Ondansetron Accord Healthcare

Package leaflet: Information for the user

Ondansetrone Accord Healthcare 2 mg/ml solution for injection or infusion

Generic medicine
Please read all of this leaflet carefully before you use 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, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

The name of the medicine is Ondansetrone Accord Healthcare 2 mg/ml solution for injection or infusion, but
it will be referred to as Ondansetrone Accord Healthcare throughout this leaflet.
Contents of this leaflet:

1. What Ondansetrone Accord Healthcare is and what it is used for
2. What you need to know before using or giving Ondansetrone Accord Healthcare to your child
3. How to use Ondansetrone Accord Healthcare
4. Possible side effects
5. How to store Ondansetrone Accord Healthcare
6. Contents of the pack and other information

1. What Ondansetrone Accord Healthcare is and what it is used for

Ondansetrone Accord Healthcare contains the active substance ondansetrone, which belongs to a group of
medicines called antiemetics. Certain treatments may make you feel sick or cause vomiting. Antiemetics
are prescribed to prevent nausea and vomiting following treatment.
In adults, Ondansetrone Accord Healthcare is used for:

• Preventing nausea and vomiting caused by chemotherapy (a course of chemo) or radiation (radiotherapy) during cancer treatment

• Preventing and treating nausea and vomiting following surgery under general anaesthesia.
  In children over 1 month of age, Ondansetrone Accord Healthcare may be used to prevent and
  treat nausea and vomiting that may occur after surgery.

• In children over 6 months of age, Ondansetrone Accord Healthcare may also be used for the treatment of nausea and vomiting during chemotherapy.

2. What you need to know before using or giving Ondansetrone Accord Healthcare to your child
   Do not use Ondansetrone Accord Healthcare

• If you or your child are taking apomorphine (a medicine used to treat Parkinson’s disease)
• If you or your child are allergic to ondansetrone or to any of the excipients of this medicine (listed in section 6)
• If you think this applies to you, contact your doctor before administration

Warnings and precautions
Talk to your doctor or pharmacist before using Ondansetrone Accord Healthcare

• if you or your child are allergic to medicines similar to ondansetrone, such as medicines containing granisetron or palonosetron
• if you or your child have ever had heart problems, such as irregular heartbeat (arrhythmia)
• if you or your child have intestinal problems
• if your liver is not functioning properly, your doctor may reduce the dose of Ondansetrone Accord Healthcare

Inform your doctor if you think any of the above may apply to you.
Other medicines and Ondansetrone Accord Healthcare
Inform your doctor or pharmacist if you or your child are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Phenytoin and carbamazepine (medicines prescribed for epilepsy) may negatively affect the concentration of ondansetrone in the body
Rifampicin (a medicine prescribed for pruritus, tuberculosis, and leprosy) may negatively affect the concentration of ondansetrone in the body
The effect of tramadol (a medicine prescribed to relieve pain) may be negatively affected by concomitant use of ondansetrone

• Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram (SSRIs) [selective serotonin reuptake inhibitors] (medicines used to treat depression and/or anxiety) may cause changes in your mental state
• Venlafaxine, duloxetine (SNRIs [serotonin-norepinephrine reuptake inhibitors]) (medicines used to treat depression and/or anxiety) may cause changes in your mental state
• Concomitant use of ondansetrone with medicines that act on the heart (e.g. anthracyclines such as doxorubicin, daunorubicin, or trastuzumab), antibiotics (such as erythromycin or ketoconazole), antiarrhythmics (such as amiodarone), and beta-blockers (such as atenolol or timolol) increases the risk of cardiac rhythm disturbances. Inform your doctor if you are taking any of these medicines.

Pregnancy and breastfeeding:
Ondansetrone Accord Healthcare must not be used during the first trimester of pregnancy, as Ondansetrone Accord Healthcare may slightly increase the risk of the baby being born with cleft lip and/or cleft palate (fissures or splits of the upper lip and/or palate). If you are already pregnant, think you might be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before taking Ondansetrone Accord Healthcare. If you are a woman of childbearing age, you may be advised to use effective contraception.
Breastfeeding:
Breastfeeding is not recommended during treatment with Ondansetrone Accord Healthcare.
Animal studies have shown that ondansetrone may be excreted in breast milk. This could affect your baby. Discuss this with your doctor.
Driving and using machines:
Ondansetrone does not impair the ability to drive or use machinery.
Ondansetrone Accord Healthcare contains sodium:
This medicine contains 3.62 mg of sodium (a key component of table salt) per ml.
This corresponds to 0.18% of the maximum daily dietary intake recommended for an adult.

3. How to use Ondansetrone Accord Healthcare

Use this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
Ondansetrone Accord Healthcare is normally administered by a nurse or doctor. The dose prescribed for you will depend on the treatment you are receiving.

To prevent nausea and vomiting caused by chemotherapy or radiotherapy

Adults
On the day of chemotherapy or radiotherapy, the recommended dose for adults is 8 mg given by injection into a vein or muscle shortly before treatment, followed by another 8 mg given twelve hours later. The usual intravenous dose for adults must not exceed 8 mg.
On the following days after chemotherapy, the medicine will usually be given orally as 8 mg ondansetrone tablets or 10 ml (8 mg) of ondansetrone syrup.
Oral administration may begin twelve hours after the last intravenous dose and may continue for up to 5 days.
If chemotherapy or radiotherapy is likely to cause severe nausea and vomiting, you or your child will be given a higher than usual dose of Ondansetrone Accord Healthcare. The exact dose will be decided by your doctor.

To prevent nausea and vomiting caused by chemotherapy

Children over 6 months of age and adolescents
Your doctor will determine the dose based on the child's weight or body surface area.
On the day of chemotherapy, the first dose is administered by intravenous injection shortly before the child's treatment. After chemotherapy, the medicine will usually be given to the child orally as tablets or syrup.
On subsequent days, the oral dose may begin twelve hours after the intravenous dose and may be continued for up to 5 days.

To prevent and treat nausea and vomiting after surgery

Adults:
The usual dose for adults is 4 mg administered by intravenous or intramuscular injection. For prevention, this will be given shortly before surgery.

Children:
For children from 1 month of age and adolescents, the doctor will determine the dose. The maximum dose is 4 mg administered by slow intravenous injection. For prevention, this will be given before surgery.

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

If you or your child feel unwell or become sick
This medicine should start working immediately after the injection. If you or your child continue to experience nausea or vomiting, inform your doctor or nurse.

If you or your child have been given more Ondansetrone Accord Healthcare than you should have
Your doctor or nurse will administer ondansetrone to you or your child, so it is unlikely that you or your child will have received too much. If you think you or your child may have received too much or have missed a dose, inform your doctor or nurse.

If you have any questions about how to use this medicine, speak to your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
SERIOUS SIDE EFFECTS
Allergic reactions
If you or your child have an allergic reaction, inform your doctor or a healthcare professional immediately. Signs may include:

• Sudden shortness of breath and chest pain or tightness in the chest
• Swelling of the eyelids, face, lips, mouth or tongue, which may make breathing difficult
• Skin rash – red spots or lumps under the skin (urticaria) anywhere on the body
• Collapse

Contact a doctor immediately if these symptoms occur. Stop taking this medicine.

Other side effects:
Very common Headache
(may affect more than 1 in 10 people)
Common Hot flushes or sensations of warmth
(may affect up to 1 in 10 people) Constipation
Abnormal liver function tests (if you receive ondansetron injection together with a medicine called cisplatin; otherwise this side effect is uncommon)
Irritation at the injection site such as pain, burning, swelling, redness or itching
Uncommon Seizures (fits or convulsions)
(may affect up to 1 in 100 people) Unusual body movements or tremors (dyskinesia)
Movement disorders (including persistent muscle contractions and/or repetitive movements, dystonia)
Irregular or slow heartbeat
Chest pain with or without depression of the ST segment on ECG
Fixed stare (oculogyric crisis)
Low blood pressure, which may make you feel weak or dizzy
Hiccups
Increased levels of substances (enzymes) produced by the liver (may be detected in blood tests). These symptoms have been commonly reported in patients receiving cisplatin (a drug used in chemotherapy).
Rare Severe allergic reactions
(may affect up to 1 in 1,000 people) Dizziness or light-headedness during rapid intravenous administration
Transient visual disturbances (such as blurred or double vision), mainly during intravenous administration
Heart rhythm disorder (which sometimes causes sudden loss of consciousness)
Diarrhoea and abdominal pain
Very rare Sudden severe allergic reaction with symptoms such as fever and blisters
(may affect up to 1 in 10,000 people) on the skin and skin peeling (toxic epidermal necrolysis; Lyell’s syndrome) and severe allergic reaction with high fever, skin blisters, joint pain and/or eye inflammation (Stevens-Johnson syndrome)
Reduced vision or temporary loss of vision, usually lasting less than 20 minutes. Most patients had received chemotherapeutic agents, including cisplatin. In some cases, transient blindness has been reported to be caused by a problem in the brain.
Fluid retention (edema)
Not known Skin rash and itching
(frequency cannot be estimated from the available data) Myocardial ischemia, signs include: sudden chest pain or chest tightness

