Ondansetron accord

Package leaflet: Information for the patient

Ondansetron Accord, 4 mg, solution for injection/infusion in ampoule-syringe
Ondansetron Accord, 8 mg, solution for injection/infusion in ampoule-syringe
Ondansetronum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

The medicine is called Ondansetron Accord, 4 mg or 8 mg, solution for injection/infusion in ampoule-syringe, and will be referred to as Ondansetron Accord throughout this leaflet.
Contents of the leaflet

1. What Ondansetron Accord is and what it is used for
2. What you need to know before using Ondansetron Accord
3. How to use Ondansetron Accord
4. Possible side effects
5. How to store Ondansetron Accord
6. 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 and belongs to a group of medicines called antiemetics. Ondansetron is a 5HT3 receptor antagonist. It works by blocking 5HT3 receptors located on neurons in the central and peripheral nervous systems. Ondansetron Accord is used:

• to prevent nausea and vomiting caused by
  • cytotoxic chemotherapy in adults and children aged ≥ 6 months;
  • radiotherapy in adults;
• to prevent and treat nausea and vomiting in the postoperative period in adults and children aged ≥ 1 month.

Please consult your doctor, nurse, or pharmacist if you need further information about the use of this medicine.

2. Important information before using Ondansetron Accord

When not to use Ondansetron Accord:

• if the patient is allergic to ondansetron or to other medicines in the group of selective 5HT3 receptor antagonists (e.g. granisetron, dolasetron), or to any of the other ingredients of this medicine (listed in section 6),
• if the patient is taking apomorphine (a medicine used in the treatment of Parkinson's disease).

Warnings and precautions
Before starting treatment with Ondansetron Accord, discuss this with your doctor, pharmacist,
or nurse:
- if the patient has had an allergic reaction to other anti-nausea or anti-vomiting medicines, such as
granisetron or palonosetron.
- if the patient has intestinal obstruction or severe constipation. This medicine may impair peristalsis in the lower gastrointestinal tract.
- if the patient has liver function disorders or is taking any medicines that may be harmful to the liver (hepatotoxic medicines used in chemotherapy).
In such cases, liver function will be closely monitored, especially in children and adolescents.
- if the patient has ever had heart problems, including irregular heartbeat (arrhythmia).
Ondansetron prolongs the QT interval (a segment measured on ECG indicating delayed cardiac repolarization, with risk of life-threatening cardiac rhythm disturbances) in a dose-dependent manner.
- if the patient is scheduled for tonsillectomy. In such cases, careful monitoring is required, as treatment with ondansetron may mask symptoms of internal bleeding.
- if the patient has disturbances in blood levels of electrolytes such as potassium and magnesium.
- if the patient is to undergo any diagnostic tests (including blood and urine analysis, skin tests with allergens, etc.). Inform the doctor about taking this medicine, as it may affect the results of the tests.
Inform your doctor or pharmacist immediately if any of these symptoms occur during or after treatment.

• If the patient experiences sudden chest pain or pressure (myocardial ischaemia).

Ondansetron Accord and other medicines
Tell your doctor, pharmacist, or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription.
In particular, inform your doctor, pharmacist, or nurse if the adult or child patient is taking any of the following medicines:
phenytoin (used in the treatment of epilepsy and cardiac arrhythmias). The effect of ondansetron may be reduced;
carbamazepine (used in the treatment of epilepsy and neuralgic pain). The effect of ondansetron may be reduced;

• rifampicin (used in the treatment of infections such as tuberculosis). The effect of ondansetron may be reduced; antibiotics such as erythromycin; ketoconazole (used in the treatment of patients with Cushing's syndrome); antiarrhythmic medicines (used to treat irregular heartbeat), such as amiodarone; beta-blockers, used in the treatment of certain heart diseases, eye conditions, anxiety states or for migraine prevention, such as atenolol or timolol; tramadol (used to treat pain). The analgesic effect of tramadol may be reduced; medicines affecting the heart (haloperidol, methadone); anticancer medicines (especially anthracyclines such as doxorubicin, daunorubicin or trastuzumab); SSRIs (selective serotonin reuptake inhibitors), used in the treatment of depression and (or) anxiety, including: fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram;
• SNRIs (serotonin and noradrenaline reuptake inhibitors), used in the treatment of depression and (or) anxiety, including venlafaxine, duloxetine.

