AERIUS 2.5mg orodispersable tablets medication leaflet

Aerius 0.5 mg/ml oral solution

Each ml of oral solution contains 0.5 mg desloratadine.

Each ml of oral solution contains 150 mg sorbitol (E420), 100.19 mg propylene glycol (E1520) and0.375 mg benzyl alcohol (see section 4.4).

For the full list of excipients, see section 6.1.

Oral solution is a clear, colourless solution.

Aerius is indicated in adults, adolescents and children over the age of 1 year for the relief of symptomsassociated with:

- allergic rhinitis (see section 5.1)

- urticaria (see section 5.1)

The recommended dose of Aerius is 10 ml (5 mg) oral solution once a day.

The prescriber should be aware that most cases of rhinitis below 2 years of age are of infectious origin(see section 4.4) and there are no data supporting the treatment of infectious rhinitis with Aerius.

Children 1 through 5 years of age: 2.5 ml (1.25 mg) Aerius oral solution once a day.

Children 6 through 11 years of age: 5 ml (2.5 mg) Aerius oral solution once a day.

The safety and efficacy of Aerius 0.5 mg/ml oral solution in children below the age of 1 year have notbeen established.

There is limited clinical trial efficacy experience with the use of desloratadine in children 1 through11 years of age and 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 than4 weeks) should be managed in accordance with the evaluation of patient’s disease history and thetreatment 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 than4 weeks), continued treatment may be proposed to the patients during the allergen exposure periods.

Oral use.

The dose can be taken with or without food.

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

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

Desloratadine should be administered with caution in patients with medical or familial history ofseizures, and mainly young children (see section 4.8), being more susceptible to develop new seizuresunder desloratadine treatment. Healthcare providers may consider discontinuing desloratadine inpatients who experience a seizure while on treatment.

Aerius oral solution contains sorbitol (E420)

This medicinal product contains 150 mg sorbitol (E420) in each ml of oral solution.

The additive effect of concomitantly administered products containing sorbitol (E420) (or fructose)and dietary intake of sorbitol (E420) (or fructose) should be taken into account. The content of sorbitol(E420) in medicinal products for oral use may affect the bioavailability of other medicinal products fororal use administered concomitantly.

Sorbitol is a source of fructose; patients with hereditary fructose intolerance (HFI) should not take thismedicinal product.

Aerius oral solution contains propylene glycol (E1520)

This medicinal product contains 100.19 mg propylene glycol (E1520) in each ml of oral solution.

Aerius oral solution contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially‘sodium-free’.

Aerius oral solution contains benzyl alcohol

This medicinal product contains 0.375 mg benzyl alcohol in each ml of oral solution.

Benzyl alcohol may cause anaphylactoid reactions.

Increased risk due to accumulation in young children. It is not recommended to be used for more thana week in young children (less than 3 years old).

High volumes should be used with caution and only if necessary, especially in subjects with liver orkidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).

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

Approximately 6 % of adults and children 2- to 11-year old are phenotypic poor metabolisers ofdesloratadine and exhibit a higher exposure (see section 5.2). 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.

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

Interaction studies have only been performed in adults.

In a clinical pharmacology trial, Aerius tablets taken concomitantly with alcohol did not potentiate theperformance impairing effects of alcohol (see section 5.1). However, cases of alcohol intolerance andintoxication have been reported during post-marketing use. Therefore, caution is recommended ifalcohol is taken concomitantly.

A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate nomalformative nor foeto/ neonatal toxicity of desloratadine. Animal studies do not indicate direct orindirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionarymeasure, it is preferable to avoid the use of Aerius during pregnancy.

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

There are no data available on male and female fertility.

Aerius has no or negligible influence on the ability to drive and use machines based on clinical trials.

Patients should be informed that most people do not experience drowsiness. Nevertheless, as there isindividual variation in response to all medicinal products, it is recommended that patients are advisednot to engage in activities requiring mental alertness, such as driving a car or using machines, untilthey have established their own response to the medicinal product.

In clinical trials in a paediatric population, the desloratadine syrup formulation was administered to atotal of 246 children aged 6 months through 11 years. The overall incidence of adverse events inchildren 2 through 11 years of age was similar for the desloratadine and the placebo groups. In infantsand toddlers aged 6 to 23 months, the most frequent adverse reactions reported in excess of placebowere diarrhoea (3.7 %), fever (2.3 %) and insomnia (2.3 %). In an additional study, no adverse eventswere seen in subjects between 6 and 11 years of age following a single 2.5 mg dose of desloratadineoral solution.

In a clinical trial with 578 adolescent patients, 12 through 17 years of age, the most common adverseevent was headache; this occurred in 5.9 % of patients treated with desloratadine and 6.9 % of patientsreceiving placebo.

Adults and adolescents

At the recommended dose, in clinical trials involving adults and adolescents in a range of indicationsincluding allergic rhinitis and chronic idiopathic urticaria, undesirable effects with Aerius werereported in 3 % of patients in excess of those treated with placebo. The most frequent of adverseevents reported in excess of placebo were fatigue (1.2 %), dry mouth (0.8 %) and headache (0.6 %).

