ONDANSETRON 4 mg Injectable Or Infusion Solution

Зміст інструкції

1. Ondansetron Accord 4 mg solution for injection/infusion in pre-filled syringe, 8 mg solution for injection/infusion in pre-filled syringe
   1. What is Ondansetron Accord and what is it used for
   2. What you need to know before you use 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

Ondansetron Accord 4 mg solution for injection/infusion in pre-filled syringe, 8 mg solution for injection/infusion in pre-filled syringe

ondansetron

Read this leaflet carefully before using this medicine as 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. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

The name of the medicine is Ondansetron Accord 4 mg/8 mg Solution for injection/infusion in syringe

Contents of this leaflet

• 1. What Ondansetron Accord is and what it is used for
• 2. What you need to know before you use 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 is Ondansetron Accord and what is it used for

Ondansetron Accord contains the active ingredient ondansetron, which belongs to a group of
medicines called antiemetics. Ondansetron is a 5HT3 receptor antagonist. It works
by inhibiting 5HT3 receptors on neurons located in the central and peripheral nervous system.
Ondansetron Accord is used for

• Preventing nausea (feeling sick) and vomiting (being sick) caused by chemotherapy for cancer in adults and children starting from 6 months of age, or radiotherapy for cancer in adults.
• Preventing and treating nausea and vomiting after surgery in adults and children starting from 1 month of age.

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

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

Do not use Ondansetron Accord:

• If you are allergic to ondansetron or other selective 5HT3 receptor antagonists (e.g. granisetron, dolaston) or to any of the other ingredients of this medicine (listed in section 6).
• If you are taking apomorphine (medicine used to treat Parkinson's disease).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Ondansetron Accord if:
₋ you have had an allergy to other medicines against nausea or feeling sick,
such as granisetron or palosetron.
₋ you have a bowel obstruction or are suffering from severe constipation. This medicine may hinder the
mobility of the lower intestine.
₋ you have liver problems or are taking medicines that could be harmful to the liver (hepatotoxic
chemotherapy drugs). In these cases, your liver function will be closely monitored, especially in
children and adolescents;
₋ you have ever had heart problems, incl. an irregular heartbeat (arrhythmias). Ondansetron
prolongs the QT interval (ECG sign of delayed heart repolarization following a heartbeat
with a risk of life-threatening arrhythmias) in a dose-dependent manner.
₋ you are going to have tonsil surgery. In this case, you need to be
carefully monitored because treatment with ondansetron may mask the symptoms of
internal bleeding.
₋ you have problems with salt levels in your blood, such as potassium, sodium and magnesium
If you are going to have any diagnostic tests (including blood tests, urine tests, skin
tests using allergens, etc.). Tell your doctor that you are taking this medicine, as
it may alter the results.
Immediately inform your doctor or pharmacist if you notice any of these symptoms during or
after treatment.

• If you experience sudden chest pain or a feeling of tightness in the chest (myocardial ischemia)

Other medicines and Ondansetron Accord
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might
take any other medicines, including those available without a prescription.
In particular, tell your doctor, nurse or pharmacist if you or your child are taking
any of the following medicines:

• Phenytoin (used to treat epilepsy and heart arrhythmias). The effect of ondansetron may be weakened.
• Carbamazepine (used to treat epilepsy and neuropathic pain). The effect of ondansetron may be weakened.
• Rifampicin used for the treatment of infections such as tuberculosis (TB). The effect of ondansetron may be weakened.
• Antibiotics such as erythromycin
• Ketoconazole (used for the treatment of Cushing's disease).
• Antiarrhythmic medicines (used to treat an irregular heartbeat), such as amiodarone
• Beta-blockers used to treat certain heart or eye problems, anxiety or to prevent migraines, such as atenolol or timolol
• Tramadol (used to treat pain). The pain-relieving effect of tramadol may be weakened.
• Apomorphine (medicine used to treat Parkinson's disease) with apomorphine, severe drops in blood pressure and loss of consciousness have been reported with simultaneous application of ondansetron.
• Medicines that act on the heart (such as haloperidol or methadone)
• Cancer medicines (especially anthracyclines such as doxorubicin, daunorubicin or trastuzumab)
• SSRIs (selective serotonin reuptake inhibitors) used to treat depression and/or anxiety including fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
• SNRIs (selective noradrenaline reuptake inhibitors) used to treat depression and/or anxiety including venlafaxine, duloxetine

Ondansetron Accord with food, drinks and alcohol
You can use Ondansetron Accord independently of food and drinks.

