Ondansetron Accord

Patient Information Leaflet

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

ondansetron
Please read all of this leaflet carefully before you start 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

The medicine is called Ondansetron Accord 4 mg/8 mg Injection/Infusion Solution in Pre-filled Syringe, but will be referred to as Ondansetron Accord in this leaflet.
Contents of this 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, which belongs to a group of
medicines called antiemetics. Ondansetron is a 5HT3 receptor antagonist. It works by
blocking 5HT3 receptors on neurons located in the central and peripheral nervous system.
Ondansetron Accord is used to

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

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

2. What you need to know before using Ondansetron Accord

Do not use Ondansetron Accord:

• If you are allergic to ondansetron or to other selective 5HT3 receptor antagonists (e.g. granisetron, dolasteron) or to 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).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Ondansetron Accord if:

• You have had an allergic reaction to other medicines used to treat nausea or vomiting, such as granisetron or palonosetron.
• You have intestinal obstruction or suffer from severe constipation. This medicine may impair lower intestinal motility.
• You have liver problems or are taking medicines that could be harmful to the liver (hepatotoxic chemotherapeutic agents). In such cases, your liver function will be closely monitored, especially in children and adolescents.
• You have ever had heart problems, including irregular heartbeat (arrhythmias). Ondansetron prolongs the QT interval (an ECG sign of delayed cardiac repolarization after a heartbeat, with risk of life-threatening arrhythmias) in a dose-dependent manner.
• You are scheduled for tonsil surgery. In this case, careful monitoring is required, as treatment with ondansetron may mask symptoms of internal bleeding.
• You have problems with blood electrolyte levels such as potassium, sodium, or magnesium.
• You are scheduled to undergo any diagnostic tests (including blood or urine tests, skin tests using allergens, etc.). Inform your doctor that you are taking this medicine, as it may alter test results.
• Inform your doctor or pharmacist immediately if you experience any of the following symptoms during or after treatment:
  • If you experience sudden pain or tightness in the chest (myocardial ischemia)

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

• Phenytoin (used to treat epilepsy and cardiac arrhythmias). The effect of ondansetron may be reduced.
• Carbamazepine (used to treat epilepsy and neuralgic pain). The effect of ondansetron may be reduced.
• Rifampicin (used to treat infections such as tuberculosis (TB)). The effect of ondansetron may be reduced.
• Antibiotics such as erythromycin.
• Ketoconazole (used to treat Cushing's disease).
• Antiarrhythmic medicines (used to treat irregular heartbeat), such as amiodarone.
• Beta-blockers used to treat certain heart or eye conditions, anxiety, or to prevent migraine, such as atenolol or timolol.
• Tramadol (used to treat pain). The pain-relieving effect of tramadol may be reduced.
• Apomorphine (used to treat Parkinson's disease). Severe drop in blood pressure and loss of consciousness have been reported when apomorphine is used together with ondansetron.
• Medicines acting 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 (serotonin-noradrenaline reuptake inhibitors) used to treat depression and/or anxiety, including venlafaxine, duloxetine.

Ondansetron Accord with food, drinks and alcohol
You may take Ondansetron Accord regardless of food or drink.
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 of the baby being born with cleft lip 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 a pregnancy, consult your doctor or pharmacist before using this medicine.
If you are a woman of childbearing age, you may be advised to use effective contraception.
Ondansetron passes into breast milk. Therefore, mothers receiving ondansetron must not breastfeed.
Consult your doctor before taking any medicine.
Driving and using machines
Ondansetron has no effect on the ability to drive or use machinery.
Ondansetron Accord contains sodium
This medicine contains 3.60 mg of sodium (a main component of table salt) per ml. This corresponds to 0.18% of the maximum recommended daily intake of sodium for an adult.

