ONDANSETRON HIKMA 4 mg/2 mL Injectable Solution

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

Do not useOndansetron Hikma:

• if you are allergic to ondansetron or 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 are not sure, consult your doctor, pharmacist, or nurse before taking ondansetron.

Warnings and precautions

Consult your doctor or pharmacist before starting ondansetron:

• if you have ever had heart problems (e.g., congestive heart failure, which causes shortness of breath and swelling of the ankles).
• if you have irregular heartbeats (arrhythmias).
• if you are allergic to medicines similar to ondansetron, such as granisetron or palonosetron (do not use this medicine).
• if you have liver problems
• if you have an intestinal obstruction.
• if you have problems with the levels of salts in your blood, such as potassium, sodium, and magnesium.

If you are not sure if any of the above applies to you, consult your doctor, pharmacist, or nurse before ondansetron injection is given to you.

Other medicines and Ondansetron Hikma

Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines. This includes medicines that you can buy without a prescription and herbal medicines. Ondansetron may affect the way some medicines work and other medicines may affect the way ondansetron works.

In particular, tell your doctor, pharmacist, or nurse 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.
• anti-arrhythmic medicines, used to treat irregular heartbeats.
• beta-blocker medicines, used to treat certain heart or eye problems, anxiety, or to prevent migraines.
• tramadol, a pain reliever.
• medicines that affect the heart (such as haloperidol or methadone).
• medicines for cancer (especially anthracyclines or trastuzumab).
• selective serotonin reuptake inhibitors (SSRIs) used to treat depression and/or anxiety, including fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram.
• serotonin and noradrenaline reuptake inhibitors (SNRIs) used to treat depression and/or anxiety, including venlafaxine, duloxetine.

If you are in any of these situations, or if you are unsure, consult your doctor, pharmacist, or nurse before using ondansetron injection.

Ondansetron injection should not be given in the same syringe or infusion (drip) as other medicines.

Pregnancy and breastfeeding

Ondansetron should not be used during the first trimester of pregnancy. This is because it 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 might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using ondansetron as this medicine may harm the fetus. If you are a woman of childbearing age, you are advised to use an effective method of contraception.

It is not recommended to breastfeed during treatment with ondansetron. This medicine may pass into breast milk. Ask your doctor or midwife for advice.

Ondansetron Hikma contains sodium citrate and sodium chloride

This medicine contains less than 1 mmol of sodium (23 mg) per milliliter, which is essentially "sodium-free.

3. How to use Ondansetron Hikma

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

To prevent nausea and vomiting caused by chemotherapy or radiotherapy in adults

On the day of chemotherapy or radiotherapy:

• The recommended dose in adults is 8 mg given as a slow injection into a vein, immediately before your treatment, and another 8 mg 12 hours later. After chemotherapy, the medicine is usually given by mouth in the form of an ondansetron 8 mg tablet or 10 ml (8 mg) of ondansetron syrup.

In the following days:

• The recommended dose in adults is one 8 mg tablet or 10 ml (8 mg) of ondansetron syrup twice a day.
• It can be given 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 than usual. Your doctor will decide what to do.

To prevent nausea and vomiting caused by chemotherapy in children over 6 months and adolescents

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

On the day of chemotherapy:

• The first dose is given as a slow injection into a vein, immediately before your child's treatment. After chemotherapy, your child's medicine is usually given by mouth 12 hours later in the form of an ondansetron tablet or syrup.

In the following days:

• 2.5 ml (2 mg) of syrup twice a day for small children and those weighing 10 kg or less
• one 4 mg tablet or 5 ml (4 mg) of syrup twice a day for older children and those weighing more than 10 kg
• two 4 mg tablets or 10 ml (8 mg) of syrup twice a day for adolescents (or those with a large body surface area)
• these doses can be given for up to 5 days.

To prevent nausea and vomiting after an operation

Adults:

• The usual dose in adults is 4 mg given as a slow injection into a vein. As a preventative measure, this dose will be given to you immediately before your operation.

Children:

• For children over 1 month and adolescents, the doctor will decide the dose. The maximum dose is 4 mg given as a slow injection into a vein. This dose will be given to you immediately before your operation.

Patients with moderate or severe liver problems

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

If you continue to feel unwell

Ondansetron should start to work quickly after the injection. If you continue to feel unwell, tell your doctor or nurse.