The frequency of the clinical trial adverse reactions reported in excess of placebo and otherundesirable effects reported during the post-marketing period are listed in the following table.

Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimatedfrom the available data).

System Organ Class Frequency Adverse reactions seen with Aerius

Metabolism and nutrition Not known Increased appetitedisorders

Psychiatric disorders Very rare Hallucinations

Not known Abnormal behaviour, aggression,depressed mood

Nervous system disorders Common Headache

Common (children less Insomniathan 2 years)

Very rare Dizziness, somnolence, insomnia,psychomotor hyperactivity, seizures

Eye disorders Not known Eye dryness

Cardiac disorders Very rare Tachycardia, palpitations

Not known QT prolongation

Gastrointestinal disorders Common Dry mouth

Common (children less Diarrhoeathan 2 years)

Very rare Abdominal pain, nausea, vomiting,dyspepsia, diarrhoea

Hepatobiliary disorders Very rare Elevations of liver enzymes, increasedbilirubin, hepatitis

Not known Jaundice

Skin and subcutaneous tissue Not known Photosensitivitydisorders

Musculoskeletal and Very rare Myalgiaconnective tissue disorders

General disorders and Common Fatigueadministration site conditions Common (children less Feverthan 2 years)

Very rare Hypersensitivity reactions (such asanaphylaxis, angioedema, dyspnoea,pruritus, rash, and urticaria)

Not known Asthenia

Investigations Not known Weight increased

Other undesirable effects reported during the post-marketing period in paediatric patients with anunknown frequency included QT prolongation, arrhythmia, bradycardia, abnormal behaviour, andaggression.

A retrospective observational safety study indicated an increased incidence of new-onset seizure inpatients 0 to 19 years of age when receiving desloratadine compared with periods not receivingdesloratadine. Among children 0-4 years old, the adjusted absolute increase was 37.5 (95 %

Confidence Interval (CI) 10.5-64.5) per 100,000 person years (PY) with a background rate of newonset seizure of 80.3 per 100,000 PY. Among patients 5-19 years of age, the adjusted absoluteincrease was 11.3 (95 % CI 2.3-20.2) per 100,000 PY with a background rate of 36.4 per 100,000 PY.

(See section 4.4.)

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

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

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 peritonealdialysis.

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

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

Pharmacotherapeutic group: antihistamines - H1 antagonist, ATC code: R06AX27

Desloratadine is a non-sedating, long-acting histamine antagonist with selective peripheral H1-receptorantagonist 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 inhibitingthe release of proinflammatory cytokines such as IL-4, IL-6, IL-8, and IL-13 from human mastcells/basophils, as well as inhibition of the expression of the adhesion molecule P-selectin onendothelial cells. The clinical relevance of these observations remains to be confirmed.

Efficacy of Aerius oral solution has not been investigated in separate paediatric trials. However, thesafety of desloratadine syrup formulation, which contains the same concentration of desloratadine as

Aerius oral solution, was demonstrated in three paediatric trials. Children, 1-11 years of age, who werecandidates for antihistamine therapy received a daily desloratadine dose of 1.25 mg (1 through 5 yearsof age) or 2.5 mg (6 through 11 years of age). Treatment was well tolerated as documented by clinicallaboratory tests, vital signs, and ECG interval data, including QTc. When given at the recommendeddoses, the plasma concentrations of desloratadine (see section 5.2) were comparable in the paediatricand adult populations. Thus, since the course of allergic rhinitis/chronic idiopathic urticaria and theprofile of desloratadine are similar in adults and paediatric patients, desloratadine efficacy data inadults can be extrapolated to the paediatric population.

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

Adults and adolescents

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

Desloratadine does not readily penetrate the central nervous system. In controlled clinical trials, at therecommended dose of 5 mg daily for adults and adolescents, there was no excess incidence ofsomnolence as compared to placebo. Aerius tablets given at a single daily dose of 7.5 mg to adults andadolescents did not affect psychomotor performance in clinical trials. In a single dose study performedin adults, desloratadine 5 mg did not affect standard measures of flight performance includingexacerbation of subjective sleepiness or tasks related to flying.

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

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

In adult and adolescent patients with allergic rhinitis, Aerius tablets were effective in relievingsymptoms 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. The efficacy of Aeriustablets 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 canalternatively be classified as intermittent allergic rhinitis and persistent allergic rhinitis according tothe duration of symptoms. Intermittent allergic rhinitis is defined as the presence of symptoms for lessthan 4 days per week or for less than 4 weeks. Persistent allergic rhinitis is defined as the presence ofsymptoms for 4 days or more per week and for more than 4 weeks.

