Translation of the instructions can be
Ondansetron solution for injection 2 mg/ml
Instruction
For medical use of the medicinal product
Ondansetron
(Ondansetron)
Composition:
Active ingredient: ondansetron;
1 ml of solution contains 0.002 g of ondansetron (as ondansetron hydrochloride dihydrate);
Excipients: citric acid monohydrate, sodium citrate, sodium chloride, water for injections.
Dosage form.
Solution for injection.
Main physicochemical properties: transparent colorless liquid, practically free of mechanical impurities.
Pharmacotherapeutic group.
Antiemetics and antinausea drugs. Serotonin (5HT3) receptor antagonists. Ondansetron.
PBX code A04A A01.
Pharmacological properties.
Pharmacodynamics.
Ondansetron is a potent, highly selective 5HT3 (serotonin) receptor antagonist. The drug prevents or eliminates nausea and vomiting caused 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 onset of the vomiting reflex by exerting an antagonistic effect on 5HT3 receptors, which are 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.
With intramuscular administration, the maximum concentration in the blood plasma is reached within 10 minutes. The volume of distribution after parenteral administration in adults 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 about 3 hours (in elderly patients - 5 hours). Binding to plasma proteins is 70-76%.
In patients with moderate renal insufficiency (creatinine clearance 15-60 ml/min), both the systemic clearance and the volume of distribution of ondansetron are reduced, resulting in a slight and clinically insignificant increase in the half-life of the drug. The pharmacokinetics of ondansetron are practically unchanged in patients with severe renal insufficiency undergoing chronic hemodialysis (the study was conducted in the interval between hemodialysis sessions). In patients with severe chronic hepatic insufficiency, the systemic clearance of ondansetron is markedly reduced with an increase in the half-life (15-32 hours).
Clinical characteristics.
Indication.
Nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy.
Prevention and treatment of postoperative nausea and vomiting.
Contraindication.
The use of ondansetron with apomorphine hydrochloride is contraindicated, as cases of severe hypotension and loss of consciousness have been observed during co-administration.
Hypersensitivity to any component of the drug.
Interaction with other drugs and other types of interactions.
Ondansetron does not accelerate or inhibit the metabolism of other drugs when used simultaneously with it. Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lignocaine, thiopental or propofol.
Ondansetron is metabolized by various hepatic cytochrome P450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the diversity of ondansetron metabolizing enzymes, inhibition or reduction of the activity of one of them (e.g. genetic deficiency of CYP2D6) is normally compensated by the other enzymes and will have no or negligible effect on total creatinine clearance.
Ondansetron should be used with caution in combination with drugs that prolong the QT interval and/or lead to electrolyte imbalance (see section "Special warnings and precautions for use").
Apomorphine.
The use of ondansetron with apomorphine hydrochloride is contraindicated, as cases of severe hypotension and loss of consciousness have been observed during co-administration.
Phenytoin, carbamazepine and rifampicin.
In patients treated with potential CYP3A4 inducers (e.g. phenytoin, carbamazepine and rifampicin), the clearance of ondansetron is increased and its blood concentration is decreased.
Serotoninergics (e.g. SSRIs and SNRIs).
Serotonin syndrome (including mental status changes, autonomic instability and neuromuscular disorders) has been described following concomitant use of ondansetron and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (see section 4.4).
Tramadol.
According to a small number of clinical studies, ondansetron may reduce the analgesic effect of tramadol.
The use of ondansetron with other drugs that prolong the QT interval may cause additional prolongation of this interval. The combined use of ondansetron with cardiotoxic drugs (e.g. anthracyclines) may increase the risk of arrhythmias (see section "Special instructions").
Application features.
Respiratory reactions are treated symptomatically. Healthcare professionals should pay special attention to them as they are signs of drug hypersensitivity reactions.
Ondansetron prolongs the QT interval in a dose-dependent manner (see section "Pharmacological properties"). In addition, there have been reports of cases of ventricular fibrillation/flutter (Torsade de Pointes) with the use of ondansetron. 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 prolongation, including patients with electrolyte imbalance, congestive heart failure, bradyarrhythmias, or patients treated with other drugs that can cause QT prolongation or electrolyte imbalance. Hypokalemia and hypomagnesemia should be corrected before starting use.
