Ondansetron-Altpharm (Suppositories) Instructions for Use

Marketing Authorization Holder

Altpharm LLC (Russia)

Contact Information

Altpharm LLC (Russia)

ATC Code

A04AA01 (Ondansetron)

Active Substance

Ondansetron (Rec.INN WHO registered)

Dosage Forms

	Ondansetron-Altpharm	Rectal suppositories 4 mg: 5 pcs.
		Rectal suppositories 8 mg: 5 pcs.
		Rectal suppositories 16 mg: 2 pcs.

Dosage Form, Packaging, and Composition

Rectal suppositories white or white with a creamy tint, torpedo-shaped, with no visible inclusions on the longitudinal section.

Excipients: Witepsol H-15.

5 pcs. – contour cell packs (1) – cardboard packs.

Rectal suppositories white or white with a creamy tint, torpedo-shaped, with no visible inclusions on the longitudinal section.

Excipients: Witepsol H-15.

5 pcs. – contour cell packs (1) – cardboard packs.

Rectal suppositories white or white with a creamy tint, torpedo-shaped, with no visible inclusions on the longitudinal section.

Excipients: Witepsol H-15.

1 pc. – contour cell packs (1) – cardboard inserts (2) – cardboard packs.

Clinical-Pharmacological Group

Centrally acting antiemetic drug blocking serotonin receptors

Pharmacotherapeutic Group

Antiemetic agents; serotonin 5-HT₃ receptor antagonists

Pharmacological Action

Antiemetic drug of central action. Selective antagonist of serotonin 5-HT₃ receptors.

Medications for cytostatic chemotherapy and radiotherapy can cause an increase in serotonin levels, which, by activating vagal afferent fibers containing serotonin 5-HT₃ receptors, triggers the vomiting reflex. Ondansetron inhibits the occurrence of the vomiting reflex by blocking serotonin 5-HT₃ receptors at the level of neurons in both the central and peripheral nervous systems. This mechanism of action is likely the basis for the prevention and treatment of postoperative nausea and vomiting, as well as nausea and vomiting induced by cytostatic chemotherapy and radiotherapy.

Pharmacokinetics

The pharmacokinetic parameters of ondansetron do not change with its repeated administration.

Absorption

After rectal administration, Ondansetron is detected in plasma within 15-60 minutes. The concentration of the active substance increases linearly, C_max is reached in approximately 6 hours and is 20-30 ng/ml. The absolute bioavailability after rectal administration is approximately 60%. The decrease in plasma concentration occurs at a slower rate than after oral administration (due to ongoing absorption).

Elimination

T_1/2 – 6 hours.

Indications

• Prevention and relief of nausea and vomiting caused by cytostatic chemotherapy and radiotherapy.

ICD codes

Dosage Regimen

The drug is used rectally. To remove a suppository from the blister pack, break off one blister with the suppository along the notch and, separating the edges of the strip, pull them in opposite directions. Insert the suppository into the anus with the pointed end, as deep as possible. For easier insertion of the suppository, it is recommended to bend over, squat, or lie on your side with your legs pulled up.

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

For moderately emetogenic chemotherapy or radiotherapy, 16 mg of ondansetron is prescribed 1-2 hours before the start of the main therapy.

For highly emetogenic chemotherapy, the recommended dose is 16 mg simultaneously with IV administration of 20 mg of dexamethasone 1-2 hours before the start of chemotherapy.

For prevention of late or prolonged vomiting, occurring 24 hours after the end of chemotherapy or radiotherapy, the drug should be continued at a dose of 16 mg once daily for 5 days.

The drug is not recommended for use in children.

In elderly patients, no dose adjustment is required.

In patients with renal insufficiency, no changes in dose, frequency of administration, or method of application are required.

For patients with impaired liver function, the daily dose of ondansetron should not exceed 8 mg.

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

Adverse Reactions

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

From the cardiovascular system: chest pain (sometimes with ST segment depression), arrhythmias, bradycardia, decreased blood pressure.

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

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

Local reactions redness, pain, burning sensation in the anus and rectum after insertion of the suppository.

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

Contraindications

• Pregnancy;
• Lactation period (breastfeeding);
• Childhood;
• Hypersensitivity to ondansetron or any other component of the drug.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

For patients with impaired liver function, the daily dose of ondansetron should not exceed 8 mg.

Use in Renal Impairment

In patients with renal insufficiency, no changes in dose, frequency of administration, or method of application are required.

Special Precautions

Patients with a history of allergic reactions to other selective serotonin 5-HT₃ receptor blockers have an increased risk of developing them when taking ondansetron.

Ondansetron may slow down colonic motility, therefore, its prescription to patients with symptoms of intestinal obstruction requires special monitoring.

Overdose

There is limited experience with ondansetron overdose. In most cases, the symptoms are similar to the adverse reactions when using the drug in recommended doses.

Treatment symptomatic and supportive therapy. A specific antidote for ondansetron is not known.

Drug Interactions

There is no evidence that Ondansetron induces or inhibits the metabolism of other drugs often prescribed in combination with it.

Ondansetron is metabolized by several cytochrome P450 isoenzymes (CYP3A4, CYP2D6 and CYP1A2). Inhibition or reduced activity of one of the isoenzymes is usually compensated by others, therefore a significant decrease in the total clearance of ondansetron is unlikely. Nevertheless, caution is required when used concomitantly

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

Special studies have shown that Ondansetron does not interact with ethanol, temazepam, furosemide, tramadol and propofol.

Storage Conditions

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

Shelf Life

Shelf life – 2 years.

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.