Ondansetron Aurobindo

Package leaflet: Information for the user

Ondansetrone Aurobindo 2 mg/ml solution for injection or infusion

Generic medicine
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What Ondansetrone Aurobindo is and what it is used for
2. What you need to know before taking Ondansetrone Aurobindo
3. How to take Ondansetrone Aurobindo
4. Possible side effects
5. How to store Ondansetrone Aurobindo
6. Contents of the pack and other information

1. What Ondansetrone Aurobindo is and what it is used for

Ondansetrone Aurobindo injection contains the active substance ondansetrone, which belongs to a
group of medicines called antiemetics.
Ondansetrone Aurobindo injection is used:

• to prevent nausea and vomiting caused by chemotherapy (in adults and children) or radiotherapy for cancer (in adults only);
• to prevent nausea and vomiting after surgery in adults and children aged ≥ 1 month.
  If you would like further information about these uses, please consult your doctor, nurse, or pharmacist.

2. What you need to know before using Ondansetrone Aurobindo

Do not use Ondansetrone Aurobindo:

• If you are allergic to ondansetron or to any of the other ingredients of this medicine (listed in section 6).
• If you are taking apomorphine (a medicine used to treat Parkinson's disease).

If you have any doubts, consult your doctor, nurse, or pharmacist before receiving the injection of Ondansetrone Aurobindo.
Warnings and precautions
Talk to your doctor or nurse before using Ondansetrone Aurobindo:

• If you have liver problems.
• If you have ever had heart problems (e.g. congestive heart failure causing shortness of breath and swollen ankles).
• If you have an irregular heartbeat (arrhythmia).
• If you are allergic to medicines similar to ondansetron, such as granisetron or palonosetron (Do not use Ondansetrone Aurobindo).
• If you suffer from chronic constipation.
• If you have intestinal obstruction.
• If you have problems with levels of salts in your blood, such as potassium, sodium, and magnesium.
• Preventing nausea and vomiting with ondansetron may mask occult bleeding after tonsillectomy. Therefore, these patients should be closely monitored after administration of ondansetron.

If you are unsure whether any of the above conditions apply to you, consult your doctor, nurse, or pharmacist before receiving the injection of Ondansetrone Aurobindo.
Other medicines and Ondansetrone Aurobindo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines you have purchased without a prescription and herbal medicines. Ondansetron may affect how some medicines work. Likewise, some other medicines may affect how ondansetron works.
In particular, it is important that you inform your doctor, nurse, and pharmacist if you are taking any of the following medicines:

• carbamazepine or phenytoin used to treat epilepsy;
• rifampicin used to treat infections such as tuberculosis (TB);
• antibiotics such as erythromycin or ketoconazole;
• antiarrhythmic medicines used to treat irregular heartbeat;
• beta-blockers used to treat certain heart or eye conditions, anxiety, or to prevent migraine;
• tramadol, a painkiller;
• medicines that affect the heart (such as haloperidol or methadone);
• cancer medicines (especially anthracyclines and trastuzumab);
• SSRIs (selective serotonin reuptake inhibitors) used to treat depression and/or anxiety, including fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram;
• SNRIs (serotonin-norepinephrine reuptake inhibitors) used to treat depression, including venlafaxine, duloxetine;
• You must not use ondansetron if you are taking apomorphine for Parkinson's disease.

If you are unsure whether any of the above apply to you, consult your doctor, nurse, or pharmacist before receiving the injection of Ondansetrone Aurobindo.
The Ondansetrone Aurobindo injection must not be administered in the same syringe or infusion (intravenous drip) as other medicines.
Pregnancy and breastfeeding
Pregnancy:
Ondansetrone Aurobindo must not be used during the first trimester of pregnancy, as Ondansetrone Aurobindo may slightly increase the risk of the baby being born with cleft lip and/or cleft palate (fissures or splits in the upper lip and/or palate). If you are already pregnant, think you may be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before taking Ondansetrone Aurobindo. If you are a woman of childbearing potential, you may be advised to use effective contraception.
Breastfeeding:
Do not breastfeed if you have been treated with Ondansetrone Aurobindo, as small amounts pass into breast milk. Consult your doctor or midwife.
Fertility:
There are no data available on the effects of ondansetron on fertility in humans.
Driving and using machines
Ondansetrone does not affect or has negligible effect on the ability to drive or use machines.
Ondansetrone Aurobindo contains sodium
This medicine contains 2.5 mmol (or 57.0 mg) of sodium per maximum daily dose of 32 mg. This should be taken into account in patients who are on a low-sodium diet.