Serotonin syndrome has been described following concomitant use of ondansetron and other serotonergic drugs (see section 4.5). If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate monitoring of the patient is recommended.
Since ondansetron reduces intestinal motility, careful monitoring of patients with signs of subacute intestinal obstruction is necessary when using ondansetron.
In patients undergoing adenotonsillar surgery, the use of ondansetron for the prevention of nausea and vomiting may mask the occurrence of bleeding. Therefore, such patients require careful observation after the use of ondansetron.
One injection of the medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is virtually sodium-free.
children
Children receiving ondansetron with hepatotoxic chemotherapeutic agents should be carefully monitored for possible liver dysfunction.
dosage regimens
When calculating the dose according to body weight and using three doses with an interval of 4 hours, the total daily dose will be higher than when using a single dose of 5 mg / m 2 and a single dose of the drug orally. The comparative effectiveness of these two dosing regimens has not been evaluated in clinical studies. Comparison of the results of different studies indicates a similar effectiveness of both dosing regimens.
Use during pregnancy or breastfeeding.
The safety of ondansetron during pregnancy has not been established for humans. In experimental animal studies, ondansetron did not impair embryonal or foetal development and did not affect the course of pregnancy, peri- and postnatal development. However, as animal studies are not always predictive of human outcomes, ondansetron is not recommended for use during pregnancy.
In experimental studies, it has been shown that ondansetron passes into breast milk in animals. If necessary, breastfeeding should be discontinued.
There is no information on the effect of ondansetron on human fertility.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
Psychomotor tests have shown that ondansetron does not affect the ability to drive and does not cause sedation, but the side effect profile of the drug should be borne in mind when deciding whether to drive or operate machinery.
Method of administration and doses.
Nausea and vomiting caused by chemotherapy and radiation therapy.
The emetogenic potential of cancer therapy varies depending on the dose and combination of chemotherapy and radiotherapy regimens. The choice of dosing regimen depends on the severity of the emetogenic effect.
Adults.
Emetogenic chemotherapy and radiation therapy.
The recommended intravenous or intramuscular dose of Ondansetron is 8 mg as
slow injection over at least 30 seconds, immediately before treatment.
For the prevention of delayed or prolonged vomiting after the first 24 hours, oral or rectal administration of the drug is recommended.
Highly emetogenic chemotherapy (e.g. high doses of cisplatin).
Ondansetron can be administered as a single dose of 8 mg intravenously or intramuscularly immediately before chemotherapy. Doses greater than 8 mg (up to 16 mg) should only be administered as an intravenous infusion in 50-100 ml of 0.9% sodium chloride solution or other suitable diluent (see below); the infusion should last at least 15 minutes. A single dose exceeding 16 mg should not be administered (see section "Special instructions").
For highly emetogenic chemotherapy, 8 mg of Ondansetron or a lower dose does not require dilution and can be administered by slow intravenous or intramuscular injection (at least 30 seconds) immediately before chemotherapy, followed by two intravenous or intramuscular injections of 8 mg at 2 and 4 hours or by a continuous infusion of 1 mg/hour for 24 hours.
For the prevention of delayed or prolonged vomiting after the first 24 hours, oral or rectal administration of the drug is recommended.
Children and adolescents (from 6 months to 17 years).
In pediatric practice, Ondansetron should be administered by intravenous infusion in 25-50 ml of 0.9% sodium chloride solution or other suitable diluent (see “Instructions for Use” below) over at least 15 minutes.
The dose of the drug can be calculated based on the child's body surface area or body weight.
Calculation of dose according to the child's body surface area.
Ondansetron should be administered immediately before chemotherapy by a single intravenous injection at a dose of 5 mg/m², the intravenous dose should not exceed 8 mg. After 12 hours, oral administration of the drug can be started, which can continue for another 5 days. Do not exceed the adult dose.
Calculation of the dose according to the child's body weight.
Ondansetron should be administered immediately before chemotherapy by a single intravenous injection at a dose of 0.15 mg/kg. The intravenous dose should not exceed 8 mg. On the first day, 2 more intravenous doses can be administered at 4-hour intervals. After 12 hours, oral administration of the drug can be started, which can continue for another 5 days. Do not exceed the adult dose.
Elderly patients.
