Ondansetron-LANS^® (Solution) Instructions for Use

Marketing Authorization Holder

Lens-Pharm, LLC (Russia)

ATC Code

A04AA01 (Ondansetron)

Active Substance

Ondansetron (Rec.INN registered by WHO)

Dosage Forms

	Ondansetron-LANS®	Solution for intravenous and intramuscular administration 2 mg/ml: 2 ml fl. 1 pc., 4 ml fl. or 8 ml fl. 1, 5, 10, 50, 85 or 100 pcs.
		Solution for injection 4 mg/2 ml: fl. 1 pc.
		Solution for injection 8 mg/4 ml: fl. 1 pc.

Dosage Form, Packaging, and Composition

2 ml – vials (1) – carton packs.
4 ml – vials (1) – carton packs.
4 ml – vials (5) – carton packs.
4 ml – vials (10) – carton packs.
4 ml – vials (50) – carton boxes.
4 ml – vials (85) – carton boxes.
4 ml – vials (100) – carton boxes.
8 ml – vials (1) – carton packs.
8 ml – vials (5) – carton packs.
8 ml – vials (10) – carton packs.
8 ml – vials (50) – carton boxes.
8 ml – vials (85) – carton boxes.
8 ml – vials (100) – carton boxes.

Solution for injection 0.2% clear, colorless or yellowish in color.

2 ml – vials (1) – carton packs.

Solution for injection 0.2% clear, colorless or yellowish in color.

4 ml – vials (1) – carton packs.

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 5-HT₃ (serotonin) receptors. Cytostatic chemotherapy drugs and radiotherapy can cause an increase in serotonin levels, which, by activating vagal afferent fibers containing 5-HT₃ receptors, triggers the vomiting reflex. It selectively blocks serotonin 5-HT₃ receptors of neurons in the central and peripheral nervous systems, vagus nerve endings in the intestine, and in the CNS centers (primarily the floor of the IV ventricle) that regulate the implementation of vomiting reflexes. 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 intramuscular administration, T_max is 10 min. Plasma protein binding is 70-76%. The volume of distribution is 140 L. After parenteral administration, T_1/2 is 3 h. The absence of the CYP2D6 isoenzyme (debrisoquine polymorphism) does not affect the pharmacokinetics of ondansetron.

Less than 5% of the administered dose is excreted unchanged in the urine. The pharmacokinetic parameters of ondansetron do not change with its repeated administration.

In patients with moderate renal impairment (creatinine clearance 15-60 ml/min), both systemic clearance and volume of distribution are reduced, resulting in a small and clinically insignificant increase in T_1/2. The pharmacokinetics of ondansetron are practically unchanged in patients with severe renal impairment on chronic hemodialysis (studies were conducted during the intervals between hemodialysis sessions). In patients with severe hepatic impairment, the systemic clearance of ondansetron is sharply reduced, resulting in an increase in its half-life to 15-20 h. The T_1/2 of ondansetron does not depend on the route of administration.

In elderly patients after oral or parenteral administration, T_1/2 may increase to 5 h.

Indications

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

ICD codes

Dosage Regimen

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 intravenously by slow bolus or intramuscularly, immediately before the start of therapy;

For highly emetogenic chemotherapy

• 8 mg intravenously by slow bolus immediately before the start of chemotherapy, then two more intravenous injections of 8 mg each, each of which is administered after 2-4 hours
• 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 effectiveness of ondansetron can be increased by a single intravenous administration of glucocorticosteroids (e.g., 20 mg dexamethasone) before the start of chemotherapy.

To prevent delayed vomiting occurring after the first 24 hours from the start of chemo- or radiotherapy both when using highly emetogenic therapy and moderately emetogenic therapy – it is recommended to continue the use of ondansetron orally for 5 days.

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

Prevention of postoperative nausea and vomiting

Adults are administered a single dose of 4 mg intramuscularly or intravenously by slow bolus at the beginning of anesthesia.

To relieve nausea and vomiting that has occurred intramuscular or slow intravenous administration of 4 mg of the drug is recommended.

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

For children to prevent 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 intravenous injection before or after anesthesia. For the treatment of developed postoperative nausea and vomiting in children, slow intravenous 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.

Elderly patients

No dosage adjustment is required.

Patients with renal impairment

It is not necessary to change the usual daily dose and frequency of administration of the drug.

Patients with hepatic impairment

In moderate or severe hepatic impairment, the clearance of ondansetron is significantly reduced, while its plasma half-life is increased, so such patients are not recommended to be prescribed more than 8 mg of ondansetron per day.

