Rupatadine

As there is no clinical experience in patients with impaired liver functions, the use of rupatadine is at present not recommended in these patients.

As there is no clinical experience in patients with impaired kidney functions, the use of rupatadine is at present not recommended in these patients.

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.

The concomitant administration of rupatadine with grapefruit juice increased 3.5 times the systemic exposure of rupatadine. Grapefruit juice should not be taken simultaneously.

Co-administration of rupatadine with potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, nefazodone) should be avoided.

The concomitant administration of rupatadine 20 mg and ketoconazole increases the systemic exposure to rupatadine 10 times. These modifications were not associated with an effect on the QT interval or with an increase of the adverse reactions in comparison with the drugs when administered separately.

Co-medication of rupatadine with moderate CYP3A4 inhibitors (erythromycin, fluconazole, diltiazem) should be used with caution.

The concomitant administration of rupatadine 20 mg and erythromycin increases the systemic exposure to rupatadine 2-3 times. These modifications were not associated with an effect on the QT interval or with an increase of the adverse reactions in comparison with the drugs when administered separately.

Asymptomatic CPK increases have been uncommonly reported in rupatadine clinical trials. The risk of interactions with statins, some of which are also metabolised by the cytochrome P450 CYP3A4 isoenzyme, is unknown. For these reasons, rupatadine should be used with caution when it is coadministered with statins.

Cardiac safety of rupatadine was assessed in a Thorough QT/QTc study. Rupatadine up to 10 times therapeutic dose did not produce any effect on the ECG and hence raises no cardiac safety concerns. However, rupatadine should be used with caution in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia.

There are limited amount of data from the use of rupatadine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of rupatadine during pregnancy.

Rupatadine is excreted in animal milk. It is unknown whether rupatadine is excreted into breast milk. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from rupatadine therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

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.

Rupatadine had no influence on the ability to drive and use machines. Nevertheless, care should be taken before driving or using machinery until the patient’s individual reaction on rupatadine has been established.

Oral administration – Tablet

Rupatadine 10 mg tablets has been administered to over 2,025 adult and adolescents patients in clinical studies, 120 of whom received rupatadine for at least 1 year.

The most common adverse reactions in controlled clinical studies were somnolence (9,5%), headache (6,9%) and fatigue (3,2%)

The majority of the adverse reactions observed in clinical trials were mild to moderate in severity and they usually did not require cessation of therapy.

The frequencies of adverse reactions are assigned as follows: Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1,000).

Infections and infestations

Uncommon: Pharyngitis, Rhinitis

Immune system disorders

Rare: Hypersensitivity reactions (including anaphylactic reactions, angioedema and urticaria)*

Metabolism and nutrition disorders

Uncommon: Increased appetite

Nervous system disorders:

Common: Somnolence, Headache, Dizziness

Uncommon: Disturbance in attention

Cardiac disorders

Rare: tachycardia and palpitations*

Respiratory, thoracic, and mediastinal disorders

Uncommon: Epistaxis, Nasal dryness, Cough, Dry throat, Oropharyngeal pain

Gastrointestinal disorders

Common: Dry mouth

Uncommon: Nausea, Abdominal pain upper, Diarrhoea, Dyspepsia, Vomiting, Abdominal pain, Constipation

Skin and subcutaneous tissue disorders

Uncommon: Rash

Musculoskeletal, connective tissues, and bone disorders

Uncommon: Back pain, Arthralgia, Myalgia

General Disorders and administration site condition

Common: Fatigue, Asthenia

Uncommon: Thirst, Malaise, Pyrexia, Irritability

Investigations

Uncommon: Blood creatine phosphokinase increased, Alanine aminotransferase increased, Aspartate aminotransferase increased, Liver function test abnormal, Weight increased

* tachycardia and palpitations and hypersensitivity reactions (including anaphylactic reactions, angioedema and urticarial) have been reported in post-marketing experience with rupatadine 10 mg tablets.

Oral administration – Oral solution

Clinical trials with rupatadine oral solution in children aged 2-11 years included 626 patients. From these, 147 patients were treated with rupatadine 2.5 mg, 159 patients were treated with rupatadine 5 mg, 249 received placebo and 71 received desloratadine.

The frequencies of adverse reactions are assigned as follows: Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100).

The frequencies of adverse reactions reported in patients treated with rupatadine oral solution during clinical trials were as follows: