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Active ingredients
Rupatadina Fumarate
Release form
Pills
Composition
Rupatadina fumarat 12.8 mg, which corresponds to the content of rupatadin 10 mg. Auxiliary substances: pregelatinized starch - 10 mg, microcrystalline cellulose - 15 mg, iron dye red oxide (E172) - 0.025 mg, iron dye yellow oxide (E172) - 0.075 mg, lactose monohydrate - 61.1 mg, magnesium stearate - 1 mg.
Pharmacological effect
Blocking histamine H1-receptor II generation. Selectively acting on peripheral histamine H1 receptors. Some of its metabolites (desloratadine and 3-hydroxydesloratadine) retain antihistamine activity and may contribute to the overall effectiveness of rupatadine. Rupatadin exhibits high affinity for the H1-histamine receptors. In vitro studies of rupatadine in high concentration showed suppression of mast cell degranulation caused by immunological and non-immunological stimuli, suppression of chemotaxis of eosinophils and neutrophils, as well as release of cytokines (interleukin (IL) -5, IL-6, IL-8, GM-CSF ( granulocyte-macrophage colony-stimulating factor)), in particular TNFα from mast cells and human monocytes. In addition, rupatadine caused a dose-dependent suppression of the expression of neutrophil adhesion molecules. Due to the selectivity of rupatadine for peripheral histamine H1 receptors, it does not have a significant effect on the central nervous system in doses of 10 or 20 mg / day.
Pharmacokinetics
Rupatadin is rapidly absorbed after ingestion, the time to reach Cmax is approximately 0.75 hours. The average Cmax is 2.6 ng / ml after a single ingestion of 10 mg of rupatadine and 4.6 ng / ml of a single ingestion of 20 mg of rupatadine. The pharmacokinetics of rupatadine is linear for doses of 10 to 40 mg. After taking 10 mg 1 time / day for 7 days, the average Cmax is 3.8 ng / ml. Plasma concentration decreases along a biexponential curve with an average T1 / 2 of 5.9 h. The coefficient of binding of rupatadine to plasma proteins is 98.5-99%. Since rupatadine has never been used in / in humans, there is no data on its absolute bioavailability. Food intake enhances the overall effect of rupatadine on the body (AUC increases by about 23%). The effect on one of its active metabolites and on the main inactive metabolite is almost the same (a decrease of about 5% and 3%, respectively). The time required to reach Cmax of rupatadine was lengthened by 1 hour. Cmax in plasma did not change as a result of co-administration with food.These differences had no clinical significance. Rupatadin undergoes a significant presystemic metabolism when taken orally. Unchanged active substance is found in the urine and in the feces only in small quantities. This means rupatadine is almost completely metabolized. Studies of in vitro metabolism in human liver indicate that rupatadin is metabolized mainly by CYP3A4 isoenzyme). In a study of excretion in humans (40 mg of 14C-rupatadin), it was found that 34.6% of the drug is excreted by the kidneys and 60.9% through the intestine within 7 days. The average T1 / 2 is 5.9 hours. In a study in healthy volunteers, when comparing the results obtained in young and old people, the AUC and Cmax values for rupatadine were higher in the elderly study participants. This is probably due to a decrease in hepatic metabolism during the first passage through the liver in the elderly. These differences were noted only for rupatadine, and not for its metabolites. The mean T1 / 2 of rupatadine in the elderly and young volunteers was 8.7 h and 5.9 h, respectively. Results for rupatadine and its metabolites were not clinically significant.
Indications
Symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.
Contraindications
Renal failure, liver failure, pregnancy, lactation (breastfeeding), children under 12 years old; hypersensitivity to rupatadine.
Use during pregnancy and lactation
contraindicated for use during pregnancy and lactation
Dosage and administration
It is taken orally. For adults and children over 12 years old, the recommended dose is 10 mg 1 time / day.
Side effects
From the nervous system: often - drowsiness, headache, dizziness, fatigue, asthenia; Infrequently - decreased concentration, irritability. From the respiratory system: rarely - nosebleeds, dry nasal mucosa, pharyngitis, cough, dry throat, pain in the throat and larynx, rhinitis. From the digestive system: often - dry mouth ; infrequently - nausea, diarrhea, dyspepsia, vomiting, abdominal pain, constipation. Metabolism and nutrition: infrequently - increased appetite. From the skin and subcutaneous tissues: rarely - rash. Musculoskeletal system: infrequently - pain in back, arthralgia, myalgia. On the whole body side: infrequently - thirst, malaise, fever, weight gain. Changing laboratory parameters: infrequently - increasing CK, ALT, AST,change in functional liver function tests.
Interaction with other drugs
The combined use of rupatadine in a dose of 20 mg and ketoconazole or erythromycin enhances the systemic effects of rupatadine 10 times and the latter - by 2-3 times. These combinations are not accompanied by changes in the QT interval or an increase in the frequency of adverse reactions compared with the separate use of these drugs. However, rupatadine should be used with caution in conjunction with these medicinal substances and with other inhibitors of the CYP3A4 isoenzyme. Simultaneous administration of rupatadine and grapefruit juice 3.5 times enhances the overall effect of rupatadine. You should not use grapefruit juice simultaneously with taking rupatadina. Rupatadin in a dose of 20 mg enhances changes in cognitive and psychomotor activity caused by taking ethanol. One cannot exclude the possibility of interaction of rupatadine with other antihistamines and CNS depressants. Due to the fact that some of the statins , as well as rupatadin, are metabolized by cytochrome P450 CYP3A4 isoenzyme, it is impossible to exclude the possibility of increasing the level of CPK when they are used together. For these reasons, rupatadine should be used with caution along with statins.
special instructions
Caution should be used in patients with an extended QT interval, uncorrected hypokalemia, persistent proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia; in elderly patients (65 years and older); simultaneously with statins, simultaneously with grapefruit juice. Impact on the ability to drive vehicles and control mechanisms During the period of treatment, patients are advised to exercise caution when driving vehicles and other potentially dangerous activities that require increased concentration and psychomotor speed, until an individual reaction to rupatadine.