Oxaliplatin eugia

Package leaflet: Information for the user

Oxaliplatin Eugia, 5 mg/mL, concentrate for solution for infusion
Oxaliplatinum
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.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Oxaliplatin Eugia is and what it is used for
2. What you need to know before you use Oxaliplatin Eugia
3. How to use Oxaliplatin Eugia
4. Possible side effects
5. How to store Oxaliplatin Eugia
6. Contents of the pack and other information

1. What Oxaliplatin Eugia is and what it is used for

The active substance in Oxaliplatin Eugia is oxaliplatin, which belongs to a group of anticancer medicines containing platinum.
Oxaliplatin Eugia is used to treat advanced colorectal cancer [particularly after complete resection of the primary tumour, metastatic colon and rectal cancer (cancer cells spreading to other parts of the body)].
Oxaliplatin Eugia is used in combination with other anticancer medicines such as 5-fluorouracil and folinic acid.

2. Important information before using Oxaliplatin Eugia

When not to use Oxaliplatin Eugia:

• if the patient is allergic to oxaliplatin or to any of the other ingredients of this medicine (listed in section 6).
• during breastfeeding.
• if the patient has a low number of blood cells.
• if the patient experiences tingling and numbness in the fingers and/or toes and problems with performing fine motor tasks such as buttoning buttons.
• if the patient has severe kidney function impairment.

Warnings and precautions
Before starting treatment with Oxaliplatin Eugia, discuss the following with your doctor or pharmacist:

• If the patient has ever had an allergic reaction to platinum-containing medicines such as carboplatin or cisplatin. Allergic reactions may occur during any infusion of oxaliplatin.
• If the patient has moderate or mild kidney function impairment.
• If the patient has low blood cell counts following previous oxaliplatin treatment. Before starting treatment, the doctor will perform tests to check whether haematological parameters are adequate.
• If the patient experiences symptoms of nerve damage such as weakness, numbness, taste disturbances, or unusual sensory sensations following previous oxaliplatin treatment. These symptoms may be triggered by cold exposure. Inform the doctor if the patient notices any of these symptoms, especially if they are severe and/or persist for more than 7 days. The doctor will perform neurological examinations before and during treatment, particularly if the patient is taking other medicines that may cause nerve damage. Nerve damage symptoms may persist after completion of treatment.
• If the patient is also receiving 5-fluorouracil, due to an increased risk of diarrhoea, vomiting, oral mucositis, and abnormal blood test results.
• If the patient has liver function disorders.
• If the patient has or has had heart problems, such as abnormal electrocardiogram (ECG) findings (e.g. QT interval prolongation), irregular heartbeat, or a family history of cardiac disorders.
• If the patient has recently received or plans to receive any vaccinations. During oxaliplatin treatment, live or attenuated vaccines (e.g. yellow fever vaccine) should not be administered.
• If the patient is pregnant or planning pregnancy (see "Pregnancy, breastfeeding and effects on fertility").
• Patients should read the section on fertility, including male patients.

Interaction of Oxaliplatin Eugia with other medicines
Inform your doctor or pharmacist if the patient is taking, has recently taken, or might take any other medicines.
Pregnancy, breastfeeding and effects on fertility
Pregnancy

• It is not recommended that patients become pregnant during treatment with oxaliplatin; effective contraception must be used. Female patients should use appropriate contraceptive measures during therapy and for 4 months after completion of treatment.
• If the patient is pregnant or planning pregnancy, it is very important to discuss this with the doctor before starting treatment.
• If the patient becomes pregnant during treatment, she must inform the doctor immediately.

Breastfeeding

• Breastfeeding must not be performed during oxaliplatin treatment.

Fertility

• Oxaliplatin may cause infertility, which may be irreversible. Before starting treatment, men should seek advice regarding the possibility of sperm storage.
• Men are advised to avoid fathering a child and to use effective contraception during treatment and for 6 months after its completion.

Always consult a doctor or pharmacist before taking any medicine.
Driving and operating machinery
Treatment with oxaliplatin may increase the risk of dizziness, nausea and vomiting, and other neurological symptoms that may affect gait and balance.
If such symptoms occur, patients should not drive or operate machinery. If the patient experiences visual disturbances during treatment with Oxaliplatin Eugia, he or she should not drive, operate machinery, or perform hazardous activities.

