ONDANSETRON ACCORD 2 mg/ml INJECTABLE SOLUTION

2. What you need to know before you use Ondansetron Accord

Do not use Ondansetron Accord:

• if you or your child are using apomorphine (used to treat Parkinson's disease)

• if you or your child are allergic to ondansetron or any of the other ingredients of this medicine (listed in section 6).

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

Warnings and precautions

Talk to your doctor, pharmacist before you start using Ondansetron Accord

• if you or your child are allergicto medicines similar to ondansetron, such as those containing granisetron or palonosetron
• if you or your child have ever had heart problems, such as irregular heartbeats(arrhythmia)
• if you or your child have intestinal problems
• if your liveris not working properly, your doctor may reduce the dose of Ondansetron Accord

Tell your doctor if you think this applies to you

Other medicines and Ondansetron Accord

Tell your doctor, pharmacist if you or your child are using, have recently used or might use any other medicines. This also applies to medicines obtained without a prescription.

• Phenytoinand carbamazepine(used to treat epilepsy). May negatively affect the concentration of ondansetron in the body.
• Rifampicin(a medicine prescribed for itching, tuberculosisand leprosy) may negatively affect the concentration of ondansetron in the body.
• The effect of Tramadol(a medicine prescribed to combat pain) may be negatively affected by the simultaneous use of ondansetron
• Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram(SSRIs) [selective serotonin reuptake inhibitors] (medicines for treating depressionand/or anxiety) may cause a change in your mental state
• Venlafaxine, duloxetine(SNRIs [serotonin-norepinephrine reuptake inhibitors]) (medicines for treating depression and/or anxiety) may cause a change in your mental state
• The simultaneous use of ondansetron with medicines that affect the heart (such as anthracyclines like doxorubicin, daunorubicin or trastuzumab), antibiotics (such as erythromycinor ketoconazole), antiarrhythmics (such as amiodarone) and beta-blockers (such as atenololor timolol) increases the risk of heart rhythm disorders

Tell your doctor if you think this applies to you

Pregnancy and breastfeeding

Ondansetron Accord should 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 a cleft lip and/or cleft palate (openings or gaps in the upper lip or palate). If you are already pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using Ondansetron Accord. If you are a woman of childbearing age, you are advised to use an effective method of birth control.

Breastfeeding is not recommended during treatment with Ondansetron Accord.

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

Driving and using machines

Ondansetron Accord does not affect your ability to drive or use machines.

Important information about some of the ingredients of Ondansetron Accord

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

3. How to use Ondansetron Accord

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are not sure, ask your doctor or pharmacist again.

Ondansetron Accord is usually given by a nurse or doctor. The dose that you have been prescribed will depend on the treatment you are having.

To prevent nausea and vomiting due to chemotherapy or radiotherapy

Adults

On the day you have chemotherapy or radiotherapy, you will be given the recommended dose in adults of 8 mg by injection into a vein or muscle immediately before your treatment, and another 8 mg 12 hours later.

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

In the following days:

• After chemotherapy, your usual medicine will usually be given by mouth in the form of ondansetron tablets of 8 mg or 10 ml (8mg) of ondansetron syrup.
• Oral administration may start 12 hours after the last intravenous dose and may continue for up to 5 days.

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

To prevent nausea and vomiting due to chemotherapy

Children over 6 months of age and adolescents

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

On the day of chemotherapy

• The first dose is given by injection into a vein, immediately before your child's treatment. Usually, after chemotherapy, your child will receive this medicine by mouth in the form of a tablet or syrup.

In the following days, oral administration may start 12 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, given by injection into a vein or muscle. This dose will be given to you immediately before surgery.

Children:

• In the case of children over 1 month and adolescents, the doctor will decide the dose. The maximum dose is 4 mg, given by slow injection into a vein. This dose will be given to you immediately before surgery.

Patients with moderate or severe liver problems

• The total daily dose should not be more than 8 mg.

If you or your child continue to feel or have nausea

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

If you receive more Ondansetron Accord than you should

Your doctor or nurse will give you Ondansetron Accord, so it is unlikely that you or your child will receive too much. If you think you or your child have been given too much, tell your doctor or nurse.

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

4. Possible side effects

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

SERIOUS SIDE EFFECTS

Allergic reactions

If you or your child have an allergic reaction, tell your doctor or a member of the medical staff immediately. The signs may include:

• Sudden wheezing, swelling of your lips, tongue and throat or itching all over the body
• Swelling of the eyelids, face, lips, mouth or tongue which may cause difficulty in breathing
• Rash, itching or hives on the skin
• Fainting

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

Other side effects that include:

Reporting of side effects:

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: http://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ondansetron Accord

• Keep out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the ampoule and carton after EXP. The expiry date is the last day of the month shown.
• This medicine does not require any special storage temperature. Keep 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 contains visible particles or crystals.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Ondansetron Accord

The active ingredient is ondansetron (as ondansetron hydrochloride dihydrate).

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

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

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

The other components are citric acid monohydrate, sodium citrate, sodium chloride, sodium hydroxide or hydrochloric acid to adjust the pH and water for injectable preparations.

Appearance of Ondansetron Accord and Container Contents

Ondansetron Accord is a clear and colorless solution for injection or infusion, packaged in a transparent 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 some pack sizes may be marketed.

