DESLORATADINA ACTAVIS 5mg film-coated tablets medication leaflet

Desloratadine Actavis 5 mg film-coated tablets

Each tablet contains 5 mg desloratadine.

For the full list of excipients, see section 6.1.

Film-coated tablet (tablet).

Blue coloured, round, with diameter of 6 mm, biconvex, film-coated tablets with the marking ‘LT’engraved on one side.

Desloratadine Actavis is indicated in adults and adolescents aged 12 years and older for the relief ofsymptoms associated with:

- allergic rhinitis (see section 5.1)

- urticaria (see section 5.1)

The recommended dose of Desloratadine Actavis is one tablet once a day.

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.

There is limited clinical trial efficacy experience with the use of desloratadine in adolescents12 through 17 years of age (see sections 4.8 and 5.1).

The safety and efficacy of Desloratadine Actavis 5 mg film-coated tablets in children below the age of12 years have not been established.

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, desloratadine 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.

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, desloratadine tablets taken concomitantly with alcohol did notpotentiate the performance impairing effects of alcohol (see section 5.1). However, cases of alcoholintolerance and intoxication have been reported during post-marketing use. Therefore, caution isrecommended if alcohol 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 desloratadine 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 desloratadine 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.

Desloratadine has no or negligible influence on the ability to drive and use machines based on clinicaltrials. Patients should be informed that most people do not experience drowsiness. Nevertheless, asthere is individual variation in response to all medicinal products, it is recommended that patients areadvised 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.

In clinical trials in a range of indications including allergic rhinitis and chronic idiopathic urticaria, atthe recommended dose of 5 mg daily, undesirable effects with desloratadine were reported in 3% ofpatients in excess of those treated with placebo. The most frequent of adverse reactions reported inexcess of placebo were fatigue (1.2%), dry mouth (0.8%) and headache (0.6%).

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.

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 withdesloratadine

Metabolism and Not known Increased appetitenutrition disorders

Psychiatric disorders Very rare Hallucinations

Not known Abnormal behaviour, aggression,depressed mood

Nervous system Common Headachedisorders 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 Common Dry mouthdisorders Very rare Abdominal pain, nausea, vomiting,dyspepsia, diarrhoea

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

Not known Jaundice

Skin and subcutaneous Not known Photosensitivitytissue disorders

Musculoskeletal and Very rare Myalgiaconnective tissuedisorders

General disorders and Common Fatigueadministration site Very rare Hypersensitivity reactions (such asconditions anaphylaxis, 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 which up to 45 mg of desloratadine was 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: R06A X27

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 anti-allergic properties from in vitro studies. These include inhibitingthe release of pro-inflammatory 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.

In a multiple dose clinical trial, in which up to 20 mg of desloratadine was administered daily for14 days, no statistically or clinically relevant cardiovascular effect was observed. In a clinicalpharmacology trial, in which desloratadine was administered at a dose of 45 mg daily (nine times theclinical dose) for ten days, no prolongation of QTc interval was seen.

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

Desloratadine does not readily penetrate the central nervous system. In controlled clinical trials, at therecommended dose of 5 mg daily, there was no excess incidence of somnolence as compared toplacebo. Desloratadine given at a single daily dose of 7.5 mg did not affect psychomotor performancein clinical trials. In a single dose study performed in adults, desloratadine 5 mg did not affect standardmeasures of flight performance including exacerbation of subjective sleepiness or tasks related toflying.

In clinical pharmacology trials, co-administration with alcohol did not increase the alcohol-inducedimpairment in performance or increase in sleepiness. No significant differences were found in thepsychomotor test results between desloratadine and placebo groups, whether administered alone orwith alcohol.

In patients with allergic rhinitis, desloratadine was 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.

The efficacy of desloratadine tablets has not been clearly demonstrated in trials with adolescentpatients 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.

Desloratadine was 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, desloratadinewas effective 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 as non-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 desloratadine 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 administration.

Desloratadine is well absorbed with maximum concentration achieved after approximately 3 hours; theterminal phase half-life is approximately 27 hours. The degree of accumulation of desloratadine wasconsistent with its half-life (approximately 27 hours) and a once daily dosing frequency. Thebioavailability 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 generalseasonal allergic rhinitis population, 4% of the subjects achieved a higher concentration ofdesloratadine. This percentage may vary according to ethnic background. Maximum desloratadineconcentration was about 3-fold higher at approximately 7 hours with a terminal phase half-life ofapproximately 89 hours. The safety profile of these subjects was not different from that of the generalpopulation.

Desloratadine is moderately bound (83 % - 87 %) to plasma proteins. There is no evidence ofclinically relevant medicine accumulation following once daily dosing of desloratadine (5 mg to20 mg) for 14 days.

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.

Microcrystalline cellulose

Starch, pregelatinised

Mannitol

Talc

Magnesium stearate

Hypromellose 6cP

Titanium dioxide (E171)

Macrogol 6000

Indigo carmine aluminum lake (E132)

Not applicable.

3 years

This medicinal product does not require any special storage conditions.

This medicinal product does not require any special temperature storage conditions.

Keep the bottle tightly closed in order to protect from light.

OPA/Aluminium/PVC-Aluminium blisters.

Pack sizes: 7, 10, 14, 20, 21, 30, 50, 90 and 100 tablets.

Polyethylene bottles containing a desiccant and closed with a polyethylene cap.

Pack sizes: 30 and 100 tablets.

Not all pack sizes may be marketed.

No special requirements.

Actavis Group PTC ehf.

Dalshraun 1220 Hafnarfjörður

Iceland

EU/1/11/745/001

EU/1/11/745/002

EU/1/11/745/003

EU/1/11/745/004

EU/1/11/745/005

EU/1/11/745/006

EU/1/11/745/007

EU/1/11/745/008

EU/1/11/745/009

EU/1/11/745/010

EU/1/11/745/011

Date of first authorisation: 13.01.2012

Date of latest renewal: 11.11.2016

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

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