3. How to use Oxaliplatin Eugia

Oxaliplatin Eugia is intended for use in adults only.
Dosage
The dose of Oxaliplatin Eugia is determined based on body surface area. It is calculated according to the patient's height and body weight.
The usual dose in adult patients is 85 mg/m² of body surface area. The dose a patient receives may also depend on blood test results and whether the patient has previously experienced adverse reactions related to Oxaliplatin Eugia.
Method and route of administration

• Oxaliplatin Eugia is prescribed by a physician specialized in cancer treatment.
• The patient will be treated by medical personnel who will prepare the required dose of Oxaliplatin Eugia.
• Oxaliplatin Eugia is administered as a slow intravenous infusion into one of the patient's veins over a period of 2 to 6 hours.
• Oxaliplatin Eugia is administered at the same time as folinic acid, and before the infusion of 5-fluorouracil.

Frequency of administration
The patient usually receives the drug as an intravenous infusion once every 2 weeks.
Duration of treatment
The physician will decide on the duration of treatment.
Treatment lasts up to a maximum of 6 months when oxaliplatin is used following complete removal of the tumor.
Use of a higher than recommended dose of Oxaliplatin Eugia
This medicine is administered by medical personnel; therefore, it is unlikely that the patient will receive too low or too high a dose.
In case of overdose, adverse reactions may become more severe. The physician may provide appropriate treatment for adverse reactions.
If there are any further doubts regarding the use of this medicine, consult a physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any adverse reactions occur, it is important to inform the doctor before
the next treatment cycle.
Seek immediate medical advice if any of the following occur:

• Signs of an allergic reaction with sudden onset symptoms such as rash, itching or hives, difficulty swallowing, swelling of the face, lips, tongue or other body parts, shortness of breath, wheezing or breathing difficulties, extreme fatigue (the patient may feel faint). In most cases, these symptoms occurred during or
  immediately after infusion, although delayed allergic reactions have also been observed several
  hours or even days after infusion. Very common (may affect more than 1 in 10 people).

• Unusual bruising or bleeding. Very common (may affect more than 1 in 10 people).

• Signs of infection such as sore throat and high fever. Common (may affect up to 1 in 10 people).

• Persistent or severe diarrhoea or vomiting. Very common (may affect more than 1 in 10 people).

• Blood in vomit or dark brown particles resembling coffee grounds. Very rare (may affect up to 1 in 10,000 people).

• Pain or sores in the mouth or lips. Very common (may affect more than 1 in 10 people).

• Unexplained respiratory symptoms such as dry or wet cough, difficulty breathing or crackling sounds in the lungs, shortness of breath and wheezing. Very common (may affect more than 1 in 10 people).

• A group of symptoms such as headache, mental disturbances, seizures and visual disturbances ranging from blurred vision to loss of vision (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder). Rare (may affect up to 1 in 1,000 people).

• Severe fatigue with a reduction in red blood cells and shortness of breath (haemolytic anaemia), occurring with or without a reduction in platelets, unusual bruising (thrombocytopenia) and kidney disease where the patient passes little or no urine (symptoms of haemolytic-uraemic syndrome). Frequency unknown (frequency cannot be estimated from available data).

Other known adverse reactions of Oxaliplatin Eugia include:
Very common (may affect more than 1 in 10 people)

• Oxaliplatin Eugia affects the nerves (peripheral neuropathy). The patient may experience tingling and/or numbness in the fingers and toes, around the mouth or in the throat, sometimes accompanied by muscle cramps. This adverse reaction is often triggered when the patient is exposed to cold, for example when opening a refrigerator or holding a cold drink. The patient may also experience difficulty performing precise movements, such as buttoning clothes. Although in most cases these symptoms resolve completely, peripheral neuropathy symptoms may persist after treatment has ended.
• Some patients may experience an electric shock-like sensation running along the arms or chest when bending the neck.
• Oxaliplatin Eugia may occasionally cause unpleasant sensations in the throat, especially during swallowing, and a feeling of breathlessness. If these sensations occur, they usually appear during or within a few hours after infusion and may be triggered by exposure to cold temperatures. These sensations are unpleasant but short-lived and resolve without requiring any treatment. The doctor may decide to modify the treatment if necessary.
• Oxaliplatin Eugia may cause diarrhoea, mild nausea and vomiting; however, the doctor will usually administer an antiemetic medicine before treatment, which may also be taken after the treatment cycle.
• Oxaliplatin Eugia causes transient decreases in blood cell counts. A reduction in red blood cells may lead to anaemia, a reduction in platelets may cause unusual bleeding or bruising, and a reduction in white blood cells may increase susceptibility to infections. Before starting treatment and before each subsequent cycle, the doctor will order blood tests to check whether the patient has an adequate number of blood cells.
• Discomfort at or around the injection site during infusion.
• Chills (shivering), mild or moderate fatigue, body aches.
• Changes in body weight, reduced or loss of appetite, taste disturbances, constipation.
• Headache, back pain.
• Swelling of nerves leading to muscles, neck stiffness, unusual sensation of the tongue which may affect speech.
• Abdominal pain.
• Mild hair loss (alopecia).
• Changes in blood test results, including those indicating abnormal liver function.

