SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Desloratadine Sandoz 5 mg Film Coated Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 5 mg desloratadine.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet.

Light blue, round shaped,biconvex film coated tablets, with “5” debossed on one side. Diameter 6.50 ± 0.10 mm.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Desloratadine is indicated for the relief of symptoms associated with:

-    allergic rhinitis (see section 5.1)

-    urticaria (see section 5.1)

4.2    Posology and method of administration

Adults and adolescents (12 years of age and over): one tablet once a day, with or without a meal for the relief of symptoms associated with allergic rhinitis (including intermittent and persistent allergic rhinitis) and urticaria (see section 5.1).

There is limited clinical trial efficacy experience with the use of desloratadine in adolescents 12 through 17 years of age (see sections 4.8 and 5.1).

Intermittent allergic rhinitis (presence of symptoms for less than 4 days per week or for less than 4 weeks) should be managed in accordance with the evaluation of patient’s disease history and the treatment could be discontinued after symptoms are resolved and reinitiated upon their reappearance.

In persistent allergic rhinitis (presence of symptoms for 4 days or more per week and for more than 4 weeks), continued treatment may be proposed to the patients during the allergen exposure periods.

4.3 Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to loratadine.

4.4 Special warnings and precautions for use

Efficacy and safety of desloratadine tablets in children under 12 years of age have not been established.

In the case of severe renal insufficiency, desloratadine should be used with caution (see section 5.2).

4.5 Interaction with other medicinal products and other forms of interaction

No clinically relevant interactions were observed in clinical trials with desloratadine tablets in which erythromycin or ketoconazole were co-administered (see section 5.1).

In a clinical pharmacology trial desloratadine taken concomitantly with alcohol did not potentiate the performance impairing effects of alcohol (see section 5.1).

4.6 Fertility, Pregnancy and lactation

Desloratadine was not teratogenic in animal studies. The safe use of the medicinal product during pregnancy has not been established. The use of desloratadine during pregnancy is therefore not recommended.

Desloratadine is excreted into breast milk, therefore the use of desloratadine is not recommended in breastfeeding women.

Effects on ability to drive and use machines

In clinical trials that assessed the driving ability, no impairment occurred in patients receiving desloratadine. 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 range of indications including allergic rhinitis and chronic idiopathic urticaria, at the recommended dose of 5 mg daily, undesirable effects with desloratadine were reported in 3 % of patients in excess of those treated with placebo. The most frequent of adverse events reported in excess of placebo were fatigue (1.2 %), dry mouth (0.8 %) and headache (0.6 %). In a clinical trial with 578 adolescent patients, 12 through 17 years of age, the most common adverse event was headache; this occurred in 5.9 % of patients treated with desloratadine and 6.9 % of patients receiving placebo.

Other undesirable effects reported very rarely during the post-marketing period are listed in the following table.

Psychiatric disorders	Hallucinations
Nervous system disorders	Dizziness, somnolence, insomnia, psychomotor hyperactivity, seizures
Cardiac disorders	Tachycardia, palpitations
Gastrointestinal disorders	Abdominal pain, nausea, vomiting, dyspepsia, diarrhoea
Hepatobiliary disorders	Elevations of liver enzymes, increased bilirubin, hepatitis
Musculoskeletal and connective tissue disorders	Myalgia
General disorders	Hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, pruritus, rash, and urticaria)

4.9 Overdose

In the event of overdose, consider standard measures to remove unabsorbed active substance. Symptomatic and supportive treatment is recommended.

Based on a multiple dose clinical trial, in which up to 45 mg of desloratadine was administered (nine times the clinical dose), no clinically relevant effects were observed.

Desloratadine is not eliminated by haemodialysis; it is not known if it is eliminated by peritoneal dialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other antihistamines for systemic use, ATC code: R06A X27

Mechanism of action

Desloratadine is a non-sedating, long-acting histamine antagonist with selective peripheral H₁-receptor antagonist activity. After oral administration, desloratadine selectively blocks peripheral histamine H₁- receptors because the substance is excluded from entry to the central nervous system.

Pharmacodynamic effects

Desloratadine has demonstrated antiallergic properties from in vitro studies. These include inhibiting the release of proinflammatory cytokines such as IL-4, IL-6, IL-8, and IL-13 from human mast cells/basophils, as well as inhibition of the expression of the adhesion molecule P-selectin on endothelial cells. The clinical relevance of these observations remains to be confirmed.

Clinical efficacy and safety

In a multiple dose clinical trial, in which up to 20 mg of desloratadine was administered daily for 14 days, no statistically or clinically relevant cardiovascular effect was observed. In a clinical pharmacology trial, in which desloratadine was administered at a dose of 45 mg daily (nine times the clinical dose) for ten days, no prolongation of QTc interval was seen.

No clinically relevant changes in desloratadine plasma concentrations were observed in multiple-dose ketoconazole and erythromycin interaction trials.

Desloratadine does not readily penetrate the central nervous system. In controlled clinical trials, at the recommended dose of 5 mg daily, there was no excess incidence of somnolence as compared to placebo. Desloratadine given at a single daily dose of 7.5 mg did not affect psychomotor performance in clinical trials. In a single dose study performed in adults, desloratadine 5 mg did not affect standard measures of flight performance including exacerbation of subjective sleepiness or tasks related to flying.

