Emetron^® (Tablets, Solution) 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 selective antagonist of serotonin 5HT₃ receptors. Cytostatic chemotherapy and radiotherapy can cause an increase in serotonin levels, which, by activating vagal afferent fibers containing serotonin 5HT₃ receptors, triggers the vomiting reflex. Ondansetron inhibits the occurrence of the vomiting reflex by blocking serotonin 5HT₃ receptors at the level of neurons in both the central (vomiting center) and peripheral (gastrointestinal tract) nervous systems.

It does not impair motor coordination, does not cause a sedative effect or reduce performance. It does not change the concentration of prolactin in blood plasma.

Pharmacokinetics

Absorption

After intramuscular administration, C_max in plasma is reached within 10 minutes after injection. Bioavailability is about 60%.

After oral administration, Ondansetron is completely absorbed from the gastrointestinal tract and undergoes a first-pass effect through the liver. C_max of ondansetron in blood plasma is reached in approximately 1.5 hours and is approximately 30 ng/ml after oral administration of an 8 mg dose. Absolute bioavailability after oral administration is about 60%. The bioavailability of ondansetron increases slightly when taken simultaneously with food but does not change when taken with antacids.

Distribution

The distribution of ondansetron is the same for oral, intramuscular, and intravenous administration. Plasma protein binding is 70-76%. V_d is 140 L.

Metabolism

The drug is metabolized in the liver with the participation of several microsomal enzymes (CYP1A2, CYP2D6, CYP3A4). The absence of the CYP2D6 isoenzyme does not affect the pharmacokinetics of ondansetron.

Excretion

Both after oral administration and after parenteral administration, T_1/2 is about 3 hours. Less than 5% of the drug is excreted unchanged in the urine.

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

Pharmacokinetics in special patient groups

In patients with moderate renal impairment (creatinine clearance 15-60 ml/min), both systemic clearance and V_d of ondansetron are reduced, resulting in a slight and clinically significant increase in T_1/2 (up to 5.4 hours). The pharmacokinetics of ondansetron are practically unchanged in patients with severe renal impairment undergoing hemodialysis.

In patients with severe hepatic impairment, the clearance of ondansetron is significantly reduced, resulting in an increased T_1/2 (up to 15-32 hours).

In elderly patients, T_1/2 can reach 5 hours.

Indications

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

ICD codes

Dosage Regimen

Tablets

Individual, depending on the indications and treatment regimen, the patient’s age, and the dosage form used.

Solution

Cytostatic therapy

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 8-32 mg; the following regimens are recommended.

For moderately emetogenic chemotherapy or radiotherapy: 8 mg IV slow bolus or IM, immediately before the start of therapy.

For highly emetogenic chemotherapy 8 mg IV bolus (slowly) immediately before the start of chemotherapy, then two more IV bolus injections of 8 mg each, administered 2-4 hours apart; or a continuous 24-hour infusion of the drug at a dose of 24 mg at a rate of 1 mg/hour; or 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 effectiveness of ondansetron can be increased by a single IV administration of a glucocorticoid (e.g., 20 mg dexamethasone) before starting chemotherapy.

To prevent delayed vomiting occurring 24 hours after the start of chemo- or radiotherapy, both for highly emetogenic therapy and for moderately emetogenic therapy, it is recommended to continue taking the drug orally at 8 mg twice daily for 5 days.

For children over 2 years old, the drug is prescribed at a dose of 5 mg/m² body surface area IV, immediately before the start of chemotherapy, followed by oral administration of 4 mg after 12 hours; treatment is recommended to continue at a dose of 4 mg twice daily orally for 5 days.

Prevention of postoperative nausea and vomiting

Adults are administered a single dose of 4 mg IM or IV bolus, slowly at the beginning of anesthesia.

For relief of nausea and vomiting that has occurred, IM or slow IV administration of 4 mg of the drug is recommended.

IM into the same area of the body, Ondansetron can be administered in a dose not exceeding 4 mg.

For children, for preventing postoperative nausea and vomiting, Ondansetron is used exclusively parenterally in a single dose of 0.1 mg/kg (maximum up to 4 mg) as a slow IV injection during or after anesthesia.

For treatment of developed postoperative nausea and vomiting in children, slow IV administration of a single dose of the drug of 0.1 mg/kg (maximum up to 4 mg) is recommended. Regarding the prevention and treatment of postoperative nausea and vomiting in children under 2 years of age, there is insufficient experience.

