Consumer medicine information

TROPISETRON MYX

Tropisetron

BRAND INFORMATION

Brand name

Tropisetron MYX Solution for injection

Active ingredient

Tropisetron

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using TROPISETRON MYX.

What is in this leaflet

This leaflet answers some common questions about tropisetron.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

All medicines have risks and benefits. Your doctor has weighed the risks of you having this medicine against the benefits they expect it will provide.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Tropisetron MYX is used for

Tropisetron is used to prevent nausea (feeling sick) and vomiting caused by surgery.

The active ingredient in Tropisetron MYX is tropisetron (as hydrochloride). It works by stopping the action of a substance in the body called SEROTONIN that is thought to cause the nausea and vomiting.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

Tropisetron is only available with a doctor's prescription. It is not addictive.

There is not enough information to recommend its use in children.

Before you have Tropisetron MYX

When you must not have it

Do not have tropisetron if you have ever had an allergy to:

  • tropisetron (the active ingredient in Tropisetron MYX)
  • any of the other ingredients listed at the end of this leaflet
  • similar medicines such as ondansetron and dolasetron

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not have tropisetron if you are pregnant.

There is not enough information to recommend its use during pregnancy.

Do not breast-feed while you are having tropisetron.

It is not known if the active ingredient in tropisetron passes into breast milk and could affect your baby.

Do not have tropisetron after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

In that case, return it to your pharmacist.

Before you start to have it

Tell your doctor if you have any of the following health problems / medical conditions:

  • kidney problems
  • liver problems
  • heart problems
  • high blood pressure that is not controlled

Your doctor may want to take special precautions if you have any of the above conditions.

Tell your doctor if you have allergies to any other medicines, foods, dyes or preservatives.

Your doctor will want to know if you are prone to allergies.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and tropisetron may interfere with each other. These include:

  • rifampicin
  • phenobarbital
  • some medicines for your heart
  • any medicine that has caused problems with your heart rhythm since this effect could be worsened
  • serotonergic drugs such as antidepressants

You may need to take different amounts of your medicines or to take different medicines while you are having tropisetron. Your doctor and pharmacist have more information. Tell your doctor if you are taking other serotonergic drugs. Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been described following the concomitant use of tropisetron and other serotonergic drugs including selective serotonin reuptake inhibitors (SNRIs).

If you have not told your doctor about any of these things, tell him/ her before you start having this medicine.

How Tropisetron MYX is used

Follow all directions given to you by your doctor and pharmacist carefully.

These directions may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

For nausea and vomiting caused by surgery

A single 2 mg dose is usually given by injection or through an intravenous drip shortly before surgery. If nausea and vomiting happen after surgery, a 2 mg dose of tropisetron can be given at that time.

If you have too much (Overdose)

Because tropisetron will be given by a doctor or nurse it is unlikely that you will be given too large a dose. Your doctor has information on how to recognise and treat an overdose.

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have had too much tropisetron. Do this even if there are no signs of discomfort or poisoning. Keep the telephone numbers for these places handy.

At very high doses, some people may have visual hallucinations (see things that are not there). People with high blood pressure may have their blood pressure raised even higher.

While you are having Tropisetron MYX

Things you must do

Before having any surgery that requires general anaesthesia, tell the anaesthetist or the doctor in charge that you are having tropisetron.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are having tropisetron.

Tell any other doctor, dentist or pharmacist who treats you that you are having tropisetron.

Things you must not do

Do not give this medicine to anyone else, even if their condition seems similar to yours.

Do not use it to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how tropisetron affects you.

This medicine may cause dizziness or tiredness in some people. If you have any of these symptoms, do not drive or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are having tropisetron.

All medicines can have side effects.

Sometimes they are serious, but most of the time they are not. You may need medical treatment if you get some of the side effects.

Some symptoms may be caused by your medical condition or by other treatments (e.g. surgery) rather than by this medicine.

Do not be alarmed by these lists of possible side effects. You may not experience any of them. Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor immediately if you notice any of the following:

  • changes in your heart beat
  • fainting
  • signs of allergy such as rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing
  • tight feeling in the chest

The above list includes serious side effects which may require medical attention. These side effects are rare.

Tell your doctor if you notice any of the following and they worry you:

  • headache
  • constipation
  • dizziness or light-headedness
  • tiredness, sleepiness
  • stomach pain
  • diarrhoea
  • loss of appetite
  • hot flushes

Tell your doctor if you notice anything else that is making you feel unwell.

