Instructions Ondansetron film-coated tablets 8 mg blister No. 10
Composition
active ingredient: ondansetron;
1 tablet contains ondansetron hydrochloride dihydrate (as ondansetron) 4 mg or 8 mg;
excipients: pregelatinized starch, lactose monohydrate, microcrystalline cellulose, magnesium stearate;
film-forming coating: hydroxypropylmethylcellulose, copovidone, polyethylene glycol, medium chain triglycerides, polydextrose, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated with a film coating from yellow to brownish-yellow in color.
Pharmacotherapeutic group
Antiemetics and antinausea drugs. Serotonin 5HT3 receptor antagonists. ATC 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 antagonizing 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.
After oral administration, ondansetron is completely absorbed by passive absorption from the gastrointestinal tract and undergoes first-pass metabolism. Plasma concentrations reach a maximum approximately 1.5 hours after administration. Doses exceeding 8 mg increase systemic exposure to ondansetron to a greater extent than those distributed proportionally. This may be a sign of reduced first-pass metabolism at high oral doses.
Ondansetron is eliminated from the systemic circulation by multiple enzymatic metabolism, primarily in the liver. Less than 5% of the drug is excreted unchanged in the urine. The distribution of ondansetron is similar after oral, intramuscular, or intravenous administration: the half-life is approximately 3 hours (5 hours in elderly patients), and the volume of distribution at steady state is approximately 140 L. Plasma protein binding is 70-76%. In patients with moderate renal impairment (creatinine clearance 15-60 ml/min), both the systemic clearance and the volume of distribution of ondansetron are reduced, resulting in a clinically insignificant increase in the half-life of the drug. The pharmacokinetics of ondansetron are practically unchanged in patients with severe renal failure who are on chronic hemodialysis (the studies were conducted in the interval between hemodialysis sessions). In patients with severe chronic liver failure, the systemic clearance of ondansetron is markedly reduced with an increase in the half-life (15-32 hours). The absence of the CYP2D6 enzyme does not affect the pharmacokinetics of ondansetron. The pharmacokinetic properties of ondansetron do not change with repeated administration. The bioavailability of oral ondansetron and the half-life are clinically slightly increased in elderly patients.
In women, absorption of an oral dose was faster and to a greater extent, and systemic clearance and volume of distribution were smaller.
The bioavailability of the drug is slightly higher when taken with food, but antacids do not affect bioavailability.
Indication
Prevention and treatment of nausea and vomiting induced by cytotoxic chemotherapy or radiotherapy. Prevention of nausea and vomiting in the postoperative period.
Contraindication
Hypersensitivity to the components of the drug and to other selective serotonin 5HT3 receptor antagonists; simultaneous use with apomorphine; severe liver dysfunction; abdominal surgery.
Interaction with other medicinal products 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 ethanol, temazepam, furosemide, alfentanil, morphine, lidocaine, thiopental or propofol.
Ondansetron is metabolized by the hepatic cytochrome P459 enzyme system: CYP3A4, CYP2D6 and CYP1A2. Due to the diversity of ondansetron metabolizing enzymes, inhibition or reduction in the activity of one of them (for example, genetic deficiency of CYP2D6) is normally compensated by the other enzymes and will have no or little effect on the overall clearance of ondansetron.
Phenytoin, carbamazepine and rifampicin: When treated with potential CYP3A4 inducers (e.g. phenytoin, carbamazepine and rifampicin), the clearance of ondansetron increases and its blood concentration decreases.
Apomorphine: concomitant use is contraindicated as cases of severe hypotension and loss of consciousness have been observed.
Drugs that prolong the QT interval: additional prolongation of the QT interval is possible. Cardiotoxic drugs (e.g. anthracyclines): possible increased risk of arrhythmias.
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).
Application features
Ondansetron is ineffective for preventing nausea and vomiting during motion sickness.
Cases of cross-hypersensitivity to different 5HT3 receptor antagonists have been described. Therefore, in the presence of hypersensitivity to one of the 5HT3 receptor antagonists, a similar reaction to other antagonists may be more pronounced due to cross-reactions. In the presence of even a weak hypersensitivity reaction to one of the 5HT3 receptor antagonists, it is not recommended to change it to another, given the possibility of an increase in the hypersensitivity reaction.
Ondansetron prolongs the QT interval in a dose-dependent manner. Cases of ventricular fibrillation/flutter (torsade de pointes) have been reported with 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, and patients treated with other drugs that may cause QT prolongation or electrolyte imbalance. Hypokalemia and hypomagnesemia should be corrected before administration.
Since ondansetron reduces intestinal motility, patients with signs of subacute intestinal obstruction should be carefully monitored during use of the drug.
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 should be carefully monitored after the use of ondansetron.
Ondansetron does not affect the cytochrome P450 system, but the use of other drugs that can affect the activity of these enzymes may lead to changes in the clearance and half-life of ondansetron.
Children receiving ondansetron with hepatotoxic chemotherapeutic agents should be carefully monitored for possible liver dysfunction.
Patients with carbohydrate intolerance, with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption, should not take this medicine, given that the tablets contain carbohydrates, including lactose.
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.
