Rupafin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Noucor Health, S.A. (Spain)

ATC Code

R06AX28 (Rupatadine)

Active Substance

Rupatadine

Dosage Form

Rupafin®

Tablets 10 mg: 7, 10, or 14 pcs.

Dosage Form, Packaging, and Composition

Tablets light orange-pink in color, round.

Excipients : pregelatinized starch – 10 mg, microcrystalline cellulose – 15 mg, iron oxide red dye (E172) – 0.025 mg, iron oxide yellow dye (E172) – 0.075 mg, lactose monohydrate – 61.1 mg, magnesium stearate – 1 mg.

7 pcs. – blisters (1) – cardboard packs.
7 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

H1 histamine receptor blocker

Pharmacological Action

A second-generation histamine H₁-receptor blocker. It acts selectively on peripheral histamine H₁ receptors. Some of its metabolites (desloratadine and 3-hydroxydesloratadine) retain antihistamine activity and may contribute to the overall efficacy of rupatadine.

Rupatadine exhibits high affinity for H₁-histamine receptors. In vitro studies of rupatadine at high concentrations showed suppression of mast cell degranulation induced by immunological and non-immunological stimuli, suppression of eosinophil and neutrophil chemotaxis, and release of cytokines (interleukin (IL)-5, IL-6, IL-8, GM-CSF (granulocyte-macrophage colony-stimulating factor)), in particular TNFα from human mast cells and monocytes. Furthermore, Rupatadine caused a dose-dependent suppression of neutrophil adhesion molecule expression.

Due to the selectivity of rupatadine for peripheral histamine H₁ receptors, it does not have a significant effect on the CNS at doses of 10 or 20 mg/day.

Pharmacokinetics

Rupatadine is rapidly absorbed after oral administration, with the time to reach C_max being approximately 0.75 hours. The mean C_max is 2.6 ng/ml after a single oral dose of 10 mg rupatadine and 4.6 ng/ml after a single oral dose of 20 mg rupatadine. The pharmacokinetics of rupatadine are linear for doses from 10 to 40 mg.

After taking 10 mg once daily for 7 days, the mean C_max is 3.8 ng/ml. Plasma concentration decreases in a bi-exponential curve with a mean T_1/2 of 5.9 hours. The plasma protein binding of rupatadine is 98.5-99%. Since Rupatadine has never been administered intravenously in humans, data on its absolute bioavailability are not available.

Food intake enhances the overall effect of rupatadine on the body (AUC increases by approximately 23%). The exposure to one of its active metabolites and to the main inactive metabolite is almost the same (a decrease of approximately 5% and 3%, respectively). The time required to reach C_max for rupatadine was prolonged by 1 hour. C_max in plasma did not change as a result of simultaneous administration with food. These differences were not clinically significant.

Rupatadine undergoes significant presystemic metabolism upon oral administration. The unchanged active substance is found in urine and feces only in negligible amounts. This means that Rupatadine is almost completely metabolized. In vitro metabolism studies in human liver microsomes indicate that Rupatadine is metabolized primarily by the CYP3A4 isoenzyme.

In a human excretion study (40 mg ¹⁴C-rupatadine), it was found that 34.6% of the drug is excreted by the kidneys, and 60.9% via the intestine over 7 days. The mean T_1/2 is 5.9 hours.

In a study in healthy volunteers comparing results obtained in young and elderly individuals, the AUC and C_max values for rupatadine were higher in the elderly study participants. This is likely due to reduced hepatic first-pass metabolism in the elderly. These differences were noted only for rupatadine, and not for its metabolites. The mean T_1/2 of rupatadine in elderly and young volunteers was 8.7 hours and 5.9 hours, respectively. The results for rupatadine and its metabolites were not clinically significant.

Indications

Symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

ICD codes

Dosage Regimen

Take orally with a glass of water.

For adults and adolescents over 12 years of age, the recommended dose is 10 mg once daily.

Administer the tablet with or without food; food intake does not significantly alter clinical efficacy.

Do not exceed the recommended daily dose of 10 mg.

For patients with renal impairment or hepatic impairment, do not use this medication; it is contraindicated.

In elderly patients (65 years and older), use with caution due to potential for increased plasma concentrations.

Exercise caution when co-administering with potent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) due to a significant increase in systemic exposure.

Avoid concurrent consumption of grapefruit juice, as it increases rupatadine exposure.

The duration of treatment depends on the indication; for allergic rhinitis, use during the allergen exposure period; for chronic idiopathic urticaria, continue as long as symptomatic control is required.

Discontinue use and consult a physician if symptoms persist or worsen.

Adverse Reactions

Nervous system disorders common – drowsiness, headache, dizziness, fatigue, asthenia; uncommon – impaired concentration, irritability.

Respiratory system disorders uncommon – epistaxis, dryness of the nasal mucosa, pharyngitis, cough, dry throat, pharyngeal and laryngeal pain, rhinitis.

Digestive system disorders common – dry mouth; uncommon – nausea, diarrhea, dyspepsia, vomiting, abdominal pain, constipation.

Metabolism and nutrition disorders uncommon – increased appetite.

Skin and subcutaneous tissue disorders uncommon – rash.

Musculoskeletal system disorders uncommon – back pain, arthralgia, myalgia.

General disorders uncommon – thirst, malaise, fever, weight gain.

Changes in laboratory parameters uncommon – increased CPK, ALT, AST, changes in liver function test parameters.

Contraindications

Renal failure, hepatic failure, pregnancy, lactation (breastfeeding), children under 12 years of age; hypersensitivity to rupatadine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Special Precautions

Use with caution in patients with prolonged QT interval, uncorrected hypokalemia, persistent proarrhythmic conditions such as clinically significant bradycardia, acute myocardial ischemia; in elderly patients (65 years and older); concurrently with statins, concurrently with grapefruit juice.

Effect on ability to drive vehicles and operate machinery

During the treatment period, patients are advised to exercise caution when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions until the individual response to Rupatadine is established.

Drug Interactions

Concomitant use of rupatadine at a dose of 20 mg and ketoconazole or erythromycin increases the systemic exposure of rupatadine by 10 times and of the latter by 2-3 times. These combinations were not accompanied by changes in the QT interval or an increase in the frequency of adverse reactions compared to the separate use of these drugs. However, Rupatadine must be used with caution in combination with these medicinal substances and with other inhibitors of the CYP3A4 isoenzyme.

Concomitant intake of rupatadine and grapefruit juice increases the overall effect of rupatadine by 3.5 times. Grapefruit juice should not be consumed simultaneously with the intake of rupatadine.

Rupatadine at a dose of 20 mg enhances the changes in cognitive and psychomotor activity caused by ethanol intake.

The possibility of interaction of rupatadine with other antihistamine drugs and agents that depress the CNS cannot be excluded.

Since some statins, like Rupatadine, are metabolized by the CYP3A4 isoenzyme of cytochrome P450, the possibility of an increase in CPK levels with their concomitant use cannot be excluded. For the reasons stated, Rupatadine should be used with caution concurrently with statins.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.