Ondator^® (Tablets) Instructions for Use

ATC Code

A04AA01 (Ondansetron)

Active Substance

Ondansetron (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Centrally acting antiemetic drug blocking serotonin receptors

Pharmacotherapeutic Group

Antiemetic agent – serotonin receptor antagonist

Pharmacological Action

Ondansetron is a highly selective antagonist of 5-HT₃ receptors (serotonin).

Drugs for cytostatic chemotherapy and radiotherapy can cause an increase in serotonin concentration, which, by activating afferent vagus nerve fibers containing 5-HT₃ receptors, triggers the vomiting reflex.

Ondansetron selectively blocks serotonin 5HT₃ receptors of neurons in the central (vomiting center) and peripheral (gastrointestinal tract) nervous systems that regulate the vomiting reflex.

It does not impair motor coordination, does not cause a sedative effect or reduced performance.

It does not change the plasma concentration of prolactin.

Pharmacokinetics

After oral administration, Ondansetron is completely absorbed in the gastrointestinal tract and undergoes first-pass metabolism in the liver.

Bioavailability is about 60%.

C_max in blood plasma is reached in 1.5 hours and is approximately 30 ng/ml after taking the drug at a dose of 8 mg.

The bioavailability of the drug increases slightly when taken simultaneously with food, but does not change when taking antacids.

The distribution of ondansetron after oral, intravenous or intramuscular administration is the same.

V_d at steady state is about 140 L.

Binding to plasma proteins is 70-76%.

Ondansetron is eliminated from the body mainly as a result of metabolism in the liver with the participation of several microsomal enzymes (CYP1A2, CYP2D6, CYP3A4).

Less than 5% of the administered dose is excreted by the kidneys unchanged.

T_1/2 is 3 hours.

The pharmacokinetic parameters of ondansetron do not change upon repeated administration.

Pharmacokinetics in special clinical cases

In children, clearance and V_d values depend on age.

Dose adjustment based on patient body weight (from 0.1 mg/kg to 4 mg maximum) compensates for these changes and normalizes the systemic exposure of ondansetron in children.

In patients with moderate renal failure (creatinine clearance CC 15-60 ml/min), systemic clearance and V_d are reduced, leading to a small and clinically insignificant increase in T_1/2 (up to 5.4 hours).

In patients with severe renal impairment on continuous hemodialysis, the pharmacokinetics of ondansetron are practically unchanged.

In patients with severe hepatic impairment, the clearance of ondansetron is significantly reduced, resulting in an increase in T_1/2 to 15-32 hours, and oral bioavailability reaches 100% due to reduced presystemic metabolism.

In elderly individuals, a slight increase in bioavailability to 65% and T_1/2 to 5 hours is observed.

The distribution of ondansetron is gender-dependent, with women showing higher absorption after oral administration, as well as reduced systemic clearance and V_d.

Indications

• Prevention and relief of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy;
• Prevention of nausea and vomiting in the postoperative period.

ICD codes

Dosage Regimen

Tablets

The drug is intended for oral administration.

The choice of dosing regimen is determined by the severity of the emetogenic effect of the ongoing antitumor therapy.

For adults, the daily dose is usually 8-24 mg.

The following dosing regimens for the drug Ondator^® are recommended.

Prevention and relief of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy.

For moderately emetogenic chemotherapy or radiotherapy, the drug Ondator^® is prescribed

• To adults and children over 12 years at a dose of 8 mg 1-2 hours before the start of the main therapy, followed by another 8 mg after 12 hours;
• To children from 3 to 12 years, 4 mg of ondansetron is prescribed 30 minutes before the start of the main chemotherapy, followed by another 4 mg every 8 hours.

There are no data on use in radiotherapy for children under 12 years.

For highly emetogenic chemotherapy, the recommended dose for adults is 24 mg of ondansetron simultaneously with oral dexamethasone at a dose of 12 mg 1-2 hours before the start of chemotherapy.

For the prevention of late or prolonged vomiting occurring after 24 hours, adults should continue taking the drug Ondator^® orally at a dose of 8 mg 2 times/day for 5 days after the end of the main therapy.

For children, for the prevention of nausea and vomiting associated with chemotherapy, Ondansetron is usually administered as an injection solution as a single intravenous dose of 5 mg/m over at least 15 minutes immediately before the start of chemotherapy, followed by oral administration of Ondator^® tablets at a dose of 4 mg after 12 hours.

After the end of the chemotherapy course, it is necessary to continue taking the drug Ondator^® orally at 4 mg 2 times/day for 5 days to prevent late or prolonged vomiting after the first 24 hours.