Common (may affect up to 1 in 10 people)

• Indigestion and heartburn, hiccups, facial flushing, dizziness.
• Excessive sweating and nail disorders, skin peeling.
• Chest pain.
• Catarrh.
• Bone and joint pain.
• Pain during urination and kidney function changes, changes in frequency of urination, dehydration.
• Blood in urine or stool, blood vessel swelling, blood clots in the lungs.
• High blood pressure.
• Depression, insomnia.
• Conjunctivitis, visual disturbances.
• Decreased blood calcium levels.
• Falls.

Uncommon (may affect up to 1 in 100 people)

• Bowel obstruction or intestinal swelling.
• Nervousness.

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

• Hearing loss.
• Lung scarring and thickening, with breathing difficulties, sometimes leading to death (interstitial lung disease).
• Transient, short-term loss of vision.

Very rare (may affect up to 1 in 10,000 people)

• Kidney disease where the patient passes little or no urine (symptoms of acute renal failure).
• Vascular liver disease.

Frequency unknown (frequency cannot be estimated from available data)

• Allergic vasculitis (inflammation of blood vessels).
• Seizures (uncontrolled shaking of the body).
• Laryngospasm causing breathing difficulties.
• Irregular heart rhythm (QT interval prolongation), which can be detected on an electrocardiogram (ECG) – a condition that may lead to death.
• Myocardial infarction (heart attack), angina pectoris (pain or discomfort in the chest).
• Oesophagitis (inflammation of the oesophageal mucosa, i.e. the tube connecting the mouth to the stomach – resulting in pain and difficulty swallowing).
• Reduced blood flow to the intestine (intestinal ischaemia) – a condition that may lead to death.
• Risk of developing new tumours. Leukaemia, a type of blood cancer, has been reported in patients receiving Oxaliplatin Eugia in combination with other medicines. The possibility of an increased risk of such tumours when taking Oxaliplatin Eugia together with certain other medicines should be discussed with the doctor.
• Non-cancerous abnormal liver nodules (focal nodular hyperplasia).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed
in this leaflet, tell 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 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps provide more information on the
safety of this medicine.
Adverse reactions can also be reported to the marketing authorisation holder.

5. How to store Oxaliplatin Eugia

Keep this medicine out of the sight and reach of children.
Oxaliplatin Eugia must not come into contact with eyes or skin. In case of accidental spillage,
a doctor or nurse must be informed immediately.
After completion of the infusion, any remaining Oxaliplatin Eugia will be carefully removed by a doctor
or nurse.
Do not use this medicine after the expiry date stated on the carton and vials after EXP.
The expiry date refers to the last day of the stated month.
No special storage instructions apply.
It has been demonstrated that the solution diluted with 5% glucose solution maintains
chemical and physical stability for 48 hours at a temperature of 2°C to 8°C and for 24 hours
at 25°C.
From a microbiological point of view, the prepared infusion solution should be used immediately.
If not used immediately, the user is responsible for the storage conditions and duration prior to use.
The storage period should not exceed 24 hours at a temperature of 2°C to 8°C, unless dilution
was carried out under controlled and validated aseptic conditions.
Do not use Oxaliplatin Eugia if the solution appears not clear or contains any particulate matter.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures will help protect
the environment.

6. Contents of the pack and other information

What Oxaliplatin Eugia contains
The active substance is oxaliplatin. Each vial contains 50 mg, 100 mg or 200 mg of oxaliplatin.
The other ingredient is water for injections.

