Aerius

Aerius

desloratadine

Manufacturer:

Merck Sharp & Dohme

Distributor:

Zuellig Pharma

Marketer:

A. Menarini
Full Prescribing Info
Contents
Desloratadine.
Description
Tablet: Each AERIUS Tablet contains 5.0 mg of desloratadine.
Syrup: Each 1 ml of AERIUS Syrup contains 0.5 mg of desloratadine.
Excipients/Inactive Ingredients: Tablet: dibasic calcium phosphate dihydrate, microcrystalline cellulose, corn starch, talc, Dye Opadry II Blue, Dye Opadry Clear, carnauba wax, white wax and purified water.
Syrup: propylene glycol, sorbitol liquid, citric acid anhydrous, sodium citrate dihydrate, sodium benzoate, disodium edetate, sucrose, natural and artificial flavor, FD&C Yellow Dye No. 6 and purified water. Preservative: sodium benzoate 1.00 mg/ml.
Action
Pharmacology: Desloratadine is a non-sedating long-acting histamine antagonist with potent, selective peripheral H1-receptor antagonist activity. Desloratadine has demonstrated antiallergic, antihistaminic, and anti-inflammatory activity.
Pharmacodynamics: After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors because the drug is effectively excluded from entry to the central nervous system (CNS).
In addition to antihistaminic activity, desloratadine has demonstrated antiallergic and anti-inflammatory activity from numerous in vitro (mainly conducted on cells of human origin) and in vivo studies. These studies have shown that desloratadine inhibits the broad cascade of events that initiate and propagate allergic inflammation, including, the release of proinflammatory cytokines including IL-4, IL-6, IL-8, IL-13; the release of important proinflammatory chemokines such as RANTES (Regulated upon Activation, Normal T-cell Expressed and Secreted); superoxide anion production by activated polymorphonuclear neutrophils; eosinophil adhesion and chemotaxis; the expression of the adhesion molecules such as P-selectin; IgE-dependent release of histamine, prostaglandin (PGD2), and leukotriene (LTC4); the acute allergic bronchoconstrictor response and allergic cough in animal models.
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 pharmacologic trial, in which desloratadine was administered at a dose of 45 mg daily (nine times the clinical dose) for ten days, no prolongation of the QTc interval was seen.
Desloratadine does not readily penetrate the central nervous system. At the recommended dose of 5 mg daily, there was no excess incidence of somnolence as compared to placebo. AERIUS even at a dose of 7.5 mg daily did not affect psychomotor performance in clinical trials. A single dose of desloratadine 5 mg did not affect standard measures of flight performance including exacerbation of subjective sleepiness or tasks related to flying.
No clinically relevant changes in desloratadine plasma concentrations were observed in multiple-dose ketoconazole, erythromycin, azithromycin, fluoxetine and cimetidine interaction trials.
In clinical pharmacologic trials, co-administration of 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 adult and adolescent patients with allergic rhinitis (AR), AERIUS tablets were effective in relieving symptoms such as sneezing, nasal discharge and itching, congestion/stuffiness, as well as ocular itching, tearing and redness, and itching of palate. AERIUS tablets effectively controlled symptoms for 24 hours.
In two 4-week trials in patients with seasonal allergic rhinitis (SAR) and concurrent asthma, desloratadine was shown to be effective in reducing the symptoms of SAR (rhinorrhea, nasal congestion, nasal itching and sneezing, itching/burning eyes, tearing/watering eyes, redness of eyes, and itching of ears or palate) and asthma (coughing, wheezing, difficulty breathing), and decreasing beta-agonist use. FEV1 was not altered in the desloratadine or placebo treatment groups.
In trials conducted in adults and adolescents with chronic idiopathic urticaria (CIU), AERIUS tablets were effective in relieving pruritus and decreasing the size and number of hives as early as 1 day after initiation of treatment. In each trial, the effects were sustained over the 24 hour dosing interval. Treatment with AERIUS tablets also improved sleep and daytime function, as measured by reduced interference with sleep and routine daily activities.
AERIUS 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.
Syrup: Safety of AERIUS Syrup was demonstrated in three pediatric trials. Children, 1-11 years of age, who were candidates for antihistamine therapy received a daily dose of (1 through 5 years of age) or 2.5 mg (6 through 11 years of age). 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 concentration of desloratadine (see PHARMACOLOGY under Actions) was comparable in the pediatric and adult populations. Thus, since the course of SAR/CIU and the profile of desloratadine are similar in adults and pediatric patients, desloratadine efficacy data in adults can be extrapolated to the pediatric population.
Pharmacokinetics: Desloratadine plasma concentrations can be detected within 30 minutes of desloratadine 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. In adults and adolescents, the bioavailability of desloratadine was dose proportional over the range of 5 mg to 20 mg.
Desloratadine is moderately bound (83% - 87%) to plasma proteins. There is no evidence of clinically relevant drug accumulation following once daily dosing of desloratadine (5 mg to 20 mg) for 14 days.
The enzyme responsible for the metabolism of desloratadine has not been identified yet, and therefore some interactions with other drugs can not be fully excluded. In vivo studies with specific inhibitors of CYP3A4 and CYP2D6 have shown that these enzymes are not important in the metabolism of desloratadine. Desloratadine does not inhibit CYP3A4 or 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.