Pregnancy, breastfeeding and fertility
Ondansetron Accord should not be used during the first trimester of pregnancy. This is because
Ondansetron Accord may slightly increase the risk that the baby is born with a cleft lip and
and/or cleft palate (openings or splits in the upper lip and/or palate).
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, ask your doctor
or pharmacist for advice before using this medicine.
If you are a woman of childbearing potential, you may be asked to use effective contraceptive measures.
Ondansetron passes into breast milk. Therefore, mothers receiving ondansetron should NOT
breastfeed.
Ask your doctor for advice before taking any medicine.

Driving and using machines
Ondansetron has no effects on the ability to drive or operate machines.

Ondansetron Accord contains sodium
This medicine contains 3.60 mg of sodium (the main component of table salt) in each ml.
This is equivalent to 0.18% of the recommended maximum daily intake of sodium for an
adult.

3. How to use Ondansetron Accord

This medicine must always be administered by infusion or injection (into a vein or a
muscle) by a qualified healthcare professional, usually a doctor or a nurse, and never by yourself.

Dose
The doctor will decide the correct treatment dose of ondansetron for you.
The dose depends on the medical treatment (chemotherapy or surgery), the proper functioning of the
liver and whether it is administered by injection or intravenous infusion.

Nausea and vomiting caused by chemotherapy or radiotherapy
Adults
On the day of chemotherapy or radiotherapy, the recommended dose for adults is 8 mg
administered by a slow injection into the vein or muscle, shortly before treatment, and another
8 mg administered twelve hours later.
In the following days

• The usual single intravenous dose for adults does not exceed 8 mg. Oral administration can begin twelve hours after chemotherapy or radiotherapy and can be continued for a maximum of 5 days. The usual dose is 8 mg twice a day. If chemotherapy or radiotherapy is expected to cause severe nausea and vomiting, you or your child will be given a higher dose of this medicine. The dose will be decided by the doctor. A single dose greater than 16 mg should not be administered due to the increased risk of heart rhythm disturbances (see section 2).

Nausea and vomiting caused by chemotherapy

Children over 6 months of age and adolescents.
The doctor will decide the dose based on the child's weight or body surface area (body surface
area).
On the day of chemotherapy
the first dose is administered by injection into the vein, immediately before the
child's treatment. After chemotherapy, the medicine will usually be given to the child by
mouth twelve hours later in the form of tablets or syrup. The usual dose is 4 mg twice
a day and can continue for a maximum of 5 days.

Nausea and vomiting after surgery
To prevent nausea and vomiting after surgery
Adults:

• The usual dose for adults is 4 mg administered by a slow intravenous injection, which will be administered immediately before surgery.

Children over 1 month of age and adolescents
The doctor will decide the dose. The maximum dose is 4 mg administered by a slow injection into the vein,
which will be administered immediately before surgery.

To treat nausea and vomiting after surgery
Adult:

• The usual dose for adults is 4 mg administered by a slow intravenous injection.

Children over 1 month of age and adolescents
The doctor will decide the dose. The maximum dose is 4 mg administered by a slow
intravenous injection.

Dosage adjustments
Patients with moderate or severe liver problems
The total daily dose should not exceed 8 mg.

Elderly, patients with impaired renal function or poor sparteine/detrosoquine metabolizers
It is not necessary to modify the daily dose or frequency of dose or route of administration.

Duration of treatment
The doctor will decide the duration of treatment with ondansetron. Do not stop treatment prematurely.

Ondansetron Accordshould start to work shortly after the injection. If you or your child
continue to experience nausea or vomiting, inform the doctor or nurse.

If you or your child have taken more Ondansetron Accord than you should
The doctor or nurse will administer this medicine to you or your child, so it is unlikely
that you or your child have taken too much. If you think that you or your child have taken
too much or have forgotten a dose, inform the doctor or nurse.
Little is known at present about ondansetron overdose. In most patients, the symptoms
were similar to those already reported in patients who have received the recommended doses of this
medicine (see possible side effects). The following effects have been observed after overdose:
visual disturbances, severe constipation, low blood pressure and loss of consciousness. In all
cases, the symptoms disappeared completely.
This medicine can alter the heart rhythm, especially if you have had an overdose. In this
case, your doctor will further monitor your heartbeat.
There is no specific antidote to ondansetron; for this reason, if an overdose is suspected,
only the symptoms should be treated.
Inform the doctor if any of these symptoms occur.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

Tell your doctor or nurse immediately if you experience any of the following effects:
Uncommon:may affect up to 1 in 100 people
₋ Chest pain, irregular (arrhythmia which can be fatal in isolated cases) and slow
heartbeat (bradycardia)

Rare:may affect up to 1 in 1,000 people

• Immediate allergic reactions, including a life-threatening allergic reaction (anaphylaxis). These reactions can be: itchy rash, swelling of the eyelids, face, lips, mouth and tongue.

