Cisplatin accord

Package leaflet: Information for the patient

Cisplatinum Accord, 1 mg/ml, concentrate for solution for infusion
Cisplatinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

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

Leaflet contents:

1. What Cisplatinum Accord is and what it is used for
2. Important information before using Cisplatinum Accord
3. How to use Cisplatinum Accord
4. Possible side effects
5. How to store Cisplatinum Accord
6. Contents of the pack and other information

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

Cisplatinum Accord contains the active substance cisplatin, which belongs to a group of medicines called
cytostatic agents, used in the treatment of cancer. Cisplatin may be used alone, but is more commonly
used in combination with other cytostatic medicines.
Cisplatin destroys cells in the body that can cause certain types of cancer (testicular cancer,
ovarian tumour, bladder tumour, squamous cell carcinoma of the head and neck, lung cancer and
cervical cancer in combination with radiotherapy).
Your doctor can provide further information.
Talk to your doctor if you do not feel better or if you feel worse.

2. Important information before using Cisplatinum Accord

When not to use Cisplatinum Accord

• if the patient is allergic to cisplatin, other similar anticancer medicines, other platinum-containing compounds, or any of the other ingredients of this medicine (listed in section 6)
• if the patient has a very low number of blood cells (so-called "myelosuppression") (the doctor will check this with a blood test)
• if the patient is breastfeeding
• if the patient has severe kidney disease
• if the patient has hearing disorders
• if the patient is dehydrated
• if the patient needs to receive yellow fever vaccine

If any of the above situations apply to the patient, contact the doctor before using this medicine.

Warnings and precautions

Before starting treatment with Cisplatinum Accord, discuss the following with the doctor, pharmacist, or nurse:

• if the patient has any symptoms of nerve damage (peripheral neuropathy), such as tingling, numbness, or reduced sense of touch. The patient will be regularly monitored for these symptoms, and treatment may be interrupted if necessary.
• if the patient has previously undergone radiotherapy to the head.

The doctor will perform tests to determine blood levels of calcium, sodium, potassium, and magnesium, and will also monitor blood counts, liver and kidney function, and the nervous system.
Cisplatin may affect the bone marrow, causing changes in blood cell production. Inform the doctor if unusual bleeding or bruising occurs. Do not take aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or other medicines without consulting the doctor. The doctor will frequently order blood tests and check for signs of infection.
Cisplatin may cause hearing problems (ototoxicity) and kidney function disorders (nephrotoxicity). Kidney function and hearing will be monitored before and during treatment. Inform the doctor if any changes in hearing occur.
Inform the doctor if the patient plans to be vaccinated during cisplatin treatment.
Avoid certain live vaccines, as they may cause severe infections. The response to other types of vaccines (inactivated) may also be weakened.

Cisplatinum Accord and other medicines

Tell the doctor, pharmacist, or nurse about all medicines the patient is currently taking, has recently taken, or plans to take, for example:

• certain antibiotics such as cephalosporins, aminoglycosides, and amphotericin B, and certain substances used in imaging studies may increase the adverse effects of cisplatin, particularly kidney function disorders
• certain diuretics called loop diuretics, antibiotics called aminoglycosides, and the anticancer medicine ifosfamide may increase the risk of hearing loss associated with cisplatin
• bleomycin (an anticancer medicine), methotrexate (used in cancer treatment or joint inflammation), and paclitaxel (an anticancer medicine) may cause more adverse effects when used together with cisplatin
• cisplatin may reduce the effectiveness of anticonvulsant medicines (used to treat epilepsy); blood phenytoin levels may need to be monitored
• the effectiveness of oral anticoagulants (e.g. warfarin) may change. The doctor will monitor blood test results.
• buclizine, cyclizine, and meclozine (antihistamines), loxapine, phenothiazines and thioxanthenes (medicines used to treat psychiatric disorders), and trimethobenzamide (medicines used to prevent nausea and vomiting) may mask symptoms of balance disorders (such as dizziness or tinnitus)
• cisplatin may increase the adverse effects of ifosfamide (an anticancer medicine)
• pyridoxine (vitamin B_), and altretamine (an anticancer medicine), when used in combination with cisplatin in the treatment of advanced ovarian cancer, may shorten recovery time. The doctor will discuss this with the patient.
• bleomycin and etoposide (anticancer medicines) used together with cisplatin and lithium (used in the treatment of psychiatric disorders) may reduce lithium blood levels. Monitoring of lithium levels is recommended.
• yellow fever vaccines must not be administered simultaneously with cisplatin treatment due to the risk of death from vaccination. Use of an inactivated vaccine is recommended.
• medicines for gout, such as allopurinol, colchicine, probenecid, or sulfinpyrazone, reduce blood uric acid levels. The doctor may adjust the dose of Cisplatinum Accord.

Pregnancy, breastfeeding, and effects on fertility

Pregnancy
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.
Due to the risk of congenital malformations, patients (both female and male) should use effective contraception during treatment with cisplatin and for at least six months after treatment ends.
Cisplatin must not be used during pregnancy unless specifically prescribed by a doctor.
Consult a doctor or pharmacist before taking any medicine.

Breastfeeding
Do not use this medicine if the patient is breastfeeding.

Fertility

Male patients treated with cisplatin are advised not to father a child during treatment and for 6 months after its completion. Cisplatin treatment may potentially cause permanent infertility in men. Men who wish to have children in the future are advised to seek advice on sperm cryopreservation (freezing and storage) before starting treatment.

Driving and operating machinery
Do not drive or operate machinery if any adverse effects occur that may impair such ability.

