Domegan (Solution) Instructions for Use

Marketing Authorization Holder

Genfamedica S.A. (Switzerland)

Manufactured By

Omega Laboratories, Ltd. (Canada)

ATC Code

A04AA01 (Ondansetron)

Active Substance

Ondansetron (Rec.INN registered by WHO)

Dosage Forms

	Domegan	Solution for intravenous and intramuscular administration 4 mg/2 ml: fl. 5 pcs.
		Solution for intravenous and intramuscular administration 8 mg/4 ml: fl. 5 pcs.

Dosage Form, Packaging, and Composition

Solution for IV and IM administration transparent, colorless.

Excipients: sodium chloride, citric acid monohydrate, sodium citrate dihydrate, water for injections.

2 ml – dark glass bottles (5) – cardboard packs.

Solution for IV and IM administration transparent, colorless.

Excipients: sodium chloride, citric acid monohydrate, sodium citrate dihydrate, water for injections.

4 ml – dark glass bottles (5) – cardboard packs.

Clinical-Pharmacological Group

Centrally acting antiemetic drug blocking serotonin receptors

Pharmacotherapeutic Group

Antiemetic agent – serotonin receptor antagonist

Pharmacological Action

Antiemetic agent. Effectively prevents and relieves nausea and vomiting occurring during anticancer chemotherapy or radiation therapy, as well as in the postoperative 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 vagus nerve fibers by serotonin released from enterochromaffin cells of the gastrointestinal mucosa plays an important role in the occurrence of nausea and vomiting during anticancer therapy.

By blocking 5-HT₃ receptors, Ondansetron prevents the occurrence of the vomiting reflex. Furthermore, Ondansetron suppresses the central links of the vomiting reflex by blocking 5-HT₃ receptors in the floor of the fourth ventricle (area postrema).

Pharmacokinetics

Ondansetron undergoes first-pass metabolism in the liver. Protein binding is high (70-76%). It is biotransformed in the liver, mainly by hydroxylation. The mean T_1/2 in adult patients is about 4 hours.

Indications

Prevention of nausea and vomiting during anticancer chemotherapy or radiation therapy; prevention and treatment of nausea and vomiting in the postoperative period.

ICD codes

Dosage Regimen

Administer the dosage regimen individually based on the clinical indication, the emetogenic potential of the therapy, and the patient’s age and renal/hepatic function.

For chemotherapy-induced nausea and vomiting in adults, administer a single 8 mg dose by slow intravenous injection immediately before chemotherapy. Alternatively, administer a single 8 mg dose intramuscularly.

For radiation-induced nausea and vomiting in adults, administer 8 mg orally or intravenously one to two hours before each fraction of radiotherapy. Repeat every eight hours as needed.

For postoperative nausea and vomiting prevention in adults, administer 4 mg undiluted by intramuscular injection or slow intravenous injection immediately before anesthesia induction. Alternatively, administer at the end of surgery.

For postoperative nausea and vomiting treatment in adults, administer a single 4 mg dose intramuscularly or by slow intravenous injection.

Do not exceed a maximum single intravenous dose of 16 mg due to the risk of serious cardiac adverse effects, including QT interval prolongation.

Administer intravenous injections slowly over at least 30 seconds, preferably over 2 to 5 minutes. Do not use the solution if it is discolored or contains particulate matter.

In patients with severe hepatic impairment, do not exceed a maximum total daily dose of 8 mg due to significantly reduced clearance.

Adverse Reactions

Immune system disorders: rarely – immediate hypersensitivity reactions (urticaria, bronchospasm, laryngospasm, angioedema), in some cases severe, including anaphylaxis.

Nervous system disorders: very common – headache; uncommon – seizures, movement disorders (including extrapyramidal symptoms such as dystonia, oculogyric crisis, and dyskinesia); rarely – dizziness, predominantly during rapid IV administration.

Eye disorders: rarely – transient visual disturbances (e.g., blurred vision, transient blindness), mainly during IV administration.

Cardiac and vascular disorders: common – feeling of warmth or flushing; uncommon – arrhythmia, chest pain, both accompanied and not accompanied by ST segment depression, bradycardia, decreased blood pressure; rarely – QT interval prolongation (including torsades de pointes).

Gastrointestinal disorders: common – constipation; uncommon – hiccups, dry oral mucosa; frequency unknown – diarrhea.

Hepatobiliary disorders: uncommon – asymptomatic increase in ALT, AST activity (mainly in patients receiving cisplatin chemotherapy).

Skin and subcutaneous tissue disorders: very rare – toxic skin rash, including toxic epidermal necrolysis.

Metabolism and nutrition disorders: rarely – hypokalemia, hypercreatininemia.

Local reactions: with IV administration – burning at the injection site; with use of suppositories – burning sensation in the anus and rectum.

Contraindications

Hypersensitivity to ondansetron; concomitant use of ondansetron with apomorphine; pregnancy, lactation (breastfeeding); pediatric age – depending on the indications and dosage form; congenital long QT syndrome.

With caution in patients with hypersensitivity to other 5HT₃ receptor antagonists, with cardiac rhythm and conduction disorders, with significant water-electrolyte balance disturbances; in patients with prolonged or at risk of QTc prolongation, including patients with water-electrolyte balance disorders, chronic heart failure, bradyarrhythmia, or in patients taking other medications that can cause QT interval prolongation, water-electrolyte balance disturbances, or decreased heart rate; in patients receiving antiarrhythmic agents and beta-blockers; in patients with subacute intestinal obstruction; with concomitant use of other serotonergic drugs.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding). If use during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

In patients with moderate and severe hepatic impairment, the clearance of ondansetron is significantly reduced, and the half-life is significantly increased.

Pediatric Use

Can be used in children of appropriate age categories strictly according to indications, in recommended doses and dosage forms. It is necessary to strictly follow the instructions in the ondansetron drug labels regarding contraindications for use in children of different ages for specific ondansetron dosage forms.

Special Precautions

There are reports of hypersensitivity reactions to ondansetron in patients with a history of hypersensitivity to other selective 5HT₃ receptor antagonists.

Ondansetron is known to increase large bowel transit time. When using ondansetron in patients with symptoms of subacute intestinal obstruction, regular monitoring of such patients is necessary.

Hypokalemia and hypomagnesemia must be corrected before using ondansetron.

It has been established that the combined use of ondansetron and other serotonergic drugs increases the risk of developing serotonin syndrome. If the use of such a combination is clinically justified, regular monitoring of the patient’s condition is necessary.

Effect on ability to drive vehicles and operate machinery

During the use of ondansetron, patients should exercise caution when driving vehicles and operating machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Since Ondansetron is metabolized in the liver by cytochrome P450 isoenzymes, concomitant use with drugs that are inducers or inhibitors of this enzyme system may lead to changes in the clearance and T_1/2 of ondansetron.

In patients receiving strong inducers of the CYP3A4 isoenzyme (phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron increases, and the blood concentration of ondansetron decreases.

There is evidence that Ondansetron may reduce the analgesic effect of tramadol.

When ondansetron is used concomitantly with other serotonergic drugs, including selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, the risk of developing serotonin syndrome increases.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.