Summary of medicine characteristics - ROLETRA 10 MG TABLETS
1 NAME OF THE MEDICINAL PRODUCT
Roletra 10 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
2 QUALITATIVE AND QUANTITATIVE COMPOSITIONEach tablet contains 10 mg loratadine.
Excipients with known effect:
Each tablet also contains 78.25mg lactose monohydrate.
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
3. PHARMACEUTICAL FORMTablets
White to off-white, round, uncoated tablets debossed with „R“ on one side and „10“ on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Roletra 10 mg 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 30kg.
4.2 Posology and method of administration
Posology
Adults and children over 12 years of age:
10mg once daily (one tablet once daily)
Paediatric population
Children 2 to 12 years of age are dosed by weight:
Body weight more than 30kg: 10mg once daily (one tablet once daily).
Body weight 30kg or less: The 10mg strength tablet is not appropriate in children with a body weight less than 30kg. There are other formulations more suitable for children 2 to 12 years old with body weight 30 kg or less.
Safety and efficacy of Roletra 10 mg tablets in children under 2 years of age has not been established. No data are available.
Patients with hepatic treatment
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.
Patients with renal impairment
No dosage adjustments are required in patients with renal insufficiency.
Older people
No dosage adjustments are required in older people.
Method of administration
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
Roletra 10 mg Tablets should be administered with caution in patients with severe liver impairment (see section 4.2).
The administration of Roletra 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.
This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
When administered concurrently with alcohol, loratadine has no potentiating effects as measured by psychomotor performance studies.
Loratadine is metabolised by hepatic cytochromes P450 3A4 and 2D6. 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 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 Roletra 10mg Tablets during pregnancy.
Breast-feeding
Physico-chemical data suggest excretion of loratadine/metabolites in human milk. A risk to the newborns/infants cannot be excluded. Roletra 10mg Tablets 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
Roletra 10mg tablets 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.
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 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.
| System Organ Class | Frequency | Adverse Experience Term |
| Immune system disorders | Very rare | Hypersensitivity reactions (including angioedema and anaphylaxis) |
| Nervous system disorders | Very rare | Dizziness, convulsion |
| Cardiac disorders | Very rare | Tachycardia, palpitation |
| Gastrointestinal disorders | Very rare | Nausea, dry mouth, gastritis |
| Hepatobiliary disorders | Very rare | Abnormal hepatic function |
| Skin and subcutaneous tissue disorders | Very rare | Rash, alopecia |
| General disorders and administration site conditions | Very rare | Fatigue |
| Investigations | Not known | Weight increased |
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
4.9 OverdoseOverdosage 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: antihistamines – H1 antagonist, ATC code: R06A X13.
Mechanism of action
Loratadine, the active ingredient in Roletra 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 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.
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.
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).
Distribution
Loratadine is highly bound (97% to 99%) and its active major metabolite desloratadine (DL) 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 (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 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.
Older people
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 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.
No evidence of mucous membrane irritation was observed after daily administration of up to 12 tablets (120mg) of oral lyophilisates into the hamster cheek pouch for five days.
6. PHARMACEUTICAL PARTICULARS
6.1 List of Excipients
Lactose monohydrate
Maize starch
Pregelatinised maize starch
Magnesium stearate
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
Blister strip comprising of clear transparent PVC film (coated uniformly with PVdC on the inner side) with a backing of aluminium foil (coated with heat seal lacquer).
Pack size: 7, 14, 30 tablets per pack.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
6.6 Special precautions for disposal and other handlingNo special requirements
7 MARKETING AUTHORISATION HOLDER
Ranbaxy (UK) Limited
5th floor, Hyde Park, Hayes 3
11 Millington Road
Hayes, UB3 4AZ
United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 14894/0207
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
21/04/2010