If you use more Ondansetron Hikma than you should

Your doctor or nurse will give you the ondansetron injection, so it is unlikely that you or your child will be given too much. If you think you or your child have been given too much or have not been given a dose, tell your doctor or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount administered.

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 member of the medical staff immediately. The signs may include:

• sudden wheezing, swelling of your lips, face, or throat, or difficulty breathing
• swelling of the eyelids, face, lips, tongue, or throat
• skin rash - red spots or lumps under your skin (hives) anywhere on your body
• collapse.

Myocardial ischemia: The signs include:

• sudden chest pain or
• chest tightness.

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

• headache

Common side effects(may affect up to 1 in 10 people)

• feeling warm or flushed
• constipation
• changes in liver function test results (if you take ondansetron with a medicine called cisplatin, otherwise this side effect is uncommon)
• irritation and redness at the injection site

Uncommon side effects(may affect up to 1 in 100 people)

• hiccups
• low blood pressure, which can make you feel faint or dizzy
• irregular heartbeat
• chest pain
• seizures
• unusual body movements or tremors.

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

• dizziness or fainting
• blurred vision
• abnormal heart rhythm (which can sometimes cause a sudden loss of consciousness)

Very rare side effects(may affect less than 1 in 10,000 people)

• loss of vision or temporary blindness, which usually resolves within 20 minutes

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. 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: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ondansetron Hikma

Keep this medicine out of the sight and reach of children.

Do not store above 30°C.

Keep the ampoules in the original packaging to protect them from light.

The diluted solution is chemically stable for 24 hours when stored between 2-8°C.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Composition ofOndansetron Hikma

• The active ingredient is ondansetron, as hydrochloride dihydrate. Each ml of solution contains 2 mg of ondansetron. Each 2 ml ampoule contains 4 mg of ondansetron and each 4 ml ampoule contains 8 mg of ondansetron.
• The other components are sodium chloride, citric acid monohydrate, sodium citrate, and water for injectable preparations.

Appearance of the Product and Container Content

Ondansetron Hikma is a clear and colorless injectable solution presented in transparent glass ampoules.

Ondansetron Hikma 4 mg/ 2 ml injectable solution EFG:

Each ampoule contains 2 ml of solution.

Container size: 5 ampoules.

Ondansetron Hikma 8 mg/4 ml injectable solution EFG:

Each ampoule contains 4 ml of solution.

Container size: containing 5 ampoules.

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n,º 8, 8A e 8B – Fervença

2705-906 Terrugem SNT

Portugal

Tel.: +351 219 608 410

Fax: +351 219 615 102

[email protected]

Manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n,º 8, 8A e 8B – Fervença

2705-906 Terrugem SNT

Portugal

or

Hikma Italia S.p.A.

Viale Certosa, 10

27100 Pavia

Italy

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

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

Date of the last revision of this leaflet: August 2024

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

This information is intended only for healthcare professionals:

Ondansetron Hikma 4 mg/2 ml injectable solutionEFG

Ondansetron Hikma 8 mg/4 ml injectable solutionEFG

For more information on this product, please refer to the Summary of Product Characteristics (SPC).

Ondansetron Hikma injectable solution EFG

Ondansetron Hikma 2 mg/ml:

• Ampoules of 2 ml containing each 4 mg of ondansetron (as hydrochloride dihydrate) in aqueous solution for intravenous administration.
• Ampoules of 4 ml containing each 8 mg of ondansetron (as hydrochloride dihydrate) in aqueous solution for intravenous administration.

Chemotherapy- and Radiotherapy-induced Nausea and Vomiting

Adults

The emetogenic potential of cancer treatment varies according to the dose and combination of chemotherapy and radiotherapy regimens used. The route of administration and dose of ondansetron should be flexible in the range of 8-32 mg per day, and should be selected as shown below.

Chemotherapy and radiotherapy emetogenic potential:Ondansetron may be administered by rectal, oral (tablet or syrup), intravenous, or intramuscular route. However, Ondansetron Hikma is only approved for intravenous administration. For most patients receiving emetogenic chemotherapy or radiotherapy, ondansetron 8 mg should be administered as a slow intravenous injection (over at least 30 seconds), immediately before chemotherapy or radiotherapy, followed by oral doses of 8 mg every 12 hours. To protect against delayed or prolonged emesis after the first 24 hours, ondansetron should be continued orally or rectally for 5 days after a treatment cycle.