Ondansetron Accord with food, drink and alcohol
Ondansetron Accord may be taken regardless of meals and drinks.
Pregnancy, breastfeeding and fertility
Pregnancy
Ondansetron Accord should not be used during the first trimester of pregnancy. This is because Ondansetron Accord may slightly increase the risk of cleft lip and/or cleft palate [an opening or fissure in the upper lip and/or palate]. If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
If the patient could become pregnant, she will be advised on effective contraception.
Breastfeeding
Ondansetron passes into breast milk. Therefore, mothers taking ondansetron should NOT breastfeed.
Before taking any medicine, consult your doctor.
Driving and operating machinery
Ondansetron does not affect the ability to drive or operate machinery.
Ondansetron Accord contains sodium.
This medicine contains 3.6 mg of sodium (the main component of table salt) per millilitre. This corresponds to 0.18% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Ondansetron Accord

This medicine should always be administered as an intravenous infusion after prior dilution or
by injection (intravenous or intramuscular) by qualified medical personnel, usually
a doctor or nurse, and never by the patient themselves.
Dosage
The doctor will determine the appropriate dose of ondansetron for the patient.
The dose depends on the treatment (chemotherapy or radiotherapy), liver function,
and whether the medicine is administered by intravenous injection or infusion.
Nausea and vomiting caused by chemotherapy or radiotherapy
Adults
On the day of chemotherapy or radiotherapy in adults, a dose of
8 mg is recommended, administered by slow intravenous or intramuscular injection, immediately before
chemotherapy or radiotherapy, followed by a second dose of 8 mg after 12 hours.
On subsequent days

• The usual intravenous dose in adults should not exceed 8 mg. Oral administration may be started 12 hours after chemotherapy or radiotherapy and may be continued for up to 5 days. The usual dose is 8 mg twice daily.

If chemotherapy or radiotherapy causes severe nausea and vomiting, it may be necessary
to administer a higher dose than the usual dose of this medicine to an adult or child patient.
The doctor will decide whether dose adjustment is necessary.
A single dose exceeding 16 mg should not be administered due to the increased risk
of cardiac rhythm disturbances (see section 2).
Nausea and vomiting caused by chemotherapy
Children over 6 months of age and adolescents:
The dose will be determined by the doctor based on body weight or body surface area.
On the day of chemotherapy

• the first dose is administered by intravenous injection, immediately before treatment. After chemotherapy, the medicine is usually given orally to children 12 hours later, in the form of tablets or syrup. The usual dose is 4 mg twice daily and may be administered for up to 5 days.

Postoperative nausea and vomiting
Prevention of postoperative nausea and vomiting
Adults:

• The usual dose in adults is 4 mg, administered intramuscularly or by slow intravenous injection immediately before surgery.

Children over 1 month of age and adolescents
The doctor will determine the dose of the medicine. The maximum dose of 4 mg is administered by slow
intravenous injection immediately before surgery.
Treatment of postoperative nausea and vomiting
Adults:

• The usual dose in adults is 4 mg, administered intramuscularly or by slow intravenous injection.