Not known (frequency cannot be estimated from available data)

• Sudden chest pain or tightness (myocardial ischemia) If you experience any of these symptoms, stop taking the medicine immediately and contact your doctor.

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

• Headache

Common (may affect up to 1 in 10 people)
Sensations of flushing or heat
Constipation
Irritation and redness at the injection site

Uncommon (may affect up to 1 in 100 people)
Seizures (fits or convulsions)
Unusual body movements or tremors
Irregular heartbeat
Chest pain
Low blood pressure, which may make you feel weak or dizzy
Hiccups
Changes in liver function tests (if you are taking Ondansetron Accord with a
medicine called cisplatin, otherwise this side effect is rare)

Rare (may affect up to 1 in 1,000 people)
Feelings of dizziness or mild confusion
Blurred vision
Heart rhythm disorder (which sometimes causes sudden loss of consciousness)

Very rare (may affect up to 1 in 10,000 people)
Reduced vision or temporary loss of vision, which usually lasts less than 20 minutes.
Widespread rash with blisters, affecting a large area of the body surface (toxic epidermal
necrosis).

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
to adverse . By reporting side effects you can help provide more information on the
safety of this medicine.

5. How to store Ondansetron Accord

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

Expiry date
Do not use this medicine after the expiry date which is stated on the pre-filled syringe and on the
pack after Exp.. The expiry date refers to the last day of that month.

Storage
This medicine does not require any particular storage temperature.
Do not use this medicine if you notice that the container is damaged or particles/crystals are visible.
Do not dispose of any medicine in waste water 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

What Ondansetron Accord contains
The active ingredient is ondansetron (as dihydrochloride dihydrate).
Each ml of solution for injection or infusion in a pre-filled syringe contains 2 mg of ondansetron
(as ondansetron dihydrochloride dihydrate).
Each pre-filled syringe of 2 ml contains 4 mg of ondansetron (as ondansetron dihydrochloride
dihydrate).
Each pre-filled syringe of 4 ml contains 8 mg of ondansetron (as ondansetron dihydrochloride
dihydrate).
The other ingredients are citric acid monohydrate, sodium citrate, sodium chloride, sodium hydroxide and/or
hydrochloric acid for pH adjustment and water for injections.

Description of the appearance of Ondansetron Accord and contents of the pack
Clear and colourless solution in a pre-filled glass syringe with amber colour.
Available in packs containing 1, 5 and 10 pre-filled syringes.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona,
s/n, Edifici Est 6ª planta
08039-Barcelona,
Spain.

Manufacturer
Accord Healthcare Limited,
Ground Floor, Sage House,
319 Pinner Road,
Harrow HA1 4HF,
United Kingdom
Accord Healthcare Polska Sp.z o.o.
ul. Lutomierska 50,
95-200 Pabianice
Poland
O
Pharmadox Healthcare Ltd.
KW20A
Kordin Industrial Park,
Paola, PLA3000,
Malta
O
Laboratori Fundació Dau
C/ C, 12-14 Pol. Ind.
Zona Franca, Barcelona, 08040,
Spain
O
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
Netherlands

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:

Other sources of information
More detailed information on this medicinal product is available on the website of the Italian Medicines
Agency.

The following information is intended exclusively for healthcare professionals:
Instructions for use
For intravenous injection or intramuscular injection or intravenous infusion after dilution.
Prescribers intending to use ondansetron in the prevention of delayed nausea and vomiting
associated with chemotherapy or radiotherapy in adults, adolescents or children should
consider current practice and appropriate guidelines.
Compatibility with other medicines
The following active ingredients can be administered via the Y-site connector of the
ondansetron administration set for ondansetron concentrations of 16 to 160 micrograms/ml (8
mg/500 ml and 8 mg/50 ml):

Chemotherapy and radiotherapy induced nausea and vomiting

Adults: the emetogenic potential of cancer treatment varies depending on the doses and
combinations of chemotherapy and radiotherapy used. The route of administration and the dose of
Ondansetron Accord should be in the range of 8-32 mg per day and selected as shown below.

Emetogenic chemotherapy and radiotherapy: Ondansetron 8 mg should be administered as a
slow intravenous injection (over no less than 30 seconds) or intramuscular injection, immediately
before treatment, followed by 8 mg orally twelve hours.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with
ondansetron should be continued for up to 5 days after a treatment cycle.

