Ondansetron Accord 2 mg/ml solution for injection EFG: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ondansetron Accord 2 mg/ml injection solution EFG

Read the entire 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, pharmacist or nurse.
This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
If you experience any side effects, talk to your doctor, pharmacist or nurse, including any side effects not listed in this leaflet. See section 4.

Leaflet contents:

What Ondansetron Accord is and what it is used for
What you need to know before using Ondansetron Accord
How to use Ondansetron Accord
Possible side effects
How to store Ondansetron Accord
Contents of the pack and other information

1. What Ondansetron Accord is and what it is used for

Ondansetron Accord contains the active substance ondansetron, which belongs to a group of
medicines called antiemetics. Some medical treatments can cause nausea or vomiting. Antiemetics are prescribed to prevent nausea and vomiting following treatment.

In adults, Ondansetron Accord is used:

to prevent nausea and vomiting that may occur during chemotherapy (a chemotherapy cycle) or radiation (radiotherapy) for cancer treatment
to prevent and treat nausea and vomiting that may occur after surgery under general anaesthesia.

In children over 1 month of age, Ondansetron Accord can be used to prevent and treat nausea and vomiting that may occur after surgery.

In children over 6 months of age, Ondansetron Accord can also be used for the treatment of nausea and vomiting during chemotherapy.

2. What you need to know before using Ondansetron Accord

Do not use Ondansetron Accord:

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

→ If you think this applies to you, contact your doctor before being given Ondansetron Accord

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Ondansetron Accord

if you or your child are allergic to medicines similar to ondansetron, such as those 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 working properly, your doctor may reduce the dose of Ondansetron Accord

? Inform your doctor if you think any of the above applies to you

Other medicines and Ondansetron Accord

Tell your doctor or pharmacist if you or your child are taking, have recently taken, or might need to take any other medicines. This also includes medicines obtained without a prescription.

Phenytoin and carbamazepine (used to treat epilepsy) may negatively affect the concentration of ondansetron in the body.
Rifampicin (a medicine prescribed for pruritus, tuberculosis, and leprosy) may negatively affect the concentration of ondansetron in the body.
The effect of tramadol (a medicine prescribed to relieve pain) may be negatively affected by concomitant use of ondansetron.
Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram (SSRIs [selective serotonin reuptake inhibitors]) (medicines used to treat depression and/or anxiety) may cause a change in mental state.
Venlafaxine, duloxetine (SNRIs [serotonin-norepinephrine reuptake inhibitors]) (medicines used to treat depression and/or anxiety) may cause a change in mental state.
Concomitant use of ondansetron with medicines that affect 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 disturbances in heart rhythm.

? Inform your doctor if you think any of the above applies to you

Pregnancy and breastfeeding

Ondansetron Accord must not be used during the first trimester of pregnancy. This is because Ondansetron Accord may slightly increase the risk of a baby being born with cleft lip and/or cleft palate (openings or splits in the upper lip or palate). If you are already pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using Ondansetron Accord. If you are a woman of childbearing age, you are advised to use an effective method of contraception.

Breastfeeding is not recommended during treatment with Ondansetron Accord.

Animal studies have shown that ondansetron may be excreted in breast milk. This could affect your baby. Discuss this with your doctor.

Driving and using machines

Ondansetron Accord does not affect your ability to drive or operate machinery.

Important information about some of the ingredients of Ondansetron Accord

This medicine contains 3.62 mg of sodium (the main component of household/table salt) per ml. This is equivalent to 0.18% of the maximum daily recommended dietary intake of sodium for an adult.

3. How to use Ondansetron Accord

Follow exactly the instructions given by your doctor for administering this medicine. If in doubt, consult your doctor or pharmacist again.

Ondansetron Accord is usually 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 you receive chemotherapy or radiotherapy, you will be given the recommended adult dose of 8 mg as an injection into a vein or muscle immediately before your treatment, followed by another 8 mg twelve hours later.

The usual intravenous dose in adults should not exceed 8 mg.

On the following days:

After chemotherapy, your usual medication will typically be given orally as ondansetron tablets of 8 mg or 10 ml (8 mg) of ondansetron syrup.
Oral administration may begin twelve hours after the last intravenous dose and may continue for up to 5 days.

If your chemotherapy or radiotherapy is likely to cause severe nausea and vomiting, you may be given a higher than usual dose of Ondansetron Accord. Your doctor will decide what action to take.

To prevent nausea and vomiting caused by chemotherapy

Children over 6 months of age and adolescents

The doctor will determine the dose based on the child's weight or body size (body surface area).