Children over 1 month of age and adolescents
The doctor will determine the dose of the medicine. The maximum dose is 4 mg and is administered by slow
intravenous injection.
Dosage adjustment
Patients with moderate or severe liver disease
A dose exceeding 8 mg per day should not be used.
Elderly patients, patients with renal impairment, and patients with slow
metabolism of mephenytoin and debrisoquine
No adjustment of daily dose, frequency, or route of administration is necessary.
Duration of treatment
The doctor will determine the duration of treatment with ondansetron. Do not discontinue treatment earlier.
Ondansetron Accord should take effect shortly after injection. If the patient still experiences
nausea or vomiting, inform the doctor or nurse.
Use of a higher than recommended dose of Ondansetron Accord
This medicine will be administered to the patient by a doctor or nurse, so the likelihood of the patient receiving an excessive
dose is low. If it is suspected that the patient has received too high a dose
or a dose has been missed, inform the doctor or nurse.
Currently, little is known about ondansetron overdose. In most patients, symptoms
were similar to those reported in patients receiving recommended doses of this medicine (see section
"Possible side effects").
The following symptoms have been observed after overdose: visual disturbances, severe
constipation, low blood pressure, and loss of consciousness. In all cases, symptoms resolved completely.
This medicine may alter heart rhythm, especially in cases of overdose. In such cases,
the doctor will monitor heart activity.
There is no specific antidote for ondansetron. Therefore, in case of suspected
overdose, only symptomatic treatment should be administered.
Inform the doctor if any of these symptoms occur.
If you have any further questions about the use of this medicine, consult your
doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
You should immediately inform your doctor or nurse if any of the following symptoms occur:
Uncommon (may occur in fewer than 1 in 100 patients)
₋ Chest pain, irregular heartbeat (arrhythmia, which in isolated cases may be fatal), and slow heartbeat (bradycardia)
Rare (may occur in fewer than 1 in 1000 patients)
₋ Immediate allergic reactions, including life-threatening allergic reaction (anaphylaxis)
These may include itchy rash, swelling of the eyelids, face, lips, mouth, and tongue
Frequency not known (frequency cannot be determined from available data)
₋ Sudden pain or pressure in the chest (myocardial ischaemia)
If any of these symptoms occur, you must immediately stop taking the medicine and contact your doctor.
Other adverse reactions include:
Very common (may occur in more than 1 in 10 patients)

• headache

Common (may occur in fewer than 1 in 10 patients)
flushing of the face, hot flushes
constipation
irritation and redness at the injection site
Uncommon (may occur in fewer than 1 in 100 patients)
seizures (convulsions)
unusual body movements or jerking
irregular heartbeat
chest pain
low blood pressure, which may lead to fainting or dizziness
hiccups
changes in liver function test results (applies when the patient is taking Ondansetron Accord with a medicine called cisplatin; otherwise, this adverse reaction occurs uncommonly)
Rare (may occur in fewer than 1 in 1000 patients)

• dizziness or feeling faint
• blurred vision
• heart rhythm disturbances (sometimes leading to sudden loss of consciousness)

Very rare (may occur in fewer than 1 in 10,000 patients)

• blurred vision or temporary loss of vision, usually lasting no longer than 20 minutes
• extensive skin rashes with blisters and peeling affecting a large part of the body surface (toxic epidermal necrolysis).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 22 49 21 201
Fax: +48 22 49 21 209
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Ondansetron Accord

Keep this medicine out of sight and reach of children.
Expiry date
Do not use this medicine after the expiry date stated on the ampoule-syringe or
carton after: EXP. The expiry date refers to the last day of the stated month.
Storage
No special temperature storage instructions apply.
Do not use this medicine if the container is damaged or if particles and/or crystals are visible.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Following this advice helps protect the environment.

6. Contents of the pack and other information

What Ondansetron Accord contains
The active substance is ondansetron (in the form of ondansetron hydrochloride dihydrate).
1 ml of injection/infusion solution in an ampoule-syringe contains 2 mg of ondansetron
(in the form of ondansetron hydrochloride dihydrate).
Each 2 ml ampoule-syringe contains 4 mg of ondansetron (in the form of ondansetron hydrochloride
dihydrate).
Each 4 ml ampoule-syringe contains 8 mg of ondansetron (in the form of ondansetron hydrochloride
dihydrate).
The other ingredients are: citric acid monohydrate, sodium citrate, sodium chloride, sodium hydroxide
and (or) concentrated hydrochloric acid (to adjust pH) and water for injections.

