Carnauba wax Talc
6.2. Incompatibilities
Not applicable
6.3 Shelf life 3 years.
6.4 Special precautions for storage
Store in the original package.
6.5 Nature and contents of container
PVC/Aluminium blister packs.
Blister pack sizes of 5, 7, 10, 14, 15, 20, 21, 30, 50 and 100 Not all pack sizes will be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited t/a Mylan
Station Close
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom.
8 MARKETING AUTHORISATION NUMBER(S)
PL 04569/0478
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
01/08/2006
10 DATE OF REVISION OF THE TEXT
05/06/2015