In clinical pharmacology trials, co-administration with alcohol did not increase the alcohol-induced impairment in performance or increase in sleepiness. No significant differences were found in the psychomotor test results between desloratadine and placebo groups, whether administered alone or with alcohol.

In patients with allergic rhinitis, desloratadine was effective in relieving symptoms such as sneezing, nasal discharge and itching, as well as ocular itching, tearing and redness, and itching of palate. Desloratadine effectively controlled symptoms for 24 hours. The efficacy of desloratadine tablets has not been clearly demonstrated in trials with adolescent patients 12 through 17 years of age.

In addition to the established classifications of seasonal and perennial, allergic rhinitis can alternatively be classified as intermittent allergic rhinitis and persistent allergic rhinitis according to the duration of symptoms. Intermittent allergic rhinitis is defined as the presence of symptoms for less than 4 days per week or for less than 4 weeks. Persistent allergic rhinitis is defined as the presence of symptoms for 4 days or more per week and for more than 4 weeks.

Desloratadine was effective in alleviating the burden of seasonal allergic rhinitis as shown by the total score of the rhino-conjunctivitis quality of life questionnaire. The greatest amelioration was seen in the domains of practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria was studied as a clinical model for urticarial conditions, since the underlying pathophysiology is similar, regardless of etiology, and because chronic patients can be more easily recruited prospectively. Since histamine release is a causal factor in all urticarial diseases, desloratadine is expected to be effective in providing symptomatic relief for other urticarial conditions, in addition to chronic idiopathic urticaria, as advised in clinical guidelines.

In two placebo-controlled six week trials in patients with chronic idiopathic urticaria, desloratadine was effective in relieving pruritus and decreasing the size and number of hives by the end of the first dosing interval. In each trial, the effects were sustained over the 24 hour dosing interval. As with other antihistamine trials in chronic idiopathic urticaria, the minority of patients who were identified as nonresponsive to antihistamines was excluded. An improvement in pruritus of more than 50 % was observed in 55 % of patients treated with desloratadine compared with 19 % of patients treated with placebo. Treatment with desloratadine also significantly reduced interference with sleep and daytime function, as measured by a four-point scale used to assess these variables.

5.2 Pharmacokinetic properties

Absorption

Desloratadine plasma concentrations can be detected within 30 minutes of administration. Desloratadine is well absorbed with maximum concentration achieved after approximately 3 hours; the terminal phase half-life is approximately 27 hours.

The degree of accumulation of desloratadine was consistent with its half-life (approximately 27 hours) and a once daily dosing frequency. The bioavailability of desloratadine was dose proportional over the range of 5 mg to 20 mg.

In a pharmacokinetic trial in which patient demographics were comparable to those of the general seasonal allergic rhinitis population, 4 % of the subjects achieved a higher concentration of desloratadine. This percentage may vary according to ethnic background. Maximum desloratadine concentration was about 3-fold higher at approximately 7 hours with a terminal phase half-life of approximately 89 hours. The safety profile of these subjects was not different from that of the general population.

Distribution

Desloratadine is moderately bound (83 % - 87 %) to plasma proteins. There is no evidence of clinically relevant medicine accumulation following once daily dosing of desloratadine (5 mg to 20 mg) for 14 days.

Biotransformation

The enzyme responsible for the metabolism of desloratadine has not been identified yet, and therefore, some interactions with other medicinal products can not be fully excluded. Desloratadine does not inhibit CYP3A4 in vivo, and in vitro studies have shown that the medicinal product does not inhibit CYP2D6 and is neither a substrate nor an inhibitor of P-glycoprotein.

In a single dose trial using a 7.5 mg dose of desloratadine, there was no effect of food (high-fat, high caloric breakfast) on the disposition of desloratadine. In another study, grapefruit juice had no effect on the disposition of desloratadine.

5.3 Preclinical safety data

Desloratadine is the primary active metabolite of loratadine. Non-clinical studies conducted with desloratadine and loratadine demonstrated that there are no qualitative or quantitative differences in the toxicity profile of desloratadine and loratadine at comparable levels of exposure to desloratadine.

Non-clinical data with desloratadine reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction. The lack of carcinogenic potential was demonstrated in studies conducted with desloratadine and loratadine.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Film-coated tablet core:

Maize starch

Cellulose, microcrystalline Hypromellose Silica, Colloidal anhydrous Hydrogenated vegetable oil (Type 1)

Film-coated tablet Coating:

Opadry Blue 03B50689 (Hypromellose E464, Titanium dioxide E171, Macrogol 400 E1521, Indigo Carmine Aluminum Lake E132)

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years

6.4    Special precautions for    storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of    container

Desloratadine is supplied in blister pack comprising of OPA/ ALU/ PVC/ ALU and in blister pack comprising of PVC/ Aclar/ ALU

Pack sizes (unit dose):

1, 2, 3, 5, 7, 10, 14, 15, 20, 21, 30, 50, 90 and 100 film coated tablets

Not all pack sizes may be marketed.

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 04416/1227

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

17/04/2012

10    DATE OF REVISION OF THE TEXT

17/04/2012