1.1   IRIS^® Syrup is indicated in adults, adolescents and children over the age of 1 year for the relief of symptoms associated with:

-          Allergic rhinitis

-          Urticaria

1.1   Route of administration: Orally.

Posology:

Adults and adolescents 12 years of age and over

The recommended dose of IRIS^® Syrup is 10 ml (5 mg) syrup once a day.

Paediatric population

The prescriber should be aware that most cases of rhinitis below 2 years of age are of infectious origin and there are no data supporting the treatment of infectious rhinitis with Desloratadine.

Children 1 through 5 years of age: 2.5 ml (1.25 mg) IRIS^® Syrup once a day.

Children 6 through 11 years of age: 5 ml (2.5 mg) IRIS^® Syrup once a day.

The safety and efficacy of Desloratadine 0.5 mg/ml syrup in children below the age of 1 year have not been established. No data are available.

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.

The dose can be taken with or without food.

Paediatric population

In children below 2 years of age, the diagnosis of allergic rhinitis is particularly difficult to distinguish from other forms of rhinitis. The absence of upper respiratory tract infection or structural abnormalities, as well as patient history, physical examinations, and appropriate laboratory and skin tests should be considered.

Approximately 6 % of adults and children 2- to 11-year old are phenotypic poor metabolisers of desloratadine and exhibit a higher exposure. The safety of desloratadine in children 2- to 11-years of age who are poor metabolisers is the same as in children who are normal metabolisers. The effects of desloratadine in poor metabolisers < 2 years of age have not been studied.

In the case of severe renal insufficiency, Desloratadine should be used with caution.

This medicinal product contains sorbitol; thus, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

 No clinically relevant interactions were observed with desloratadine tablets when erythromycin or ketoconazole were co-administered.

Paediatric population

Interaction studies have only been performed in adults.

However, cases of alcohol intolerance and intoxication have been reported during post-marketing use. Therefore, caution is recommended if alcohol is taken concomitantly.

Desloratadine tablets observed when taken concomitantly with alcohol did not potentiate the performance impairing effects of alcohol. However, cases of alcohol intolerance and intoxication have been reported during post-marketing use. Therefore, caution is recommended if alcohol is taken concomitantly.

 Pregnancy

As a precautionary measure, it is preferable to avoid the use of Desloratadine during pregnancy.

Breast-feeding

Desloratadine has been identified in breastfed newborns/infants of treated women. The effect of desloratadine on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Desloratadine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

  IRIS^® Syrup has no or negligible influence on the ability to drive and use machines. Patients should be informed that most people do not experience drowsiness. Nevertheless, as there is individual

variation in response to all medicinal products, it is recommended that patients are advised not to

engage in activities requiring mental alertness, such as driving a car or using machines, until they have established their own response to the medicinal product.

1.1   The frequency of undesirable effects reported are listed in the following table. 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).

Paediatric population

Other undesirable effects reported during the post-marketing period in paediatric patients with an unknown frequency included QT prolongation, arrhythmia, and bradycardia.

To report any side effect(s):

·      Saudi Arabia:

- Other GCC States:

 The adverse event profile associated with overdosage, as seen during post-marketing use, is similar to that seen with therapeutic doses, but the magnitude of the effects can be higher.

Treatment

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

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

Symptoms

In adults and adolescents, in which up to 45 mg of desloratadine was administered no clinically relevant effects were observed.

1.1   Pharmacotherapeutic group: antihistamines – H1 antagonist, 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.

Desloratadine has demonstrated antiallergic 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

Paediatric population

Treatment was well tolerated as documented by clinical laboratory tests, vital signs, and ECG interval data, including QTc. When given at the recommended doses, the plasma concentrations of desloratadine were comparable in the paediatric and adult populations. Thus, since the course of allergic rhinitis/chronic idiopathic urticaria and the profile of desloratadine are similar in adults and paediatric patients, desloratadine efficacy data in adults can be extrapolated to the paediatric population.

Efficacy of Desloratadine syrup has not been investigated in paediatric trials in children less than 12 years of age.

Adults and adolescents

Desloratadine does not readily penetrate the central nervous system. The recommended dose of 5 mg daily for adults and adolescents, there was no excess incidence of somnolence.

Desloratadine tablets given at a single daily dose of 7.5 mg to adults and adolescents did not affect psychomotor performance in adults, desloratadine 5 mg did not affect standard measures of flight performance including exacerbation of subjective sleepiness or tasks related to flying.

In adults, co-administration with alcohol did not increase the alcohol-induced impairment in performance or increase in sleepiness.

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

In adult and adolescent patients with allergic rhinitis, Desloratadine tablets were 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.

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 tablets were 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 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 patients with chronic idiopathic urticaria, Desloratadine was effective in relieving pruritus In chronic idiopathic urticaria, the minority of patients who were identified as non-responsive to antihistamines was excluded. An improvement in pruritus was observed in patients treated with Desloratadine. Treatment with Desloratadine also significantly reduced interference with sleep and daytime function, as measured by a four-point scale used to assess these variables.

Absorption

Desloratadine plasma concentrations can be detected within 30 minutes of desloratadine administration in adults and adolescents. 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.

Distribution

Desloratadine is moderately bound (83 % - 87 %) to plasma proteins. There is no evidence of clinically relevant active substance accumulation following once daily adult and adolescent 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 cannot be fully excluded. Desloratadine does not inhibit CYP3A4 in vivo.

Elimination

There was no effect of food (high-fat, high caloric breakfast) on the disposition of Desloratadine. Grapefruit juice had no effect on the disposition of desloratadine.

Renal impaired patients

Changes in exposure (AUC and Cmax) of desloratadine and 3-hydroxydesloratadine were not clinically relevant.

Not applicable.

-          Citric Acid monohydrate,

-          Tri-Sodium Citrate,

-          Propylene Glycol,

-          Sorbitol Solution 70%,

-          Sucrose,

-          Sodium Benzoate,

-          Disodium Ethylene Di-amine Tetra Acetic Acid (EDTA),

-          Tutti Frutti liquid flavor ,

-          Spectracol FD & C yellow no. 6,

-          Purified water.

Not applicable.

Store below 30° C.

IRIS^® Syrup are packed in amber glass bottles (100 ml) (glass type III),with white, cylindrical, polypropylene inner and outer caps, low density polyethylene ring and insert (child resistant), then with a colored adhesive label and a multi folded leaflet packed in cardboard cartons.

Pack size: 100 ml/bottle.

Any unused product or waste should be disposed of in accordance with local requirements.