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HENPLATIN (Oxaliplatin) HENTAXEL (Docetaxel) TPIAO (Thrombopoietin) ZEFEI (Gemcitabine) ZILONGJIN (Astragalus) HENSETRON (Tropisetron HCl)
Hematology Division
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Nephrology Division
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GoodFellow Pharma Corporation

HENSETRON (Tropisetron HCl)

1mg/mL Solution for IV Injection Antiemetic Formulation
Each 1 mL contains Tropisetron HCl 1 mg

Indications
It is used by patients to prevent nausea and vomiting caused by cancer chemotherapy. IU

Specification
5ml: 5mg (calculated on Tropisetron)

Uses and Administration
Tropisetron HCl is a highly selective 5-HT3 receptor antagonist with a potent antiemetic action similar to that of Ondansetron but more prolonged. It is used in the management of nausea and vomiting induced by cytotoxic therapy and in the treatment and prevention of post operative nausea and vomiting.

Tropisetron HCl is given intravenously, as a slow injection or into running intravenous infusion, or by mouth - doses are calculated in terms of Tropisetron base. For the prophylaxis of nausea and vomiting associated with cytotoxic chemotherapy a single dose equivalent to 5mg of Tropisetron may be given intravenously on the day of treatment shortly before chemotherapy. Subsequent doses of Tropisetron 5mg daily are given by mouth, at least one hour before food, for further 5 days.

Storage
Store in room temperature not exceeding 30oC. Do not store under direct sunlight. Keep out of children's reach.

Package
Box of 1 ampoule x 5 mL.

Shelf-Life
24 months

BFAD Drug Approval
BFAD Drug Reg. #: DR-XY36014

Caution
Foods, Drugs and Cosmetic Act prohibit dispensing without prescription.

For the treatment of post operative nausea and vomiting the equivalent of Tropisetron 2mg may be given by slow intravenous injection, or by infusion over 15 mins., within 2 hours of the end of anesthesia.

For prophylaxis, the same dose may be given shortly before induction of anesthesia.

Adverse Reactions
In general it is well tolerated and the side effects are transient at recommended dose. The most frequently reported adverse reaction at the 5mg dose was constipation (11%), these adverse reactions occur more frequent in patients with slow metabolism. Other common adverse reactions include headache, dizziness, fatigue and gastrointestinal disorders, such as 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 following type I hypersensitivity reactions has been reported: facial flushing and/or general urticaria, chest tightness, dyspnea, acute bronchospasm and hypotension.

Contraindications
It is contraindicated in patients who are hypersensitive to Tropisetron.

Precautions
  • 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 10mg per day.
  • The common adverse reactions of Tropisetron HCl are dizziness and fatigue, thus, it will be given to the patients with caution who drive and operate machinery after administration.
  • Administered by patients with impaired hepatic or renal function, its half-life will prolong, but no drug accumulation occurs during six-day courses of 5mg per day, thus no dosage adjustment is necessary.


Use in pregnancy and 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 breast-feed.

Drug Interaction:
  • Concomitant administration with rifampicin or with other liver enzyme-inducing (e.g.phenobarbital) results in lower plasma concentration of Tropisetron HCl; therefore, the dosage should be increased in normal metabolisers (but not in poor metabolisers).
  • The effects on Tropisetron HCl plasma levels of cytochrome P450 enzyme inhibitors such as 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 excised in patients with cardiac rhythm or conduction disturbances, or in patients treated with anti-arrhythmic or beta-adrenergic blocking agents.
Symptoms
At very high doses, visual hallucinations and in patients with hypertension, an increase in blood pressure, have been observed.

Symptoms
At very high doses, visual hallucinations and in patients with hypertension, an increase in blood pressure, have been observed.

Pharmacology
Tropisetron HCl is a highly potent and selective competitive antagonist of the 5-HT3 receptor. 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 anti-emetic 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 show 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 intravenously Tropisetron HCl; the elimination half-life is about 7.3-30.3 hours, the apparent distribution volume (V) is about 400-600L, and the protein binding rate is about 59%-71%.

The metabolism of Tropisetron is linked to sparteine/debrisoquine polymorphism (cytochrome P450D6). 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 sulphate 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 half-life (β-phase) is about 7-10 hours in normal metabolisers; in poor metabolisers this could be extended to 45 hours. The total clearance rate is about 1L/min, among which 10% is excreted in the kidney, in poor metabolisers, 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 half-life, AUC increase 5-7 times, and there are no significant changes in Cmax and distribution volume with normal metabolisers. In poor metabolisers, the ratio of unchanged drug excreted via urine is larger in comparison with normal metabolisers.

During many days of administration of Tropisetron HCl at dose of over 10mg and twice daily, the metabolic capability of liver enzyme system involving in the metabolism of the drug may reach storable and may result in the increase of dose dependence of plasma drug concentration. However, even in poor metabolisers, 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 5mg per day.

Manufactured By
Jiangsiu-Hengrui Medicine Co., Ltd.
# 145 East Renmin Rd. Xinpu District
Lianyungang, Jiangsu Province, China

Imported By
Goodfellow-Hengrui Pharma Inc.
Unit 3009 Jollibee Plaza Condominium
Emerald Ave. Ortigas, Pasig City
Copyright © 2008 Goodfellow Pharma Corporation
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Emerald Ave., Ortigas Center 1605 Pasig City

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