For patients over 65 years of age, all doses for intravenous injections should be dissolved and administered within 15 minutes; with repeated use, the interval between injections should be at least 4 hours.
For patients aged 65 to 74 years, the initial dose of ondansetron is 8 mg or 16 mg, administered by intravenous infusion over 15 minutes, which can be continued by administering two doses of 8 mg over 15 minutes with an interval between infusions of at least 4 hours.
In patients over 75 years of age, the initial intravenous injection of ondansetron should not exceed 8 mg infused over at least 15 minutes. After an initial dose of 8 mg, administration may be continued with two doses of 8 mg, infused over 15 minutes with an interval of at least 4 hours between infusions.
Patients with renal failure.
There is no need to change the dosage regimen or route of administration in patients with renal impairment.
Patients with liver failure.
In patients with moderate to severe hepatic impairment, the clearance of ondansetron is significantly reduced and the serum half-life is prolonged. For such patients, the maximum daily dose 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 is not altered. In such patients, repeated administration results in the same drug concentration as in patients with intact metabolism. Therefore, no change in dosage or frequency of administration is required.
Postoperative nausea and vomiting.
Adults.
For the prevention of postoperative nausea and vomiting, the recommended dose of Ondansetron 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 Ondansetron is 4 mg as an intramuscular or intravenous slow injection.
Children and adolescents (from 1 month to 17 years).
For the prevention and treatment of postoperative nausea and vomiting in children undergoing surgery under general anesthesia, ondansetron can be administered at a dose of 0.1 mg/kg body weight (maximum - up to 4 mg) by slow intravenous injection (not less than 30 seconds) before, during, after induction of anesthesia or after surgery.
Elderly patients.
Experience with the use of ondansetron for the prevention and treatment of postoperative nausea and vomiting in the elderly is limited, however, ondansetron is well tolerated in patients aged 65 years and older receiving chemotherapy.
Patients with renal failure.
There is no need to change the dosage regimen or route of administration in patients with renal impairment.
Patients with liver failure.
In patients with moderate to severe hepatic impairment, the clearance of ondansetron is significantly reduced and the serum half-life is prolonged. For such patients, the maximum daily dose should not exceed 8 mg.
Patients with impaired metabolism of sparteine/debrisoquine.
The half-life of ondansetron in subjects with impaired metabolism of sparteine and debrisoquine is not altered. In such patients, repeated administration results in the same drug concentration as in patients with intact metabolism. Therefore, no change in dosage or frequency of administration is required.
Instructions for use.
Ondansetron ampoules do not contain preservatives and should be used immediately after opening; any remaining solution should be discarded.
Ondansetron ampoules should not be autoclaved.
Intravenous solutions should be prepared immediately prior to infusion. However, ondansetron solution has been shown to be stable for 7 days at room temperature (up to 25°C) in daylight or refrigerated conditions when reconstituted 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.
Ondansetron has been shown to be stable in polyethylene and glass vials. Ondansetron has been shown to be stable in polypropylene syringes when diluted with 0.9% sodium chloride or 5% glucose. Stability in polypropylene syringes has also been shown to be stable when diluted with other recommended solutions.
If long-term storage of the drug is necessary, dissolution should be carried out under appropriate aseptic conditions.
Compatibility with other drugs.
Ondansetron can be administered as an intravenous infusion at a rate of 1 mg/h. Via a Y-injector together with ondansetron at ondansetron concentrations of 16 to 160 μg/ml (i.e. 8 mg/500 ml or 8 mg/50 ml respectively) the following can be administered:
- cisplatin at a concentration of up to 0.48 mg/ml, for 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 not exceeding 20 ml/h. Higher concentrations of 5-fluorouracil may cause precipitation of ondansetron. The 5-fluorouracil infusion solution may contain up to 0.045% magnesium chloride in addition to other compatible excipients;
- carboplatin at a concentration of 0.18 mg/ml to 9.9 mg/ml (e.g. 90 mg in 500 ml to 990 mg in 100 ml) for 10-60 minutes;
- etoposide at a concentration of 0.14 mg/ml to 0.25 mg/ml (e.g. 72 mg in 500 ml to 250 mg in 1 l) for 30-60 minutes;
- ceftazidime in a dose of 250 mg to 2 g, diluted in water for injections (for example 2.5 ml per 250 mg or 10 ml per 2 g of ceftazidime) as an intravenous bolus injection over 5 minutes;
- cyclophosphamide in a dose of 100 mg to 1 g, diluted in water for injection (5 ml per 100 mg of cyclophosphamide), as an intravenous bolus injection over 5 minutes;
- doxorubicin in a dose of 10 mg to 100 mg, diluted in water for injection (5 ml per 10 mg of doxorubicin), as an intravenous bolus injection over 5 minutes;
- dexamethasone at a dose of 20 mg, as a slow intravenous injection over 2-5 minutes (with simultaneous administration of 8 mg or 16 mg of ondansetron dissolved in 50-100 ml of injection solution), for about 15 minutes. Since these drugs are compatible, they can be administered through one dropper, while in the solution the concentration of dexamethasone phosphate (in the form of sodium salt) will be from 32 μg to 2.5 mg per 1 ml, and ondansetron - from 8 μg to 1 mg per 1 ml.
