Pharmacology: Tropisetron HCl is a highly potent and selective competitive antagonist of the 5-HT3 receptor with a potent antiemetic action similar to that of ondansetron but more prolonged. Some substances, including some chemotherapeutic agents, may trigger the release of serotonin (5-HT) from enterochromaffin-like cells in the visceral mucosa and initiate the emesis reflex. Moreover, its antiemetic effect may be related to the inhibition of the stimulation of vagus nerve in the area postrema by its direct block of CNS 5-HT3 receptors.
Genotoxicity: The literature reports that tropisetron HCl has no significant effect on the mouse bone marrow micronucleus, even at vitro high concentration, no chromosomal anomaly and mutagenic action have been observed.
Reproductive Toxicity: Animal reproductive toxicity test shows that it has potential embryotoxicity. It is not known whether it is excreted into human milk and women during lactation should not receive it.
Pharmacokinetics: Healthy volunteers administered tropisetron HCl IV, the elimination t½ is about 7.3-30.3 hrs, the apparent volume of distribution (V) is about 400-600 L and the protein binding rate is about 59-71%.
The metabolism of tropisetron is linked to sparteine/debrisoquine polymorphism (cytochrome P-450D6). About 8% of the Caucasian population lacks the enzyme. 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 sulfate and excretion in the urine or bile (urine to feces ratio 5:1). The metabolites have greatly reduced potency for the 5-HT3 receptor and do not contribute to the pharmacological action of the drug. The elimination t½ (β-phase) is about 7-10 hrs in normal metabolizers; in poor metabolizers this could be extended to 45 hrs. The total clearance rate is about 1 L/min, among which 10% is excreted in the kidney, in poor metabolizers, even the ratio of excretion in the kidney does not change, the total clearance reduces to be 0.1-0.2 L/min. The decrease may result in the 4-5 times of prolongation of clearance t½, AUC increase 5-7 times and there are no significant changes in Cmax and V with normal metabolizers. In poor metabolizers, the ratio of unchanged drug excreted via urine is larger in comparison with normal metabolizers.
During many days of administration of tropisetron HCl at dose of >10 mg twice daily, the metabolic capability of liver enzyme system involving in the metabolism of tropisetron may reach storable and may result in the increase of dose dependence of plasma drug concentration. However, even in poor metabolizers, the drug exposure at the dose still belong to the level well tolerated. Thus, it is unnecessary to worry about the drug accumulation of the regimen as 6-day courses of 5 mg/day.
Treatment and prevention of postoperative nausea and vomiting.
Prevention of nausea and vomiting induced by cytotoxic chemotherapy.
Tropisetron HCl is given IV, as a slow injection or into running IV infusion or orally. Doses are calculated in terms of tropisetron base.
For the prophylaxis of nausea and vomiting associated with cytotoxic chemotherapy, a single dose equivalent to 5 mg of tropisetron may be given IV on the day of treatment shortly before chemotherapy. Subsequent doses of tropisetron 5 mg daily are given orally, at least 1 hr before food, for further 5 days.
For the treatment of postoperative nausea and vomiting, the equivalent of tropisetron 2 mg may be given by slow IV inj or by infusion over 15 min, within 2 hrs of the end of anesthesia.
For prophylaxis, the same dose may be given shortly before induction of anesthesia.
Symptoms: At very high doses, visual hallucinations and in patients with hypertension, an increase in blood pressure have been observed.
Treatment: Symptomatic treatment with frequent monitoring of vital signs and close observation of the patient is indicated.
Patients who are hypersensitive to tropisetron.
The blood pressure of uncontrolled hypertension patients will increase after administration of tropisetron HCl, thus, it should be used by hypertension patients with caution with dosage not more than 10 mg/day.
When administered in patients with impaired hepatic or renal function, its t½ will prolong, but no drug accumulation occurs during 6-day courses of 5 mg/day, thus no dosage adjustment is necessary.
Effects on the Ability to Drive or Operate Machinery: The common adverse reactions of tropisetron HCl are dizziness and fatigue, thus, it should be given with caution to patients who drive and operate a machinery after administration.
Use in pregnancy & lactation: The use in pregnant women is not recommended. It is not known whether tropisetron HCl is excreted into human milk and therefore patients receiving the drug should not breastfeed.
The use in pregnant women is not recommended. It is not known whether tropisetron HCl is excreted into human milk and therefore patients receiving the drug should not breastfeed.
In general, it is well tolerated and the side effects are transient at recommended dose. The most frequently reported adverse reaction at the 5-mg dose was constipation (11%), these adverse reactions occur more frequent in patients with slow metabolism. Other common adverse reactions include headache, dizziness, fatigue and GI disorders, eg abdominal pain, diarrhea, etc. Collapse, syncope or cardiovascular arrest has been reported, but the relation with tropisetron HCl has not been established. One or more of the following type I hypersensitivity reactions has been reported: Facial flushing and/or general urticaria, chest tightness, dyspnea, acute bronchospasm and hypotension.
Concomitant administration with rifampicin or with other liver enzyme-inducing drug (eg, phenobarbital) resulted in lower plasma concentration of tropisetron HCl, therefore, the dosage should be increased in normal metabolizers (but not in poor metabolizers).
The effects on tropisetron HCl plasma levels of cytochrome P-450 enzyme inhibitors, eg cimetidine do not require dose adjustment.
As QTc prolongation has been observed in patients administered high dose of tropisetron HCl, thus care should be taken when other drugs that are likely to prolong the QT interval are taken concomitantly with tropisetron HCl.
Caution should be exercised in patients with cardiac rhythm or conduction disturbances or in patients treated with anti-arrhythmic or β-adrenergic blocking agents.
Store at temperatures not exceeding 30°C. Do not store under direct sunlight.
Shelf-Life: 24 months.
A04AA03 - tropisetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.
Hensetron inj 5 mg/5 mL
(amp) 5 × 1's
Sign Out
Continue with Google
Sign up with email
Already a member?
Sign in
