Palonosetron (Solution) Instructions for Use

Marketing Authorization Holder

Hetero Labs, Limited (India)

Manufactured By

Aspiro Pharma, Limited (India)

ATC Code

A04AA05 (Palonosetron)

Active Substance

Palonosetron (Rec.INN registered by WHO)

Dosage Form

Palonosetron

Solution for intravenous administration 0.25 mg/5 ml

Dosage Form, Packaging, and Composition

Solution for intravenous administration

5 ml – vials – cardboard boxes – In-Bulk
5 ml – vials – cardboard packs – By prescription

Clinical-Pharmacological Group

Centrally acting antiemetic drug blocking serotonin receptors

Pharmacotherapeutic Group

Antiemetic agents; serotonin 5-HT3 receptor antagonists

Pharmacological Action

Palonosetron is a highly selective serotonin receptor antagonist. Its mechanism of action is associated with the suppression of the vomiting reflex by blocking serotonin 5-HT₃ receptors at the level of neurons in the central and peripheral nervous systems.

This mechanism underlies the prevention and treatment of nausea and vomiting induced by cytotoxic chemo- and radiotherapy, which are associated with increased serotonin levels.

Serotonin activates vagal afferent fibers containing 5-HT₃ receptors, thereby triggering the vomiting reflex. Palonosetron does not inhibit or stimulate cytochrome P450 isoenzymes.

Pharmacokinetics

Following intravenous administration at recommended doses, the plasma concentration of the drug decreases slowly as it is eliminated from the body.

The distribution half-life is 40 hours, and the mean plasma concentration is generally proportional to the administered dose. Palonosetron is well distributed in tissues, with a volume of distribution (V_d) of 6.9-7.9 L/kg.

Plasma protein binding is 62%. It is eliminated by the kidneys, with approximately 50% excreted as metabolites whose activity is less than 1% of palonosetron’s activity.

After a single intravenous dose of 10 mcg/kg, approximately 80% of the active substance is detected in the urine within 144 hours. After a single bolus injection, the total clearance is 173±73 mL/min, and renal clearance is 53±29 mL/min. The elimination half-life (T_1/2) can exceed 100 hours in 10% of patients.

Indications

Prevention of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy (moderately and highly emetogenic), during the initial and repeated courses.

Dosage Regimen

Administer intravenously only.

For adults, administer a single 0.25 mg dose.

Infuse the dose over at least 30 seconds.

Time the administration to complete 30 minutes before the start of cytotoxic chemotherapy.

For pediatric patients aged 1 month to 18 years, calculate the dose at 0.02 mg/kg.

Do not exceed the maximum pediatric dose of 1.5 mg.

Infuse the pediatric dose over at least 15 minutes.

Administer the pediatric dose 30 minutes before chemotherapy initiation.

This regimen is for the prevention of acute nausea and vomiting.

Use for moderately and highly emetogenic chemotherapy or radiotherapy courses.

No dosage adjustment is required for renal impairment or hepatic impairment.

No dosage adjustment is required for geriatric patients.

Adverse Reactions

From the cardiovascular system infrequently – tachycardia, bradycardia, extrasystoles, myocardial ischemia, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles, decreased blood pressure, increased blood pressure, QT interval prolongation; vein discoloration, varicose veins.

From the nervous system frequently – headache; infrequently – dizziness, drowsiness, insomnia, paresthesia, peripheral sensory neuropathy, feeling of restlessness, euphoria.

From the digestive system frequently – constipation; infrequently – diarrhea, abdominal pain, dry mouth, flatulence, anorexia, hiccups.

From the urinary system infrequently – urinary retention.

From the skin and skin appendages: infrequently – allergic dermatitis, itching, rash.

From the musculoskeletal system infrequently – arthralgia;

From the sensory organs infrequently – increased eye sensitivity – irritation, diplopia, amblyopia, impaired coordination, tinnitus.

Changes in laboratory parameters infrequently – increased activity of “hepatic” transaminases, hypo- or hyperkalemia, hypocalcemia, hyperglycemia, hyperbilirubinemia, glucosuria, metabolic acidosis.

Other infrequently – increased fatigue, weakness, increased body temperature, flushing, feeling of “heat”, flu-like syndrome.

Local reactions rarely – burning, induration, pain at the injection site.

Contraindications

Hypersensitivity to palonosetron, pregnancy, breastfeeding period, children under 1 month of age.

With caution

Hypersensitivity reactions to other 5-HT₃ receptor antagonists; patients with cardiac rhythm and conduction disorders receiving antiarrhythmic drugs and beta-blockers; patients with significant electrolyte imbalances; patients prone to QT interval prolongation (congenital long QT syndrome).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Dosage adjustment in patients with hepatic impairment is not required.

Use in Renal Impairment

Dosage adjustment in patients with renal impairment is not required.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Dosage adjustment in elderly patients is not required.

Special Precautions

Palonosetron may increase intestinal transit time. Therefore, special monitoring of the condition of patients with signs of intestinal obstruction is required.

As with other 5-HT₃ receptor antagonists, caution should be exercised when using palonosetron in patients with existing or potential for QT interval prolongation, including patients with a personal or family history of long QT syndrome, electrolyte imbalances, congestive heart failure, bradyarrhythmias, conduction disorders, and patients receiving antiarrhythmic drugs or other medications that cause QT interval prolongation or electrolyte imbalances.

Hypokalemia and hypomagnesemia must be corrected prior to the use of 5-HT₃ receptor antagonists.

Serotonin syndrome may develop with the use of 5-HT₃ receptor antagonists, either as monotherapy or in combination with other serotonergic drugs, including SSRIs and SNRIs. Therefore, appropriate monitoring of patients for symptoms resembling serotonin syndrome is recommended.

It should not be used for the prevention or treatment of nausea and vomiting after chemotherapy, except in cases of another chemotherapy session.

Effect on the ability to drive vehicles and operate machinery

Since adverse reactions such as dizziness, drowsiness, and increased fatigue may occur with the use of palonosetron, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Palonosetron is primarily metabolized by the CYP2D6 isoenzyme, with the participation of CYP3A4 and CYP1A2 isoenzymes.

Concomitant use of palonosetron with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors increases the risk of developing serotonin syndrome (altered mental status, autonomic nervous system instability, and neuromuscular abnormalities).

Storage Conditions

Store at 2°C (36°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.