Highly emetogenic chemotherapy:In patients treated with highly emetogenic chemotherapy, for example, with high-dose cisplatin, ondansetron may be administered by rectal, oral, intravenous, or intramuscular route. However, Ondansetron Hikma is only approved for intravenous administration.

Ondansetron has been shown to be equally effective 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) immediately before chemotherapy;
• A dose of 8 mg by slow intravenous injection (over at least 30 seconds) immediately before chemotherapy, followed by two additional intravenous doses of 8 mg (over at least 30 seconds) spaced 4 hours apart, or by a continuous infusion of 1 mg/hour for 24 hours;
• An initial maximum dose of 16 mg intravenously, diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6), and administered by infusion over at least 15 minutes, immediately before chemotherapy. The initial dose of ondansetron may be followed by two additional intravenous doses of 8 mg (over at least 30 seconds), spaced 4 hours apart.

• A dose greater than 16 mg should not be administered due to the increased risk of dose-dependent QT interval prolongation (see sections 4.4, 4.8, and 5.1).

The choice of dosage regimen should be determined based on the emetogenic potential of the treatment. The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of 20 mg of sodium dexamethasone phosphate before chemotherapy.

To protect against delayed or prolonged emesis after the first 24 hours, ondansetron should be continued orally or rectally for 5 days after a treatment cycle.

Pediatric Population

Chemotherapy-induced Nausea and Vomiting in Children ≥ 6 months and Adolescents

The dose for chemotherapy-induced nausea and vomiting can be calculated based on body surface area (BSA) or weight (see below). In pediatric clinical studies, ondansetron was administered by infusion diluted in 25 to 50 ml of saline or other compatible infusion fluid and administered over at least 15 minutes.

Weight-based dosing gives rise to a higher daily dose than BSA-based dosing (see sections 4.4 and 5.1 of the SPC).

Ondansetron should be diluted in 5% dextrose or 0.9% sodium chloride or other compatible infusion fluid (see Instructions for use/handling) and administered by intravenous infusion over at least 15 minutes.

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

Dose Calculation by Body Surface Area:

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 dosing can start 12 hours later and may continue for 5 days (see dosing tables in the SPC). The daily dose in 24 hours (administered in divided doses) should not exceed the adult dose of 32 mg.

Dose Calculation by Body Weight:

Weight-based dosing gives rise to a higher daily dose than BSA-based dosing. 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 may be administered at 4-hour intervals. Oral dosing can start 12 hours later and may continue for 5 days. The total dose in 24 hours (administered in divided doses) should not exceed the adult dose of 32 mg (for more information, refer to the SPC).

Elderly

For patients aged 65 to 74 years,the same dosage regimen as for adults can be followed. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid (see Instructions for use/handling) and administered by infusion over 15 minutes.

For patients aged 75 years or older, the initial intravenous dose of ondansetron should not exceed 8 mg. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid (see Instructions for use/handling) and administered by infusion over 15 minutes. After the initial dose of 8 mg, two additional doses of 8 mg may be administered by infusion over 15 minutes, spaced at least 4 hours apart (see SPC).

Postoperative Nausea and Vomiting (PONV)

Adults

For the prevention of PONV, ondansetron may be administered orally or by intravenous injection. However, Ondansetron Hikma is only approved for intravenous administration. Ondansetron may be administered as a single dose of 4 mg by slow intravenous injection at the time of induction of anesthesia. For the treatment of established PONV, a single dose of 4 mg by slow intravenous injection is recommended.

Pediatric Population

Children (older than 1 month and adolescents)

For the prevention of PONV in pediatric patients undergoing surgery with general anesthesia, a single dose of ondansetron may be administered by slow intravenous injection (over at least 30 seconds) at 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 after surgery with general anesthesia, a single dose of ondansetron may be administered by slow intravenous injection (over at least 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 ondansetron injectable for the treatment of postoperative vomiting in children under 2 years of age.

Elderly

There is limited experience with 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.

For all Indications:

Patients with Renal Impairment

No modification of the daily dose, frequency of administration, or route of administration is required.