Some people may have other side effects not yet known or mentioned in this leaflet. Some side effects will only be found by laboratory testing (e.g. changes in your heart rhythm on an electrocardiogram).

After having Tropisetron MYX

Storage

Store below 25ºC.

Product description

What it looks like

Tropisetron MYX 2 mg/2mL solution for injection is supplied in glass ampoules containing a clear, colourless or faintly yellow-brown solution; packs of 5 ampoules.

Ingredients

Tropisetron MYX ampoules contain 2 mg of the active ingredient, tropisetron (as hydrochloride). They also contain:

  • acetic acid-glacial
  • sodium acetate trihydrate
  • sodium chloride
  • water for injections

Sponsor

Mayne Pharma International Pty Ltd
ABN 88 007 870 984
1538 Main North Road
Salisbury South SA 5106

Australian Registration Numbers

2 mg/2 mL solution for injection ampoule AUST R 246633

Date of preparation

This leaflet was prepared in April 2016.

MYX is a trade mark of Mayne Pharma International Pty Ltd.

BRAND INFORMATION

Brand name

Tropisetron MYX Solution for injection

Active ingredient

Tropisetron

Schedule

S4

 

Name of the medicine

Tropisetron hydrochloride.

Excipients.

Glacial acetic acid, sodium acetate trihydrate, sodium chloride and water for injections. The pH of the solution is 4.6-5.2.

Description

Tropisetron hydrochloride is 1αH,5αH-tropan-3α-yl indole-3-carboxylate hydrochloride. CAS: 89565-68-4 (tropisetron); CAS: 105826-92-4 (tropisetron hydrochloride).
Tropisetron hydrochloride is a white or off-white crystalline powder. It is soluble >5% in water, 1.6% in ethanol (95% v/v) and poorly soluble (0.02%) in acetone. The molecular weight of the free base is 284.4 and of the hydrochloride salt is 320.8.
Tropisetron MYX injection is a clear, colourless to very faintly yellow-brown aqueous solution which contains 1 mg/mL tropisetron in ampoules containing 2 mL of solution. The pH of the solution is 4.6-5.2. The ampoules contain as excipients, glacial acetic acid, sodium acetate trihydrate, sodium chloride and water for injections.
Product is for single use in one patient only. Discard any residue.

Pharmacology

Tropisetron is a highly potent and selective competitive antagonist of the 5-HT3 receptor, a subclass of serotonin receptors located on peripheral neurons and within the CNS. Surgery and treatment with certain 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 and its accompanying feeling of nausea. Tropisetron selectively blocks the excitation of the presynaptic 5-HT3 receptors of the peripheral neurons in this reflex, and may exert additional direct actions within the CNS on 5-HT3 receptors mediating the actions of vagal input to the area postrema. These effects are considered to be the underlying mechanism of action of the anti-emetic effect of tropisetron.
Tropisetron has a 24-hour duration of action which allows once-a-day administration.
Tropisetron prevents nausea and vomiting induced by surgery without causing extrapyramidal side-effects.

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%. As this metabolism is saturable, the absolute bioavailability increases with the dose (up to 100% at a dose of 45 mg).

Distribution.

The peak plasma concentration is attained within three hours. Tropisetron is 71% bound to plasma protein in a non-specific manner. The volume of distribution is 400-600 L.

Metabolism.

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 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. The metabolism of tropisetron is linked to the genetically determined sparteine/debrisoquine polymorphism. About 8% of the Caucasian population are known to be poor metabolisers for the sparteine/debrisoquine pathway.

Excretion.

The elimination half-life (beta-phase) is about eight hours in extensive metabolisers; in poor metabolisers this could be extended to 45 hours (see Precautions).
In extensive metabolisers, about 8% of tropisetron is excreted in the urine as unchanged drug, 70% as metabolites; 15% is excreted in the faeces, almost entirely as metabolites. In poor metabolisers, a greater proportion of unchanged tropisetron is excreted in the urine than in extensive metabolisers.

Clinical Trials

Use in post-operative nausea and vomiting.

