1. NAME OF THE MEDICINAL PRODUCT
Aerius® 5 mg film-coated tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5 mg desloratadine.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Aerius® is indicated for the relief of symptoms associated with:
- allergic rhinitis (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).
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.
Hypersensitivity to the active substance, to any of the excipients, or to loratadine.
4.4 Special warnings and precautions for use
Efficacy and safety of Aerius® tablets in children under 12 years of age have not been established.
In the case of severe renal insufficiency, Aerius® should be used with caution (see section 5.2).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.
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 Aerius® taken concomitantly with alcohol did not potentiate the
performance impairing effects of alcohol (see section 5.1).
4.6 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 Aerius® during pregnancy is therefore not
Desloratadine is excreted into breast milk, therefore the use of Aerius® is not recommended in breastfeeding
4.7 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 Aerius® 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 %). 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
Cardiac disorders Tachycardia, palpitations
Gastrointestinal disorders Abdominal pain, nausea, vomiting, dyspepsia,
Hepato-biliary disorders Elevations of liver enzymes, increased bilirubin,
Musculoskeletal and connective tissue
General disorders Hypersensitivity reactions (such as anaphylaxis,
angioedema, dyspnoea, pruritus, rash, and urticaria)
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
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antihistamines – H1 antagonist, ATC code: R06A X27
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 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.
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. Aerius® 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
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
In patients with allergic rhinitis, Aerius® was effective in relieving symptoms such as sneezing, nasal
discharge and itching, as well as ocular itching, tearing and redness, and itching of palate. Aerius®
effectively controlled symptoms for 24 hours. Efficacy has not been clearly demonstrated in patients
12–17 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.
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.
In two placebo-controlled six week trials in patients with chronic idiopathic urticaria, Aerius® 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 Aerius® 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
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
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
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 loratadine.
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.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core:Dibasic calcium phosphate dihydrate, microcrystalline cellulose, maize starch,
talc,carnauba wax, white wax.
Tablet coating: film coat (contains lactose monohydrate, hydroxypropyl methycellulose, titanium
dioxide, polyethylene glycol, indigotin (E132)), clear coat (contains, hydroxypropyl methycellulose,
6.3 Shelf life
6.4 Special precautions for storage
Store below 30°C.
Store in the original package.
6.5 Nature and contents of container
Aerius® is supplied in unit dose blisters comprised of laminant blister film with foil lidding.
The materials of the blister consist of a polychlorotrifluoroethylene (PCTFE)/Polyvinyl Chloride (PVC)
film (product contact surface) with an aluminium foil lidding coated with a vinyl heat seal coat (product
contact surface) which is heat sealed.
Packs of, 2, 5, 7, 10, 14, 15, 20, 30 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Schering-Plough Labo N.V., Heist-op-den-berg, Belgium
8. License holder:
Merck Sharp & Dohme (Israel-1996) Company Ltd., P.O.Box 7121, Petah-Tikva 49170