Rupafin, 10 mg tablets, 7 pcs.

Rupatadine belongs to the second generation of antihistamines and is a long-lasting and selective blocker of peripheral H1-histamine receptors. Some of its metabolites (desloratadine and 3-hydroxydesloratadine) retain antihistamine activity and may contribute to the overall effectiveness of the drug.

Rupatadine shows high affinity for H1-histamine receptors. Studies of rupatadine in vitro in high concentration have shown suppression of mast cell degranulation caused by immunological and non-immunological stimuli, suppression of eosinophil and neutrophil chemotaxis, as well as release of cytokines (IL-5 (interleukin-5), IL-6, IL-8, GM-CSF (granulocyte-macrophage colony-stimulating factor)), in particular TNF-ϖ (tumor necrosis factor alpha), from human mast cells and monocytes. In addition, rupatadine caused a dose-dependent suppression of neutrophil adhesion molecule expression.

Due to the selectivity of rupatadine toward peripheral H1-histamine receptors, it has no significant effect on central nervous system (CNS) activity at doses of 10 or 20 mg/day.

Because histamine release is a key link in the pathogenesis of all urticaria, it is expected that when rupatadine is prescribed according to clinical guidelines, it can effectively reduce the severity of symptoms not only of chronic idiopathic urticaria, but also of other variants of urticaria.

Pharmacokinetics

Rupatadine is rapidly absorbed when taken orally, with a time to reach maximum concentration (TC_max.) of approximately 0.75 hours. The mean maximum concentration (C_max) is 2.6 ng/mL after a single oral dose of 10 mg 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 a dose of 10 mg once daily for 7 days, the average Stah is 3.8 ng/ml. Plasma concentrations decrease according to a biexponential curve, with a mean half-life (T_1/2) of 5.9 hours. The binding coefficient of rupatadine to plasma proteins is 98.5 – 99%.

Since rupatadine has never been used intravenously in humans, there are no data on its absolute bioavailability.

Eating increases the overall effect of rupatadine on the body (AUC – area under the concentration-time curve) by approximately 23%. The effects on one of its active metabolites and on the main inactive metabolite are almost identical (reduction by approximately 5% and 3%, respectively). The time required to reach maximum plasma concentration (TC_max) of rupatadine was prolonged by 1 hour. C_max in plasma was not altered by food intake. These differences had no clinical significance.

A study of excretion in humans (40 mg 14C-rupatadine) found that 34.6% of the drug was excreted by the kidneys and 60.9% through the intestine within 7 days. Rupatadine undergoes significant presystemic metabolism when administered orally. The unchanged active substance is found only in small amounts in urine and feces. This means that rupatadine is almost completely metabolized. In vitro metabolism studies in human liver microsomes indicate that rupatadine is metabolized predominantly by cytochrome P450 (CYP3A4 isoenzyme).

In a study on healthy volunteers comparing results obtained in young and elderly subjects, the AUC and C_max values for rupatadine were higher in elderly study participants. This is probably due to reduced hepatic metabolism during “first passage through the liver” in the elderly. These differences were noted only for rupatadine and not for its metabolites. The mean T_1/2 of rupatadine in older and younger volunteers was 8.7 hours and 5.9 hours, respectively. Because the results for rupatadine and for its metabolites were not clinically significant, it was concluded that no dose adjustment of the drug was necessary when administered to elderly patients at a dose of 10 mg.

Indications

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

Composition

Active ingredient:

Rupatadine fumarate-12.8 mg, which corresponds to 10 mg of rupatadine;

Ancillary substances:

Pregelatinized starch-10.0 mg,

microcrystalline cellulose – 15.0 mg,

Red iron oxide dye E-172-0.025 mg,

iron oxide yellow dye E-172-0.075 mg,

lactose monohydrate – 61.1 mg,

magnesium stearate-1.0 mg

How to take, the dosage

In adults and children over 12 years of age, the recommended dose is 10 mg (one tablet) once daily.

Interaction

Interaction with ketoconazole and erythromycin
Co-administration of rupatadine at a dose of 20 mg and ketoconazole or erythromycin increases the systemic effects of rupatadine by 10 times and the latter – by 2-3 times. These combinations are not accompanied by changes in QT interval or increased frequency of adverse reactions compared to the separate use of these drugs. However, rupatadine should be used with caution together with these drugs and with other CYP3A4 isoenzyme inhibitors.

Interaction with grapefruit juice
Simultaneous use of rupatadine and grapefruit juice increases the overall effect of rupatadine by 3.5 times. Grapefruit juice should not be taken at the same time as the drug.

Interaction with alcohol
When used concomitantly with alcohol, rupatadine at a dose of 10 mg does not cause more pronounced changes in cognitive, psychomotor activity compared to taking alcohol alone. A dose of 20 mg intensifies the changes caused by alcohol intake.

Interaction with CNS depressant drugs
Interaction of rupatadine with other antihistamines and CNS depressant drugs cannot be ruled out

Interaction with statins Interaction with statins
Due to the fact that some of statins, as well as rupatadine, are metabolized by CYP3A4 isoenzyme of cytochrome Р450, the possibility of increasing of creatinine phosphokinase level in case of their combined use cannot be excluded. For these reasons, rupatadine should be used with caution concomitantly with statins.

Impact on the ability to drive and operate vehicles
No effect on the ability to drive and operate vehicles has been noted when using the drug in a dose of 10 mg. At the same time, there are reports of somnolence observed during treatment with Rupafin®. In this regard, caution is recommended when driving or engaging in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions until the patient’s individual response to Rupatadine is established.

Contraindications

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

Side effects

Nervous system disorders: drowsiness, headache, dizziness, fatigue, asthenia, decreased concentration, irritability.

Respiratory system, chest and mediastinal organs: nasal bleeding, dry nasal mucosa, pharyngitis, cough, dry throat, pain in the throat and larynx, rhinitis.

Gastrointestinal tract: dry mouth, nausea, diarrhea, dyspepsia, vomiting, abdominal pain, constipation.

Metabolism and nutrition: increase in appetite.

Skin and subcutaneous tissue disorders: rash.

Skeletal, muscular and connective tissue disorders: back pain, arthralgia, myalgia.

General disorders: thirst, malaise, fever, weight gain.

Change in laboratory parameters: increase in creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase; change in liver function tests.

Overdose

No cases of drug overdose have been described in the literature. In a study on the study of clinical safety rupatadine was well tolerated in a daily dose of 100 mg for 6 days.

Symptoms: the most common adverse reaction is drowsiness.

Treatment: if the drug is accidentally ingested in very high doses, it is indicated to induce vomiting in the patient, followed by administration of activated charcoal. If this manipulation proves impossible or ineffective, the stomach should be flushed with isotonic sodium chloride solution.

Pregnancy use

Rupafin® is contraindicated during pregnancy and lactation.