The use of tropisetron in the treatment and prevention of post-operative nausea and vomiting (PONV) was supported by the results of three prospective, double-blind, placebo-controlled trials conducted in adult patients. All three studies had one primary endpoint (the proportion of patients without emetic episodes over a 24 h postoperative period, regardless of rescue treatment received) and two secondary endpoints (the proportion of patients without nausea and without rescue treatment over a 24 h period). As patients could receive rescue treatment for nausea and remain free of emetic episodes or receive rescue treatment for vomiting while remaining free of nausea, the rescue treatment endpoint was thus a reflection of a combined response. In the treatment study, only patients who experienced PONV within 2 hours of recovering from anaesthesia were included.
In two of the studies, a 0.5, 2 or 5 mg i.v. dose of tropisetron was compared with placebo in the prevention of PONV in women undergoing abdominal and gynaecological surgery (n=385), and in the treatment of PONV in men and women with established PONV (n=314). In the study on the prevention of PONV, 68%, 74%, 70% and 56% of patients had no emetic episodes in the 0.5 mg, 2 mg, 5 mg and placebo groups respectively. Similarly, in the treatment study, 52%, 58%, 60% and 29% of patients responded in the 0.5 mg, 2 mg, 5 mg and placebo groups respectively. The results for the secondary endpoints were in line with the primary endpoint of the studies and indicate that the 2 mg dose is optimal both for prevention and treatment of PONV. Tropisetron did not suppress the retching or vomiting associated with the removal of the endotracheal tube.
In the third study, 2 mg i.v. tropisetron, 4 mg i.v. ondansetron and placebo were compared in the prevention of PONV (n=908). This study was prospectively stratified for sex and type of surgery (abdominal versus non-abdominal surgery). Tropisetron 2 mg and ondansetron 4 mg were shown to have similar efficacy in preventing PONV following abdominal surgery, with response rates of 70 and 72% respectively, compared with 59% for the placebo group.
However, in the non-abdominal surgery types tested the efficacy results for both agents were not significantly different from those of the placebo group.

Indications

For the treatment and prevention of post-operative nausea and vomiting in adults (2 mg/2 mL ampoule only).

Contraindications

Hypersensitivity to tropisetron, other 5-HT3 receptor antagonists, or any other components of the formulations. Pregnancy and lactation (see Precautions).

Precautions

General.

Serotonin syndrome has been described following the concomitant use of tropisetron and other serotonergic drugs (see Interactions with Other Medicines). If concomitant treatment with tropisetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised.
Caution should be exercised in patients with cardiac rhythm or conduction disturbances, or in patients treated with anti-arrhythmic or beta-adrenergic blocking agents since, in these patient groups, limited experience is available with concurrent use of tropisetron and anaesthetics.
Prolongations of the QTc interval which were not clinically significant have been observed after high (up to 80 mg) i.v. doses of tropisetron. Therefore it cannot be excluded that lower doses of tropisetron have also contributed to the QTc interval prolongation seen occasionally in patients undergoing general anaesthesia.

Effects on ability to drive and use machinery.

No data exist on the effect of tropisetron on the ability to drive or operate machinery. The occurrence of dizziness and fatigue as side effects should be taken into account.

Use in pregnancy.

(Category B3)
Reproductive studies have been performed in rats, rabbits and monkeys at oral doses up to 60, 120 and 180 mg/kg/day, respectively, and have revealed no evidence of a drug related teratogenic effect. In rats and rabbits there were increased incidences of post implantation loss and delayed development of pups at doses greater than 20 and 60 mg/kg/day, respectively. Studies in rats also showed an increased incidence of post-natal loss at doses of 15 mg/kg/day and above.

Use in lactation.

Tropisetron is excreted in the breast milk of rats. It is not known whether tropisetron is excreted into human milk and therefore patients on tropisetron should not breast-feed.

Use in children.

Since experience with tropisetron in children is still limited, its use cannot be recommended.

Use in the elderly.

There is no evidence that elderly patients require different dosages or experience different side-effects from younger patients.

Use in poor metabolisers of sparteine/debrisoquine.

In patients belonging to this group (about 8% of the Caucasian population) the elimination half-life of tropisetron is prolonged (4-5 times longer than in extensive metabolisers). However, when tropisetron was given intravenously at doses up to 40 mg twice a day over a period of seven days to healthy volunteers known to be poor metabolisers, no serious adverse events occurred.

Use in patients with impaired hepatic or renal function.

No change in the pharmacokinetics of tropisetron occurs in patients with acute hepatitis or fatty liver disease. In contrast, patients with liver cirrhosis or impaired kidney function may have plasma concentrations up to 50% higher than those found in healthy volunteers belonging to the group of extensive metabolisers of sparteine/debrisoquine.
In patients who have renal impairment and who are also poor metabolisers of sparteine/debrisoquine, there is a possibility of increased plasma tropisetron levels.

Use in patients with uncontrolled hypertension.

