Oxaliplatin accord

Package leaflet: Information for the patient

Oxaliplatinum Accord, 5 mg/ml, concentrate for solution for infusion
Oxaliplatinum
Please read carefully all the information in this leaflet before the medicine is administered, as it contains important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet:

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

1. What Oxaliplatinum Accord is and what it is used for

The active substance in Oxaliplatinum Accord is oxaliplatin.
Oxaliplatinum Accord is an anticancer medicine used in the treatment of colorectal cancer
(treatment of stage III colon cancer after complete resection of the primary tumour, and metastatic colon and rectal cancer).
It is used in combination with other anticancer medicines called 5-fluorouracil (5-FU) and folinic acid (FA).
Before intravenous injection, the oxaliplatin concentrate for solution for infusion must be diluted.
The oxaliplatin concentrate for solution for infusion is a platinum-containing anticancer medicine.

2. Important information before using Oxaliplatinum Accord

When not to use Oxaliplatinum Accord:

• if the patient is allergic to oxaliplatin or any of the other ingredients of Oxaliplatinum Accord
• during breastfeeding,
• if the patient has a reduced number of blood cells;
• if the patient experiences tingling and (or) numbness in fingers of hands and (or) feet and has difficulty performing precise movements, such as buttoning buttons,
• if the patient has severe kidney function impairment.

Warnings and precautions
Before starting treatment with Oxaliplatinum Accord, consult a doctor or pharmacist:

• if the patient has ever had allergic reactions to platinum-containing medicines, such as carboplatin or cisplatin. Allergic reactions may occur during any oxaliplatin infusion;
• if the patient has moderate or mild kidney function impairment;
• if the patient has any liver function disorders or abnormal liver function test results during treatment;
• if the patient has or has had heart disorders, such as abnormal electrical activity called QT prolongation, irregular heartbeat, or if there is a family history of heart disorders;
• if the patient has received or plans to receive any vaccines. During treatment with oxaliplatin, "live" or "attenuated" vaccines, such as the yellow fever vaccine, should not be administered.

If at any time any of the following conditions apply to the patient, the doctor must be informed immediately. The doctor may decide to initiate appropriate treatment, reduce the dose of Oxaliplatinum Accord, or delay or discontinue treatment.
If the patient experiences discomfort in the throat, especially when swallowing, and has difficulty breathing, inform the doctor.
If the patient has nerve disorders in the hands or feet, such as numbness, tingling, or reduced sensation in the hands or feet, inform the doctor.
If the patient experiences headache, mental disturbances, seizures, or vision disorders ranging from blurred vision to loss of vision, inform the doctor.
If the patient has nausea or vomiting, inform the doctor.
If the patient has severe diarrhoea, inform the doctor.
If the patient has ulceration of the lips or oral cavity (mucositis and (or) stomatitis), inform the doctor.
If the patient has diarrhoea or a reduced number of white blood cells or platelets, inform the doctor. The doctor may reduce the dose of Oxaliplatinum Accord or delay administration.
If the patient has unexplained respiratory symptoms, such as cough or any breathing difficulties, inform the doctor. The doctor may decide to discontinue treatment with Oxaliplatinum Accord.
If the patient experiences severe fatigue, shortness of breath, or has kidney disease and passes little or no urine (symptoms of acute kidney failure), inform the doctor.
If the patient has fever (38°C or higher) or chills, which may indicate infection, inform the doctor immediately due to the risk of developing blood infection (septicaemia).
If the patient has a fever >38°C, inform the doctor. The doctor may check whether there is also a reduction in the number of white blood cells.
If the patient experiences unexpected bleeding or develops bruises (disseminated intravascular coagulation), inform the doctor, as these may be symptoms of blood clot formation in small blood vessels.
If the patient faints (loses consciousness) or has an irregular heartbeat during treatment with Oxaliplatinum Accord, inform the doctor immediately, as these may be symptoms of severe heart disorders.
If the patient experiences muscle pain and has swelling along with weakness, fever, or red-brown discoloration of urine, inform the doctor, as these may be symptoms of muscle damage (rhabdomyolysis), which may lead to kidney dysfunction or other complications.
If the patient has abdominal pain, nausea, vomiting of blood or coffee-ground-like material, or very dark (tarry) stools, which may indicate intestinal ulcer (symptoms of gastric or intestinal ulceration, possibly with bleeding or perforation), inform the doctor.
If the patient experiences abdominal pain, has bloody diarrhoea, and nausea and (or) vomiting, which may be caused by reduced blood flow to the intestinal wall (intestinal ischaemia), inform the doctor.