Children.
Use in children from 6 months of age (during chemotherapy) and from 1 month of age (for the prevention and treatment of postoperative nausea and vomiting).
Overdose.
There is limited information on overdose with ondansetron. In most cases, the symptoms are similar to those described in patients given recommended doses (see section 4.8).
Ondansetron increases the QT interval in a dose-dependent manner. In case of overdose, ECG monitoring is recommended.
Among the manifestations of overdose, visual disturbances, severe constipation, hypotension, vasovagal manifestations with transient second-degree AV block were reported. In all cases, these phenomena resolved completely.
There is no specific antidote, therefore, in case of overdose, symptomatic and supportive therapy should be used.
The use of ipecacuanha to treat ondansetron overdose is not recommended because its effect may not be due to the antiemetic effects of ondansetron.
Children: Serotonin syndrome has been reported in infants and children aged 12 months to 2 years after accidental overdose of the oral drug (doses exceeding the recommended level of 4 mg/kg).
Adverse reactions.
On the part of the immune system: immediate-type hypersensitivity reactions, sometimes severe, up to anaphylaxis.
Nervous system: headache; convulsions, movement disorders (including extrapyramidal reactions such as oculogyric crisis, dystonic reactions and dyskinesia without persistent clinical consequences); dizziness mainly during rapid intravenous administration of the drug.
On the part of the organs of vision: transient visual disturbances (clouding of the eyes), mainly during intravenous administration; transient blindness, mainly during intravenous administration. In most cases, blindness resolves within 20 minutes.
Cardiac: arrhythmias, chest pain (with or without ST segment depression), bradycardia; QT interval prolongation (including ventricular flutter/fibrillation (Torsade de Pointes)).
Vascular: feeling of warmth or flushing; hypotension.
Respiratory and thoracic disorders: hiccups.
Gastrointestinal: constipation.
Hepatobiliary system: asymptomatic increase in liver function tests. These cases are observed mainly in patients treated with chemotherapeutic drugs containing cisplatin.
Cases of hepatic failure have been reported in cancer patients receiving concomitant treatments, including potentially hepatotoxic chemotherapy and antibiotics.
General disorders: local reactions at the site of intravenous administration.
The following adverse reactions have been reported from post-marketing surveillance.
From the cardiovascular system: 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, skin rash, urticaria.
Nervous system disorders: gait disturbance, chorea, myoclonus, restlessness, burning sensation, tongue protrusion, diplopia, paresthesia.
General disorders and local reactions: fever, pain, redness, burning at the injection site.
Other: hypokalemia.
Expiration date.
2 years.
Storage conditions.
Store out of the reach of children in the original packaging at a temperature not exceeding 30 °C.
Incompatibility.
Ondansetron should not be used in the same syringe or infusion solution with other drugs. Ondansetron injection should only be combined with recommended infusion solutions (see section "Method of administration").
Packaging.
2 ml or 4 ml in an ampoule; 5 or 100 ampoules in a pack, or 5 ampoules in a blister, 1 blister in a pack.
Vacation category.
According to the recipe.
Producer.
Private Joint-Stock Company "Lekhim-Kharkiv".
Location of the manufacturer and address of its place of business.
Ukraine, 61115, Kharkiv region, Kharkiv city, Severyna Pototskoho street, building 36.