3. How to use Ondansetron Accord

This medicine must always be administered by infusion or injection (intravenously or into a muscle) by a qualified healthcare professional, usually a doctor or nurse, and never by yourself.
Dose
Your doctor will decide the correct dose of ondansetron treatment for you.
The dose depends on the medical treatment (chemotherapy or surgery), how well your liver is functioning, and whether it is given 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 slow injection into a vein or muscle, shortly before treatment, followed by another 8 mg administered twelve hours later.
On subsequent days

• The usual single intravenous dose for adults does not exceed 8 mg. Oral administration may begin twelve hours after chemotherapy or radiotherapy and may continue for up to 5 days. The usual dose is 8 mg twice daily. If it is expected that chemotherapy or radiotherapy may cause severe nausea and vomiting, a higher dose of this medicine will be given to you or your child. The dose will be determined by the doctor. A single dose exceeding 16 mg must 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 doctor will determine the dose based on the child's weight or body surface area.
On the day of chemotherapy
the first dose is administered by intravenous injection, immediately before the child's treatment. After chemotherapy, the medicine will usually be given to the child orally twelve hours later in the form of tablets or syrup. The usual dose is 4 mg twice daily and may continue for up to 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 slow intravenous injection, given just before surgery.

Children over 1 month of age and adolescents
The doctor will determine the dose. The maximum dose is 4 mg administered by slow intravenous injection, given just before surgery.
To treat nausea and vomiting after surgery
Adult:

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

Children over 1 month of age and adolescents
The doctor will determine the dose. The maximum dose is 4 mg administered by slow intravenous injection.
Dosage adjustments
Patients with moderate or severe liver problems
Total daily dose must not exceed 8 mg.
Elderly patients, patients with renal impairment, or poor metabolizers of sparteine/debrisoquine
There is no need to modify the daily dose, frequency of dosing, or route of administration.
Duration of treatment
Your doctor will decide the duration of treatment with ondansetron. Do not stop treatment prematurely.
Ondansetron Accord should start working immediately after injection. If you or your child continue to experience nausea or vomiting, inform your doctor or nurse.
If you or your child have taken more Ondansetron Accord than you should have
Your doctor or nurse will administer this medicine to you or your child, so it is unlikely that you or your child will have taken too much. If you think you or your child may have taken too much or missed a dose, inform your doctor or nurse.
Currently, little is known about overdose with ondansetron. In most patients, symptoms were similar to those already reported in patients receiving 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, symptoms completely resolved.
This medicine may alter heart rhythm, especially if an overdose has occurred. In such a case, your doctor will monitor your heartbeat more closely.
There is no specific antidote for ondansetron; therefore, if an overdose is suspected, only symptomatic treatment should be given.
Inform your doctor if any of these symptoms occur.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately inform your doctor or nurse if any of the following occur:
Uncommon: may affect up to 1 in 100 people

• Chest pain, irregular heartbeat (arrhythmia, which may be fatal in individual cases), and slow heartbeat (bradycardia)
  Rare: may affect up to 1 in 1,000 people
• Itchy rash, swelling of the eyelids, face, lips, mouth, and tongue.
  Frequency not known (frequency cannot be estimated from the 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 warmth or flushing
• 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 test results (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)

• 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, usually lasting less than 20 minutes.
• Widespread blistering rash affecting most of the body surface (toxic epidermal necrolysis).

Reporting of side effects
If you get any side effect, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system. 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
Do not use this medicine after the expiry date stated on the pre-filled syringe and on the
carton after Exp.. The expiry date refers to the last day of that month.
Storage
This medicine has no special storage temperature requirements.
Do not use this medicine if you notice that the container is damaged or if particles/crystals are visible.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ondansetron Accord contains
The active substance is ondansetron (as dihydrochloride dihydrate).
Each ml of injectable or infusion solution in a pre-filled syringe contains 2 mg of ondansetron
(as ondansetron dihydrochloride dihydrate).
Each 2 ml pre-filled syringe contains 4 mg of ondansetron (as ondansetron dihydrochloride
dihydrate).
Each 4 ml pre-filled syringe contains 8 mg of ondansetron (as ondansetron dihydrochloride
dihydrate).
The other components are monohydrate citric acid, 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, colourless solution in an amber glass pre-filled syringe.
Available in packs containing 1, 5 and 10 pre-filled syringes.
Not all pack sizes may be marketed.

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

This medicinal product is authorised in the European Economic Area countries under the
following names:

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, intramuscular injection, or intravenous infusion after dilution.
Prescribers who intend to use ondansetron for 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 medicinal products
The following active substances may be administered via the Y-site connection of the ondansetron administration set at ondansetron concentrations ranging from 16 to 160 micrograms/ml (8 mg/500 ml and 8 mg/50 ml):

Chemotherapy and radiotherapy cause nausea and vomiting
Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy used. The route and dose of Ondansetron Accord should range between 8–32 mg daily, selected as shown below.