Children and adolescents
Do not use Oxaliplatinum Accord in children and adolescents under 18 years of age.

Oxaliplatinum Accord and other medicines
Inform the doctor or pharmacist about all medicines currently used or recently used, as well as any medicines the patient plans to take.

• 5-fluorouracil (anticancer medicine)
• erythromycin (antibiotic)
• salicylates (painkillers)
• granisetron (antiemetic medicine)
• paclitaxel (anticancer medicine)
• sodium valproate (antiepileptic medicine)

Pregnancy and breastfeeding
Pregnancy

• It is not recommended for a woman to become pregnant during treatment with oxaliplatin; effective contraception must be used. Women should use appropriate contraceptive methods during therapy and for 15 months after completion of treatment.
• Men are advised to avoid fathering children and to use appropriate contraceptive methods during treatment and for 12 months after its completion.
• If the patient is pregnant or plans to become pregnant, it is very important to discuss this with the doctor before starting any treatment.
• If the patient becomes pregnant during treatment, inform the doctor immediately.

Breastfeeding
Breastfeeding must not be performed during treatment with oxaliplatin.

Fertility

• Oxaliplatin may cause infertility, which may be irreversible. Before starting treatment, men should seek advice regarding sperm cryopreservation.
• If the patient plans pregnancy after completion of oxaliplatin treatment, genetic counselling is recommended.

Before using any medicine, consult a doctor or pharmacist.
Driving and operating machinery
During treatment with oxaliplatin, there is an increased risk of dizziness, nausea, vomiting, and other neurological symptoms affecting gait and balance, which may have a slight or moderate effect on the ability to drive motor vehicles and operate mechanical equipment.
If the patient experiences drowsiness and (or) dizziness after receiving oxaliplatin, driving motor vehicles, operating machinery, or performing any activities that could be dangerous due to reduced alertness must be avoided.

3. How to use Oxaliplatinum Accord

Oxaliplatinum Accord concentrate for solution for infusion is intended for use in adults only.
For single use only.
Dosage
The oxaliplatin dose is based on body surface area, calculated according to body weight and height. The standard dose used in adults, including elderly patients, is 85 mg/m² of body surface area.
The dose administered may be adjusted based on blood test results and whether the patient has previously experienced adverse reactions related to Oxaliplatinum Accord administration.
Method and route of administration
Oxaliplatinum Accord will be prescribed by a physician specializing in cancer treatment. The patient will be managed by a specialist who will prepare the required dose of oxaliplatin concentrate for infusion solution.
Oxaliplatin is administered as an intravenous infusion into one of the veins. The infusion time ranges from 2 to 6 hours.
The oxaliplatin concentrate for infusion solution is administered concomitantly with folinic acid and prior to intravenous 5-fluorouracil.
Frequency of administration
Typically, the patient receives an infusion once every 2 weeks.
Duration of treatment
The treating physician will determine the duration of treatment. Following tumor resection, oxaliplatin treatment is recommended for 6 months.
Overdose of Oxaliplatinum Accord
The drug will be administered by experienced medical staff, usually in specialized oncology units, so the likelihood of receiving too low or too high a dose is minimal. In the event of overdose, adverse reactions may be intensified. In case of overdose, the physician will decide on symptomatic treatment.
If you have any questions regarding treatment, please consult your treating physician, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If any side effect occurs, it is essential to inform your doctor before receiving the next dose of the medicine.
The possible side effects are described below.
Contact your doctor immediately if any of the following symptoms occur:

• signs of allergy or anaphylactic reaction with sudden symptoms such as rash, itching or hives on the skin, difficulty swallowing, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing, extreme tiredness (the patient may feel they are about to faint).
• unusual bruising, bleeding or signs of infection such as sore throat and high fever;
• persistent or severe diarrhoea, or vomiting;
• presence of blood in vomit or vomit resembling coffee grounds;
• inflammation of the mouth and (or) mucositis (pain in lips or mouth ulcers);
• respiratory symptoms such as dry or wet cough, difficulty breathing or crackling sounds, shortness of breath and wheezing;
• a group of symptoms such as: headache, changes in mental status, seizures and vision disturbances from blurred vision to loss of vision (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder);
• stroke symptoms (including sudden severe headache, confusion, vision problems in one or both eyes, numbness or weakness of the muscles of the face, arm or leg, usually on one side, facial drooping, difficulty walking, dizziness, loss of balance and problems with speaking);
• extreme exhaustion with decreased number of red blood cells and shortness of breath (haemolytic anaemia), occurring with or without decreased platelet count, abnormal bruising (thrombocytopenia) and kidney disease in which the patient passes little or no urine (symptoms of haemolytic-uraemic syndrome).