Patients with Hepatic Impairment

The clearance of ondansetron is significantly reduced and the serum half-life significantly prolonged in subjects with moderate or severe hepatic impairment. In these patients, the total daily dose should not exceed 8 mg by parenteral or oral route.

Patients who are Poor Metabolizers of Sparteine/Debrisoquine

The elimination half-life of ondansetron is not altered in individuals classified as poor metabolizers of sparteine and debrisoquine. Consequently, the levels of exposure to the drug after repeated administration in these patients do not differ from those achieved in the general population. No dose adjustment is required.

For single use. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

The solution should be inspected visually before use. Only solutions that are clear and practically free of particles should be used.

Compatibility with Intravenous Fluids

Ondansetron Hikma should only be mixed with those infusion solutions that are recommended:

• Intravenous infusion of sodium chloride 0.9% (w/v).
• Intravenous infusion of glucose 5% (w/v).
• Intravenous infusion of mannitol 10% (w/v).

• Intravenous infusion of Ringer's solution.

• Intravenous infusion of potassium chloride 0.3% (w/v) in sodium chloride 0.9% (w/v).

• Intravenous infusion of potassium chloride 0.3% (w/v) in glucose 5% (w/v).

In accordance with good pharmaceutical practice, dilutions of Ondansetron Hikma in intravenous fluids should be prepared at the time of infusion or stored at 2-8°C for no more than 24 hours before the start of administration.

Compatibility with Other Medicinal Products

Ondansetron can be administered by intravenous infusion at 1 mg/hour, for example, from an infusion bag or a syringe pump. The following medicinal products can be administered through the Y-connector of the infusion equipment for ondansetron concentrations of 16 to 160 micrograms/ml (e.g., 8 mg/500 ml and 8 mg/50 ml, respectively);

Cisplatin -Concentrations up to 0.48 mg/ml (i.e., 240 mg in 500 ml) administered over a period of 1-8 hours

5-Fluorouracil -Concentrations up to 0.8 mg/ml (i.e., 2.4 g in 3 liters or 400 mg in 500 ml) administered at a rate of at least 20 ml/hour (500 ml/24 hours). Higher concentrations of 5-fluorouracil may cause precipitation of ondansetron. The 5-fluorouracil solution may contain up to 0.045% (w/v) magnesium chloride in addition to other compatible excipients.

Carboplatin -Concentrations between 0.18 mg/ml and 9.9 mg/ml (i.e., 90 mg in 500 ml to 990 mg in 100 ml), administered over a period of 10 minutes to 1 hour.

Etoposide -Concentrations between 0.144 mg/ml and 0.25 mg/ml (i.e., 72 mg in 500 ml to 250 mg in 1 liter), administered over a period of 30 minutes to 1 hour.

Ceftazidime -Doses between 250 mg and 2000 mg reconstituted with water for injectable preparations BP according to the manufacturer's recommendations (i.e., 2.5 ml for 250 mg and 10 ml for 2 g of ceftazidime), administered as a bolus injection over approximately 5 minutes.

Cyclophosphamide -Doses between 100 mg and 1 g reconstituted with water for injectable preparations BP, 5 ml for 100 mg of cyclophosphamide, according to the manufacturer's recommendations, and administered as a bolus injection over approximately 5 minutes.

Doxorubicin -Doses between 10 mg and 100 mg reconstituted with water for injectable preparations BP, 5 ml for 10 mg of doxorubicin, according to the manufacturer's recommendations, and administered as a bolus injection over approximately 5 minutes.

Dexamethasone -Sodium dexamethasone phosphate can be administered at a dose of 20 mg as a slow intravenous injection over 2-5 minutes through the Y-connector of an infusion system with which 8 or 16 mg of ondansetron are administered diluted in 50-100 ml of a compatible infusion solution over a period of approximately 15 minutes. Compatibility between sodium dexamethasone phosphate and ondansetron has been confirmed, which supports the administration of these medicinal products through the same system with concentrations of 32 micrograms to 2.5 mg/ml for sodium dexamethasone phosphate and 8 micrograms to 1 mg/ml for ondansetron.

Shelf Life

3 years.

Special Precautions for Storage

Store below 30°C.

Store in the original package to protect from light.