Rupastral 10 mg tablet

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.

Method of administration

For oral use.

• Hypersensitivity to rupatadine or to any of the excipients (see section 6.1).
• RUPASTRAL 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 renal or liver functions, the use of RUPASTRAL is not recommended in these patients.

Grapefruit juice

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

Cardiac safety

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

Use in the elderly

RUPASTRAL should be used with caution in elderly patients (65 years and older).

CYP3A4 inhibitors

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.

(2) The concomitant administration of RUPASTRAL and ketoconazole or erythromycin increases the systemic exposure to rupatadine 10 times and 2 to 3 times respectively.

Alcohol

RUPASTRAL should be used with caution when administered with alcohol.

(1) Grapefruit

The concomitant administration of grapefruit juice with RUPASTRAL increased the systemic exposure of rupatadine by 3,5 times. It is recommended to avoid intake of grapefruit juice along with RUPASTRAL.

CNS depressants

Interactions with CNS depressants cannot be excluded.

SSRI antidepressant

No interactions have been observed with fluoxetine.

Statins

Asymptomatic CPK increases have been reported. The risk of interactions with statins, some of which are also metabolized by the cytochrome P450 CYPA4 isoenzyme, is unknown. RUPASTRAL should be used with caution when co-administered with statins.

Midazolam

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

Medicines with narrow therapeutic windows

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

Pregnancy

RUPASTRAL is contraindicated during pregnancy (see section 4.3).

Breastfeeding

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

Fertility

There are no clinical data on fertility. Studies in animals have shown a significant reduction of fertility at exposure levels higher than those observed in humans at the maximum therapeutic dose.

At the recommended dosage, RUPASTRAL is not expected to influence the ability to drive or use machinery. Nevertheless, RUPASTRAL may cause somnolence, headache, dizziness and a disturbance in attention; thus, care should be taken before driving or using machinery until the patient's individual reaction to RUPASTRAL has been established (see section 4.8).

a. Summary of the safety profile

The most frequent adverse reactions reported were somnolence, headache, fatigue, asthenia, dry mouth and dizziness.

b. Tabulated summary of adverse reactions

MedDRA System Organ Class

Frequency Side Effects

Infections and Infestations Less frequent Pharyngitis, rhinitis

Immune system disorders Frequency unknown Hypersensitivity reactions (including anaphylactic reactions, angioedema and urticarial)

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, abnormal gait, increased sweating

Eye disorders Frequency unknown Conjunctiva! hyperaemia, blepharitis and blister

Cardiac disorders Frequency unknown 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 Increase weight, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase, abnormal liver function test

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

The most common adverse reaction when 100 mg rupatadine was taken for 6 days 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 taken into account.