Yunorm 2mg/ml 4ml 5 ampoules

YUNORM Composition: Active substance: Ondansetron. 1 ml of solution contains Ondansetron hydrochloride dihydrate, equivalent to 2 mg of Ondansetron; Excipients: Sodium chloride, anhydrous citric acid, sodium citrate, water for injection. Dosage form. Solution for injection. Main physicochemical properties: Clear, colorless or slightly yellowish liquid. Pharmacotherapeutic group. Antiemetics and antinauseants. Serotonin 5HT3 receptor antagonists. Pharmacological properties Pharmacodynamics. Ondansetron is a potent, highly selective antagonist of 5HT3 (serotonergic) receptors. The drug prevents or eliminates nausea and vomiting induced by cytotoxic chemotherapy and/or radiotherapy, as well as postoperative nausea and vomiting. The mechanism of action of ondansetron is not fully understood. It is possible that the drug blocks the generation of the vomiting reflex by exerting an antagonistic effect on 5HT3 receptors located in neurons of both the peripheral and central nervous systems. The drug does not reduce the patient's psychomotor activity and does not have a sedative effect. Pharmacokinetics. The volume of distribution in adults after parenteral administration is 140 L. The main part of the administered dose is metabolized in the liver. Less than 5% of the drug is excreted unchanged in the urine. The half-life is approximately 3 hours (in elderly patients - 5 hours). Plasma protein binding is 70-76%. In patients with moderate renal impairment (creatinine clearance 15-60 ml/min), both systemic clearance and volume of distribution of ondansetron decrease, leading to a slight and clinically insignificant increase in the drug's half-life. The pharmacokinetics of ondansetron are practically unchanged in patients with severe renal impairment undergoing regular hemodialysis (studies were conducted between hemodialysis sessions). In patients with severe chronic liver failure, the systemic clearance of ondansetron is significantly reduced with an increase in half-life (15-32 hours). Clinical features. Indications: Nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Prevention and treatment of postoperative nausea and vomiting. Contraindications: The use of ondansetron with apomorphine hydrochloride is contraindicated due to reported cases of severe arterial hypotension and syncope with concomitant use. Hypersensitivity to any component of the drug. Interactions with other medicinal products and other types of interactions. Ondansetron does not accelerate or inhibit the metabolism of other drugs when used concomitantly. Specific studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental, or propofol. Ondansetron is metabolized by various enzymes of the cytochrome P450 hepatic system: CYP3A4, CYP2D6, and CYP1A2. Due to the diversity of enzymes involved in the metabolism of ondansetron, the inhibition or reduction of the activity of one of them (e.g., genetic deficiency of CYP2D6) is usually compensated by other enzymes under normal conditions and does not affect the overall creatinine clearance or the effect will be insignificant. Ondansetron should be used with caution with medicinal products that prolong the QT interval and/or cause electrolyte imbalance (see section "Special precautions for use"). The use of YUNORM with other medicinal products that prolong the QT interval may lead to additional prolongation of the QT interval. Combined use of ondansetron with cardiotoxic agents (e.g., anthracyclines, such as doxorubicin, daunorubicin) or trastuzumab), antibiotics (e.g., erythromycin), antifungal agents (e.g., ketoconazole), antiarrhythmics (e.g., amiodarone), and beta-blockers (e.g., atenolol or timolol) may increase the risk of arrhythmias (see section "Special precautions for use"). Serotonergic agents (e.g., selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)). Serotonin syndrome (including changes in mental status, autonomic instability, and neuromuscular disorders) has been reported following concomitant use of ondansetron and other serotonergic agents, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (see section "Special precautions for use"). Apomorphine. The use of ondansetron with apomorphine hydrochloride is contraindicated due to reported cases of severe arterial hypotension and syncope with concomitant use. Phenytoin, carbamazepine, and rifampicin. In patients treated with potential CYP3A4 inducers (e.g., phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron increases, and its concentration in the blood decreases. Tramadol. According to some clinical studies, ondansetron may reduce the analgesic effect of tramadol. Special precautions for use. Hypersensitivity reactions have been observed in patients with a history of hypersensitivity to other selective 5HT3 receptor antagonists. Respiratory system-related reactions are treated symptomatically. Healthcare professionals should pay special attention to them, as these are signs of hypersensitivity reactions to the drug. Ondansetron dose-dependently prolongs the QT interval (see section "Pharmacological