INSTRUCTIONS FOR MEDICAL USE
Trade name of the drug: Danetro
Active substance (INN): Ondansetron
Dosage form: solution for injection. Composition per 1 ml:
Active substance: Ondansetron hydrochloride – 2.494 mg (equivalent to ondansetron 2 mg )
Excipients: citric acid monohydrate, sodium citrate, sodium chloride, water for injection.
Description: clear, colorless solution.
Pharmacotherapeutic group: Antiemetic
ATX code: A04AA01
Anti-emetic drug. It effectively prevents and eliminates nausea and vomiting arising against the background of anti-tumor chemotherapy and radiation therapy and in post-operative period. The mechanism of action is due to the ability of ondansetron to selectively block serotonin 5-HT3 -receptors. It is believed that stimulation of afferent fibers of vagus nerve by serotonin released from enterochromaffin cells of gastrointestinal mucosa plays an important role in the occurrence of nausea and vomiting during antitumor therapy. By blocking 5-HT3 -receptors, ondansetron prevents the gag reflex. Moreover, ondansetron inhibits central part of gag reflex by blocking 5-HT3 receptors at floor of IV ventricle (area postrema).
Pharmacokinetic parameters of ondansetron do not change with repeated administration.
Absorption. Ondansetron has the same systemic effect when administered v/m and intravenously.
Distribution. Ondansetron is moderately bound to plasma proteins (70-76%).
Metabolism. Ondansetron is metabolized mainly in liver with the help of different enzyme systems. Absence of CYP2D6 enzyme (sparteine/debrisoquine polymorphism) does not influence on ondansetron pharmacokinetics. Excretion. Ondansetron is eliminated from the systemic bloodstream mainly by metabolism in the liver. Less than 5% of the administered dose is excreted unchanged through the kidneys. T1/2 of ondansetron when administered v/m and intravenously is about 3 hours. T1/2 in elderly patients may be up to 5 hours, in liver and kidney disorders – 15-32 hours.
Indications for use
Prevention of nausea and vomiting during antitumor chemo- or radiation therapy;
Prevention and treatment of nausea and vomiting in postoperative period.
Methods of administration and dosages
The choice of dosage regimen is determined by the severity of the emetogenic effects of the antitumor therapy.
For adults, the daily dose is 8-32 mg, the following regimens are recommended:
For moderately emetogenic chemotherapy or radiotherapy:
8 mg intravenously slowly or intramuscularly just before therapy;
For highly emetogenic chemotherapy:
- 8 mg intravenous jet slowly just before the start of chemotherapy, followed by two more intravenous injections of 8 mg, each 2-4 hours later
- A continuous 24-hour infusion of the drug at a dose of 24 mg at a rate of 1 mg/hour;
- 16-32 mg diluted in 50-100 ml of an appropriate infusion solution, as a 15-minute infusion, immediately before the start of chemotherapy. The efficacy of ondansetron may be increased by a single intravenous injection of glucocorticosteroids (e.g., 20 mg dexamethasone) prior to the start of chemotherapy.
To prevent delayed vomiting that occurs after the first 24 hours from the start of chemo- or radiotherapy for both high-emetogenic and moderate-emetogenic therapy, it is recommended that ondansetron be continued orally for 5 days.
In children over 2 years of age, the drug is administered in a dose of 5 mg/m2 of body surface intravenously, immediately before the start of chemotherapy, followed by an oral dose of 4 mg after 12 hours; treatment is recommended to be continued in a dose of 4 mg twice daily orally for 5 days.
Prevention of postoperative nausea and vomiting
In adults, a single dose of 4 mg is administered intramuscularly or intravenously slowly in the beginning of anesthesia.
Intramuscular or slow intravenous injection of 4 mg of the drug is recommended to relieve the resulting nausea and vomiting.
Intramuscularly to the same area of the body ondansetron may be administered in a dose not exceeding 4 mg!
In children, to prevent postoperative nausea and vomiting, ondansetron is used exclusively parenterally in a single dose of 0.1 mg/kg (up to a maximum of 4 mg) as a slow intravenous injection before or after anesthesia.
There is insufficient experience with regard to the prevention and treatment of postoperative nausea and vomiting in children under 2 years of age.
For dilution of ondansetron injection solution the following solutions may be used: 0.9% sodium chloride solution, 5% dextrose solution, Ringer’s solution, 0.3% potassium chloride solution and 0.9% sodium chloride solution, 0.3% potassium chloride solution and 5% dextrose solution.
CNS: headaches; rarely – transient visual disturbances and dizziness (when rapidly injected intravenously), involuntary movements.
Cardiovascular system: rarely – chest pain, arrhythmias, bradycardia, arterial hypotension.
Digestive system: constipation, diarrhea, abdominal pain, transient increase in serum transaminase levels.
Allergic reactions: rare – bronchospasm, angioedema, urticaria, in some cases – anaphylactic reactions.
Others: feeling of heat and blood rush to the head and epigastrium.
First trimester of pregnancy, hypersensitivity to ondansetron.
Ondansetron is metabolized in liver by cytochrome P450 isoenzymes; clearance and T1/2 of ondansetron may be changed if concomitantly used with medicinal products inducible or inhibited of this enzyme system.
When administered in patients with moderate to severe liver dysfunction it is not recommended to exceed the dose of 8 mg/day.
Use ondansetron with caution during abdominal surgery because its use may mask progressive intestinal obstruction.
Use during pregnancy and lactation
Ondansetron is contraindicated for use in the first trimester of pregnancy. Breast-feeding should be discontinued if administration during lactation is necessary.
Symptoms: development of more severe side effects. In cases of suspected overdose symptomatic therapy is indicated. The specific antidote is unknown.
Form of production
Solution for injection 4 ml, ; №5, №10 (2×5) (ampules).
Store in a dry place protected from light at a temperature not exceeding 25°C. Keep out of the reach of children!
2 years. Do not use after the expiration date.
Conditions for dispensing from pharmacies.
Released by a doctor’s prescription.