For elderly patients, dose adjustment is not required.

For patients with impaired renal function, it is not necessary to change the usual daily dose and frequency of drug administration.

In patients with moderate or severe hepatic impairment, the clearance of ondansetron is significantly reduced, and the T_1/2 from plasma is increased, so the daily dose should not exceed 8 mg/day.

The following solutions can be used to dilute the injection solution: 0.9% sodium chloride solution, 5% dextrose solution, Ringer’s solution, 0.3% potassium chloride and 0.9% sodium chloride solution, 0.3% potassium chloride and 5% dextrose solution.

Adverse Reactions

Allergic reactions urticaria, bronchospasm, laryngospasm, angioedema, anaphylaxis.

From the digestive system hiccups, dry mouth, diarrhea, constipation; sometimes – asymptomatic transient increase in serum aminotransferase levels.

From the cardiovascular system chest pain, in some cases with ST-segment depression, arrhythmias, bradycardia, decreased blood pressure.

From the nervous system headache, dizziness, spontaneous movement disorders, convulsions.

Local reactions redness, pain, burning at the injection site.

Other facial flushing, feeling of heat, temporary visual acuity impairment, hypokalemia, hypercreatinemia.

Contraindications

• Pregnancy;
• Lactation period;
• Children under 2 years of age.
• Hypersensitivity to any component of the drug.

Use in Pregnancy and Lactation

The safety of using ondansetron during pregnancy has not been established.

The use of the drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

In patients with moderate or severe hepatic impairment, the daily dose should not exceed 8 mg/day.

Use in Renal Impairment

Patients with impaired renal function do not require changes to the usual daily dose and frequency of drug administration.

Pediatric Use

The use of the drug is contraindicated in children under 2 years of age.

Geriatric Use

Elderly patients do not require dose adjustment.

Special Precautions

In patients who have previously experienced allergic reactions when using other selective serotonin 5HT₃ receptor antagonists, similar reactions may also develop when using ondansetron.

Since Ondansetron may slow colonic motility, patients with signs of intestinal obstruction after using the drug require regular monitoring.

The infusion solution must be prepared immediately before use. If necessary, the prepared infusion solution can be stored for 24 hours at a temperature of 2-8°C (35.6-46.4°F) under normal lighting.

Protection from light is not required during the infusion; the diluted injection solution remains stable for at least 24 hours under natural or artificial light.

Effect on the ability to drive vehicles and operate machinery

In case of adverse reactions from the nervous system, patients are advised to refrain from driving vehicles and operating machinery, as well as from other activities requiring increased concentration and speed of psychomotor reactions.

Overdose

Currently, there is insufficient knowledge about ondansetron overdose.

The following symptoms are most often noted: visual impairment, constipation, decreased blood pressure, and a vasovagal reaction with transient second-degree AV block. All symptoms are completely reversible.

Treatment symptomatic and supportive therapy; a specific antidote is unknown.

Drug Interactions

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

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

Ondansetron at a concentration of 16-160 µg/ml is pharmaceutically compatible with the following drugs, which can be administered intravenously via a Y-site injector

• Cisplatin (at a concentration up to 0.48 mg/ml) for 1-8 hours;
• 5-fluorouracil (at a concentration up to 0.8 mg/ml at a rate of 20 ml/hour – higher concentrations may cause precipitation of ondansetron);
• Carboplatin (at a concentration of 0.18-9.9 mg/ml for 10-60 minutes);
• Etoposide (at a concentration of 0.14-0.25 mg/ml for 30-60 minutes);
• Ceftazidime (at a dose of 0.25-2 g, as an IV bolus injection over 5 minutes);
• Cyclophosphamide (at a dose from 0.1-1 g, as an IV bolus injection over 5 minutes);
• Doxorubicin (at a dose of 10-100 mg, as an IV bolus injection over 5 minutes);
• Dexamethasone: IV administration of 20 mg dexamethasone sodium phosphate slowly, over 2-5 minutes, is possible. The drugs can be administered through one system, with the concentrations of dexamethasone sodium phosphate in the solution ranging from 32 µg to 2.5 mg/ml, and ondansetron from 8 µg to 1 mg/ml.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature from 15°C (59°F) to 30°C (86°F).

Shelf Life

The shelf life of the injection solution is 4 years. Do not use after the expiration date.

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.