3. How to use Ondansetrone Aurobindo

Use this medicine exactly as described in this leaflet, or as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
This medicine is usually administered by a doctor or nurse. The prescribed dose will depend on the treatment you are receiving.

To prevent nausea and vomiting caused by chemotherapy or radiotherapy
On the day of chemotherapy or radiotherapy

• The usual dose in adults is 8 mg given by intravenous or intramuscular injection just before treatment, followed by another 8 mg dose 12 hours later.

On the following days

• The intravenous dose in adults must not exceed 8 mg.
• This may be administered for up to 5 days.

If your chemotherapy or radiotherapy is expected to cause severe nausea and vomiting, you may be given a higher than usual dose of Ondansetrone Aurobindo. Your doctor will decide this.

To prevent nausea and vomiting caused by chemotherapy in children over 6 months of age and adolescents
The doctor will determine the dose based on the child's size (body surface area) or weight.
On the day of chemotherapy

• The first dose is given as a slow intravenous injection just before your child's treatment. After chemotherapy, your child's medicine will be administered orally. The usual dose is 4 mg.

To prevent nausea and vomiting after surgery
Adults:

• The usual dose in adults is 4 mg given by slow intravenous injection or intramuscular injection. For prevention, it will be administered just before surgery.

Children (over 1 month of age) and adolescents:
The doctor will determine the dose for children over 1 month of age and for adolescents. The maximum dose is 4 mg given as a slow intravenous injection. For prevention, it will be administered just before surgery.

Patients with impaired kidney function
Dose adjustment is not required.

Patients with moderate or severe liver problems
The total dose must not exceed 8 mg.

If you continue to have nausea or vomiting
Ondansetrone Aurobindo injection should start working immediately after administration. If you continue to experience nausea or vomiting, inform your doctor or nurse.

If you take more Ondansetrone Aurobindo than you should
Since the injection of ondansetrone will be administered by a doctor or nurse, it is unlikely that you or your child will receive an excessive dose. If you think that you or your child has received too high a dose or has missed a dose, inform your doctor or nurse. In some patients, the following effects have been observed after overdose: visual disturbances, severe constipation, low blood pressure, heart rhythm disturbances, and loss of consciousness.

If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions
If you have an allergic reaction, tell your doctor or a medical staff member immediately. Signs include:

• sudden breathlessness, chest pain or tightness in the chest;
• swelling of the eyelids, face, lips, mouth or tongue;
• skin rash – red spots and lumps under the skin (urticaria) all over the body;
• collapse.

Other side effects include:
Very common (may affect more than 1 in 10 people):

• Headache.

Common (may affect up to 1 in 10 people):

• Sensations of flushing or warmth.
• Constipation.
• Changes in liver function test results (if you were given ondansetron injection with a medicine called cisplatin; otherwise this side effect is uncommon).
• Irritation and redness at the injection site.

Uncommon (may affect up to 1 in 100 people):

• Seizures.
• Unusual body movements or tremor.
• Irregular heartbeat.
• Chest pain.
• Low blood pressure which may cause you to faint or feel dizzy.
• Hiccups.
• Hypersensitivity reactions around the injection site (e.g. skin rash, urticaria, itching), which sometimes extend along the vein where the medicine was administered.
• Abnormal blood test results for liver function.

Rare (may affect up to 1 in 1,000 people):

• Feeling dizzy or confused.
• Blurred vision.
• Heart rhythm disorders (which sometimes cause sudden loss of consciousness).
• Diarrhoea and abdominal pain.

Very rare (may affect up to 1 in 10,000 people), including isolated cases:

• Visual disturbances or temporary loss of vision, which usually returns within 20 minutes.
• Depression.
• Widespread rash with blisters and peeling of the skin over a large part of the body (toxic epidermal necrolysis).

Not known (frequency cannot be estimated from the available data):
Myocardial ischaemia
Signs include:

• sudden chest pain or
• chest tightness.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ondansetrone Aurobindo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store the vials in the carton to protect the medicine from light.
Do not use this medicine if you notice the presence of particles or changes in colour.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ondansetrone Aurobindo contains
The active substance is ondansetron (as dihydrochloride).
Each ml of injectable or infusion solution contains 2 mg of ondansetron (as
ondansetron dihydrochloride).