On the day of chemotherapy

The first dose is administered as an injection into a vein, immediately before your child's treatment. Usually, after chemotherapy, your child will receive this medicine orally in the form of tablets or syrup.

In the following days, oral dosing may begin twelve hours after the last intravenous dose and may continue for up to 5 days.

To prevent and treat nausea and vomiting after surgery

Adults:

The usual dose in adults is 4 mg, administered as an injection into a vein or muscle. This dose will be given immediately before surgery.

Children:

For children over 1 month of age and adolescents, the doctor will determine the dose. The maximum dose is 4 mg, administered as a slow injection into a vein. This dose will be given immediately before surgery.

Patients with moderate or severe liver problems

The total daily dose should not exceed 8 mg.

If you or your child continue to feel nausea or vomiting

This medicine should start working soon after you have received the injection. If you or your child continue to experience nausea or vomiting, contact your doctor or nurse.

If you receive more Ondansetron Accord than you should

Your doctor or nurse will administer Ondansetron Accord to you or your child, so it is unlikely that you or your child will receive too much. If you think that you or your child have been given too high a dose or have missed a dose, inform your doctor or nurse.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

SERIOUS ADVERSE EFFECTS

Allergic reactions

If you or your child experience an allergic reaction, inform your doctor or a healthcare professional immediately. Signs may include:

Sudden wheezing and chest pain or tightness
Swelling of the eyelids, face, lips, mouth or tongue that may cause difficulty breathing
Skin rash, red spots or lumps under the skin (wheals) anywhere on the body
Fainting

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

Other adverse effects include:

Very common (may affect more than 1 in 10 patients)	Headache.
Common (may affect up to 1 in 10 patients)	Feeling of warmth or hot flushes. Constipation. Changes in liver function tests (in patients treated with a medicine called cisplatin; otherwise this adverse effect is uncommon). Injection site irritation such as pain, burning, swelling, redness, or itching.
Uncommon (may affect up to 1 in 100 patients)	Seizures (fits or attacks). Unusual body movements or restlessness (dyskinesia). Motor disorders (including persistent muscle contractions and/or repetitive movements, dystonia). Irregular or slow heartbeats. Chest pain with or without ST segment depression on ECG. Fixed stare (oculogyric crisis). Low blood pressure, which may make you feel faint or dizzy. Hiccups. Increase in substances (enzymes) produced by the liver (may show up in blood tests). These symptoms have been commonly reported in patients receiving cisplatin (a drug used for chemotherapy).
Rare (may affect up to 1 in 1,000 patients)	Serious allergic reactions. Feeling dizzy or lightheaded during rapid intravenous administration. Transient visual disturbances (such as blurred or double vision), mainly during intravenous administration. Changes in heart rhythm (sometimes causing sudden loss of consciousness). Diarrhea and abdominal pain.
Very rare (may affect up to 1 in 10,000 patients)	Sudden, severe allergic reaction with symptoms such as fever, skin blisters, 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). Poor vision or temporary loss of vision, usually returning within 20 minutes. Most of these patients had received chemotherapeutic agents, including cisplatin. In some cases, transient blindness has been reported to be caused by a problem in the brain.
Not known (frequency cannot be estimated from available data) Uncommon	Fluid retention (edema). Rash and itching. Myocardial ischemia. Signs include: sudden chest pain or tightness in the chest.

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: http://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Ondansetron Accord Storage Instructions

Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the ampoule and outer carton following EXP. The expiry date refers to the last day of the month indicated.
This medicine does not require any special storage temperature. Store the ampoules in the outer packaging to protect them from light.
Do not use this medicine if you notice that the packaging is damaged or if it contains visible particles or crystals.
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. Contents of the pack and other information

Composition of Ondansetron Accord

The active substance is ondansetron (as ondansetron dihydrochloride dihydrate).

Each ml of injectable or infusion solution contains 2 mg of ondansetron (as ondansetron dihydrochloride dihydrate).

Each 2 ml ampoule contains 4 mg of ondansetron (as ondansetron dihydrochloride dihydrate).

Each 4 ml ampoule contains 8 mg of ondansetron (as ondansetron dihydrochloride dihydrate).

The other components are monohydrate citric acid, sodium citrate, sodium chloride, sodium hydroxide or hydrochloric acid (to adjust pH), and water for injections.

Appearance of Ondansetron Accord and contents of the pack

Ondansetron Accord is a clear, colourless solution for injection or infusion, presented in a clear glass ampoule.

Ondansetron Accord is marketed in packs of 5 ampoules of 2 ml and 5 ampoules of 4 ml. It is also marketed in packs of 10 ampoules of 2 ml and 10 ampoules of 4 ml.

