Rupafin® (Rupafin®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceRupatadineRupatadine
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  • Rupafin®
    pills inwards 
    H. Uriyah and Sia S.A.     Spain
    • Dosage form: & nbspPills.
    Composition:

    1 tablet contains:

    Active substance: rupatadine fumarate - 12.8 mg, which is equivalent to 10 mg of rupatadine.

    Excipients: pregelatinized starch - 10.0 mg; microcrystalline cellulose - 15.0 mg; iron dye red oxide (E-172) - 0.025 mg; ferric iron oxide yellow (E-172) - 0.075 mg; lactose monohydrate - 61.1 mg; magnesium stearate 1.0 mg.

    Description:Round tablets of light orange-pink color.
    Pharmacotherapeutic group:antiallergic agent - H1-histamine receptor blocker
    ATX: & nbsp
  • Rupatadine
    • Pharmacodynamics:

    Rupatadine belongs to the second generation of antihistamines and is a long-term and selectively acting blocker of peripheral H1-gistaminovyh receptors. Some of its metabolites (desloratadine and its hydroxylated derivatives) retain antihistamine activity and can contribute to the overall efficacy of the drug.

    Rupatadine shows a high affinity for H1-histamine receptors. Studies of rupatadine in vitro in a high concentration showed inhibition of degranulation of mast cells caused by immunological and non-immunological stimuli,suppression of the chemotaxis of eosinophils and neutrophils, as well as the release of cytokines (IL-5 (interleukin-5), IL-6, IL-8, GM-CSF (granulocyte-macrophage colony stimulating factor)), in particular, TNF-α (tumor necrosis factor alpha), from mast cells and human monocytes. Besides, rupatadine induced a dose-dependent suppression of the expression of neutrophil adhesion molecules.

    In clinical studies on healthy volunteers (n= 375) and in patients with allergic rhinitis and chronic idiopathic urticaria (n= 2650) there was no significant effect of rupatadine on the results of the electrocardiogram in the dose range from 2 to 100 mg.

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

    Pharmacokinetics:

    Absorption and bioavailability

    Rupatadine is rapidly absorbed after oral administration; time to reach the maximum concentration in the blood plasma (TSmOh) is approximately 0.75 hours.The mean maximum concentration in blood plasma (CmOh) is 2.6 ng / ml after a single oral intake of 10 mg and 4.6 ng / ml after single ingestion of 20 mg of rupatadine.

    Pharmacokinetics of rupatadine in the dose range from 10 mg to 20 mg is linear in single and multiple doses of the drug.

    After taking a dose of 10 mg once a day for 7 days, the average CmOh is 3.8 ng / ml. The concentration in the plasma decreases according to the biexponential curve; mean half-life (T1/2) - 5.9 hours. The binding of rupatadine to plasma proteins is 98.5-99%.

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

    Effect of food intake

    The intake of food enhances the systemic action of rupatadine on the body (AUC - area under the pharmaceutical curve "concentration-time") by approximately 23%. The effect of food on one of its active metabolites and on the basic inactive metabolite is almost the same (a decrease of about 5% and 3%, respectively). TSmOh rupatadine was extended by 1 hour. Indicator CmOh did not change as a result of eating. These differences were not of clinical significance.

    Metabolism and excretion

    In the study of excretion in humans (labeled 14C-rupatadine, 40 mg) found that 34.6% of the drug is excreted by the kidneys, and 60.9% through the intestine within 7 days. Rupatadine undergoes significant pre-systemic metabolism when ingested. The amount of unchanged active ingredient in urine and in stool was negligible. It means that rupatadine almost completely metabolized. Active metabolites, such as desloratadine and other hydroxylated derivatives, accounted for 27% and 48% of systemic exposure to active substances, respectively. Metabolic Studies in vitro, carried out on microsomes of the human liver show that rupatadine metabolized primarily through the cytochrome P450 system (isoenzyme CYP3A4).

    Special patient groups

    In a study on healthy volunteers, when comparing the results obtained in young and AUC and CmOh for rupatadine were higher in elderly participants in the study. This is probably due to a decrease in hepatic metabolism during "first passage through the liver" in elderly patients. These differences were noted only for rupatadine, and not for its metabolites. The mean value of T1/2 Rupatadine in elderly and young patients was 8.7 hours and 5.9 hours, respectively. Since the results for rupatadine and its metabolites were not clinically significant, it was concluded that when a drug is prescribed for elderly patients, a dose adjustment of 10 mg is not required.

    Indications:

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

    Contraindications:

    - Hypersensitivity to the components of the drug;

    - children under 12 years of age (efficacy and safety not established);

    - kidney failure;

    - liver failure;

    - pregnancy and the period of breastfeeding;

    - hereditary intolerance to galactose, lactase deficiency, glucose malabsorption syndrome and galactose.

    Carefully:

    Patients with an elongated interval QT, unadjusted hypokalemia, persistent predisposing to arrhythmia states, such as clinically significant bradycardia, with acute myocardial ischemia, over the age of 65; simultaneous reception with statins, simultaneous administration with grapefruit juice, simultaneous intake with moderate isoenzyme inhibitors CYP3A4; simultaneous administration with strong inhibitors of isoenzyme CYP3A4 should be avoided; simultaneous application with isoenzyme substrates CYP3A4.

    Pregnancy and lactation:

    Pregnancy

    The drug Rupafin® is contraindicated for use during pregnancy.

    Breastfeeding period

    The drug is contraindicated in the period of breastfeeding. If you need to use the drug during lactation should stop breastfeeding.

