Tropisetron

Tropisetron is a Selective 5-HT₃ Receptor Antagonist belonging to Antiemetic agent.

Tropisetron is a 5HT-3 receptor antagonist used as an antiemetic in the treatment of chemotherapy-induced nausea and vomiting.

The absorption of Tropisetron from the gastrointestinal tract is rapid (mean half-life of about 20 minutes) and nearly complete (more than 95%). Due to first-pass metabolism in the liver, the absolute bioavailability of a 5 mg oral dose is 60%. The peak plasma concentration is attained within three hours. The volume of distribution is about 400-600 L. Plasma protein binding: 71%. The metabolism of Tropisetron occurs by hydroxylation at the 5, 6 or 7 positions of its indole ring, followed by a conjugation reaction to the glucuronide or sulphate with excretion in the urine or bile (urine to faeces ratio 5:1). The metabolites have a greatly reduced potency for the 5-HT3 receptor and do not contribute to the pharmacological action of the drug. About 8% of Tropisetron is excreted in the urine as unchanged drug, 70% as metabolites; 15% is excreted in the feces.

Tropisetron shows side effects like QT prolongation, hypersensitivity reactions (e.g. anaphylaxis), Headache, constipation, dizziness, fatigue, visual hallucinations, somnolence, syncope, HTN, hypotension, Abdominal pain, diarrhoea, anorexia, Dyspnoea, acute bronchospasm, chest discomfort, Urticaria.

Tropisetron is available in the form of Oral Capsule and Injectable solution.

Tropisetron is available in India, Europe, Australia, New Zealand, Japan, South Korea and Philippines.

Tropisetron belongs to the Antiemetic agent acts as a Selective 5-HT₃ Receptor Antagonist.

Tropisetron competitively binds to and blocks the action of serotonin at 5HT3 receptors peripherally on vagus nerve terminals located in the gastrointestinal (GI) tract as well as centrally in the chemoreceptor trigger zone (CTZ) of the area postrema of the central nervous system (CNS). This results in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.

The Data of Onset of action of Tropisetron is clinically not established.

The duration of action of Tropisetron is about 24 hours.

The Tmax of Tropisetron is via IV route is about 3 hours.

Tropisetron is a 5HT-3 receptor antagonist used as an antiemetic in the treatment of chemotherapy-induced nausea and vomiting.

Tropisetron is approved for use in the following clinical indications

• Prophylaxis of nausea and vomiting associated with cytotoxic therapy
• Treatment and prophylaxis of postoperative nausea and vomiting

• Prophylaxis of nausea and vomiting associated with cytotoxic therapy

Adult Oral Dose: 5 mg once daily before chemotherapy on day 2-6 following IV dose given on day 1. Duration of treatment: 5 days.

Child Oral Dose: >2 years >25 kg 0.2 mg/kg once daily before chemotherapy on day 2-6 following IV dose given on day 1. Duration of treatment: 5 days.

Adult IV Dose: 5 mg by slow IV injection over at least 1 min or by IV infusion over 15 min to be given 15 min before chemotherapy on day 1, followed by oral preparation on day 2-6.

Child IV Dose: >2 years 0.2 mg/kg (max: 5 mg) by slow IV injection over at least 1 min or by IV infusion at a concentration of 0.05 mg/ mL over 15 min to be given as a single dose before chemotherapy on day 1. <25 kg: Continue once daily at the same dose up to day 5 of chemotherapy.

• Treatment and prophylaxis of postoperative nausea and vomiting

Adult IV Dose: 2 mg as single dose or once daily by bolus injection over 30 sec or by IV infusion over 15 min w/in 2 hours at the end of anaesth (treatment) or before induction of anaesth (prophylaxis).

Tropisetron is available in various strengths as 2mg/2mL; 5mg/5mL; and 5mg.

Tropisetron is available in the form of Oral capsule and injectable solution.

Tropisetron is contraindicated in patients with

• Pregnancy and lactation.

• Caution should take patient with cardiac rhythm or conduction disturbances, uncontrolled HTN.
• Risk of QT interval prolongation, electrolyte disturbances.
• This drug may cause dizziness or fatigue, if affected, do not drive, or operate machinery.

Avoid consumption of alcohol.

Tropisetron is contraindicated during lactation.

Tropisetron is contraindicated in pregnancy.

Common

● QT prolongation, Rarely, hypersensitivity reactions (e.g., anaphylaxis), Headache, constipation, dizziness, fatigue, visual hallucinations, somnolence, syncope, HTN, hypotension, Abdominal pain, diarrhea, anorexia, Dyspnoea, acute bronchospasm, chest discomfort, Urticaria, Rarely, collapse and CV arrest.

• Rifampicin

Decreased plasma concentration within rifampicin.

• Antiarrhythmics

Increased risk of conduction abnormalities w/ antiarrhythmics.

• liver enzyme-inducers

Decreased plasma concentration with liver enzyme-inducers (e.g. phenobarbital).

• β-blockers

Increased risk of conduction abnormalities within β-blockers.

• Serotonergic drugs

Risk of serotonin syndrome within serotonergic drugs (e.g. serotonin and norepinephrine reuptake inhibitors [SNRIs or SSRIs]).

The common side effects of Tropisetron include the following

Common side effects

● QT prolongation, hypersensitivity reactions (e.g. anaphylaxis), Headache, constipation, dizziness, fatigue, visual hallucinations, somnolence, syncope, HTN, hypotension, Abdominal pain, diarrhoea, anorexia, Dyspnoea, acute bronchospasm, chest discomfort, Urticaria.

Symptoms: Visual hallucinations, increased BP. Management: Symptomatic treatment. Monitor vital signs closely.

Pharmacodynamic

Information not available.

Pharmacokinetics

• Absorption

The absorption of Tropisetron from the gastrointestinal tract is rapid (mean half-life of about 20 minutes) and nearly complete (more than 95%). Due to first-pass metabolism in the liver, the absolute bioavailability of a 5 mg oral dose is 60%. The peak plasma concentration is attained within three hours.

• Distribution

Volume of distribution: 400-600 L. Plasma protein binding: 71%.

• Metabolism and Excretion

The metabolism of Tropisetron occurs by hydroxylation at the 5, 6 or 7 positions of its indole ring, followed by a conjugation reaction to the glucuronide or sulphate with excretion in the urine or bile (urine to faeces ratio 5:1). The metabolites have a greatly reduced potency for the 5-HT3 receptor and do not contribute to the pharmacological action of the drug. About 8% of Tropisetron is excreted in the urine as unchanged drug, 70% as metabolites; 15% is excreted in the feces.

• https://www.mims.com/india/drug/info/tropisetron?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB11699