• Each 2 ml vial contains 4 mg of ondansetron (as ondansetron dihydrochloride).
• Each 4 ml vial contains 8 mg of ondansetron (as ondansetron dihydrochloride).
• The other components are citric acid monohydrate, sodium citrate, sodium chloride, water for injections.

Description of the appearance of Ondansetrone Aurobindo and package contents
Injectable or infusion solution.
Clear, transparent solution free from visible particles.
Ondansetrone Aurobindo is a clear, colourless injectable or infusion solution contained in clear type I glass vials. To facilitate breaking, the vials may have a pre-scored point (One-Point cut (OPC) opening system) or may be scored.
Ondansetrone Aurobindo 2 mg/ml is available in 2 ml and 4 ml fill volumes in vials, packaged in boxes of 1, 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront, Floriana FRN 1914, Malta

Manufacturer
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far,
Birzebbugia, BBG 3000
Malta

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Belgium: Ondansetron Eugia 2 mg/ml oplossing voor injectie of infusie/solution injectable ou pour perfusion/Injektions-/Infusionslösung
Germany: Ondansetron Aurobindo 2 mg/ml Injektions-/Infusionslösung
Italy: Ondansetrone Aurobindo
Luxembourg: Ondansetron Eugia 2 mg/ml solution injectable ou pour perfusion
Portugal: Ondansetrom Aurovitas
Spain: Ondansetrón Aurovitas 2 mg/ml solución inyectable y para perfusión
EFG

The following information is intended exclusively for physicians or healthcare professionals:
Nausea and vomiting induced by chemotherapy and radiotherapy:
Adults: The emetogenic potential of anticancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of ondansetron should be flexible within the range of 8–32 mg/day and selected as described below.
Chemotherapy and radiotherapy with emetogenic potential:
For most patients undergoing emetogenic chemotherapy or radiotherapy, 8 mg of ondansetron should be administered as a slow intravenous injection (over no less than 30 seconds) or intramuscular injection, or via other routes of administration over at least 15 minutes, immediately before treatment. However, this medicinal product is for injection or infusion only.
To prevent delayed or prolonged vomiting beyond the first 24 hours, oral ondansetron treatment should be continued for up to 5 days after a treatment cycle.
Highly emetogenic chemotherapy: For patients undergoing highly emetogenic chemotherapy, e.g. high-dose cisplatin, ondansetron may be administered intravenously or intramuscularly.
The following dosing regimens have demonstrated efficacy of ondansetron beyond the first 24 hours of chemotherapy:

• A single dose of 8 mg administered as a slow intravenous injection (over no less than 30 seconds) or intramuscular injection over at least 15 minutes immediately before chemotherapy.
• An 8 mg dose administered as a slow intravenous injection (over no less than 30 seconds) or intramuscular injection over at least 15 minutes immediately before chemotherapy, followed by two additional intravenous (over no less than 30 seconds) or intramuscular 8 mg doses administered at intervals of at least four hours, or by a continuous infusion of 1 mg/hour up to 24 hours.
• Doses higher than 8 mg and up to a maximum of 16 mg diluted in 50–100 ml of physiological saline or another compatible liquid infusion solution (see Instructions for use/handling) and infused over no less than 15 minutes immediately before chemotherapy.
• Single doses exceeding 16 mg must not be administered due to the dose-dependent increased risk of QT interval prolongation (see sections 4.4, 4.8 and 5.1 of the SmPC).

The choice of dosing regimen should be based on the severity of the emetogenic challenge.
The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by adding a 20 mg intravenous dose of sodium phosphate dexamethasone administered before chemotherapy.
To prevent delayed or prolonged vomiting beyond the first 24 hours, oral ondansetron treatment should be continued for up to 5 days after a treatment cycle.

Paediatric population:
CINV in children ≥ 6 months and adolescents
The dose for CINV may be calculated based on body surface area (BSA) or body weight – see below.
In clinical paediatric studies, ondansetron was administered via intravenous infusion diluted in 25–50 ml of physiological saline or another compatible infusion fluid and infused over a period of no less than 15 minutes.
Weight-based dosing results in higher total daily doses compared to BSA-based dosing – see sections 4.4 and 5.1.
Ondansetron hydrochloride must be diluted in 5% glucose or 0.9% sodium chloride or another compatible infusion fluid (see Instructions for use/handling) and administered intravenously over no less than 15 minutes.
There are no data from controlled clinical studies on the use of injectable ondansetron in the prevention of delayed or prolonged chemotherapy-induced nausea and vomiting. There are no data from controlled clinical studies on the use of injectable ondansetron for radiotherapy-induced nausea and vomiting in children.