Other side effects occurring after administration of Oxaliplatinum Accord:
Very common (may affect more than 1 in 10 people):

• tingling or numbness in fingers and toes, around the mouth or throat, sometimes occurring with muscle cramps (peripheral neuropathy);
• discomfort or pain at or near the infusion site during infusion;
• fever, stiffness (tremor), mild or severe fatigue, weakness and (or) tiredness, body pain;
• weight changes, loss of appetite or appetite changes, taste disturbances, constipation;
• stomach pain;
• abnormal bleeding, including nosebleeds;
• mild hair loss (alopecia).

Common (may affect up to 1 in 10 people):

• infection due to decreased white blood cell count;
• severe blood infection associated with decreased white blood cell count (neutropenic sepsis), which may lead to death;
• decreased white blood cell count accompanied by fever > 38.3°C or persistent fever > 38°C for more than one hour (febrile neutropenia);
• indigestion and heartburn, hiccups, sudden flushing of the face, dizziness;
• excessive sweating and nail disorders, skin peeling;
• chest pain;
• lung disorders and cough;
• joint and bone pain;
• pain during urination, kidney changes and changes in frequency of urination, dehydration;
• presence of blood in urine and stool, swollen veins, blood clots in the lungs;
• high blood pressure;
• depression, insomnia;
• conjunctivitis, vision disturbances;
• decreased calcium levels in the blood;
• falls.

Uncommon (may affect up to 1 in 100 people):

• severe blood infection (sepsis), which may lead to death;
• bowel obstruction or intestinal swelling;
• feeling of anxiety or nervousness.

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

• deafness;
• lung scarring and thickening, with breathing difficulties, sometimes leading to death (interstitial lung disease);
• transient, short-term loss of vision;
• unexpected bleeding or bruising due to blood clots forming in small blood vessels (disseminated intravascular coagulation) – a condition which may lead to death.

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

• vascular disorders of the liver (symptoms include abdominal pain and swelling, weight gain, and swelling of the feet, ankles and other body parts).

Frequency not known (cannot be estimated from available data):

• allergic vasculitis (inflammation of blood vessels);
• autoimmune reaction causing a decrease in all blood cells (autoimmune pancytopenia), pancytopenia;
• seizures (uncontrolled shaking of the whole body);
• laryngospasm causing difficulty breathing;
• irregular heart rhythm (QT interval prolongation), which can be detected on an electrocardiogram (ECG) – a condition which may lead to death;
• muscle pain and swelling with weakness, fever or red-brown discoloration of urine (symptoms of muscle damage known as rhabdomyolysis) – a condition which may lead to death;
• abdominal pain, nausea, vomiting blood or vomit resembling coffee grounds, or very dark (tarry) stools (symptoms of stomach or intestinal ulcer, possibly with bleeding or perforation) – a condition which may lead to death;
• reduced blood flow to the intestine (intestinal ischaemia) – a condition which may lead to death;
• myocardial infarction (heart attack), angina pectoris (chest pain or discomfort);
• oesophagitis (inflammation of the oesophageal mucosa, i.e. the lining of the tube connecting the mouth to the stomach – resulting in pain and difficulty swallowing);
• risk of developing new tumours, e.g. leukaemia, when oxaliplatin is taken concomitantly with certain other medicines;
• abnormal, non-cancerous liver nodules (focal nodular hyperplasia).

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the responsible entity.