Reporting of side effects
If you or your child experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects via the national reporting system: \hyperref[www.agenziafarmaco.gov.it/it/responsabili-segnalazione-reattivita-avverse]{www.agenziafarmaco.gov.it/it/responsabili-segnalazione-reattivita-avverse}. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ondansetrone Accord Healthcare

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or carton after "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Keep the vials in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice that the container is damaged or if particles/crystals are visible.
Do not dispose of any medicine 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 Ondansetron Accord Healthcare contains:
The active substance in Ondansetron Accord Healthcare is ondansetron (as dihydrochloride dihydrate).
Each ml of injectable or infusion solution contains 2 mg of ondansetron (as ondansetron
dihydrochloride dihydrate).
Each 2 ml vial contains 4 mg of ondansetron (as ondansetron dihydrochloride dihydrate).
Each 4 ml vial contains 8 mg of ondansetron (as ondansetron dihydrochloride dihydrate).
The other ingredients are citric acid monohydrate, sodium citrate, sodium chloride, sodium hydroxide and/or hydrochloric acid for pH adjustment, and water for injections.

Description of the appearance of Ondansetron Accord Healthcare and package contents:
Ondansetron Accord Healthcare is a clear, colourless solution for injection or infusion, contained in a transparent/amber glass vial.
Ondansetron Accord Healthcare 2 mg/ml is available in packs containing 5 vials of 2 ml and 5 vials of 4 ml, and in packs containing 10 vials of 2 ml and 10 vials of 4 ml.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder:
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona,
s/n, Edifici Est 6ª planta
08039-Barcelona,
Spain

Manufacturer:
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
The Netherlands
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50, 95-200 Pabianice, Poland

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

The following information is intended for medical or healthcare professionals only:
Instructions for use:
For intravenous injection, intramuscular injection, or intravenous infusion after dilution.
Prescribers intending to use ondansetron for the prevention of delayed nausea and vomiting associated with chemotherapy or radiotherapy in adults, adolescents, or children should consider current practice and appropriate guidelines.

Nausea and vomiting induced by chemotherapy and radiotherapy:
Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations used in chemotherapy and radiotherapy regimens. The route of administration and dose of ondansetron should be flexible, within the range of 8–32 mg daily, and selected as described below.

Emetogenic chemotherapy and radiotherapy:
Ondansetron may be administered rectally, orally (tablets or syrup), intravenously, or intramuscularly.
For most patients undergoing emetogenic chemotherapy or radiotherapy, 8 mg of ondansetron should be administered via intramuscular injection or slow intravenous injection (over not less than 30 seconds) or intramuscular infusion, immediately before treatment, followed by 8 mg orally every twelve hours.
To prevent delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after a treatment cycle.

Highly emetogenic chemotherapy:
For patients receiving highly emetogenic chemotherapy, such as high-dose cisplatin, ondansetron may be administered orally, rectally, intravenously, or intramuscularly. Ondansetron has shown equal efficacy at the following doses during the first 24 hours of chemotherapy:

• A single dose of 8 mg via intramuscular injection or slow intravenous injection (over not less than 30 seconds) administered immediately before chemotherapy.
• A dose of 8 mg via intramuscular injection or slow intravenous injection (over not less than 30 seconds), repeated every two or four hours, or by continuous infusion of 1 mg/hour for up to 24 hours. A maximum initial intravenous dose of 16 mg diluted in 50–100 ml of physiological saline or another compatible infusion fluid (see section 6.6) administered by infusion over at least 15 minutes immediately before chemotherapy. The initial dose of ondansetron may be followed by two additional 8 mg intravenous doses (over not less than 30 seconds) or intramuscular doses given 4 hours apart.
• The choice of dosing regimen should be determined by the severity of the emetogenic challenge. A single intravenous dose greater than 16 mg should not be administered due to the dose-dependent risk of QT interval prolongation (see sections 4.4, 4.8, and 5.1 of the Summary of Product Characteristics).