Use during pregnancy or breastfeeding
The drug is contraindicated for use during pregnancy.
Breastfeeding should be discontinued during treatment with the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given the possibility of developing adverse reactions from the nervous system, patients are advised to refrain from driving or operating machinery during treatment with the drug.
Method of administration and doses
The drug is to be used internally.
When conducting cytostatic therapy, the dosage regimen should be set individually, depending on the severity of the vomiting reaction.
Moderately emetogenic chemotherapy and radiation therapy
Adults should be administered orally: initially 8 mg 1-2 hours before the start of anticancer therapy, followed by another 8 mg 12 hours later.
To prevent late or prolonged nausea and vomiting after the first 24 hours, the drug should be continued at 8 mg every 12 hours for 5 days.
In case of partial high-dose irradiation of the abdominal area, 8 mg should be prescribed every 8 hours. The drug is taken throughout the entire course of chemotherapy and radiotherapy, as well as 1-2 days (if necessary - 3-5 days) after its completion.
Highly emetogenic chemotherapy
Children. This dosage form should not be used in children under 4 years of age. Doses for children should be calculated based on body surface area or body weight. If ondansetron 2 mg is required, an appropriate dosage form or other dosage form should be used.
Dosing based on body surface area. Ondansetron (solution for injection) is administered as a single intravenous injection at a dose of 5 mg/m2 immediately before chemotherapy; the intravenous dose should not exceed 8 mg. Oral administration should be initiated 12 hours later and continued for up to 5 days. The total daily dose of ondansetron should not exceed 32 mg.
Dosing calculation by body weight. Immediately before chemotherapy, ondansetron (solution for injection) should be administered as a single intravenous injection at a dose of 0.15 mg/kg body weight; the intravenous dose should not exceed 8 mg. Subsequently, two intravenous injections may be administered at 4-hour intervals. The total daily dose of ondansetron should not exceed 32 mg. Oral administration should be initiated 12 hours later and continued for up to 5 days.
Body weight
1 day
2-6 days
> 10 kg
Up to 3 doses of 0.15 mg/kg every 4 hours intravenously
Oral 4 mg every 12 hours
Postoperative nausea and vomiting
Adults should be prescribed 16 mg 1 hour before the start of anesthesia.
The maximum daily dose of ondansetron is 32 mg, for patients with impaired liver function - 8 mg.
For children, it is recommended to use ondansetron in the form of an injection solution for this indication.
For all types of therapy
Elderly patients.
There is no need to change the dosage for patients over 65 years of age.
Patients with renal failure.
There is no need to change the dosage regimen or route of administration in patients with renal impairment.
Patients with moderate hepatic impairment.
In patients with moderate hepatic impairment, the clearance of ondansetron is significantly reduced and the serum half-life is prolonged. In 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 is not altered. In such patients, after repeated administration, the drug concentration is the same as in patients with normal metabolism. Therefore, there is no need to change the dosage regimen in this group of patients.
Children
Do not prescribe the drug in this dosage form to children under 4 years of age.
Overdose
Symptoms: visual disturbances, constipation, hypotension, vasovagal disorders with transient atrioventricular block. Ondansetron prolongs the QT interval in a dose-dependent manner. In case of overdose, ECG monitoring is recommended.
Treatment: drug withdrawal, symptomatic and supportive therapy. The use of antiemetic measures is not recommended due to the antiemetic effect of the drug itself. There is no specific antidote.
Adverse reactions
Immune system: immediate allergic reactions, sometimes severe, including anaphylactic reactions, angioedema, anaphylactic shock, bronchospasm, angioedema, itching, skin rashes, urticaria.
Nervous system: headache, myoclonus, convulsions, movement disorders (including extrapyramidal reactions such as oculogyric crisis, dystonic reactions and dyskinesia without persistent clinical consequences), gait disturbance, chorea, restlessness, burning sensation, tongue protrusion, diplopia, central nervous system depression, paresthesia; dizziness, mainly during rapid intravenous administration of the drug.
Visual organs: transient visual disturbances (cloudiness in the eyes), transient blindness, mainly during intravenous administration. In most cases, blindness resolves within 20 minutes.
Cardiovascular system: chest pain and discomfort, pain in the heart area (with or without ST segment depression), arrhythmias, extrasystoles, tachycardia, including ventricular and supraventricular tachycardias, atrial fibrillation, palpitations, bradycardia, hypotension, hypertension, QT prolongation (including ventricular flutter/fibrillation ("torsade de pointes")), feeling of warmth, flushing, syncope, ECG changes.
Respiratory system: hiccups, cough.
Digestive tract: constipation, diarrhea, dry mouth.
Hepatobiliary system: asymptomatic increase in liver function tests, liver failure.
General disorders: weakness, fainting.
These cases are observed mainly in patients treated with chemotherapy drugs containing cisplatin.
Other: increased body temperature, hypokalemia.
Expiration date
3 years.
Storage conditions
In the original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister, 1 blister in a pack.
Vacation category
According to the recipe.
Producer
Public Joint Stock Company "Research and Production Center "Borshchagov Chemical and Pharmaceutical Plant".
Location of the manufacturer and its business address
Ukraine, 03134, Kyiv, Myru St., 17.