In patients with uncontrolled hypertension, daily doses of tropisetron higher than 10 mg should be avoided since they may cause a further increase in blood pressure.

Genotoxicity.

Tropisetron was not mutagenic in standard tests for mutagenicity.

Carcinogenicity.

Carcinogenicity studies showed no evidence of a drug related carcinogenic response at doses up to 45 mg/kg/day in the rat and 90 mg/kg/day in the female mouse. In the male mouse there was a statistically significant increase in the incidence of benign hepatocellular neoplasia at doses of 30 mg/kg/day and above.

Interactions

Serotonergic drugs (e.g. SSRIs and SNRIs).

Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been described following the concomitant use of tropisetron and other serotonergic drugs, including selective serotonin re-uptake inhibitors (SNRIs) (see Precautions).
Ingestion of the capsule with food results in a slight increase in bioavailability, from approx. 60% to approx. 80%, which is not clinically relevant.
Concomitant administration of tropisetron with rifampicin or with other liver enzyme-inducing drugs (e.g. phenobarbital) results in lower plasma concentrations of tropisetron and, therefore, requires an increase in dosage in extensive metabolisers (but not in poor metabolisers). The effects on tropisetron plasma levels of cytochrome P450 enzyme inhibitors such as cimetidine are negligible and do not require dose adjustment.
As a prolongation of the QTc interval has been observed in patients administered tropisetron (see Precautions, General), care should be taken when other drugs that are likely to prolong the QT interval are taken concomitantly with tropisetron.
No interaction studies have been performed with tropisetron and drugs used in anaesthesia (see Precautions, General).

Adverse Effects

In general, tropisetron is well tolerated and the side-effects are transient at the recommended dose. The most frequently reported adverse reaction at the 2 mg dose was headache. At the 5 mg dose, constipation and, less frequently, dizziness, fatigue, somnolence, and gastrointestinal disorders, such as abdominal pain, diarrhoea and anorexia were observed as well.
As with other 5-HT3 receptor antagonists, hypersensitivity reactions (“type 1-reactions”) with one or more of the following symptoms have been observed: flushing and/or generalised urticaria, chest discomfort, dyspnoea, hypotension.
Tropisetron was found to cause prolongation of the QT interval although this was not of clinical significance.
Listed in Table 1 are the frequencies of adverse events observed in more than 1% of patients exposed to each treatment in the clinical trials discussed under Clinical Trials, Use in post-operative nausea and vomiting.
With the exception of headache, the frequency, severity and relationship to the study drug of these events was similar for tropisetron and placebo. Therefore it is likely that these events can be attributed to the anaesthesia or the surgical procedures.
The following adverse reactions have been observed in less than 1% of patients exposed to each treatment in the clinical trials: syncope, urticaria generalized.

Post-marketing experience.

The following adverse reactions have been reported during post approval use of tropisetron. Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following hypersensitivity reactions have been rarely observed: rash, erythema and anaphylactic reactions/shock. In very rare instances, collapse, cardiovascular arrest and bronchospasm have been reported. Some may have been caused by the concomitant chemotherapy or the underlying disease.

Dosage and Administration

Treatment and prevention of post-operative nausea and vomiting.

Tropisetron is recommended as a 2 mg dose given intravenously either as an infusion or as a slow injection (not less than 30 seconds). In the case of prevention of post-operative nausea and vomiting, tropisetron should be administered shortly before the induction of anaesthesia.
For infusion, one ampoule can be diluted in 100 mL of sodium chloride 0.9%; glucose 5%; potassium chloride, sodium chloride and calcium chloride intravenous solution (Ringer's solution); fructose intravenous solution (Levulose 5%); mannitol 10%; potassium chloride 0.3% and sodium chloride 0.9%; potassium chloride 0.3% and glucose 5%. To reduce microbiological hazard, use as soon as practicable after reconstitution/preparation. If storage is necessary, hold at 2-8°C for not more than 24 hours.

Overdosage

Symptoms.

At very high repeated doses, visual hallucinations and, in patients with pre-existing 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.
Contact the Poisons Information Centre on 131 126 for advice on management.

Presentation

Ampoules: 2 mg/2 mL injection solution, box of 5 glass ampoules.
Tropisetron solution for injection is a clear, colourless to very faintly yellow brown aqueous solution, pH 4.6-5.2.
The ampoules contain as excipients, glacial acetic acid, sodium acetate trihydrate, sodium chloride and water for injections.

Storage

Store below 25°C.

Poison Schedule

S4.