FREBRES

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FREEBRIS (FREEBRIS)

Composition:

Active substance: desloratadine;

5 ml of syrup contains 2.5 mg of desloratadine;

Excipients: sucrose, disodium edetate, sodium benzoate (E 211), propylene glycol, glycerin, citric acid monohydrate, sodium citrate, colouring agent: sunset yellow (E 110), fruit flavouring, purified water.

Pharmaceutical form. Syrup.

Main physicochemical characteristics: a clear syrup-like liquid of yellow-orange colour with a fruity odour.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X27.

Pharmacological properties.

Desloratadine is a selective blocker of peripheral histamine H1-receptors and does not exhibit sedative effects. Desloratadine is the principal active metabolite of loratadine. Desloratadine also exerts antiallergic and anti-inflammatory effects by inhibiting histamine release from mast cells.

Desloratadine selectively blocks peripheral H1-histamine receptors and does not cross the blood-brain barrier, as demonstrated by tissue distribution studies of radiolabeled compounds in rats and radioligand H1-receptor binding studies in guinea pigs. Due to desloratadine's ability to bind to the histamine receptor at concentrations as low as 2–3 ng/mL (7 nmol), it has high affinity for human H1 receptors.

Desloratadine suppresses multiple cytotoxic reactions underlying the development of allergic inflammation, including the release of proinflammatory cytokines such as interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-13 (IL-13), chemokines of the RANTES type, superoxide anion production by activated polymorphonuclear neutrophils, eosinophil adhesion and chemotaxis, expression of adhesion molecules including P-selectin, IgE-dependent histamine release, as well as production of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4).

Desloratadine does not cross the blood-brain barrier but does cross the placental barrier and is excreted into breast milk. It is extensively metabolized via glucuronidation and hydroxylation, forming 3-OH-desloratadine. It is excreted in urine (less than 2% unchanged) and feces (at least 7% unchanged). No accumulation occurs after administration at doses of 5–20 mg/day over 2 weeks.

Clinical characteristics.

Indications.

For relief of symptoms associated with allergic rhinitis, such as sneezing, nasal discharge, itching, nasal swelling and congestion, as well as eye redness and itching, lacrimation, itching of the palate, and cough.

For relief of symptoms associated with urticaria, such as itching and skin rash.

Contraindications.

Hypersensitivity to the active substance or to any component of the medicinal product, as well as to loratadine.

Interaction with other medicinal products and other forms of interaction.

No clinically significant interactions were observed when desloratadine was co-administered with erythromycin or ketoconazole.

According to clinical pharmacological studies, concomitant use of desloratadine and alcohol did not result in enhanced negative effects of ethanol on psychomotor function. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been reported during treatment with the drug. Therefore, caution should be exercised when consuming alcohol during desloratadine therapy.

Special precautions for use.

Children.

The drug should be used with caution in children under 2 years of age, since differential diagnosis between allergic and other forms of rhinitis may be difficult. Additional examination of patients in this age group is required, taking into account the existing symptoms of the disease, medical history, and appropriate laboratory and skin tests.

Reduced desloratadine metabolism.

Approximately 6% of adults and children aged 2 to 11 years have reduced desloratadine metabolism, which is associated with higher drug exposure. No differences in safety of desloratadine use have been observed in children aged 2 to 11 years with either reduced or normal metabolism. The efficacy and safety of desloratadine in children under 2 years of age with reduced metabolism have not been studied.

Severe renal impairment.

The drug should be used with caution in patients with severe renal impairment.

Excipients.

The drug contains sunset yellow dye, which may cause allergic reactions.

The drug contains sucrose. If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product. The drug may also be harmful to teeth.

Use during pregnancy or breastfeeding.

Pregnancy.

Desloratadine has not shown teratogenic effects in animal studies. The safety of the drug during pregnancy has not been established; therefore, its use during pregnancy is not recommended.

Breastfeeding period.

Desloratadine passes into breast milk; therefore, the drug is not recommended for use in breastfeeding women.

Fertility.

There are no data available on the effects of desloratadine on male or female fertility.

Ability to influence reaction rate while driving or operating machinery.

In clinical studies assessing the ability to drive, no impairments were observed in patients taking desloratadine. However, patients should be informed that somnolence may very rarely occur, which could affect their ability to drive or operate complex machinery.

Dosage and Administration

To relieve symptoms associated with allergic rhinitis (including intermittent and persistent forms) and urticaria, the medication should be administered regardless of food intake, in the following doses:

Children:

• from 6 to 12 months of age: 2 mL of syrup (1 mg of desloratadine) once daily;
• from 1 to 5 years of age: 2.5 mL of syrup (1.25 mg of desloratadine) once daily;
• from 6 to 11 years of age: 5 mL of syrup (2.5 mg of desloratadine) once daily.

Adults and adolescents from 12 years of age: 10 mL of syrup (5 mg of desloratadine) once daily.

Treatment of intermittent allergic rhinitis (symptoms present less than 4 days per week or less than 4 weeks) should be guided by patient history: discontinue upon symptom resolution and resume upon symptom recurrence. For persistent allergic rhinitis (symptoms present more than 4 days per week or more than 4 weeks), treatment should continue throughout the entire period of allergen exposure.

Children.

The efficacy and safety of the medication in children under 6 months of age have not been established.

Overdose.

When desloratadine is administered at doses up to 45 mg (9 times higher than the recommended dose), clinically significant adverse reactions have not been observed; however, an increase in the severity of adverse reactions is possible.

Treatment. In case of overdose, standard measures to remove the unabsorbed active substance should be applied. Symptomatic and supportive therapy is recommended. Desloratadine is not removed by hemodialysis; its elimination by peritoneal dialysis has not been established.

Adverse Reactions

Immune system disorders: hypersensitivity reactions, including anaphylaxis, angioedema (Quincke's edema), dyspnea, pruritus, rash, and urticaria.

Skin and subcutaneous tissue disorders: photosensitivity reactions.

Musculoskeletal and connective tissue disorders: myalgia.

Cardiac disorders: arrhythmia, bradycardia, tachycardia, palpitations, QT interval prolongation, supraventricular tachyarrhythmia.

Nervous system disorders: headache**, dizziness, somnolence, insomnia*, psychomotor hyperactivity, seizures.

Psychiatric disorders: hallucinations, behavioral disturbances in children (including temper tantrums, aggression, agitation), depressive mood.

Gastrointestinal disorders: abdominal pain, nausea, vomiting, dyspepsia, diarrhea*, dry mouth**.

Hepatobiliary disorders: increased liver enzyme levels, increased bilirubin levels, hepatitis, jaundice.

Sensory organ disorders: dry eyes.

General disorders: increased fatigue**, fever (pyrexia)*.

*Most frequently observed in children under 2 years of age;
**Most frequently observed in adults.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25 °C, in the original packaging, in a place inaccessible to children.

Packaging. 100 mL of syrup in a bottle with a 5 mL plastic dosing spoon, in a cardboard box.

Supply category. Over-the-counter (without prescription).

Manufacturer.

Gracure Pharmaceuticals LTD.

Manufacturer's address and place of business.

E-1105, Industrial Area, Phase III, Bhiwadi, Alwar District, Rajasthan, 301019, India.