5. How to store Oxaliplatinum Accord

Keep this medicine out of sight and reach of children.
Store the vial in its outer packaging to protect it from light. Do not freeze.
Do not use this medicine after the expiry date stated on the vial or cardboard box following EXP.
The expiry date refers to the last day of the stated month.
The prepared infusion solution is chemically and physically stable for 48 hours at a temperature of 2°C to
8°C and for 24 hours at 25°C.
From a microbiological standpoint, the prepared infusion solution should be administered immediately. If the
solution is not administered immediately, the person administering the medicine is responsible for the storage
conditions and duration prior to administration. The storage period should not exceed 24 hours at a temperature
of 2°C to 8°C, except when the solution has been diluted under controlled and validated aseptic conditions.
Do not administer oxaliplatin concentrate for infusion solution if the solution is not clear or contains any particles.
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.
Oxaliplatinum Accord must not come into contact with the eyes. In case of accidental exposure to the eyes,
immediately inform a doctor or nurse.
After completion of the infusion, the doctor or nurse will remove any remaining medicine, taking appropriate
precautions.

6. Contents of the pack and other information

What Oxaliplatinum Accord contains
Oxaliplatinum Accord contains oxaliplatinum as the active substance.
The other component is water for injections.

What Oxaliplatinum Accord looks like and contents of the pack
1 ml of concentrate for solution for infusion contains 5 mg of oxaliplatinum.
Oxaliplatinum Accord is available as a clear, colourless solution free from visible particles.
Each glass vial is individually packed in a carton.
10 ml concentrate for solution for infusion contains 50 mg of oxaliplatinum.
20 ml concentrate for solution for infusion contains 100 mg of oxaliplatinum.
40 ml concentrate for solution for infusion contains 200 mg of oxaliplatinum.
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
Accord Healthcare Single Member S.A.
64th Km National Road Athens
32009 Lamia, Schimatari
Greece

This medicinal product is authorised for sale in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

The following information is intended solely for medical or healthcare personnel
Instructions for Use
Before beginning the preparation of OXALIPLATINUM ACCORD CONCENTRATE FOR INFUSION SOLUTION, read the entire procedure carefully

1. PHARMACEUTICAL FORM
Oxaliplatinum concentrate for infusion solution is a clear solution containing 5 mg/ml of oxaliplatinum.

2. PRESENTATION
Oxaliplatinum concentrate for infusion solution is supplied in single vials. One vial per cardboard box.

For 10 ml:
Oxaliplatinum concentrate for infusion solution in a 15 ml colourless Type I glass vial (siliconised), closed with a 20 mm chlorobutyl rubber stopper (type V9048 FM259/0 OMNIFLEX PLUS 2500/RF) and a 20 mm lavender flip-off aluminium cap.

For 20 ml:
Oxaliplatinum concentrate for infusion solution in a 20 ml colourless Type I glass vial (siliconised), closed with a 20 mm chlorobutyl rubber stopper (type V9048 FM259/0 OMNIFLEX PLUS 2500/RF) and a 20 mm lavender flip-off aluminium cap.

For 40 ml:
Oxaliplatinum concentrate for infusion solution in a 50 ml colourless Type I glass vial (siliconised), closed with a 20 mm chlorobutyl rubber stopper (type V9048 FM259/0 OMNIFLEX PLUS 2500/RF) and a 20 mm lavender flip-off aluminium cap.

Shelf life and storage:
2 years

After dilution in 5% glucose solution, chemical and physical stability of the solution has been demonstrated for 48 hours at +2°C to +8°C and for 24 hours at +25°C.

From a microbiological standpoint, the prepared infusion solution should be administered immediately. If not administered immediately, the person administering the drug is responsible for the storage time and conditions prior to administration. The storage period should not exceed 24 hours at 2°C to 8°C, except when the solution has been diluted under controlled and validated aseptic conditions.

Store the vial in its outer packaging to protect from light. Do not freeze.

Before administration, inspect the solution visually. Only clear, particle-free solutions should be used.

This medicine is for single use only. Any unused portion of the prepared solution must be discarded.

3. SAFETY HANDLING INSTRUCTIONS
As with other potentially toxic compounds, caution must be exercised when handling and preparing oxaliplatinum solutions.

Instructions for handling the medicine
Handling this cytotoxic medicinal product by medical personnel requires all necessary precautions to ensure protection of the user and the 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 particularly protection of personnel involved, in accordance with hospital procedures. This requires a dedicated workspace designated exclusively for these activities. Smoking, drinking, and eating are prohibited in such areas.

Personnel must be equipped with appropriate protective equipment, including long-sleeved gowns, protective masks, head covers, protective eyewear, sterile disposable gloves, protective covers for the work surface, and appropriate waste containers and collection bags.

