Instructions Blis oral solution 1 mg/ml bottle 100 ml
Composition
active ingredient: rupatadine fumarate;
1 ml contains rupatadine fumarate 1.28 mg equivalent to rupatadine 1 mg;
excipients: sodium hydrogen phosphate anhydrous, citric acid anhydrous, methyl parahydroxybenzoate (E 218), propylene glycol, sucrose, sodium saccharin, banana flavoring, purified water.
Dosage form
Oral solution.
Main physicochemical properties: clear colorless or yellowish liquid with a banana odor.
Pharmacotherapeutic group
Other antihistamines for systemic use. ATX code R06A X28.
Pharmacological properties
Pharmacodynamics
Rupatadine belongs to the second generation of antihistamines and is a long-acting histamine antagonist with selective peripheral antagonistic activity at H1 receptors. Some of its metabolites (desloratadine and its hydroxylated metabolites) retain antihistamine activity and may contribute in part to the overall efficacy of the drug.
In vitro studies with rupatadine at high concentrations have shown inhibition of mast cell degranulation induced by immunological and non-immunological stimuli, as well as the release of cytokines, in particular TNF, from human mast cells and monocytes. The clinical significance of the observed experimental data remains to be confirmed.
The pharmacodynamic effect (reduction in the area with blisters, antihistamine effect) was observed 4 weeks after treatment.
Because rupatadine has the ability to block the release of histamine and other inflammatory mediators, it is expected to be effective in treating the symptoms of other types of urticaria besides chronic spontaneous urticaria.
Pharmacokinetics
Children
Rupatadine is rapidly absorbed after a mean dose of 5 mg with a mean Tmax of 0.5 hours after administration. The mean Cmax was 2.5 ng/ml after a single oral dose. Regarding exposure, the mean total area under the curve (AUC) was 8.86 ng•h/ml. All these values are similar to those obtained in adults and adolescents.
The mean half-life of rupatadine in children was 3.12 hours, which is shorter than for tablets taken by adults and adolescents.
The effect of eating
No food interaction studies have been conducted with rupatadine oral solution. A food interaction study was conducted in adults and adolescents using rupatadine 10 mg tablets. Food intake increases the systemic exposure (AUC) of rupatadine by approximately 23%. The maximum plasma concentration (Cmax) is not affected by food intake. These differences are not clinically relevant.
Metabolism and excretion
In an excretion study in adults, 34.6% of the administered rupatadine was excreted in the urine and 60.9% in the faeces collected over 7 days. Rupatadine undergoes extensive first-pass metabolism following oral administration. Only minor amounts of unchanged active substance are found in the urine and faeces. This indicates that rupatadine is almost completely metabolised. Overall, the active metabolites of desloratadine and other hydroxylated derivatives accounted for 27% and 48% of the total systemic exposure of the active substances, respectively. In vitro metabolism studies in human liver microsomes showed that rupatadine is metabolised mainly by cytochrome P450 (CYP 3A4).
Indication
Symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis) and urticaria in children aged 2 to 11 years.
Contraindication
Hypersensitivity to rupatadine or to any other component of the drug.
Interaction with other medicinal products and other types of interactions
Interaction studies with rupatadine oral solution have not been conducted in children.
Interaction studies have only been conducted in adults and adolescents (aged 12 years and over) using rupatadine 10 mg tablets.
Effects of other medicinal products on rupatadine
Co-administration with potent CYP3A4 inhibitors (including itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, nefazodone) should be avoided. Co-administration with moderate CYP3A4 inhibitors (erythromycin, fluconazole, diltiazem) should be used with caution.
Co-administration of rupatadine 20 mg with ketoconazole or erythromycin increases the systemic exposure of rupatadine by 10-fold and the latter by 2-3-fold. 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.
Interaction with grapefruit
Concomitant administration of rupatadine 10 mg tablets and grapefruit juice increases the total exposure of rupatadine by 3.5 times. This is because grapefruit juice contains one or more components that inhibit CYP3A4 and may increase the plasma concentrations of drugs metabolised by CYP3A4, such as rupatadine. It has also been suggested that grapefruit may affect intestinal drug transport systems such as P-glycoprotein. Grapefruit juice should not be consumed at the same time as the drug.
Caution should be exercised when co-administering rupatadine with other drugs that are metabolized and have a narrow therapeutic index, as data on the effects of rupatadine on other drugs are limited.
Interaction with alcohol
After alcohol intake, a dose of 10 mg rupatadine had a slight effect on the results of some psychomotor performance tests, which was not significantly different from the effect of alcohol intake alone. A dose of 20 mg enhanced the changes caused by alcohol intake.