The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of 20 mg sodium phosphate dexamethasone administered before chemotherapy.
To prevent delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after a treatment cycle.

Paediatric population:
Chemotherapy-induced nausea and vomiting in children aged ≥ 6 months and adolescents:
The dose of ondansetron for chemotherapy-induced nausea and vomiting may be calculated based on body surface area (BSA) or body weight. See below.

Dosing based on body surface area (BSA):
Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m². The single intravenous dose must not exceed 8 mg.
Oral administration may begin twelve hours after and may continue for up to 5 days. (See SmPC for the dosing table.)
The total daily dose (administered as divided doses) must not exceed the adult maximum of 32 mg.

Dosing based on body weight:
Weight-based dosing results in higher total daily doses compared to BSA-based dosing. Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The single intravenous dose must not exceed 8 mg.
Two additional intravenous doses may be administered at 4-hour intervals. Oral administration may begin 12 hours after and may be continued for up to 5 days. (See SmPC for further details.)

Ondansetrone Accord Healthcare must be diluted in 5% dextrose, 0.9% sodium chloride, or another compatible infusion fluid (see SmPC section 6.6) and administered intravenously over not less than 15 minutes.

No clinical study data are available on the use of Ondansetrone Accord Healthcare in the prevention of delayed or prolonged chemotherapy-induced nausea and vomiting. No controlled clinical study data are available on the use of Ondansetrone Accord Healthcare for radiotherapy-induced nausea and vomiting in children.

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

Children (children aged ≥ 1 month and adolescents)
Oral formulation:
No studies have been conducted on the use of orally administered ondansetron for the prevention or treatment of postoperative nausea and vomiting; therefore, slow intravenous injection is recommended for this indication.

Injection:
For the prevention of PONV in paediatric patients undergoing surgery under general anaesthesia, a single dose of ondansetron may be administered via slow intravenous injection (over not less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg, either before or after induction of anaesthesia.
For the prevention of PONV after surgery in paediatric patients undergoing surgery under general anaesthesia, a single dose of ondansetron may be administered via slow intravenous injection (over not less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg.

No data are available on the use of Ondansetrone Accord Healthcare for the treatment of postoperative vomiting in children under 2 years of age.

Elderly: Experience with ondansetron in the prevention and treatment of postoperative nausea and vomiting (PONV) in elderly patients is limited; however, ondansetron is well tolerated in patients over 65 years of age receiving chemotherapy.

Renal impairment: No adjustments to daily dose, frequency, or route of administration are required.

Hepatic impairment: Ondansetron clearance is significantly reduced and serum half-life significantly prolonged in patients with moderate to severe hepatic impairment. In these patients, the total daily dose should not exceed 8 mg; therefore, parenteral or oral administration is recommended.

Slow sparteine/debrisoquine metabolisers: The elimination half-life of ondansetron is not altered in individuals classified as slow 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 adjustments to daily dose or dosing frequency are required.

Incompatibilities:
This medicinal product must not be mixed with other medicinal products except those recommended below.
The solution must not be autoclaved.
Ondansetrone Accord Healthcare must only be mixed with the following recommended infusion solutions:

• Intravenous infusion solution of Sodium Chloride 0.9% w/v, BP
• Intravenous infusion solution of Glucose 5% w/v, BP
• Intravenous infusion solution of Mannitol 10% w/v, BP
• Intravenous infusion solution of Ringer
• Intravenous infusion solution of Potassium Chloride 0.3% w/v and Sodium Chloride 0.9% w/v, BP
• Intravenous infusion solution of Potassium Chloride 0.3% w/v and Glucose 5% w/v, BP

The stability of Ondansetrone Accord Healthcare after dilution with the recommended infusion fluids has been demonstrated at concentrations of 0.016 mg/ml and 0.64 mg/ml.
Use only clear, colourless solutions.
Diluted solutions must be protected from light.

Shelf life and storage
Unopened pack:
3 years
This medicinal product does not require any special temperature storage conditions.
Store vials in the outer packaging to protect from light.

Injection:
After initial opening, the product must be used immediately.

Infusion:
After dilution with the recommended diluents, chemical and physical stability during use has been demonstrated for 7 days at 25°C and 2–8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the in-use storage time 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 occurred under controlled and validated aseptic conditions.