Dosing by BSA:
Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m². The intravenous dose must not exceed 8 mg. Oral dosing may begin twelve hours later and may be continued for up to 5 days (see SmPC for dosing tables). The total daily dose must not exceed the adult dose of 32 mg.

Dosing by body weight:
Weight-based dosing results in higher daily doses compared to BSA-based dosing. Injectable ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The intravenous dose must not exceed 8 mg. Two additional intravenous doses may be administered at 4-hour intervals. Oral dosing may begin twelve hours after and may be continued for up to 5 days. The total dose within 24 hours (administered in separate doses) must not exceed the adult dose of 32 mg (see SmPC for further details).

Elderly
In patients aged 65 to 74 years, the adult dosing regimen may be followed. All intravenous doses must be diluted in 50–100 ml of physiological saline or another compatible infusion fluid (see Instructions for use/handling) and infused over 15 minutes.
In patients aged 75 years and older, the initial intravenous dose of ondansetron must not exceed 8 mg. All intravenous doses must be diluted in 50–100 ml of physiological saline or another compatible infusion fluid (see Instructions for use/handling) and infused over 15 minutes. The initial 8 mg dose may be followed by two additional 8 mg intravenous doses, each infused over 15 minutes and administered at intervals of at least four hours (see SmPC).

Postoperative nausea and vomiting (PONV):
Adults: For the prevention of PONV, ondansetron may be administered orally or by intravenous or intramuscular injection.
Ondansetrone Aurobindo may be administered as a single 4 mg dose by slow intravenous or intramuscular injection at the time of anaesthesia.
For the treatment of established PONV, a single 4 mg dose by slow intravenous or intramuscular injection is recommended.

Children (age ≥1 month and adolescents)
Injection
For the prevention of PONV in paediatric patients undergoing surgery under general anaesthesia, a single dose of ondansetron may be administered by slow intravenous injection (over no less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg before, during or after induction of anaesthesia. For the treatment of PONV after surgery in paediatric patients undergoing surgery under general anaesthesia, a single dose of ondansetron may be administered by slow intravenous injection (over no less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg. There are no data on the use of injectable ondansetron for the treatment of postoperative vomiting in children under 2 years of age.

Elderly: Experience with ondansetron for the prevention and treatment of PONV in elderly patients is limited; however, ondansetron is well tolerated in patients over 65 years of age undergoing chemotherapy.

For all indications:
Renal impairment: No adjustment of daily dose, dosing frequency or route of administration is required.
Hepatic impairment: Clearance of ondansetron is significantly reduced and serum half-life is significantly prolonged in patients with moderate to severe hepatic impairment. In these patients, the total daily dose must not exceed 8 mg.
Reduced sparteine/debrisoquine metabolism: The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Therefore, repeated dosing in these patients results in drug exposure levels not different from those in the general population. No adjustment of daily dose or dosing frequency is required.

Ondansetron solution for injection/infusion must not be autoclaved.

Incompatibilities
The ondansetron solution for injection/infusion is physically compatible and chemically stable when mixed with the following infusion solutions within the concentration range of 0.016–0.64 mg/ml:

• 0.9% w/v Sodium chloride
• 5% w/v Dextrose
• 10% w/v Mannitol
• Ringer's solution
• 0.3% w/v Potassium chloride and 0.9% w/v Sodium chloride
• 0.3% w/v Potassium chloride and 5% w/v Dextrose

Compatibility studies with the above diluents were conducted using polyvinyl chloride infusion bags and polyvinyl chloride administration sets. Adequate stability is also expected when using polyethylene infusion bags or type I glass infusion bottles. Dilutions of ondansetron solution for injection/infusion in 0.9% w/v Sodium chloride for infusion or 5% w/v Dextrose for infusion have been shown to be stable in polypropylene syringes. Diluted ondansetron solutions for injection/infusion with other compatible infusion fluids are considered stable in polypropylene syringes.

Shelf life and storage
Unopened: 3 years.
Injection: After first opening, the medicinal product must be used immediately.
Infusion: Chemical and physical in-use stability has been demonstrated for 7 days at 15–25°C and at 2–8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.