What Oxaliplatin Eugia looks like and contents of the pack
Concentrate for solution for infusion.
A clear, colourless solution, essentially free from visible particles. Each vial contains 50 mg, 100 mg or 200 mg of oxaliplatin in water for injections. Vials are packed in cardboard boxes. The pack contains one vial.
1 vial with 10 mL concentrate for solution for infusion contains 50 mg oxaliplatin.
1 vial with 20 mL concentrate for solution for infusion contains 100 mg oxaliplatin.
1 vial with 40 mL concentrate for solution for infusion contains 200 mg oxaliplatin.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Eugia Pharma (Malta) Ltd.
Vault 14, level 2
Valletta Waterfront
Floriana, FRN 1914
Malta
e-mail: [email protected]

Manufacturer/Importer:
APL Swift Services (Malta) Ltd.
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
Generis Farmacêutica, S.A.
Rua João de Deus 19, Venda Nova
2700-487 Amadora
Portugal
Arrow Génériques
26 Avenue Tony Garnier
69007 Lyon
France

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Belgium: Oxaliplatin Eugia 5 mg/ml concentraat voor oplossing voor infusie / solution à diluer pour perfusion / Konzentrat zur Herstellung einer Infusionslösung
France: OXALIPLATINE ARROW LAB 5mg/ml, solution à diluer pour perfusion
Germany: Oxaliplatin PUREN 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Italy: Oxaliplatino Aurobindo Italia
Poland: Oxaliplatin Eugia
Portugal: Oxaliplatina Generis
Spain: Oxaliplatino Aurovit 5 mg/ml concentrado para solución para perfusión EFG
Sweden: Oxaliplatin Eugia

Information intended exclusively for healthcare professionals:

INSTRUCTIONS FOR PREPARATION AND USE OF OXALIPLATIN EUGIA, 5 MG/ML,
CONCENTRATE FOR INJECTION SOLUTION

Before preparing the infusion solution of Oxaliplatin Eugia, read the entire content of
this procedure.

1. MEDICINAL PRODUCT FORM

Oxaliplatin Eugia 5 mg/mL concentrate for infusion solution is a clear,
colorless solution containing 5 mg/mL oxaliplatin in water for injections.

2. PRESENTATION

Oxaliplatin Eugia is supplied in single-dose vials. Each carton contains one
vial of Oxaliplatin Eugia (50 mg, 100 mg or 200 mg).
The 10 mL vial of Oxaliplatin Eugia is made of colorless type I glass and contains 50 mg
of oxaliplatin concentrate for infusion solution, with a bromobutyl rubber stopper.
The 20 mL vial of Oxaliplatin Eugia is made of colorless type I glass and contains 100 mg
of oxaliplatin concentrate for infusion solution, with a bromobutyl rubber stopper.
The 40 mL vial of Oxaliplatin Eugia is made of colorless type I glass and contains 200 mg
of oxaliplatin concentrate for infusion solution, with a bromobutyl rubber stopper.
Oxaliplatin Eugia packaging:
No special storage conditions required.
Infusion solution:
After dilution of the concentrate for infusion solution with 5% (50 mg/mL) glucose solution,
the solution has been shown to maintain chemical and physical stability for 48 hours at
temperatures from 2°C to 8°C and for 24 hours at +25°C. From a microbiological standpoint,
the prepared infusion solution should be used immediately. If not used immediately,
the user is responsible for storage time and conditions prior to use. The storage period
should not exceed 24 hours at 2°C to 8°C, unless dilution was performed under controlled
and validated aseptic conditions (up to 48 hours).
The solution should be inspected visually before administration. Only clear solutions without
visible particles should be used.
This medicinal product is intended for single use only. Any unused solution must be discarded.

3. SAFETY HANDLING INSTRUCTIONS

As with other potentially toxic substances, caution should be exercised when handling
and preparing oxaliplatin solutions.
User instructions
Handling this cytotoxic medicinal product by healthcare personnel requires all necessary
precautions to ensure protection of the user and the surrounding environment.
Preparation of injection solutions of cytotoxic products must be performed by specially
trained personnel with knowledge of the medicinal product, under conditions ensuring
product integrity, environmental protection, and in particular, protection of personnel
handling the product, in accordance with hospital procedures. This requires dedicated
work areas designated exclusively for these activities.
Smoking, drinking, and eating are prohibited in these areas.
Personnel must wear appropriate protective equipment, including a long-sleeved gown,
protective mask, head covering, protective goggles, sterile disposable gloves, protective
covers for the work area, and appropriate containers and collection bags for waste.
Patient excreta and vomit must be handled with caution.
Pregnant women should be warned against contact with cytotoxic drugs.
Any damaged container should be handled with the same precautions as contaminated waste.
Contaminated waste should be incinerated in appropriately labeled rigid containers. See section "Disposal" below.
If the oxaliplatin concentrate for infusion solution or the infusion solution comes into contact
with the skin, the skin should be immediately and thoroughly rinsed with large amounts of water.
In case of contact of the oxaliplatin concentrate for infusion solution or the infusion solution
with mucous membranes, the affected area should be immediately and thoroughly rinsed with water.