Only certain pack sizes may be commercially available.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center,

Moll de Barcelona s/n,

Edifici Est, 6a planta,

08039 Barcelona - Spain

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50, 95-200 Pabianice,

Poland

Accord Healthcare Single Member S.A.,

64th Km National Road Athens Lamia,

Schimatari, 32009, Greece

This medicinal product is authorized in the Member States of the European Economic Area under the following names

Member State Name	Medicinal Product Name
Austria	Ondansetron Accord 2 mg/ml solution for injection or infusion
Belgium	Ondansetron Accord Healthcare 2 mg/ml solution for injection or perfusion / solution for injection or infusion / solution for injection or infusion
Cyprus	Ondansetron Accord 2 mg/ml injectable solution / solution for infusion
Czech Republic	Ondansetron Accord 2 mg/ml concentrate for solution for injection or infusion
Denmark	Ondansetron Accord 2 mg/ml injection and infusion solution, solution
Germany	Ondansetron Accord 2 mg/ml solution for injection or infusion
Slovenia	Ondansetron Accord 2 mg/ml solution for injection or infusion
Estonia	Ondansetron Accord 2 mg/ml
Greece	Ondansetron Accord 2 mg/ml injectable solution / solution for infusion
Spain	Ondansetron Accord 2 mg/ml solution for injection EFG
Finland	Ondansetron Accord 2 mg/ml injection or infusion solution / solution for injection and infusion
Ireland	Ondansetron 2 mg/ml Solution for Injection or Infusion
Italy	Ondansetron Accord Healthcare 2 mg/ml Solution for Injection or Infusion
Latvia	Ondansetron Accord 2 mg/ml solution for injection or infusion
Malta	Ondansetron 2 mg/ml Solution for Injection or Infusion
Norway	Ondansetron Accord 2 mg/ml solution for injection and infusion
Poland	Ondansetron Accord 2 mg/ml
Portugal	Ondansetron Accord
United Kingdom (Northern Ireland)	Ondansetron 2 mg/ml Solution for Injection or Infusion
Sweden	Ondansetron Accord 2 mg/ml solution for injection and infusion
Slovenia	Ondansetron Accord 2 mg/ml solution for injection or infusion
Slovakia	Ondansetron Accord 2 mg/ml concentrate for solution for injection or infusion

Date of last review of this leaflet: May 2022

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS)

http://www.aemps.gob.es/

Information intended exclusively for medical or healthcare professionals

Instructions for use:

For intravenous or intramuscular injection or for intravenous infusion after dilution.

When ondansetron is prescribed for the prevention of delayed nausea and vomiting associated with chemotherapy or radiotherapy in adults, adolescents, or children, current clinical practice and relevant guidelines should be taken into consideration.

Nausea and vomiting induced by chemotherapy and radiotherapy:

Adults: The emetogenic potential of oncological treatment varies depending on the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dosage of ondansetron should be flexible within a range of 8–32 mg/day and selected as indicated below.

Emetogenic chemotherapy and radiotherapy:

Ondansetron may be administered rectally, orally (tablets or syrup), intravenously, or intramuscularly.

In most patients receiving emetogenic chemotherapy or radiotherapy, 8 mg of ondansetron should be administered as an intravenous injection (over no less than 30 seconds) or intramuscular injection immediately before treatment, followed by 8 mg orally every 12 hours.

As preventive treatment for delayed or prolonged vomiting after the first 24 hours, oral or rectal ondansetron treatment should continue up to 5 days after each treatment cycle.

Highly emetogenic chemotherapy: In patients receiving highly emetogenic chemotherapy, such as high-dose cisplatin, ondansetron may be administered orally, rectally, intravenously, or intramuscularly. The efficacy of ondansetron has been shown to be similar when used according to the following dosage regimens during the first 24 hours of chemotherapy:

A single dose of 8 mg by slow intravenous injection (over no less than 30 seconds) or intramuscular injection, administered immediately before chemotherapy.
A dose of 8 mg by slow intravenous injection (over no less than 30 seconds) or 8 mg intramuscularly after a 2–4 hour interval, 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 saline solution or another compatible infusion fluid (see section 6.6 of the summary of product characteristics) and infused over no less than 15 minutes immediately before chemotherapy. This initial dose may be followed by two additional doses of 8 mg by intravenous injection (over no less than 30 seconds) or intramuscular injection administered at 4-hour intervals.
The choice of dosage regimen should be determined based on the intensity of the emetogenic risk.