Aerius tablets were effective in alleviating the burden of seasonal allergic rhinitis as shown by the totalscore of the rhino-conjunctivitis quality of life questionnaire. The greatest amelioration was seen in thedomains of practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria was studied as a clinical model for urticarial conditions, since theunderlying pathophysiology is similar, regardless of etiology, and because chronic patients can bemore 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, Aerius waseffective in relieving pruritus and decreasing the size and number of hives by the end of the firstdosing interval. In each trial, the effects were sustained over the 24 hour dosing interval. As with otherantihistamine trials in chronic idiopathic urticaria, the minority of patients who were identified asnon-responsive to antihistamines was excluded. An improvement in pruritus of more than 50 % wasobserved in 55 % of patients treated with desloratadine compared with 19 % of patients treated withplacebo. Treatment with Aerius also significantly reduced interference with sleep and daytimefunction, as measured by a four-point scale used to assess these variables.

Desloratadine plasma concentrations can be detected within 30 minutes of desloratadineadministration in adults and adolescents. Desloratadine is well absorbed with maximum concentrationachieved after approximately 3 hours; the terminal phase half-life is approximately 27 hours. Thedegree of accumulation of desloratadine was consistent with its half-life (approximately 27 hours) anda once daily dosing frequency. The bioavailability of desloratadine was dose proportional over therange of 5 mg to 20 mg.

In a series of pharmacokinetic and clinical trials, 6 % of the subjects reached a higher concentration ofdesloratadine. The prevalence of this poor metaboliser phenotype was comparable for adult (6 %) andpaediatric subjects 2- to 11-year old (6 %), and greater among Blacks (18 % adult, 16 % paediatric)than Caucasians (2 % adult, 3 % paediatric) in both populations.

In a multiple-dose pharmacokinetic study conducted with the tablet formulation in healthy adultsubjects, four subjects were found to be poor metabolisers of desloratadine. These subjects had a Cmaxconcentration about 3-fold higher at approximately 7 hours with a terminal phase half-life ofapproximately 89 hours.

Similar pharmacokinetic parameters were observed in a multiple-dose pharmacokinetic studyconducted with the syrup formulation in paediatric poor metaboliser subjects 2- to 11-year olddiagnosed with allergic rhinitis. The exposure (AUC) to desloratadine was about 6-fold higher and the

Cmax was about 3 to 4 fold higher at 3-6 hours with a terminal half-life of approximately 120 hours.

Exposure was the same in adult and paediatric poor metabolisers when treated with age-appropriatedoses. The overall safety profile of these subjects was not different from that of the general population.

The effects of desloratadine in poor metabolizers < 2 years of age have not been studied.

In separate single dose studies, at the recommended doses, paediatric patients had comparable AUCand Cmax values of desloratadine to those in adults who received a 5 mg dose of desloratadine syrup.

Desloratadine is moderately bound (83 % - 87 %) to plasma proteins. There is no evidence ofclinically relevant active substance accumulation following once daily adult and adolescent dosing ofdesloratadine (5 mg to 20 mg) for 14 days.

In a single dose, crossover study of desloratadine, the tablet and the syrup formulations were found tobe bioequivalent. As Aerius oral solution contains the same concentration of desloratadine, nobioequivalence study was required and it is expected to be equivalent to the syrup and tablet.

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 notinhibit 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, highcaloric breakfast) on the disposition of desloratadine. In another study, grapefruit juice had no effecton the disposition of desloratadine.

The pharmacokinetics of desloratadine in patients with chronic renal insufficiency (CRI) wascompared with that of healthy subjects in one single-dose study and one multiple dose study. In thesingle-dose study, the exposure to desloratadine was approximately 2 and 2.5-fold greater in subjectswith mild to moderate and severe CRI, respectively, than in healthy subjects. In the multiple-dosestudy, steady state was reached after Day 11, and compared to healthy subjects the exposure todesloratadine was ~1.5-fold greater in subjects with mild to moderate CRI and ~2.5-fold greater insubjects with severe CRI. In both studies, changes in exposure (AUC and Cmax) of desloratadine and3-hydroxydesloratadine were not clinically relevant.

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

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproductionand development. The lack of carcinogenic potential was demonstrated in studies conducted withdesloratadine and loratadine.

sorbitol (E420)propylene glycol (E1520)sucralose (E955)hypromellose 2910sodium citrate dihydratenatural and artificial flavour (bubblegum, which contains propylene glycol (E1520) and benzylalcohol)citric acid anhydrousdisodium edetatepurified water

Not applicable.

2 years

Do not freeze. Store in the original package.

Aerius oral solution, is supplied in 30, 50, 60, 100, 120, 150, 225 and 300 ml size Type III amber glassbottles closed with a plastic child resistant (C/R) screw closure having a multi-ply polyethylene-facedliner. All packages except the 150 ml package are supplied with a measuring spoon marked for dosesof 2.5 ml and 5 ml. For the 150 ml package, a measuring spoon or an oral measuring syringe isprovided, marked for doses of 2.5 ml and 5 ml.

Not all pack sizes may be marketed.

No special requirements.

N.V. Organon

Kloosterstraat 65349 AB Oss

The Netherlands

EU/1/00/160/061-069

Date of first authorisation: 15 January 2001

Date of latest renewal: 9 February 2006

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.