Package Insert: Information for the User

Ondansetrón Accord 2 mg/ml Injectable Solution EFG

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms of illness as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1. What is Ondansetrón Accord and how is it used

2. What you need to know before starting to use Ondansetrón Accord

3. How to use Ondansetrón Accord

4. Possible adverse effects

5. Storage of Ondansetrón Accord

6. Contents of the package and additional information

Ondansetrón 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 after treatment.

Ondansetrón Accord is used in adults for:

• preventing nausea and vomiting that may occur if undergoing chemotherapy (a cycle of chemo) or radiation (radiation therapy) during cancer treatment
• preventing and treating nausea and vomiting that may occur after a surgical procedure under general anesthesia.

Ondansetrón Accord may be used in children over 1 month to prevent and treat nausea and vomiting that may occur after surgery.

Ondansetrón Accord may also be used in children over 6 months to treat nausea and vomiting during chemotherapy.

No use Ondansetrón 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 components of this medication (listed in section 6)

→ If you think this applies to you, contact your doctorbefore Ondansetrón Accord is administered to you

Warnings and precautions

Consult your doctor, pharmacist before starting to use Ondansetrón Accord

• if you or your child areallergicto similar medications to ondansetron, such as those containing granisetron or palonosetron
• if you or your child have ever hadheart problems, such asirregular heartbeats(arrhythmia)
• if you or your child have intestinal problems
• if yourliverdoes not function properly, your doctor may reduce the dose of Ondansetrón Accord

?Inform your doctor if you think this applies to you

Other medications and Ondansetrón Accord

Inform your doctor, pharmacist if you or your child are using, have used recently or may need to use any other medication. This also applies to medications obtained without a prescription.

• Phenytoinandcarbamazepine(used to treat epilepsy). It may negatively affect the concentration of ondansetron in the body.
• Rifampicin(a prescribed medication forpruritus,tuberculosis, andleprosy) may negatively affect the concentration of ondansetron in the body.
• The effect ofTramadol(a prescribed medication for pain relief). may be negatively affected by the simultaneous use of ondansetron
• fluoxetine,paroxetine,sertraline,fluvoxamine,citalopram,escitalopram(SSRIs) [selective serotonin reuptake inhibitors] (medications for treatingdepressionand/oranxiety) may cause a change in your mental state
• venlafaxine, duloxetine(SNRIs [serotonin and norepinephrine reuptake inhibitors]) (medications for treating depression and/or anxiety) may cause a change in your mental state
• The simultaneous use of ondansetron with medications affecting the heart (e.g., anthracyclines such asdoxorubicin, daunorubicin, or trastuzumab), antibiotics (such aserythromycinorketoconazole), antiarrhythmics (such asamiodarone) and beta-blockers (such asatenololortimolol) increases the risk of cardiac rhythm disturbances

?Inform your doctor if you think this applies to you

Pregnancy and breastfeeding

Ondansetrón Accord should not be used during the first trimester of pregnancy. This is because Ondansetrón Accord may slightly increase the risk of a baby being born with cleft lip and/or cleft palate (openings or fissures in the upper lip or palate).If you are already pregnant, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using Ondansetrón Accord.If you are a fertile woman, it is recommended that you use an effective contraceptive method.

It is not recommended to breastfeed during treatment with Ondansetrón 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 operating machinery

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

Important information about some of the components of Ondansetrón Accord

This medication contains 3.62 mg of sodium (main component of table salt) in each ml. This is equivalent to 0.18% of the maximum daily recommended sodium intake for an adult.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again..

Ondansetrón Accord is usually administered by a nurse or doctor. The dose prescribed will depend on the treatment you are receiving.

To prevent nausea and vomiting due to chemotherapy or radiation therapy

Adults

The recommended dose in adults is 8 mg administered via injection into a vein or muscle immediately before treatment, and another 8 mg 12 hours later.

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

In the following days:

• After chemotherapy, your medication will usually be administered orally in the form of ondansetron tablets of 8 mg or 10 ml (8mg) of ondansetron syrup.
• Oral administration can begin 12 hours after the last intravenous dose and can continue for a period of up to 5 days.

If it is likely that your chemotherapy or radiation therapy will cause intense nausea and vomiting, you may be administered a higher dose of Ondansetrón Accord. Your doctor will decide what to do.

To prevent nausea and vomiting due to chemotherapy

Children over 6 months of age and adolescents

Your 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 administered via injection into a vein, immediately before the child's treatment. Normally, after chemotherapy, the child will receive this medication orally in the form of a tablet or syrup.

In the following days, oral dosing can begin 12 hours after the last intravenous dose and can 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 via injection into a vein or muscle. This dose will be administered immediately before the procedure.

Children:

• In the case of children over 1 month and adolescents, the doctor will decide the dose. The maximum dose is 4 mg, administered via slow injection into a vein. This dose will be administered immediately before the procedure.

Patients with moderate or severe liver problems

• The total daily dose should not exceed 8 mg.

If you or your child continue to feel or have nausea

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

If you receive more Ondansetrón 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 more than you should. If you think you or your child have received more or have not received a dose, inform your doctor or nurse.

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

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

SEVERE SIDE EFFECTS

Allergic reactions

If you or your child experience an allergic reaction, inform your doctor or a medical staff member immediately. Symptoms may include:

• Sudden onset of wheezing and chest pain or tightness
• Swelling of your eyelids, face, lips, mouth, or tongue that may make it difficult to breathe
• Skin rash, red spots, or lumps under your skin (hives) anywhere on your body.
• Syncope

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

Other side effects that include:

Reporting side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: http://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the ampoule and the box after CAD. The expiration date is the last day of the month indicated.
• This medication does not require any special storage temperature. Store the ampoules in the outer packaging to protect them from light.
• Do not use this medication if you observe that the packaging is damaged or contains visible particles or crystals.
• Do not dispose of the medications through the drains or in the trash. Ask your pharmacist

where to dispose of the medications that you no longer use. This will help protect the environment.