A single dose exceeding 16 mg should not be administered due to dose-dependent risk of QT 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 adding a single intravenous dose of 20 mg of dexamethasone sodium phosphate administered before chemotherapy.

As preventive treatment for delayed or prolonged vomiting after the first 24 hours, oral or rectal ondansetron treatment should continue up to 5 days after each treatment cycle.

Paediatric population:

Nausea and vomiting induced by chemotherapy in children ≥ 6 months of age and adolescents

Dosage for chemotherapy-induced nausea and vomiting may be calculated based on body surface area (BSA) or body weight, as shown below.

Dosage according to BSA:

Ondansetron should be administered immediately before chemotherapy at a single intravenous dose of 5 mg/m². The single intravenous dose must not exceed 8 mg. Oral administration may begin 12 hours later and may continue for up to 5 days (see summary of product characteristics for dosing tables). The total dose over 24 hours (administered in divided doses) must not exceed the adult dose of 32 mg.

Dosage according to body weight:

Weight-based dosing results in a higher total daily dose than BSA-based dosing. Ondansetron should be administered immediately before chemotherapy at 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 later and may continue for up to 5 days (see summary of product characteristics for dosing tables).

Ondansetron must be diluted in 5% dextrose or 0.9% sodium chloride or another compatible infusion solution (see section 6.6) and administered intravenously over at least 15 minutes.

There are no data from controlled clinical trials on the use of ondansetron in the prevention of delayed or prolonged chemotherapy-induced nausea and vomiting. There are no data from controlled clinical trials on the use of ondansetron for radiotherapy-induced nausea and vomiting in children.

Postoperative nausea and vomiting (PONV):

Adults: For the prevention of PONV, ondansetron may be administered orally or by intravenous or intramuscular injection.

Ondansetron may be given as a single 4 mg dose intramuscularly or by slow intravenous injection at the time of induction of anaesthesia.

For the treatment of established PONV, a single 4 mg dose is recommended intramuscularly or by slow intravenous injection.

Paediatric population (over 1 month of age 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. In this indication, slow intravenous injection is recommended.

Injection:

For the prevention of PONV in paediatric patients undergoing surgery with 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 in paediatric patients undergoing surgery with 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. There are no data on the use of ondansetron for the treatment of postoperative vomiting in children under 2 years of age.

Elderly patients: Limited experience exists with the use of ondansetron in the prevention and treatment of PONV in elderly patients; however, ondansetron is well tolerated in patients over 65 years of age receiving chemotherapy.

Patients with renal impairment: No adjustment of daily dose, frequency, or route of administration is required.

Patients with hepatic impairment: Clearance of ondansetron is considerably reduced and serum half-life is significantly prolonged in subjects with moderate or severe hepatic impairment. In these cases, a total daily dose exceeding 8 mg should not be administered; therefore, parenteral or oral administration is recommended.

Patients with deficient metabolism of sparteine and debrisoquine: The elimination half-life of ondansetron is not altered in patients classified as poor metabolizers of sparteine and debrisoquine. Consequently, repeated administration in these patients results in drug exposure levels not different from those in the general population. No adjustment of daily dose or administration frequency is required.

Incompatibilities:

This medicinal product must not be mixed with other medicinal products except those recommended below.

The solution must not be sterilized in an autoclave.

Ondansetrón Accord must only be mixed with the recommended infusion solutions:

Intravenous infusion solution BP 0.9% w/v sodium chloride
Intravenous infusion solution BP 5% w/v glucose
Intravenous infusion solution BP 10% w/v mannitol
Ringer's intravenous infusion solutions
Intravenous infusion solution BP 0.3% w/v potassium chloride and 0.9% w/v sodium chloride
Intravenous infusion solution BP 0.3% w/v potassium chloride and 5% w/v glucose

Stability of Ondansetrón Accord has been demonstrated after dilution with the recommended infusion fluids at concentrations between 0.016 mg/ml and 0.64 mg/ml.

Use only clear, colourless solutions.

Diluted solutions must be stored protected from light.

Shelf life and storage

Unopened container:

3 years.

This medicinal product does not require any special storage temperature.

Store ampoules in the outer packaging to protect from light.

Injection:

The medicine should be used immediately after first opening of the container.

Infusion:

After dilution with the recommended diluents, physical and chemical stability has been demonstrated under conditions of use for 7 days at 25°C and between 2°C and 8°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the conditions and duration of storage under conditions of use prior to use are the responsibility of the user and should not exceed 24 hours at a temperature between 2°C and 8°C, unless dilution has been carried out under validated aseptic and controlled conditions.