properties"). Furthermore, according to post-marketing surveillance data, there have been reports of cases of ventricular tachycardia/fibrillation (torsade de pointes) with the use of ondansetron. The use of ondansetron should be avoided in patients with congenital long QT syndrome. Ondansetron should be used with caution in patients who have or may develop QT interval prolongation, including patients with electrolyte imbalance, congestive heart failure, bradyarrhythmia, or patients being treated with other drugs that may cause QT interval prolongation or electrolyte imbalance. There have been reports of myocardial ischemia in patients taking ondansetron. Some patients, mainly during intravenous administration, experienced symptoms immediately after ondansetron administration, but they resolved with prompt treatment. Therefore, caution should be exercised during and after the administration of ondansetron. Hypokalemia and hypomagnesemia should be corrected before using ondansetron. Serotonin syndrome has been reported following concomitant use of ondansetron and other serotonergic agents (see section "Interactions with other medicinal products and other types of interactions"). If concomitant treatment with ondansetron and other serotonergic agents is clinically justified, appropriate patient monitoring is recommended. Since ondansetron slows intestinal motility, patients with signs of subacute intestinal obstruction should be adequately monitored when using YUNORM. In patients undergoing surgery in the adenotonsillar region, the use of ondansetron for the prevention of nausea and vomiting may mask the occurrence of bleeding. Therefore, such patients should be adequately monitored after the use of ondansetron. Children. In children receiving ondansetron concomitantly with hepatotoxic chemotherapeutic agents, adequate monitoring for possible liver function abnormalities is necessary. Dosage regimen. When calculating the dose by body weight and using three doses at 4-hour intervals, the total daily dose will be higher than a single dose of 5 mg/m2 and a single oral dose of the drug. The comparative efficacy of these two dosing regimens has not been evaluated in clinical trials. Comparison of results from different studies indicates similar efficacy for both dosing regimens. Excipients with known effect. The medicinal product YUNORM (4 ml) contains less than 1 mmol (23 mg) of sodium per dose (1 ml of solution contains 0.157 mmol (3.6 mg) of sodium), i.e., it is practically sodium-free. The medicinal product in the maximum daily dose (16 ml) contains 2.512 mmol (or 57.6 mg) of sodium. This is equivalent to approximately 2.9% of the maximum recommended daily intake of sodium from food for an adult. Use during pregnancy or lactation. Women of reproductive age. Women of reproductive age should use contraception. Pregnancy. Based on human experience, epidemiological studies suggest a suspicion of the development of craniofacial defects with the use of ondansetron in the first trimester of pregnancy. In one cohort study involving 1.8 million pregnancies, the use of ondansetron in the first trimester of pregnancy was associated with an increased risk of oral cleft development (three additional cases per 10,000 women receiving treatment; adjusted relative risk 1.24 (95% confidence interval 1.03-1.43)). Conducted epidemiological studies of congenital heart defects have shown conflicting results. Animal studies have not shown direct or indirect harmful effects on reproductive toxicity. The use of ondansetron in the first trimester of pregnancy is not recommended. Breastfeeding. Experimental studies have shown that ondansetron passes into the milk of lactating animals. If the drug needs to be used, breastfeeding should be discontinued. Fertility. There is no information on the effect of ondansetron on human fertility. Ability to affect reaction speed when driving vehicles or operating other machinery. Psychomotor tests have shown that ondansetron does not affect the ability to operate machinery and does not have a sedative effect, but the drug's side effect profile should be considered when deciding on the ability to drive vehicles or operate other machinery. Method of administration and dosage: Nausea and vomiting induced by chemotherapy and radiotherapy. Adults. The emetogenic potential of cancer therapy varies depending on the doses and combinations of chemotherapy and radiotherapy regimens. The choice of dosing regimen depends on the severity of the emetogenic effect. The dose of YUNORM (range 8 mg to 32 mg per day) and the method of administration are selected as indicated below. Emetogenic chemotherapy and radiotherapy. The recommended intravenous or intramuscular dose of YUNORM is 8 mg as a slow intravenous injection, over at least 30 seconds, or intramuscular injection immediately before treatment. For the prevention of delayed or prolonged vomiting, oral or rectal administration of the drug is recommended for up to 5 days after the end of the treatment course. Highly emetogenic chemotherapy (e.g., high doses of cisplatin). YUNORM can be administered