Chemotherapy-induced and radiotherapy-induced emesis: Ondansetron 8 mg should be administered as a slow intravenous injection (over not less than 30 seconds) or intramuscular injection, immediately before treatment, followed by 8 mg orally twelve hours later.
To prevent delayed or prolonged emesis after the first 24 hours, oral or rectal ondansetron treatment should be continued for up to 5 days after a 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 has demonstrated equal efficacy in the following dosage regimens during the first 24 hours of chemotherapy:

• A single dose of 8 mg administered as a slow intravenous injection (over not less than 30 seconds) or intramuscular injection immediately before chemotherapy.
• A dose of 8 mg administered as a slow intravenous injection (over not less than 30 seconds) or intramuscular injection immediately before chemotherapy, followed by two additional intravenous injections (over not less than 30 seconds) or intramuscular doses of 8 mg given at 4-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 sodium chloride solution or another compatible infusion fluid (see section 6.6 of the SmPC) and infused over not less than 15 minutes immediately before chemotherapy. The initial dose of Ondansetron Accord may be followed by two additional 8 mg intravenous doses (administered over not less than 30 seconds) or intramuscular doses given 4 hours apart.
• A single dose exceeding 16 mg must not be administered due to the dose-dependent increased risk of QT interval prolongation (see sections 4.4, 4.8 and 5.1 of the SmPC).

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

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

Dosing by BSA: Ondansetron Accord injection should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m². The single intravenous dose must not exceed 8 mg. Oral administration may begin twelve hours later and may be continued for up to 5 days (see SmPC for dosing tables). The total daily dose (administered in divided doses) must not exceed the adult dose of 32 mg.

Dosing 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 must not exceed 8 mg. Two additional intravenous doses may be administered at 4-hour intervals. Oral administration may begin 12 hours later and may be continued for up to 5 days (see SmPC for further details).
Ondansetron Accord must be diluted in 5% dextrose or 9 mg/ml (0.9%) sodium chloride or another compatible infusion fluid (see section 6.6 of the SmPC) and infused intravenously over not less than 15 minutes.

There are no data from controlled clinical studies on the use of Ondansetron Accord in the prevention of delayed or prolonged CINV. There are no data from controlled clinical studies on the use of Ondansetron Accord for radiotherapy-induced nausea and vomiting in children.

Postoperative nausea and vomiting (PONV)
Adults: For the prevention of PONV, ondansetron may be administered as a single 4 mg dose given by intramuscular or slow intravenous injection before surgery.
For the treatment of established PONV, a single 4 mg dose administered by intramuscular or slow intravenous injection is recommended.

Children (over 1 month of age and adolescents)
Oral formulation:
No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of postoperative nausea and vomiting; slow intravenous 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 may be administered by slow intravenous injection (over not less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg before, during, or after induction of anaesthesia. For the treatment of PONV after surgery in paediatric patients undergoing general anaesthesia, a single dose of ondansetron may be administered by slow intravenous injection (over not 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 ondansetron in the prevention and treatment of PONV in elderly patients is limited; however, ondansetron is well tolerated in patients over 65 years of age receiving chemotherapy.

Patients with renal impairment: No adjustment of daily dose, 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 patients with moderate or severe hepatic impairment. In such patients, the total daily dose must not exceed 8 mg; therefore, parenteral or oral administration is recommended.

Patients who are poor metabolizers of sparteine/debrisoquine: The elimination half-life of ondansetron is not altered in subjects classified as poor metabolizers of sparteine and debrisoquine. Consequently, repeated administration in these patients will result in drug exposure levels no different from those in the general population. No adjustment of daily dose or frequency of administration is required.

Incompatibilities
The solution must not be sterilized in an autoclave.
Ondansetron Accord should only be mixed with the following recommended infusion solutions:
Sodium chloride for intravenous infusion BP 9 mg/ml (0.9%)
Glucose intravenous infusion BP 5% w/v
Mannitol intravenous infusion BP 10% w/v
Ringers 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.
Use only clear, colourless solutions.
Diluted solutions must be protected from light.

Expiry and storage
3 years.
This medicinal product does not require special temperature storage conditions.

Injection
After first opening, the medicinal product should be used immediately.

Infusion
After dilution with 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 standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature between 2 and 8°C, unless dilution has been carried out under validated aseptic and controlled conditions.