Highly emetogenic chemotherapy: for patients undergoing highly emetogenic chemotherapy, such
as high-dose cisplatin, ondansetron can be administered orally, rectally, intravenously or
intramuscularly. Ondansetron has been shown to be equally effective in the following dosage
regimens in 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 immediately before chemotherapy.
• A dose of 8 mg by slow intravenous injection (over no less than 30 seconds) or intramuscular injection immediately before chemotherapy, followed by two further intravenous injections (over no less than 30 seconds) or intramuscular doses of 8 mg at four-hour intervals, or by a 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 no less than 15 minutes immediately before chemotherapy. The initial dose of Ondansetron Accord

can be followed by two additional 8 mg intravenous doses (over no less than 30
seconds) or intramuscular doses at four-hour intervals.

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

The selection of the dosage regimen should be determined by the severity of the emetogenic challenge.
The efficacy of ondansetron in highly emetogenic chemotherapy can be enhanced
by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20 mg administered
before chemotherapy.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with
ondansetron should be continued for up to 5 days after a treatment cycle.

Paediatric population:
CINV in children ≥ 6 months and adolescents
The dose for CINV can be calculated based on body surface area (BSA) or weight – see below.

Dosage by BSA: Ondansetron Accord Injection 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 twelve hours later and can be continued for
up to 5 days (see SmPC for dosage tables). The total dose in 24 hours
(administered in divided doses) should not exceed the adult dose of 32 mg.

Dosage by body weight: weight-based dosing results in higher total daily doses compared to BSA-based dosing. Ondansetron Accord 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 further intravenous doses may be given at
four-hour intervals. Oral administration can start 12 hours later and can be
continued for up to 5 days (see SmPC for further details).
Ondansetron Accord should be diluted in 5% dextrose or 0.9% sodium chloride solution (9 mg/ml) or in
other compatible infusion fluid (see section 6.6 of the SmPC) and infused intravenously in
no less than 15 minutes.
There are no data from controlled clinical trials on the use of Ondansetron Accord in the
prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of
Ondansetron Accord for radiotherapy-induced nausea and vomiting in children.
Post-operative nausea and vomiting (PONV)

Adults: for the prevention of PONV, ondansetron can be administered as a single dose of 4 mg
administered by intramuscular or slow intravenous injection before surgery.
For the treatment of established PONV, a single dose of 4 mg is recommended administered by
intramuscular or slow intravenous injection.
Children (over 1 month of age and adolescents)

Oral formulation:
Studies on the use of orally administered ondansetron in the prevention or
treatment of post-operative nausea and vomiting have not been conducted; slow i.v. injection is recommended for this
purpose.

Injection:
For the prevention of PONV in paediatric patients undergoing surgery under general anaesthesia, a single dose of ondansetron can be administered by slow intravenous
injection (no less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg before
induction of anaesthesia, during or after. For the treatment of PONV after surgery in
paediatric patients undergoing surgery under general anaesthesia, a single dose of ondansetron can be
administered by slow intravenous injection (no less than
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 in the treatment of PONV in children under 2 years of age.

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

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

Patients with hepatic impairment: the clearance of Ondansetron Accord is significantly reduced
and the serum half-life significantly prolonged in subjects with moderate or severe hepatic
impairment. In such patients, a total daily dose of more than 8 mg should not be exceeded
and therefore parenteral or oral administration is recommended.

Patients with poor sparteine/debrisochine metabolism:the elimination half-life of ondansetron
is not altered in subjects classified as poor sparteine and debrisochine metabolizers. Consequently, in such patients, repeated administration will give exposure levels no different from those of the general population. No adjustment of the daily dose or frequency of administration is required.
Incompatibilities
The solution must not be autoclaved.
Ondansetron Accord should only be mixed with those infusion solutions recommended:
Sodium chloride infusion BP 9 mg/ml (0.9%)
Glucose intravenous infusion BP 5% w/v
Mannitol intravenous infusion BP 10% w/v
Ringer’s intravenous infusion
Potassium chloride 0.3% w/v and sodium chloride 9 mg/ml (0.9%) intravenous infusion BP
Potassium chloride 0.3% w/v and glucose 5% w/v intravenous infusion BP
The stability of Ondansetron Accord after dilution with the recommended infusion fluids has been
demonstrated at concentrations of 0.016 mg/ml and 0.64 mg/ml.
Only clear and colourless solutions should be used.
Diluted solutions should be protected from light.
Shelf life and storage
2 years.
This medicinal product does not require special storage conditions.

Injection
After first opening, the medicine must be used immediately.

Infusion
After dilution with the recommended diluents, chemical and physical stability in use 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 storage times and conditions before use are the responsibility of
the user and should normally not exceed 24 hours at a temperature between 2 and 8°C,
unless the dilution has been carried out in controlled and validated aseptic conditions.