Interaction with CNS depressants
As with other antihistamines, interactions with CNS depressants cannot be ruled out.
Interaction with statins
Asymptomatic elevations of creatine phosphokinase have occasionally been reported in clinical trials with rupatadine. The risk of interaction with statins (some of which are also metabolised by the cytochrome P450 isoenzyme CYP3A4) is unknown. Therefore, rupatadine should be used with caution when co-administered with statins.
Application features
The combination of rupatadine with potent CYP3A4 inhibitors should be avoided, and should be administered with caution with moderate CYP3A4 inhibitors.
Dose adjustment of sensitive CYP3A4 substrates (e.g. simvastatin, lovastatin) and CYP3A4 substrates with a narrow therapeutic index (e.g. cyclosporine, tacrolimus, sirolimus, everolimus, cisapride) may be required, as rupatadine may increase the plasma concentrations of these drugs.
The effect of rupatadine 10 mg tablets on cardiac function was evaluated in the Thorough QT/QTc study in adults, in which rupatadine at a dose exceeding the therapeutic dose by 10 times did not affect the ECG and thus did not raise any cardiac safety concerns. However, rupatadine should be administered with caution to patients with prolonged QT interval, patients with uncorrected hypokalemia, patients with persistent proarrhythmic conditions such as clinically significant bradycardia, acute myocardial ischemia.
Elevations in creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase, and changes in liver function tests have been reported as uncommon adverse reactions to rupatadine 10 mg tablets in adults.
Concomitant administration of rupatadine with grapefruit juice is not recommended.
Patients with renal or hepatic insufficiency: Due to the lack of clinical experience, the use of the drug in patients with impaired renal or hepatic function is not recommended.
Children: The safety and efficacy of rupatadine in children under 2 years of age have not been established.
This medicine contains saccharin sodium, which may be harmful to teeth. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
The medicine contains methyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).
Ability to influence reaction speed when driving vehicles or other mechanisms
The medicine is used for children.
Rupatadine 10 mg had no effect on the ability to drive or use machines in clinical studies. However, the patient should first assess their own response to treatment with the drug before driving or operating machinery.
Use during pregnancy or breastfeeding
The medicine is used for children.
Pregnancy
Data on a limited number (2) exposed pregnancies indicate no adverse effects of rupatadine on pregnancy or on the health of the foetus/newborn child. No other relevant epidemiological data are available. 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 use during pregnancy.
Breast-feeding
Rupatadine is excreted in animal milk. It is not known whether rupatadine is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from rupatadine therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no clinical data on the effect of the drug on fertility. Animal studies have shown a significant reduction in fertility at exposure levels higher than in humans at the maximum therapeutic dose.
Method of administration and doses
To ensure accurate dosing, the package contains a syringe-doser.
Insert the syringe-doser into the neck of the bottle and measure the required amount of solution, taking into account the age and body weight of the child.
Please note that if the bottle contains an adapter placed in the neck, in this case, firmly insert the syringe-doser into the neck of the adapter and turn the bottle upside down, carefully pull the piston, drawing the liquid into the syringe-doser to the desired mark. Having drawn the required amount of solution, turn the bottle to its original position and carefully remove the syringe-doser from the bottle.
After use, rinse the parts of the syringe-dispenser with warm water.
Dosage
With a body weight of 10 kg or more but less than 25 kg: 2.5 ml (2.5 mg of rupatadine) oral solution once daily, regardless of meals.
With a body weight of 25 kg or more: 5 ml (5 mg of rupatadine) oral solution once a day, regardless of meals.
Children
The medicine should be used in children aged 2 to 11 years.
Since there is insufficient data on the use of the medicinal product in children under 2 years of age, its use in this age group is not recommended.
Overdose
No cases of overdose have been reported in adults or children. In a clinical safety study, rupatadine was well tolerated at a daily dose of 100 mg for 6 days. The most common adverse reaction was drowsiness. In case of accidental ingestion of very high doses, symptomatic treatment and appropriate supportive measures should be taken.
Adverse reactions
The frequency of adverse reactions is defined as follows: common (≥ 1/100 < 1/10); uncommon (≥ 1/1000 < 1/100).
From the blood and lymphatic system: infrequently - eosinophilia, neutropenia.
From the nervous system: often - headache, drowsiness; infrequently - dizziness.
Gastrointestinal: infrequently - nausea.
Skin and connective tissue disorders: uncommon – eczema, night sweats.
Infections and infestations: uncommon – influenza, nasopharyngitis, upper respiratory tract infections.
General disorders: infrequently - fatigue.
Expiration date
2 years.
The shelf life after first opening the bottle is 12 months.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
100 ml in a bottle without an adapter. 1 bottle with a dosing syringe in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