4. PREPARATION FOR INTRAVENOUS ADMINISTRATION

Special precautions for administration

• DO NOT use injection materials containing aluminum.
• DO NOT administer undiluted solutions.
• For dilution, use only 5% (50 mg/mL) glucose solution for infusion. DO NOT dilute the infusion solution with sodium chloride solution or chloride-containing solutions.
• DO NOT mix with other medicinal products in the same bag or administer simultaneously through the same infusion set.
• DO NOT mix with alkaline medicinal products or basic solutions, particularly with 5-fluorouracil, folinic acid preparations containing tromethamine as an excipient, or other active substances that are tromethamine salts. Alkaline medicinal products or basic solutions negatively affect the stability of oxaliplatin.

Instructions for use with folinic acid (as calcium folinate or disodium folinate)
Oxaliplatin at a dose of 85 mg/m² as an intravenous infusion, diluted in 250 to 500 mL of 5%
(50 mg/mL) glucose solution, may be administered concurrently with an intravenous infusion of folinic acid diluted in 5% (50 mg/mL) glucose solution. The infusions are administered via a Y-connector placed immediately before the injection site. These two medicinal products should not be mixed in the same infusion bag. Folinic acid must not contain tromethamine as an excipient and should be diluted exclusively in isotonic 5% (50 mL) glucose solution. Basic solutions, sodium chloride solution, or chloride-containing solutions must never be used for dilution.
Instructions for use with 5-fluorouracil
Oxaliplatin should always be administered before fluoropyrimidine derivatives, e.g.,
5-fluorouracil. After administration of oxaliplatin, the infusion set should be flushed before administering 5-fluorouracil.
Additional information on medicinal products used in combination with oxaliplatin can be found in the respective product characteristics.

• USE ONLY the recommended solvents (see below).
• Use only clear solutions without visible solid particles.

4.1 Preparation of the infusion solution

Withdraw the required amount of concentrate from the vial(s), then dilute in 250 mL
to 500 mL of 5% (50 mg/mL) glucose solution to achieve an oxaliplatin concentration of
not less than 0.2 mg/mL up to 0.7 mg/mL. The concentration range for which physico-chemical
stability of oxaliplatin has been demonstrated is from 0.2 mg/mL to 2 mg/mL.
Administer as intravenous infusion.
The solution diluted with 5% (50 mg/mL) glucose solution has been shown to maintain
chemical and physical stability for 48 hours at temperatures from 2°C to 8°C and for 24 hours
at +25°C.
From a microbiological standpoint, this prepared infusion solution should be administered
immediately.
If not used immediately, the user is responsible for storage time and conditions prior to use. The storage period should not exceed 24 hours at 2°C to 8°C, unless dilution was performed under controlled and validated aseptic conditions (up to 48 hours).
The solution should be inspected visually before administration. Only clear solutions without
visible solid particles should be used.
This medicinal product is intended for single use only. Any unused portion of the prepared solution must be discarded (see section "Disposal of residues" below).
NEVER use sodium chloride solutions or chloride-containing solutions for dilution.
Compatibility of the oxaliplatin infusion solution has been tested with representative PVC infusion sets.

4.2 Infusion of the solution

Prehydration of the patient is not required prior to oxaliplatin administration.
Oxaliplatin diluted in 250 to 500 mL of 5% (50 mg/mL) glucose solution to achieve a concentration of not less than 0.2 mg/mL must be administered via a peripheral or central vein over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion must be completed before administration of 5-fluorouracil.

4.3 Disposal of residues

Any unused medicinal product, as well as all materials used for dilution and administration, must be destroyed in accordance with standard hospital procedures for handling cytotoxic agents, taking into account local requirements for disposal of hazardous waste.