Composition of Ondansetron Accord

The active ingredient is ondansetron (as hydrochloride dihydrate).

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

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

Each 4 ml ampoule contains 8 mg of ondansetron (as 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 injection preparations.

Ondansetron Accord is a transparent 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, 6th floor,

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 with the following names

Last review date of this leaflet:May 2022

For detailed and updated information on this medicinal product, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)

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

Information intended exclusively for medical or healthcare professionals

Instructions for use:

Ondansetron Accord is for intravenous or intramuscular injection or for intravenous infusion after dilution.

When prescribing ondansetron for the prevention of nausea and vomiting induced by chemotherapy or radiotherapy in adults, adolescents, or children, the usual practice and relevant guidelines should be taken into consideration.

Nausea and vomiting induced by chemotherapy and radiotherapy:

Adults:The emetogenic potential of the oncological treatment varies according to the doses and combinations of chemotherapy and radiotherapy used. The route of administration and the dosage of ondansetron should be flexible in the range of 8-32 mg/day and should be selected as follows.

Emetogenic chemotherapy and radiotherapy:

Ondansetron can be administered by rectal, oral (tablets 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 (in no less than 30 seconds) or intramuscular injection, immediately before treatment, followed by the administration of 8 mg orally every 12 hours.

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

Highly emetogenic chemotherapy: in patients receiving highly emetogenic chemotherapy, such as high-dose cisplatin, ondansetron can be administered by oral, rectal, intravenous, or intramuscular route. It has been shown that the efficacy of ondansetron is 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 (in no less than 30 seconds) or intramuscular injection, immediately before chemotherapy.
• A dose of 8 mg by slow intravenous injection (in no less than 30 seconds) or intramuscular dose of 8 mg after an interval of 2-4 hours, or by continuous infusion of 1 mg/hour for a period of up to 24 hours.

• A maximum initial intravenous dose of 16 mg diluted in 50-100 ml of saline solution or other compatible infusion liquid (see section 6.6 of the technical dossier) and infused for no less than 15 minutes immediately before chemotherapy. The initial dose of ondansetron may be followed by two additional doses of 8 mg by intravenous injection (in no less than 30 seconds) or intramuscular injection after an interval of 4 hours.
• The dosage regimen should be selected according to the intensity of the emetogenic problem.

A single dose of more than 16 mg should not be administered due to the risk of QT interval prolongation (see sections 4.4, 4.8, and 5.1 of the technical dossier).

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

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

Pediatric population:

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

The dosage in the case of nausea and vomiting induced by chemotherapy can be calculated from the body surface area (SC) or weight, as follows.

Dosage according to SC:

Ondansetron should be administered immediately before chemotherapy, at a single intravenous dose of 5 mg/m2. The single intravenous dose should not exceed 8 mg. Oral administration may begin 12 hours later and may continue for a period of up to 5 days (see the technical dossier for dosage tables).

Dosage according to body weight:

The dosage based on body weight results in a higher total daily dose than that calculated from the SC. Ondansetron should be administered immediately before chemotherapy, at a single intravenous dose of 0.15 mg/kg. The single intravenous dose should not exceed 8 mg. Two additional intravenous doses of 0.15 mg/kg may be administered at intervals of 4 hours. Oral administration may begin 12 hours later and may continue for a period of up to 5 days (see the technical dossier for dosage tables).

Ondansetron should be diluted in dextrose 5% or sodium chloride 0.9% or other compatible infusion liquid and should be infused intravenously for at least 15 minutes.

There are no data from controlled clinical trials on the use of ondansetron for the prevention of delayed or prolonged nausea and vomiting after chemotherapy. There are no data from controlled clinical trials on the use of ondansetron for nausea and vomiting induced by radiotherapy 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 by slow intravenous injection at the time of anesthesia induction.

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

Injection:

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

Geriatric patients: there is limited experience with the use of ondansetron for 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 insufficiency:No dose adjustment or frequency or route of administration is required.

Patients with hepatic insufficiency:The clearance of ondansetron is significantly reduced and the serum half-life is significantly prolonged in patients with moderate or severe hepatic insufficiency. In these cases, the total daily dose should not exceed 8 mg and, 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 deficient metabolizers of sparteine and debrisoquine. Consequently, in these patients, repeated administration will result in exposure to the drug that is not different from that of the general population. No dose adjustment or frequency of administration is required.

Incompatibilities:

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

The solution should not be sterilized by autoclave.

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

Sodium chloride 0.9% w/v infusion liquid BP

Glucose 5% w/v infusion liquid BP

Manitol 10% w/v infusion liquid BP

Ringer's solution for infusion

Sodium chloride 0.9% w/v and potassium chloride 0.3% w/v infusion liquid BP

Sodium chloride 0.9% w/v and glucose 5% w/v infusion liquid BP

It has been demonstrated that Ondansetron Accord is stable after dilution with the recommended infusion liquids at concentrations of 0.016 mg/ml and 0.64 mg/ml.

Only use transparent and colorless solutions.

The diluted solutions should be stored in the dark.

Shelf life and storage conditions

Unopened pack:

3 years.

This medicinal product does not require any special storage conditions.

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

Injection:

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

Infusion:

After dilution with the recommended diluents, it has been demonstrated that the physical and chemical stability is maintained for 7 days at25°Cand 2º-8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage conditions and times before use are the responsibility of the user and should not exceed 24 hours at a temperature of between2°Cand8°C, unless the dilution has been carried out in validated and controlled aseptic conditions.