    Fertility

    There are no clinical data on the effect of the drug on human reproductive function.

    Dosing and Administration:

    Inside, regardless of food intake.

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

    Special patient groups

    Patients over 65 years of age

    The drug should be used with caution in patients over 65 years of age.
    Side effects:

    Most often in patients who received rupatadine, reported adverse reactions to the drug, such as drowsiness, headache and fatigue, manifested in 9.5%, 6.9% and 3.2% of patients, respectively. In most cases, the side effects were mild and moderate severity, drug withdrawal was not required.

    Classification of adverse reactions according to the frequency of development (number of reported cases / number of patients): often - (≥ 1/100 to <1/10); infrequently (≥ 1/1000 to <1/100); rarely - (≥1 / 10000 to <1/1000).

    From the nervous system:

    Often: drowsiness, headache, dizziness.

    Infrequent: decreased concentration of attention.

    On the part of the respiratory system, the organs of the thorax and the mediastinum:

    Infrequent: nosebleeds, dry nasal mucosa, rhinitis, pharyngitis, cough, dryness in the throat, pain in the oropharynx.

    Co side of the gastrointestinal tract:

    Often: dryness in the oral cavity.

    Infrequently: nausea, diarrhea, indigestion, vomiting, constipation, abdominal pain, including in the upper abdomen.

    From the side of metabolism and nutrition:

    Infrequent: increased appetite.

    Co side of the immune system*:

    Rarely: hypersensitivity reactions (including anaphylactoid reactions, angioedema and hives).

    Co cardiovascular system*:

    Infrequent: tachycardia, palpitation.

    From the skin and subcutaneous tissues:

    Infrequent: rash.

    Co the side of the musculoskeletal and connective tissue:

    Infrequent: back pain, arthralgia, myalgia.

    General disorders:

    Often: fatigue, asthenia.

    Infrequently: thirst, malaise, fever, irritability.

    Change in laboratory indicators:

    Infrequent: increased concentrations of creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase; change in indicators of functional hepatic tests, weight gain.

    * - violations of the cardiovascular system, skin and subcutaneous tissue were reported during postmarketing studies.

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

    Overdose:

    No cases of drug overdose have been reported. In a clinical study on safety of use rupatadine well tolerated in a daily dose of 100 mg for 6 days. The most common adverse reaction is drowsiness. In case of accidental ingestion of very high doses of the drug, it is indicated to induce vomiting in the patient with the subsequent intake of activated charcoal. If this manipulation is impossible or ineffective, it is necessary to wash the stomach with an isotonic sodium chloride solution.

    Interaction:

    The effect of other drugs on the metabolism of rupatadine

    The combined use of rupatadine with strong inhibitors of isoenzyme CYP3A4 systems of cytochrome P450 (eg, itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, nefazodone) should be avoided, and the drug should be administered simultaneously with moderate isoenzyme inhibitors CYP3A4 (erythromycin, fluconazole, diltiazem) with caution.

    Simultaneous administration of rupatadine in a dose of 20 mg with ketoconazole or erythromycin increased the systemic effect of the drug 10 times and 2-3 times, respectively. Simultaneous administration did not affect the length of the QT interval and did not increase the incidence of adverse reactions compared with the separate administration of the drugs.

    The combined use of rupatadine together with grapefruit juice 3.5 times increased the systemic effect of the drug. Grapefruit juice should not be drunk while taking rupatadine.

    Effect of rupatadine on other drugs

    With the simultaneous use of rupatadine, an increase in the concentration in the blood plasma of substances metabolized with the participation of isoenzyme CYP3A4 and having a narrow therapeutic range (eg, ciclosporin, tacrolimus, sirolimus, everolimus, cisapride), it may be necessary to adjust their dose.

    Interaction with alcohol

    With simultaneous use with alcohol, rupatadine in a dose of 10 mg does not cause a more pronounced change in cognitive, psychomotor activity compared with taking only alcohol. A dose of 20 mg increases the changes caused by taking alcohol.

    Interaction with medicines, oppressive central nervous system

    As in the case of other antihistamines, the interaction of rupatadine with substances depressing the central nervous system can not be ruled out.

    Interaction with statins

    Due to the fact that some of the statins (for example, simvastatin, lovastatin), as well as rupatadine, are metabolized by isoenzyme CYP3A4 systems of cytochrome P450, it is impossible to exclude the possibility of increasing the activity of creatinine phosphokinase when they are used together. For these reasons rupatadine should be used with caution at the same time as statins.

    Effect on the ability to drive transp. cf. and fur:

    When using the drug at a dose of 10 mg, there was no effect on the ability to drive and othermechanisms. At the same time, there are reports of drowsiness observed during drug treatment. In this regard, it is recommended to be cautious when driving a car or engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions until an individual patient's reaction to rupatadine.

    Form release / dosage:

    Tablets, 10 mg.

    Packaging:

    For 7 tablets in PVC / PVDC / Al blister. For 1, 2 blisters together with instructions for use in cardboard pack.

    For 10 tablets in PVC / PVDC / Al blister. 1 blister with instructions for use in a cardboard box.

    Storage conditions:

    In a dry place, at a temperature of no higher than 25 ° C, in the original packaging.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:Without recipe
    Registration number:LP-000960
    Date of registration:18.10.2011 / 07.11.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:H. Uriyah and Sia S.A.H. Uriyah and Sia S.A. Spain
    Manufacturer: & nbsp
    Representation: & nbspABBOTT LABORATORIES LLC ABBOTT LABORATORIES LLC Russia
    Information update date: & nbsp18.12.2016
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