What Ondansetron Accord looks like and contents of the pack
Ondansetron Accord is a clear, colourless solution in an ampoule-syringe made of amber glass.
The medicine is available in packs containing 1, 5 and 10 ampoule-syringes.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: + 48 22 577 28 00

Manufacturer / Importer:
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA3000
Malta
Laboratori Fundació Dau
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain
Accord Healthcare single member S.A.
64th Km National Road Athens
32009 Lamia, Schimatari
Greece

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

The following information is intended exclusively for healthcare professionals

Instructions for use
For intravenous or intramuscular injection or for intravenous infusion after dilution.
Physicians prescribing ondansetron for the prevention of delayed nausea and vomiting associated with radiotherapy or chemotherapy in adults, adolescents, and children should consider appropriate guidelines relating to the use of the medicinal product and practically accepted administration practices.
Compatibility with other medicinal products
The following active substances may be administered via the Y-site of an ondansetron infusion set at ondansetron concentrations ranging from 16 to 160 micrograms/ml (8 mg/500 ml and 8 mg/50 ml):

Nausea and vomiting induced by chemotherapy and radiotherapy
Adults: The severity of vomiting induced by anti-cancer treatment varies depending on the drug doses and combination of chemotherapy and radiotherapy used in the treatment regimens. The route of administration and dosage of Ondansetron Accord should be flexibly selected within the range of 8 mg to 32 mg per day, according to the recommendations below.
Chemotherapy and radiotherapy with emetogenic potential:
Immediately before treatment, ondansetron should be administered at a dose of 8 mg by slow intravenous injection (lasting no less than 30 seconds) or intramuscularly immediately before chemotherapy, followed by oral administration of 8 mg every 12 hours.
To prevent delayed or prolonged vomiting after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after completion of the treatment cycle.
Highly emetogenic chemotherapy:
For patients receiving highly emetogenic chemotherapy, e.g. high-dose cisplatin, ondansetron may be administered orally, rectally, intravenously, or intramuscularly. Ondansetron administered according to the following dosing regimens during the first 24 hours after initiation of chemotherapy has shown comparable efficacy:

• Single dose of 8 mg administered by slow intravenous injection (lasting no less than 30 seconds) or intramuscularly immediately before chemotherapy.
• Dose of 8 mg administered by slow intravenous injection (lasting at least 30 seconds) or intramuscularly immediately before the start of chemotherapy. Two additional doses of 8 mg should be administered intravenously (by injection lasting at least 30 seconds) or intramuscularly at 4-hour intervals, or administered as a continuous 24-hour infusion at a rate of 1 mg/hour.
• Maximum initial dose is 16 mg, diluted in 50 to 100 ml of 0.9% sodium chloride solution for intravenous infusion or in another suitable infusion fluid (see section 6.6 of the Summary of Product Characteristics) and administered as an infusion lasting no less than 15 minutes immediately before chemotherapy. After the initial dose, two additional doses of 8 mg of Ondansetron Accord may be administered intravenously at 4-hour intervals (by injection lasting no less than 30 seconds) or intramuscularly.
• A single dose exceeding 16 mg should not be administered due to dose-dependent increased risk of QT interval prolongation (see sections 4.4, 4.8 and 5.1 of the Summary of Product Characteristics).