Patient excreta and vomit must be handled with caution.

Pregnant women should be warned against contact with cytotoxic drugs.

Any damaged or broken containers must be handled with the same precautions as contaminated waste. Contaminated waste must be incinerated in appropriately labelled rigid containers. See section “Waste Disposal” below.

If oxaliplatinum concentrate for infusion solution comes into contact with the skin, the skin must be rinsed immediately and thoroughly with large amounts of water.

4. PREPARATION FOR INTRAVENOUS ADMINISTRATION
Special precautions for administration

• DO NOT use administration sets or infusion materials containing aluminium.
• DO NOT administer in undiluted form.
• The only acceptable diluent is 5% glucose solution for infusion. DO NOT reconstitute or dilute with sodium chloride solution or chloride-containing solutions.
• DO NOT mix with other medicinal products in the same bag or bottle, nor administer simultaneously through the same infusion set.
• DO NOT mix with alkaline medicinal products or alkaline solutions, particularly 5-fluorouracil, folinic acid preparations containing tromethamine as an excipient, or other tromethamine salts. Alkaline solutions or products may affect the stability of oxaliplatinum.

Instructions for use with folinic acid (FA) (as calcium folinate or disodium folinate)
Oxaliplatinum at a dose of 85 mg/m² BSA, administered as an intravenous infusion in 250 to 500 ml of 5% (50 mg/ml) glucose solution, may be given simultaneously with an intravenous infusion of folinic acid (FA) in 5% (50 mg/ml) glucose solution lasting over 2 to 6 hours, using a Y-connector placed immediately before the infusion site. The two drugs must not be mixed in the same infusion bag. Folinic acid (FA) must not contain tromethamine as an excipient and must be diluted exclusively with isotonic 5% (50 mg/ml) glucose solution. Alkaline solutions, sodium chloride solution, or chloride-containing solutions must never be used for dilution.

Instructions for use with 5-fluorouracil (5-FU)
Oxaliplatinum Accord must always be administered before fluoropyrimidine derivatives, such as 5-fluorouracil (5-FU).
After administration of Oxaliplatinum Accord, the intravenous infusion lines must be flushed before administering 5-fluorouracil (5-FU).

For additional information on medicinal products used concomitantly with Oxaliplatinum Accord, refer to the respective product characteristics.

• USE ONLY the recommended solvents (see below).
• Use only clear solutions free from visible particles.

4.1 Preparation of infusion solution
Withdraw the required volume from the vial(s) and dilute in 250 ml to 500 ml of 5% glucose solution to achieve a concentration of Oxaliplatinum Accord of not less than 0.2 mg/ml up to 0.7 mg/ml. The concentration range for which physicochemical stability of Oxaliplatinum Accord has been demonstrated is 0.2 mg/ml to 2 mg/ml.

The solution must be administered by intravenous infusion only.

After dilution in 5% (50 mg/ml) glucose solution, chemical and physical stability has been demonstrated at 2°C to 8°C.

From a microbiological standpoint, the prepared infusion solution should be administered immediately. If not administered immediately, the person administering the drug is responsible for the storage time and conditions prior to administration. The storage period should not exceed 24 hours at 2°C to 8°C, except when the solution has been diluted under controlled and validated aseptic conditions.

Before administration, inspect the solution visually. Only clear, particle-free solutions should be used.

This medicine is for single use only. Any unused portion of the prepared solution must be discarded (see section “Waste Disposal” below).

NEVER use sodium chloride solutions or chloride-containing solutions for preparation or dilution.

Compatibility of oxaliplatinum infusion solution with infusion sets has been tested with a representative PVC-based set.

4.2 Infusion of the solution
Pre-hydration of the patient is not required prior to administration of Oxaliplatinum Accord.

Oxaliplatinum diluted in 250 to 500 ml of 5% glucose solution to achieve a concentration of not less than 0.2 mg/ml must be administered via a peripheral or central venous line over 2 to 6 hours. When oxaliplatinum is administered with 5-fluorouracil, the oxaliplatinum infusion must be completed before administration of 5-fluorouracil.

4.3 Waste Disposal
Any unused medicinal product and all materials used in its preparation, dilution, and administration must be disposed of in accordance with standard hospital procedures for cytotoxic agents, taking into account local regulations for disposal of hazardous waste.