Loratadine 10mg Orodispersible Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Loratadine 10 mg Orodispersible Tablets
Boots Hayfever Relief Instant-Melts 10 mg Orodispersible Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each orodispersible tablet contains 10 mg loratadine.
Excipients:
Aspartame (E951) (0.5 mg per tablet)
Lactose anhydrous (15 mg per tablet)
Sorbitol (E420) (not more than 7mg per tablet).
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Orodispersible tablet.
White, round, flat tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Loratadine 10mg Orodispersible Tablet is indicated for the symptomatic treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU).
4.2 Posology and method of administration
Loratadine 10mg Orodispersible Tablets should be handled with caution and with dry hands only.
Loratadine 10mg Orodispersible Tablets are intended for oral use.
The tablet shall be put on the tongue and wait until it is thoroughly disintegrated. Water or other liquid is not needed to swallow the dose.
The orodispersible tablet may be taken without regard to mealtime.
Adults and children over 12 years of age
10 mg once daily (one orodispersible tablet once daily).
Paediatric population
Children 2 to 12 years of age with body weight more than 30 kg: 10 mg once daily (one orodispersible tablet once daily).
The 10 mg strength orodispersible tablet is not appropriate in children with a body weight less than 30 kg.
Efficacy and safety of loratadine in children under 2 years of age has not been established.
Severe Hepatic impairment
Patients with severe hepatic 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.
Elderly or Renal impairment
No dosage adjustments are required in the elderly or in patients with renal insufficiency.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
Loratadine should be administered with caution in patients with severe hepatic impairment (see section 4.2).
This product contains lactose and sorbitol. Patients with rare hereditary problems of fructose intolerance, galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This product contains aspartame. Aspartame is a source of phenylalanine, which may be harmful for people with phenylketonuria.
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.
4.6 Pregnancy and lactation
Loratadine was not teratogenic in animal studies. The safe use of loratadine during pregnancy has not been established. The use of loratadine during pregnancy is therefore not recommended.
Loratadine is excreted in breast milk, therefore the use of loratadine is not recommended in breastfeeding women.
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
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%).
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%).
Other adverse reactions reported very rarely during the post-marketing period are listed in the following table.
Immune system disorders: Nervous system disorders: Cardiac disorders: Gastrointestinal disorders: Hepatobiliary disorders:
Skin and subcutaneous tissue
Anaphylaxis
Dizziness
Tachycardia, palpitation Nausea, dry mouth, gastritis Abnormal hepatic function Rash, alopecia
disorders:
General disorders and administration Fatigue site conditions:
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 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antihistamines - Hi antagonist, ATC code: R06A X13.
Loratadine, the active ingredient in the medicinal product, is a tricyclic antihistamine with selective, peripheral Hl-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 el ectrocardi ogram s.
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.
5.2 Pharmacokinetic properties
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 el ectrocardi ographi c).
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 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.
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
Sweet orange flavour
Aspartame (E951)
Citric acid anhydrous (E330)
Silica, colloidal anhydrous (E551)
Maize starch, dried Lactose anhydrous Magnesium stearate (E470b)
Croscarmellose sodium (E468)
Mannitol (E421)
Sorbitol (E420)
Crospovidone
Silica, colloidal hydrated (E551)
Polysorbate 80 (E433)
Povidone (E1201)
Microcrystalline cellulose (E460)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in the original package in order to protect from moisture.
6.5 Nature and contents of container
Unit dose perforated blisters (Alu/Alu).
Packs of 7x1, 14x1, 21x1, 30x1 tablets. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Sandoz Limited Frimley Business Park,
Frimley,
Camberley,
Surrey,
GU16 7SR.
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 04416/0693
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
18/11/2011
10 DATE OF REVISION OF THE TEXT
18/11/2011