Desloratadine Gedeon Richter 5 Mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Desloratadine Gedeon Richter 5 mg film-coated tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 5 mg desloratadine (as desloratadine hemisulphate). Excipient with known effect:
Each film-coated tablet contains 0.080 mg of soya lecithin.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet.
Yellow, round, biconvex film-coated tablets, of about 6 mm diameter, one side engraved with “R03”.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Desloratadine is indicated in adults and adolescents aged 12 years and older for the relief of symptoms associated with:
- allergic rhinitis (see section 5.1)
- urticaria (see section 5.1).
4.2 Posology and method of administration
Posology
Adults and adolescents (12 years of age and over): The recommended dose of Desloratadine Gedeon Richter is one tablet once a day.
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.
Paediatric population
There is limited clinical trial efficacy experience with the use of desloratadine in adolescents 12 through 17 years of age (see sections 4.8 and 5.1).
The safety and efficacy of desloratadine 5 mg film-coated tablets in children below the age of 12 years have not been established. No data are available.
Method of administration Oral use.
The dose can be taken with or without food.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, peanut, soya oil or to loratadine.
This medicinal product contains 0.080 mg soya lecithin per tablet. Patients with hypersensitivity to peanut or soya should not take this medicine.
4.4 Special warnings and precautions for use
In the case of severe renal insufficiency, {Invented name} should be used with caution (see section 5.2).
Desloratadine Gedeon Richter contains soya oil.
This medicinal product contains soya oil. Patients with hypersensitivity to peanut or soya 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).
Paediatric population
Interaction studies have only been performed in adults.
In a clinical pharmacology trial desloratadine taken concomitantly with alcohol did not potentiate the
performance impairing effects of alcohol (see section 5.1). However, cases of alcohol intolerance and intoxication have been reported during post-marketing use. Therefore, caution is recommended if alcohol is taken concomitantly.
4.6 Fertility, pregnancy and lactation
Pregnancy
A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate no malformative nor foeto/ neonatal toxicity of desloratadine. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a
precautionary measure, it is preferable to avoid the use of Desloratadine Gedeon Richter during pregnancy.
Breast-feeding
Desloratadine has been identified in breastfed newborns/infants of treated women. The effect of desloratadine on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Desloratadine Gedeon Richter therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Fertility
There are no data available on male and female fertility.
4.7 Effects on ability to drive and use machines
Desloratadine Gedeon Richter 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 is
individual variation in response to all medicinal products, it is recommended that patients are advised
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.
4.8 Undesirable effects Summary of the safety profile
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 desloratadine were reported in 3 % of patients in excess of those treated with placebo. The most frequent of adverse events reactions reported in excess of placebo were fatigue (1.2 %), dry mouth (0.8 %) and headache (0.6 %).
Paediatric population
In a clinical trial with 578 adolescent patients, 12 through 17 years of age, the most common adverse event was headache; this occurred in 5.9 % of patients treated with desloratadine and
6.9 % of patients receiving placebo.
Tabulated list of adverse reactions
The frequency of the clinical trial adverse reactions reported in excess of placebo and other undesirable 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 (> 1/1,000 to < 1/100), rare (> 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot
be estimated from the available data).
|
System organ class |
Frequency |
Adverse reactions seen with {Invented name} |
|
Psychiatric disorders |
Very rare |
Hallucinations, |
|
Nervous system disorders |
Common Very rare |
Headache Dizziness, somnolence, insomnia, psychomotor hyperactivity, seizures |
|
Cardiac disorders |
Very rare Not known |
Tachycardia, palpitations QT prolongation |
|
Gastrointestinal disorders |
Common Very rare |
Dry mouth Abdominal pain, nausea, vomiting, dyspepsia, diarrhoea |
|
Hepatobiliary disorders |
Very rare Not known |
Elevations of liver enzymes, increased bilirubin, Hepatitis, Jaundice |
|
Skin and subcutaneous tissue disorders |
Not known |
Photosensitivity |
|
Musculoskeletal and connective tissue disorders |
Very rare |
Myalgia |
|
General disorders and administration site conditions |
Common Very rare Not known |
Fatigue Hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, pruritus, rash, and urticaria), Asthenia |
Paediatric population
Other undesirable effects reported during the post-marketing period in paediatric patients with an unknown frequency included QTprolongation, arrhythmia, and bradycardia.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V*.
4.9 Overdose
The adverse event profile associated with overdosage, as seen during post-marketing use, is similar to that seen with therapeutic doses, but the magnitude of the effects can be higher. Treatment 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 peritoneal dialysis.
Symptoms
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.
Paediatric population
The adverse event profile associated with overdosage, as seen during post-marketing use, is similar to that seen with therapeutic doses, but the magnitude of the effects can be higher.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antihistamines - H1 antagonist, ATC code: R06A X27 Mechanism of action
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.
Clinical efficacy and safety
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. Desloratadine 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 flying.
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 with 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.
Paediatric population
The efficacy of desloratadine tablets 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 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.
Desloratadine 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.
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.
In two placebo-controlled six week trials in patients with chronic idiopathic urticaria, desloratadine 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 desloratadine 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
Absorption
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 population.
Distribution
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 14 days.
Biotransformation
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.
Elimination
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.
Renally impaired patients
The pharmacokinetics of desloratadine in patients with chronic renal insufficiency (CRI) was compared with that of healthy subjects in one single-dose study and one multiple dose study. In the single-dose study, the exposure to desloratadine was approximately 2 and 2.5-fold greater in subjects with mild to moderate and severe CRI, respectively, than in healthy subjects. In the multiple-dose study, steady state was reached after Day 11, and compared to healthy subjects the exposure to desloratadine was ~1.5-fold greater in subjects with mild to moderate CRI and ~2.5-fold greater in subjects with severe CRI. In both studies, changes in exposure (AUC and Cmax) of desloratadine and 3-hydroxydesloratadine were not clinically relevant.
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, carcinogenic potencial and toxicity to reproduction and development. The lack of carcinogenic potential was demonstrated in studies conducted with desloratadine and loratadine.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core:
Cellulose, microcrystalline Calcium hydrogen phosphate dihydrate Maize starch, pregelatinised Silica, colloidal anhydrous Magnesium stearate
Film-coating
Poly(vinyl alcohol) (E 1203)
Titanium dioxide (E 171)
Talc (E 553b)
Lecithin (soya) (E 322)
Quinoline yellow aluminium lake (E 104)
Xanthan gum (E 415)
Iron oxide yellow (E 172)
Indigo carmine aluminium lake (E 132)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Desloratadine 5 mg film-coated tablets are packaged in PVC/PE/PVDC//Al blisters. The blisters are packed into cardboard cartons.
Pack sizes are: 7, 10, 20, 30, 50, 90, 100 film-coated tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements for disposal.
7 MARKETING AUTHORISATION HOLDER
Gedeon Richter Plc.
Gyomroi ut 19-21 H-1103 Budapest Hungary
8 MARKETING AUTHORISATION NUMBER(S)
PL 4854/0125
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
31/07/2015
10 DATE OF REVISION OF THE TEXT
31/07/2015