as a single 8 mg dose intravenously or intramuscularly, immediately before chemotherapy. For highly emetogenic chemotherapy, dilution of YUNORM at a dose of 8 mg or less is not required and can be administered as a slow intravenous or intramuscular injection (at least 30 seconds), immediately before chemotherapy, followed by two intravenous or intramuscular administrations of 8 mg every 2 or 4 hours, or as a continuous infusion at a dose of 1 mg/h for 24 hours. Doses higher than 8 mg (16 mg) can only be used as an intravenous infusion in 50-100 ml of 0.9% sodium chloride solution or other compatible diluent (see "Use of solution for injection" below); the infusion should last at least 15 minutes. A single dose exceeding 16 mg cannot be used, as the risk of QT interval prolongation increases with increasing dose (see section "Special precautions for use"). The choice of dosing regimen depends on the severity of the emetogenic effect. The efficacy of YUNORM in highly emetogenic chemotherapy can be enhanced by the additional single intravenous administration of 20 mg of dexamethasone sodium phosphate before chemotherapy. For the prevention of delayed or prolonged vomiting, oral or rectal administration of the drug is recommended after the first 24 hours. Children aged 6 months to 17 years. In pediatric practice, YUNORM administration is recommended by intravenous infusion in 25-50 ml of 0.9% sodium chloride solution or other compatible diluent (see "Use of solution for injection" below) over at least 15 minutes. The drug dose can be calculated based on body surface area or body weight. Dose calculation based on body surface area. YUNORM administration is recommended immediately before chemotherapy at a dose of 5 mg/m2 as a single intravenous injection; the intravenous dose should not exceed 8 mg. 12 hours later, oral administration of the drug can be initiated, which can be continued for another 5 days. The adult dose cannot be exceeded. YUNORM should be diluted with 5% glucose solution or 0.9% sodium chloride solution or other appropriate infusion solution and administered by intravenous infusion over at least 15 minutes. There are no controlled clinical trial data on the use of ondansetron in children for the prevention of delayed or prolonged vomiting during chemotherapy, nor data on its use in children for the treatment of nausea and vomiting induced by radiotherapy. Dose calculation based on body weight. YUNORM administration is recommended immediately before chemotherapy at a dose of 0.15 mg/kg as a single intravenous injection. The intravenous dose should not exceed 8 mg. On the first day, 2 more intravenous doses can be administered at 4-hour intervals. 12 hours later, oral administration of the drug can be initiated, which can be continued for another 5 days. The adult dose cannot be exceeded. Elderly patients. For patients over 65 years of age, all intravenous injection doses should be diluted and administered over 15 minutes; the interval between repeated administrations should be at least 4 hours. In patients aged 65 to 74 years, the initial dose of ondansetron should be 8 mg or 16 mg, administered by intravenous infusion over at least 15 minutes, which can be continued with two 8 mg doses administered over 15 minutes with at least 4 hours between infusions. In patients over 75 years of age, the initial intravenous injection of ondansetron should not exceed 8 mg by infusion over at least 15 minutes. After an initial dose of 8 mg, administration can be continued with two 8 mg doses, administered by infusion over 15 minutes, with at least 4 hours between infusions. Patients with renal impairment. There is no need to change the dosing regimen or method of administration of the drug in patients with impaired renal function. Patients with hepatic impairment. In patients with moderate and severe hepatic impairment, the clearance of YUNORM is significantly reduced, and the half-life from blood serum increases. For such patients, the maximum dose of the drug should not exceed 8 mg. Patients with impaired metabolism of sparteine/debrisoquine. The half-life of ondansetron in patients with impaired metabolism of sparteine and debrisoquine does not change. After repeated administration in such patients, the drug concentration is the same as in patients without metabolic impairment. Therefore, there is no need to change the dosage or frequency of administration. Postoperative nausea and vomiting. Adults. For the prevention of postoperative nausea and vomiting, the recommended dose of YUNORM is 4 mg as a single intramuscular or slow intravenous injection during induction of anesthesia. For the treatment of postoperative nausea and vomiting, the recommended single dose of YUNORM is 4 mg as an intramuscular or slow intravenous injection. Children aged 1 month to 17 years. For the prevention and treatment of postoperative nausea and vomiting in children undergoing surgery under general anesthesia, YUNORM can be administered at a dose of 0.1 mg/kg body weight (maximum - up to 4 mg) as a slow intravenous injection (over at least 