The choice of dosing regimen should depend on the severity of vomiting.
The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by adding a single intravenous dose of 20 mg of sodium phosphate dexamethasone before chemotherapy.
To prevent delayed or prolonged vomiting after the first 24 hours, rectal or oral treatment with ondansetron should be continued for up to 5 days after completion of the treatment cycle.
Children and adolescents
Treatment of nausea and vomiting induced by chemotherapy in children aged ≥6 months and adolescents.
The dose of the drug used to treat chemotherapy-induced nausea and vomiting should be calculated based on body surface area (BSA) or body weight.
Dose calculation based on body surface area (BSA):
Ondansetron Accord should be administered intravenously as a single dose of 5 mg/m² immediately before chemotherapy. The single intravenous dose must not exceed 8 mg.
Oral administration may be initiated after 12 hours and continued for up to 5 days. See dosing tables in the Summary of Product Characteristics.
The total daily dose (given in divided doses) must not exceed 32 mg (the dose used in adults).
Dose calculation based on body weight:
Total daily doses based on body weight are higher than doses calculated based on body surface area (BSA). Ondansetron Accord should be administered intravenously as a single dose of 0.15 mg/kg body weight immediately before chemotherapy. The single intravenous dose must not exceed 8 mg. Two additional intravenous doses may be administered at 4-hour intervals. Oral administration may be initiated after 12 hours and continued for up to 5 days (further information, see Summary of Product Characteristics).
Ondansetron Accord should be diluted in 5% glucose solution or 0.9% sodium chloride solution (9 mg/ml), or another compatible infusion fluid (see section 6.6 of the Summary of Product Characteristics) and administered by intravenous infusion lasting no less than 15 minutes.
There are no data from controlled clinical trials on the use of Ondansetron Accord for the prevention of delayed or prolonged nausea and vomiting induced by chemotherapy. There are no data from controlled clinical trials on the use of Ondansetron Accord in the treatment of nausea and vomiting induced by radiotherapy in children.
Postoperative nausea and vomiting
Adults: To prevent postoperative nausea and vomiting, ondansetron may be administered as a single 4 mg dose intramuscularly or by slow intravenous injection before surgery.
For treatment of postoperative nausea and vomiting, administration of a single 4 mg dose intramuscularly or by slow intravenous injection is recommended.
Children (over 1 month of age) and adolescents
Oral administration:
No studies have been conducted on oral administration of ondansetron for the prevention or treatment of postoperative nausea and vomiting. In such cases, slow intravenous injection is recommended.
Injection:
To prevent postoperative nausea and vomiting (PONV) in pediatric patients undergoing general anesthesia during surgery, ondansetron may be administered by slow intravenous injection (lasting at least 30 seconds) as a single dose of 0.1 mg/kg body weight, up to a maximum of 4 mg, before, during, or after induction of anesthesia.
For treatment of nausea and vomiting in pediatric patients after surgery under general anesthesia, ondansetron may be administered by slow intravenous injection (lasting at least 30 seconds) as a single dose of 0.1 mg/kg body weight, up to a maximum of 4 mg.
There are no data on the use of ondansetron in the treatment of postoperative nausea and vomiting in children under 2 years of age.
Elderly patients: Data on the use of ondansetron for the prevention and treatment of PONV in elderly patients are limited; however, ondansetron is well tolerated in patients over 65 years of age receiving chemotherapy.
Patients with renal impairment: There is no need to adjust the daily dose, frequency, or route of administration of Ondansetron Accord.
Patients with hepatic impairment: Ondansetron clearance is significantly reduced and serum half-life significantly prolonged in patients with moderate to severe hepatic impairment. In such patients, the total daily dose should not exceed 8 mg; therefore, oral or parenteral administration is recommended.
Patients with slow metabolism of sparteine and debrisoquine: The elimination half-life of ondansetron is not altered in patients classified as slow metabolizers of sparteine and debrisoquine. Consequently, repeated doses in these patients will result in similar exposure levels as in other patient groups. No change in daily dose or dosing frequency is necessary.
Pharmaceutical incompatibilities
The solution must not be sterilized in an autoclave.
Ondansetron Accord should only be mixed with the recommended solutions listed below:
0.9% sodium chloride solution for intravenous infusion (BP) (9 mg/ml)
5% glucose solution for intravenous infusion (BP) (5% w/v)
10% mannitol solution for intravenous infusion (BP) (10% w/v)
Ringer's solution for intravenous infusion
0.3% potassium chloride (0.3% w/v) and 0.9% sodium chloride (9 mg/ml) solution for intravenous infusion (BP)
0.3% potassium chloride (0.3% w/v) and 5% glucose (5% w/v) solution for intravenous infusion (BP)
Chemical and physical stability of Ondansetron Accord after dilution with the recommended solutions has been demonstrated for concentrations of 0.016 mg/ml and 0.64 mg/ml.
Only clear, colorless solutions should be used.
Diluted solutions should be protected from light during storage.
Shelf life and storage
3 years
No special requirements for storage temperature of the medicinal product.
Injection
The medicinal product should be used immediately after first opening.
Infusion
After dilution using the recommended diluents, chemical and physical in-use stability has been demonstrated 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 responsibility for storage conditions and duration prior to use lies with the user. Storage time should generally not exceed 24 hours at 2-8°C, unless dilution was performed under controlled and validated aseptic conditions.