Syrup: In a single dose, crossover trial of desloratadine, the tablet and Syrup formulations were bioequivalent and not affected by the presence of food (high-fat, high caloric breakfast).
In separate single dose studies, at the recommended doses, pediatric patients had comparable AUC and Cmax values of desloratadine to those in adults who received a 5 mg dose of desloratadine Syrup.
Toxicology: Preclinical Toxicology: Desloratadine is the primary active metabolite of loratadine. Preclinical 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.
Preclinical 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 loratadine.
Indications/Uses
AERIUS is indicated for the rapid relief of symptoms associated with allergic rhinitis, such as sneezing, nasal discharge and itching, congestion/stuffiness, as well as ocular itching, tearing and redness.
AERIUS is also indicated for the relief of symptoms associated with chronic idiopathic urticaria such as the relief of itching and the size and number of hives.
Dosage/Direction for Use
Tablet: Adults and Adolescents (12 years of age and older): One AERIUS 5 mg film-coated tablet once a day regardless of mealtime. For oral use.
Syrup: The prescriber should be aware that most cases of rhinitis below 2 years of age are of infections origin and there are no data supporting the treatment of infectious rhinitis with AERIUS.
Children 6 through 11 years of age: 5 ml (2.5 mg) AERIUS Syrup 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.
Children 1 through 5 years of age: 2.5 ml (1.25 mg) AERIUS Syrup 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.
In adults and adolescents (12 years of age and over): 10 ml (5 mg) AERIUS Syrup 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.
Intermittent allergic rhinitis (presence of symptoms for less than 4 days per week or 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 allergen exposure periods.
Overdosage
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 adults and adolescents, in which up to 45 mg of desloratadine was administered (9 times the clinical dose), no clinically relevant effects were observed.
Desloratadine is not eliminated by hemodialysis; it is not known if it is eliminated by peritoneal dialysis.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Special Precautions
Desloratadine should be administered with caution in patients with a medical or family history of seizures. In particular, young children may be more susceptible to developing new seizures under desloratadine treatment. Healthcare providers may consider discontinuing desloratadine in patients who experience a seizure while on treatment.
Effects on ability to drive and use machines: No effects on the ability to drive and use machines have been observed (see Pharmacology: Pharmacodynamics under Actions).
Tablet: Efficacy and safety of AERIUS Tablets in children under 12 years of age have not been established.
Syrup: Efficacy and safety of AERIUS Syrup in children under 1 years of age have not been established.
Use In Pregnancy & Lactation
No overall effect on rat fertility was observed with desloratadine at an exposure that was 34 times higher than the exposure in humans at the recommended clinical dose.
No teratogenic or mutagenic effects were observed in animal trials with desloratadine (see Pharmacology: Toxicology: PRECLINICAL TOXICOLOGY under Actions). Since no clinical data on exposed pregnancies are available with desloratadine, the safe use of AERIUS during pregnancy has not been established. AERIUS is not to be used during pregnancy unless the potential benefits outweigh the risks.
Desloratadine is excreted into breast milk; therefore the use of AERIUS is not recommended in breast-feeding women.
Adverse Reactions
In clinical trials in a range of indications including SAR and CIU, at the recommended dose of 5 mg daily, undesirable effects with AERIUS tablets were reported in 3 % of patients in excess of those treated with placebo. The most frequent adverse events reported in excess of placebo were fatigue (1.2 %), dry mouth (0.8 %), and headache (0.6 %).
Very rare cases of hypersensitivity reactions, including anaphylaxis and rash, have been reported during the marketing of desloratadine. In addition, cases of tachycardia, palpitations, psychomotor hyperactivity, somnolence, seizures, elevations of liver enzymes, hepatitis, increased bilirubin and increased appetite have been reported very rarely.
Syrup: In clinical trials in a paediatric population, AERIUS Syrup was administered to a total of 246 children aged 6 months through 11 years. The overall incidence of adverse events in children 2 through 11 years of age was similar for the AERIUS Syrup and the placebo groups. In infants and toddlers aged 6 to 23 months, the most frequent adverse events reported in excess of placebo were diarrhoea (3.7%), fever (2.3%) and insomnia (2.3%).
Drug Interactions
No clinically relevant interactions with AERIUS tablets were observed in clinical trials (see Pharmacology: Pharmacodynamics under Actions). There was no effect of food or grapefruit juice on the disposition of desloratadine.
AERIUS Syrup taken concomitantly with alcohol did not potentiate the performance impairing effects of alcohol (see Pharmacology: Pharmacodynamics under Actions).
Storage
Store below 30°C. Store in the original container.
Tablet: Protect AERIUS Tablets from excessive moisture.
ATC Classification
R06AX27 - desloratadine ; Belongs to the class of other antihistamines for systemic use.
Presentation/Packing
FC tab 5 mg (a light blue round tablet, embossed with elongated letters 'S' and 'P' on one side and plain on the other) x 10's. Syr 0.5 mg/mL (a clear, orange solution) x 60 mL.
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