30 seconds) before, during, or after anesthesia, or after surgery. Elderly patients. Experience with the use of YUNORM for the prevention and treatment of postoperative nausea and vomiting in elderly patients is limited; however, the drug is well tolerated in patients over 65 years of age undergoing chemotherapy. Patients with renal impairment. There is no need to change the dosing regimen or method of administration of the drug in patients with impaired renal function. Patients with hepatic impairment. In patients with moderate and severe hepatic impairment, the clearance of YUNORM is significantly reduced, and the half-life from blood serum increases. For such patients, the maximum daily dose of the drug should not exceed 8 mg. Patients with impaired metabolism of sparteine/debrisoquine. The half-life of ondansetron in patients with impaired metabolism of sparteine and debrisoquine does not change. After repeated administration in such patients, the drug concentration is the same as in patients without metabolic impairment. Therefore, there is no need to change the dosage or frequency of administration. Use of solution for injection. Ampoules. YUNORM ampoules do not contain preservatives, so the solution should be used immediately after opening. Any remaining solution should be discarded. YUNORM ampoules cannot be autoclaved. Compatibility with other fluids. Solutions for intravenous administration should be prepared immediately before infusion. However, it has been established that ondansetron solution remains stable for 7 days at room temperature (up to 25°C) in daylight or in the refrigerator when diluted in the following media: 0.9% sodium chloride solution, 5% glucose solution, 10% mannitol solution, Ringer's solution, 0.3% potassium chloride solution and 0.9% sodium chloride solution, 0.3% potassium chloride solution and 5% glucose solution. It has been established that ondansetron also remains stable when using polyethylene and glass bottles. Ondansetron, diluted with 0.9% sodium chloride solution or 5% glucose solution, has been shown to remain stable in polypropylene syringes. Stability in polypropylene syringes has also been confirmed when diluting ondansetron with other recommended solutions. If prolonged storage of the drug is necessary, dilution should be carried out under appropriate aseptic conditions. Compatibility with other drugs. YUNORM can be administered by intravenous infusion at a rate of 1 mg/h. YUNORM can be administered together with ondansetron at concentrations from 16 to 160 mcg/ml (i.e., 8 mg/500 ml or 8 mg/50 ml respectively) via a Y-connector with: - cisplatin at a concentration of up to 0.48 mg/ml over 1-8 hours; - 5-fluorouracil at a concentration of up to 0.8 mg/ml (e.g., 2.4 g in 3 L or 400 mg in 500 ml) at a rate of not less than 20 ml/h. Higher concentrations of 5-fluorouracil may cause precipitation of ondansetron. The infusion solution of 5-fluorouracil may contain up to 0.045% magnesium chloride in addition to other compatible excipients; - carboplatin at a concentration of 0.18 to 9.9 mg/ml (e.g., 90 mg in 500 ml to 990 mg in 100 ml) administered over 10-60 minutes; - etoposide at a concentration of 0.14 to 0.25 mg/ml (e.g., 72 mg in 500 ml to 250 mg in 1 L) administered over 30-60 minutes; - ceftazidime at doses from 250 mg to 2 g, diluted with water for injection (e.g., 2.5 ml for 250 mg or 10 ml for 2 g ceftazidime), administered as an intravenous bolus injection over 5 minutes; - cyclophosphamide at doses from 100 mg to 1 g, diluted with water for injection (5 ml per 100 mg cyclophosphamide), administered as an intravenous bolus injection over 5 minutes; - doxorubicin at doses from 10 to 100 mg. Diluted with water for injection (5 ml per 10 mg doxorubicin), administered as an intravenous bolus injection over 5 minutes; - dexamethasone at a dose of 20 mg as a slow intravenous injection over 2-5 minutes (when administering 8 mg or 16 mg of ondansetron simultaneously, diluted in 50-100 ml of infusion solution), over approximately 15 minutes. Since these drugs are compatible, they can be administered through the same infusion line, and the concentration of dexamethasone phosphate (as sodium salt) in the solution will be from 32 mcg to 2.5 mg per ml, and ondansetron - from 8 mcg to 1 mg per ml. Children. The drug is used in children from 6 months of age (during chemotherapy) and from 1 month of age (for prevention and treatment of postoperative nausea and vomiting). Overdose. Data on overdose with the drug are insufficient. In most cases, the symptoms are similar to those described in patients who received recommended doses (see section "Adverse reactions"). Among the manifestations of overdose, there have been reports of visual disturbances, arterial hypotension, and vasovagal manifestations with transient atrioventricular block of grade II. In all cases, these events resolved completely. Ondansetron prolongs the QT interval in a dose-dependent manner. In case of overdose, ECG monitoring is recommended. There have been reports of serotonin syndrome in young children after oral