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

Or

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

Date of Last Revision of this Leaflet:May 2022

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

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

Information intended exclusively for 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, consideration should be given to usual practice and relevant guidelines.

Chemotherapy- and radiotherapy-induced nausea and vomiting:

Adults:the emetogenic potential of oncology treatment varies according to 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 will be selected as indicated below.

Emetogenic chemotherapy and radiotherapy:

Ondansetron can be administered by rectal, oral (tablet or syrup), intravenous, or intramuscular route.

In most patients receiving emetogenic chemotherapy or radiotherapy, 8 mg of ondansetron should be administered as an intravenous injection (over at least 30 seconds) or intramuscularly, immediately before treatment, followed by administration of 8 mg orally every 12 hours.

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

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

• A single dose of 8 mg by slow intravenous injection (over at least 30 seconds) or intramuscular injection, immediately before chemotherapy.
• A dose of 8 mg by slow intravenous injection (over at least 30 seconds) or 8 mg intramuscularly after an interval of 2-4 hours, or by continuous infusion of 1 mg/hour for up to 24 hours.

• An initial intravenous dose of up to 16 mg diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6 of the SmPC) and infused over at least 15 minutes immediately before chemotherapy. The initial dose of ondansetron may be followed by two additional doses of 8 mg by intravenous injection (over at least 30 seconds) or intramuscularly at 4-hour intervals.
• The choice of dosage regimen will depend on the intensity of the emetogenic problem.

A single dose greater than 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 SmPC).

The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of 20 mg of dexamethasone sodium phosphate administered before chemotherapy.

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

Pediatric population:

Chemotherapy-induced nausea and vomiting in children ≥ 6 months of age and adolescents

The dosage in case of chemotherapy-induced nausea and vomiting can be calculated based on body surface area (BSA) or weight, as follows.

Dosage based on BSA:

Ondansetron should be administered immediately before chemotherapy, as a single intravenous dose of 5 mg/m2. The single intravenous dose should not exceed 8 mg. Oral administration can start 12 hours later and can continue for up to 5 days (see SmPC for dosage tables). The total dose during 24 hours (administered in separate doses) should not exceed the adult dose of 32 mg.

Dosage based on body weight:

The weight-based dosage gives rise to a higher total daily dose than that calculated from BSA. Ondansetron should be administered immediately before chemotherapy, as a single intravenous dose of 0.15 mg/kg. The single intravenous dose should not exceed 8 mg. Two additional intravenous doses can be administered at 4-hour intervals. Oral administration can start 12 hours later and can continue for up to 5 days (see SmPC for dosage tables).

Ondansetron should be diluted in 5% dextrose or 0.9% sodium chloride or other compatible infusion solution (see section 6.6) and infused 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 can be administered orally or by intravenous or intramuscular injection.

Ondansetron can be administered as a single dose of 4 mg by intramuscular injection or slow intravenous injection at the time of induction of anesthesia.

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

Pediatric population (over 1 month of age and adolescents):

Oral formulation:

No studies have been conducted on the use of ondansetron administered orally 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 pediatric patients undergoing surgery with general anesthesia, a single dose of ondansetron can be administered by slow intravenous injection (over at least 30 seconds) with a dose of 0.1 mg/kg up to a maximum of 4 mg before, during, or after induction of anesthesia. For the treatment of PONV in pediatric patients undergoing surgery with general anesthesia, a single dose of ondansetron can be administered by slow intravenous injection (over at least 30 seconds) with a dose of 0.1 mg/kg up to a maximum of 4 mg before, during, or after induction of anesthesia. There are no data on the use of ondansetron for the treatment of postoperative vomiting in children under 2 years of age.

Elderly patients: there is limited experience in the use of ondansetron in the prevention and treatment of PONV in the elderly, although ondansetron is well tolerated in patients over 65 years of age treated with chemotherapy.

Patients with renal impairment:No modification of the daily dose or frequency of administration is required.

Patients with hepatic impairment:The clearance of ondansetron is considerably reduced and the serum half-life significantly prolonged in subjects with moderate or severe hepatic impairment. In these cases, a total daily dose of 8 mg should not be exceeded, and 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, in these patients, repeated administration will give rise to drug exposure levels that are no different from those in the general population. No modification of the daily dose or frequency of administration is required.

Incompatibilities:

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

The solution should not be sterilized by autoclaving.

Ondansetron Accord should only be mixed with the recommended infusion solutions:

Intravenous infusion solution BP of sodium chloride 0.9% p/v

Intravenous infusion solution BP of glucose 5% p/v

Intravenous infusion solution BP of mannitol 10% p/v

Ringer's solutions for intravenous infusion

Intravenous infusion solution BP of potassium chloride 0.3% p/v and sodium chloride 0.9% p/v

Intravenous infusion solution BP of potassium chloride 0.3% p/v and glucose 5% p/v

The stability of Ondansetron Accord has been demonstrated after dilution with the recommended infusion fluids in concentrations of 0.016 mg/ml and 0.64 mg/ml.

Only use clear and colorless solutions.

Diluted solutions should be stored protected from light.

Shelf Life and Storage

Unopened container:

3 years.

This medicinal product does not require any special storage temperature.

Store the ampoules in the outer packaging to protect them from light.

Injection:

The medicinal product should be used immediately after opening the container for the first time.

Infusion:

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

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