Prevention of nausea and vomiting in the postoperative period.Adults are recommended to take the drug Ondator^® orally at a dose of 16 mg 1 hour before anesthesia.

For the relief of postoperative nausea and vomiting, the use of ondansetron for injection is recommended.

For children, for the prevention and relief of postoperative nausea and vomiting, Ondansetron is prescribed only intravenously.

No adjustment of the daily dose or frequency of administration of the drug Ondator^® is required for elderly patients (over 65 years) and for patients with impaired renal function.

In patients with impaired liver function, the dose of the drug Ondator^® should not exceed 8 mg/day.

No adjustment of the daily dose or frequency of administration of the drug Ondator^® is required for patients with slow sparteine/debrisoquine metabolism.

Adverse Reactions

According to the World Health Organization (WHO), adverse effects are classified according to their frequency of occurrence as follows: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000) and very rare (<1/10,000), including isolated reports.

From the immune system: rare – urticaria, bronchospasm, laryngospasm, angioedema, immediate-type hypersensitivity reactions, sometimes severe, including anaphylaxis.

From the nervous system: common – headache; rare – dizziness, seizures, spontaneous movement disorders, including extrapyramidal disorders (dystonic reactions, oculogyric crisis, dyskinesia), which are reversible and do not lead to persistent clinical consequences.

From the cardiovascular system: rare – chest pain, in some cases with ST segment depression, arrhythmia, bradycardia, decreased blood pressure.

From the digestive system: common – hiccups, dry oral mucosa, diarrhea, constipation, asymptomatic transient increase in liver enzyme activity.

Other: common – sensation of heat and facial flushing; uncommon – hypercreatininemia; rare – hypokalemia, temporary decrease in visual acuity.

Contraindications

• Children under 3 years of age (for 4 mg dosage);
• Children under 12 years of age (for 8 mg dosage);
• Pregnancy;
• Lactation period;
• Hypersensitivity to ondansetron or any other selective antagonist of 5-HT₃ receptors (serotonin) and other auxiliary components of the drug.

With caution, the drug Ondator^® should be prescribed to patients with subacute intestinal obstruction; with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Use in Pregnancy and Lactation

The drug Ondator^® is contraindicated for use during pregnancy and during lactation.

Use in Hepatic Impairment

In patients with impaired liver function, the dose of the drug Ondator^® should not exceed 8 mg/day.

Use in Renal Impairment

No adjustment of the daily dose or frequency of administration of the drug Ondator^® is required for patients with impaired renal function.

Pediatric Use

Contraindicated

• Children under 3 years of age (for 4 mg dosage);
• Children under 12 years of age (for 8 mg dosage).

Ondansetron in this dosage form should not be prescribed to children with a body surface area of less than 0.6 m².

Geriatric Use

No adjustment of the daily dose or frequency of administration of the drug Ondator^® is required for elderly patients (over 65 years).

Special Precautions

Ondansetron in this dosage form should not be prescribed to children with a body surface area of less than 0.6 m².

Since Ondansetron slows intestinal motility, patients with symptoms of subacute intestinal obstruction require regular medical supervision.

Effect on ability to drive vehicles and operate machinery

Ondansetron does not have a negative effect on psychomotor activity and does not cause a sedative effect.

During treatment with the drug Ondator^®, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: visual impairment, constipation, decreased blood pressure and a vasovagal episode with transient second-degree atrioventricular block. In the studied cases, the phenomena of overdose were completely reversible.

Treatment: symptomatic and supportive therapy is carried out, a specific antidote is not known.

Drug Interactions

Since Ondansetron is metabolized by the hepatic enzyme system (cytochrome P450), caution is required when used concomitantly

• With inducers of cytochrome P450 (isoenzymes CYP2D6 and CYP3A) – barbiturates, carbamazepine, carisoprodol, glutethimide, griseofulvin, nitrous oxide, papaverine, phenylbutazone, phenytoin (and probably other hydantoins), rifampicin, tolbutamide;
• With inhibitors of cytochrome P450 (isoenzymes CYP2D6 and CYP3A) – allopurinol, macrolide antibiotics, antidepressants (monoamine oxidase inhibitors), chloramphenicol, cimetidine, estrogen-containing oral contraceptives, diltiazem, disulfiram, valproic acid and its salts, erythromycin, fluconazole, fluoroquinolones, isoniazid, ketoconazole, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil.

Special studies have shown that Ondansetron does not interact with alcohol, temazepam, furosemide and propofol, alfentanil, thiopental.

Data from special studies indicate that Ondansetron may reduce the analgesic effect of tramadol.

Storage Conditions

Store the drug in a dry, light-protected place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years. Do not use the drug after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.