overdose. There is no specific antidote, so symptomatic and supportive therapy should be used in case of overdose. Further management of patients should be carried out according to clinical indications or, if possible, according to the recommendations of the national poison control center. The use of ipecacuanha is not recommended for the treatment of ondansetron overdose, as its action may not be manifested due to the antiemetic effect of YUNORM. Children: There have been reports of serotonin syndrome in newborns and children aged 12 months to 2 years after accidental overdose of the oral form of the drug (doses exceeded the recommended level of 4 mg/kg). Adverse reactions: Adverse reactions, information on which is provided below, are classified by organ systems and frequency of occurrence. By frequency of occurrence, they are divided into the following categories: very common (≥ 1/10), common (≥ 1/100 and <1/10), uncommon (≥ 1/1000 and <1/100), rare (≥ 1/10000 and <1/1000), very rare (<1/10000), unknown frequency (frequency cannot be determined from available sources). Adverse reactions with frequency - very common and uncommon are usually determined based on clinical trial data. The frequency of reactions in the placebo group was taken into account. Adverse reactions with frequency - rare, very rare, and unknown are usually determined based on post-registration data. The frequency of adverse reactions indicated below was assessed based on the use of standard recommended doses of ondansetron. The adverse reaction profile in children and adolescents was comparable to that in adults. Immune system disorders: Rare: Immediate hypersensitivity reactions, sometimes severe, including anaphylaxis. Nervous system disorders: Very common: headache; Uncommon: convulsions, movement disorders (including extrapyramidal reactions such as oculogyric crisis, dystonic reactions, and dyskinesia without persistent clinical consequences); Rare: dizziness, mainly during rapid intravenous administration of the drug. Eye disorders: Rare: transient visual disturbances (blurred vision), mainly during intravenous administration; Very rare: transient blindness, mainly with intravenous use; in most cases, blindness resolves within 20 minutes. Most patients received chemotherapeutic drugs containing cisplatin. There were reports of some cases of transient blindness as cortical blindness. Cardiac disorders: Uncommon: arrhythmia, chest pain (with or without ST segment depression), bradycardia; Rare: QT interval prolongation (including ventricular tachycardia/fibrillation (torsade de pointes)); Unknown: myocardial ischemia* (see section "Special precautions for use"). Vascular disorders: Common: sensation of warmth or heat; Uncommon: arterial hypotension. Respiratory, thoracic and mediastinal disorders: Uncommon: hiccups. Gastrointestinal disorders: Common: constipation. Hepatobiliary disorders: Uncommon: asymptomatic increase in liver function parameters. These cases are mainly observed in patients treated with chemotherapeutic agents containing cisplatin. Skin and subcutaneous tissue disorders: Very rare: toxic rash, including toxic epidermal necrolysis. General disorders and administration site reactions: Common: local reactions at the site of intravenous injection. According to post-marketing surveillance, reports of the following adverse reactions have been received: Cardiovascular system disorders: chest pain and discomfort, extrasystoles, tachycardia, including ventricular and supraventricular tachycardia, atrial fibrillation, palpitations, syncope, ECG changes. Hypersensitivity reactions: anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock, itching, rash, urticaria. Nervous system disorders: gait disturbance, chorea, myoclonus, restlessness, burning sensation, tongue protrusion, diplopia, paresthesia. General disorders and local reactions: increased body temperature, pain, redness, burning at the injection site. Other: hypokalemia. *Information on adverse reactions was obtained from post-marketing experience of drug use through spontaneous reports and publications. Since reports of these reactions are submitted voluntarily from the population, it is impossible to reliably estimate their frequency. Reporting suspected adverse reactions. Reporting suspected adverse reactions after drug registration is an important procedure. It allows for continued monitoring of the benefit/risk balance for the drug. Healthcare professionals should report suspected adverse reactions through the national pharmacovigilance system. Shelf life. 2 years. Storage conditions: Store at a temperature not exceeding 30°C, protected from light. Do not freeze. Incompatibility. YUNORM cannot be used in the same syringe or infusion solution with other drugs. YUNORM in injectable form can only be combined with recommended infusion solutions (see section "Method of administration and dosage"). Packaging. 4 ml #5 ampoules in a contour cell package; one contour cell package in a cardboard box. Dispensing category: Pharmaceutical product group II, dispensed by prescription №3.