Raputeze 10 mg Tablets

Symptomatic treatment of allergic rhinitis and urticaria in adults and adolescents (over 12 years of age).

Posology

Adults and adolescents (over 12 years of age) The recommended dose is 10 mg (one tablet) once a day, with or without food.

Special populations

Elderly RAPUTEZE should be used with caution in elderly people (see section 4.4).

Method of administration

For oral use.

• Hypersensitivity to rupatadine or to any of the excipients listed in section 6.1.
• RAPUTEZE is not recommended for use in children below 12 years of age.
• Pregnancy and lactation (see section 4.6).

Renal and hepatic impairment

As there is no data of patients with impaired kidney or liver functions, the use of RAPUTEZE is not recommended in these patients.

Grapefruit juice

The administration with grapefruit juice is not recommended (see section 4.5).

CYP3A4 inhibitors

The combination of RAPUTEZE with potent CYP3A4 inhibitors should be avoided and with moderate CYP3A4 inhibitors should be administered with caution (see section 4.5). Dose adjustment of sensitive CYP3A4 substrates (e.g., simvastatin, lovastatin) and CYP3A4 substrates with a narrow therapeutic index (e.g., ciclosporin, tacrolimus, sirolimus, everolimus, cisapride) could be required as rupatadine may increase plasma concentrations of these medicines (see section 4.5).

Cardiac safety

RAPUTEZE should be used with caution in patients with known prolongation of the QT interval, patients with uncorrected hypokalaemia, patients with ongoing pro-dysrhythmia conditions, such as clinically significant bradycardia and acute myocardial ischemia.

Use in the elderly

RAPUTEZE should be used with caution in elderly patients (65 years and older). Although no overall differences in effectiveness or safety were documented, higher sensitivity of some older individuals cannot be excluded (see section 5.2).

Special precaution necessary relating to excipients

RAPUTEZE contains lactose monohydrate (see section 2 and 6.1). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose/galactose malabsorption should not take RAPUTEZE.

Effects of other medicines on rupatadine

Co-administration with potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, nefazodone) should be avoided and co-medication with moderate CYP3A4 inhibitors (erythromycin, fluconazole, diltiazem) should be used with caution. The concomitant administration of rupatadine 20 mg and ketoconazole or erythromycin increases the systemic exposure to rupatadine 10 times and 2-3 times respectively. These modifications were not associated with an effect on the QT interval or with an increase of the adverse reactions in comparison with these medicines when administered separately.

Interaction with grapefruit:

The concomitant administration of grapefruit juice with RAPUTEZE increased the systemic exposure of rupatadine by 3,5 times. Grapefruit juice should not be taken along with RAPUTEZE.

Effects of rupatadine on other medicines

Caution should be taken when RAPUTEZE is co-administered with other metabolised medicines with narrow therapeutic windows since knowledge of the effect of rupatadine on other medicines is limited.

Interaction with alcohol:

After administration of alcohol, a dose of 10 mg of rupatadine produced marginal effects in some psychomotor performance tests although they were not significantly different from those induced by intake of alcohol only. A dose of 20 mg increased the impairment caused by the intake of alcohol.

Interaction with central nervous system (CNS) depressants:

As with other antihistamines, such as RAPUTEZE, interactions with CNS depressants cannot be excluded.

Interaction with statins:

Asymptomatic creatine phosphokinase (CPK) increases have been reported. The risk of interactions with statins, some of which are also metabolised by the cytochrome P450 CYP3A4 isoenzyme, is unknown. Rupatadine should be used with caution when co-administered with statins.

Interaction with midazolam:

After the administration of 10 mg rupatadine in combination with 7,5 mg midazolam, a mildly higher increase of exposure (C max and AUC) of midazolam was observed. For this reason, rupatadine acts as a mild inhibitor of CYP3A4.

Pregnancy: RAPUTEZE is contraindicated (see section 4.3).

Breastfeeding: RAPUTEZE is excreted in animal milk. Due to potential harmful effects in neonates, the use of RAPUTEZE should be avoided during breastfeeding (see section 4.3).

Fertility: There are no clinical data on fertility.

RAPUTEZE causes somnolence and dizziness as per section 4.8. Nevertheless, care should be taken before driving or using machinery until the patient's individual reaction to RAPUTEZE has been established (see section 4.8).

a. Summary of the safety profile

The most frequent adverse reactions reported were somnolence, headache and fatigue.

b. Tabulated summary of adverse reactions

MedDRA System Organ Class/ Frequency Side effects

Infections and Infestations Less frequent: Pharyngitis, rhinitis

Immune system disorders Less frequent: Hypersensitivity reactions (including anaphylactic reactions, angioedema and urticaria)

Metabolism and nutrition disorders Less frequent: Increased appetite

Psychiatric disorders Less frequent: Irritability

Nervous system disorders Frequent: Somnolence, headache, dizziness Less frequent Disturbance in attention Frequency unknown Disorientation, tremor, increased sweating, abnormal gait

Eye disorders Frequency unknown Conjunctival hyperaemia, blepharitis and blisters

Cardiac disorders Less frequent Tachycardia and palpitations

Respiratory, thoracic and mediastinal disorders Less frequent Epistaxis, nasal dryness, upper respiratory disorders (e.g., cough, dry throat, oropharyngeal/ pain).

Gastrointestinal disorders Frequent Dry mouth Less frequent Nausea, upper abdominal pain, diarrhoea, dyspepsia, vomiting, abdominal pain, constipation

Skin and subcutaneous tissue disorders Less frequent Rash Frequency unknown Genital erythema, erythema

Musculoskeletal, connective tissue and bone disorders Less frequent Back pain, arthralgia, myalgia

General disorders and administrative site conditions Frequent Fatigue, asthenia Less frequent Thirst, malaise, pyrexia

Investigations Less frequent Increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase, abnormal liver function test

The most common adverse reaction observed was somnolence. If accidental ingestion of very high doses occurs symptomatic treatment together with the required supportive measures should be given. Concomitant medicines taken should also be considered.