The following solutions can be used to dilute the ondansetron 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

Adverse reactions are classified by organ systems.

Immune system immediate hypersensitivity reactions (including severe ones, up to anaphylaxis)

Allergic reactions urticaria, bronchospasm, laryngospasm, angioedema.

Nervous system headache; extrapyramidal reactions such as oculogyric crisis, dystonic reactions without persistent clinical consequences, convulsions; dizziness during rapid intravenous administration of the drug, dyskinesia.

Visual disorders transient visual disturbances (blurred vision), mainly during intravenous administration; transient blindness, mainly during intravenous use. In most cases of blindness, it resolves within 20 minutes.

Cardiovascular system feeling of heat or “flushing”; arrhythmias, chest pain (with or without ST segment depression), bradycardia, arterial hypotension, QT interval prolongation.

Respiratory system hiccups.

Digestive system constipation; in isolated cases – asymptomatic increase in liver tests.

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

Contraindications

• Hypersensitivity to ondansetron or other components of the drug;
• Pregnancy and breastfeeding period;
• Children under 2 years of age.

With caution in patients with cardiac rhythm and conduction disorders, patients receiving antiarrhythmic drugs and beta-blockers and patients with significant electrolyte disturbances (isolated cases of transient ECG changes, including QT interval prolongation, have been reported)

Use in Pregnancy and Lactation

Due to the lack of clinical safety data, the use of ondansetron during pregnancy and during breastfeeding is contraindicated. If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

In moderate or severe hepatic impairment, the clearance of ondansetron is significantly reduced, while its plasma half-life is increased, so such patients are not recommended to be prescribed more than 8 mg of ondansetron per day.

Use in Renal Impairment

It is not necessary to change the usual daily dose and frequency of administration of the drug.

Pediatric Use

Regarding the prevention and treatment of postoperative nausea and vomiting in children under 2 years of age, there is insufficient experience.

Geriatric Use

No dosage adjustment is required.

Special Precautions

Precautions for use

Patients who have previously had allergic reactions to other selective 5-HT₃ receptor blockers have an increased risk of developing them while taking ondansetron. Ondansetron may slow colonic motility, so its prescription to patients with signs of intestinal obstruction requires regular monitoring.

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

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

Effect on ability to drive vehicles and operate machinery

Studies on the effect of the drug on the ability to drive a car and work with machinery have not been conducted. Considering the safety profile, caution should be exercised when driving and operating machinery while taking ondansetron.

Overdose

Symptoms development of adverse reactions in a more pronounced form. In cases of suspected overdose, symptomatic therapy is indicated. A specific antidote is unknown. In case of ondansetron overdose, the use of ipecac is not recommended, as it is unlikely that this drug will be effective during the antiemetic action of ondansetron,

Drug Interactions

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

• With inducers of P450 isoenzymes (CYP2D6 and CYP3A) – barbiturates, carbamazepine, carisoprodol, glutethimide, griseofulvin, nitrous oxide, papaverine, phenylbutazone, phenytoin (and probably other hydantoins), rifampicin, tolbutamide;
• With inhibitors of 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.

Ondansetron at a concentration of 16-160 µg/ml is pharmaceutically compatible and can be administered through a Y-site injector intravenously by drip together with the following drugs

• Cisplatin (at a concentration of up to 0.48 mg/ml) for 1-8 h;
• Fluorouracil (at a concentration of up to 0.8 mg/ml at a rate of 20 ml/h – higher concentrations may cause precipitation of ondansetron);
• Carboplatin (at a concentration of 0.18-9.9 mg/ml for 10-60 min);
• Etoposide (at a concentration of 0.14-0.25 mg/ml for 30-60 min);
• Ceftazidime (at a dose of 0.25-2.0 g, as an intravenous bolus injection over 5 min);
• Cyclophosphamide (at a dose of 0.1-1.0 g, as an intravenous bolus injection over 5 min);
• Doxorubicin (at a dose of 10-100 mg, as an intravenous bolus injection over 5 min);
• Dexamethasone: intravenous administration of 20 mg dexamethasone slowly, over 2-5 min is possible. The drug can be administered through one dropper, while the concentrations of dexamethasone in the solution can range from 32 µg to 2.5 mg/ml, ondansetron – from 8 µg/ml to 0.1 mg/ml.

When used concomitantly with potent inducers of CYP3A isoenzymes, a decrease in the blood concentration of ondansetron is possible

With tramadol: there have been reports of a decrease in the analgesic effect of tramadol when used concomitantly with ondansetron.

Storage Conditions

Store at a temperature not exceeding 30°C (86°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.