Cisplatinum Accord contains sodium
This medicine contains 3.5 mg of sodium (a main component of table salt) per ml. This corresponds to 0.18% of the maximum recommended daily dietary sodium intake for adults.
This medicine may be prepared using solutions containing sodium. This should be taken into account if the patient is on a low-salt (low-sodium) diet.

3. How to use Cisplatinum Accord

Dosage and method of administration
Cisplatinum Accord must be administered only by a specialist in cancer treatment.
The concentrate should be diluted with sodium chloride solution.
Cisplatin is usually given as an intravenous infusion lasting from 6 to 8 hours.
To manage possible anaphylactic reactions, appropriate supportive equipment should be available.
Contact between cisplatin and materials containing aluminium must be avoided.
The recommended dose of Cisplatinum Accord depends on the patient's condition, expected treatment outcomes, and whether cisplatin is administered alone (monotherapy) or in combination with other drugs (combination chemotherapy).

Recommended dose
Cisplatin (monotherapy):
The following dosing regimens are recommended:

• Single dose of 50 to 120 mg/m^2 of body surface area every 3 to 4 weeks.
• 15 to 20 mg/m^2 per day for 5 consecutive days, repeated every 3 to 4 weeks.

Cisplatin in combination with other chemotherapeutic agents (combination chemotherapy):

• 20 mg/m^2 or higher dose, once every 3 to 4 weeks.

In the treatment of cervical cancer, cisplatin is used in combination with radiotherapy or other anticancer drugs.
The typical dose is 40 mg/m^2 once weekly for 6 weeks.
To prevent or reduce kidney-related adverse effects, it is recommended to drink large amounts of fluids during the 24 hours following administration of Cisplatinum Accord.

Overdose of Cisplatinum Accord
The physician will ensure that the appropriate dose is administered according to the patient's condition. In case of overdose, adverse reactions may be intensified. The physician may provide symptomatic treatment for these adverse effects. If the patient believes they have received too high a dose of Cisplatinum Accord, they should contact their doctor immediately.
If in doubt about the use of this medicine, consult the doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone gets them.
If the patient experiences any of the following symptoms, contact a doctor immediately:

• severe allergic reaction – sudden itchy rash (urticaria), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), sudden redness of the skin, and a feeling of fainting
• severe chest pain spreading to the jaw or arm, sweating, shortness of breath, and nausea (heart attack)
• fainting or seizures
• hearing problems – ringing in the ears or hearing loss (ototoxicity)
• kidney and urine problems
• excessive tiredness and general malaise, which may indicate reduced blood cell counts (myelosuppression). This will be confirmed by a blood test.

These are serious adverse reactions. The patient may require urgent medical attention.

Very common (may affect more than 1 in 10 patients)

• decreased bone marrow function (may affect blood cell production)
• reduced white blood cell count, increasing the risk of infections (leukopenia)
• reduced platelet count, increasing the risk of bruising and bleeding (thrombocytopenia)
• reduced red blood cell count, possibly causing weakness and pale skin (anaemia)
• low blood sodium levels
• high fever

Common (may affect up to 1 in 10 patients)

• severe pain or swelling in the legs, chest pain, or breathing difficulties (which may indicate dangerous blood clots in veins)
• fast, irregular, or slow heartbeat
• sepsis (blood poisoning)

Uncommon (may affect up to 1 in 100 patients)

• severe allergic reaction (see above)
• hearing disturbances (ototoxicity)
• low blood magnesium levels
• impaired sperm production

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

• increased risk of acute leukaemia
• seizures (epileptic fits)
• fainting, headache, disorientation, and loss of vision
• loss of certain brain functions, including brain dysfunction characterized by seizures and reduced consciousness
• brain dysfunction (disorientation, slurred speech, sometimes blindness, memory loss, and paralysis)
• heart attack
• inflammation of the mucous membrane of the mouth
• peripheral sensory neuropathy, characterized by tingling, itching, or numbness without cause, sometimes with loss of taste, touch, or vision, and sudden sharp pain in the neck, back, and legs when bending forward

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

• cardiac arrest

Frequency not known (cannot be estimated from available data)

• signs of infection such as fever or sore throat
• haemolytic anaemia
• inappropriate vasopressin (ADH) secretion, which may lead to low blood sodium levels and water retention in the body
• increased blood amylase (enzyme) activity
• dehydration
• low blood calcium, phosphate, and potassium levels
• high blood uric acid levels
• muscle cramps
• spine disease causing a sensation of "electric shocks" in the limbs
• loss of taste
• vision problems (blurred vision, unusual colours, vision loss, or eye pain)
• ringing in the ears or deafness
• heart problems
• unusual sensation of coldness or pale hands and feet
• tingling, numbness, or trembling in the hands, feet, arms, or legs
• persistent headache
• nausea or vomiting
• loss of appetite, anorexia
• hiccups
• diarrhoea
• increased liver enzyme activity, increased bilirubin levels
• breathing difficulties
• shortness of breath, chest pain (especially on breathing in), coughing up blood
• kidney problems or problems with urination
• hair loss
• rash
• severe fatigue/weakness
• swelling or pain at the injection site
• muscle cramps
• burning or stinging sensation
• unexpected bleeding or bruising
• haemolytic-uraemic syndrome, which may cause changes in the kidneys and blood.

Cisplatin may cause disturbances in blood, liver, and kidneys. Your doctor will order blood tests
to check for these disturbances and monitor electrolyte levels.

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
Faks: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Cisplatinum Accord

Keep out of the sight and reach of children.
Store the vial in the outer packaging to protect from light.
Do not store in the refrigerator or freeze.
If crystals or a precipitate form due to exposure to low temperatures, the medicinal product should be
re-dissolved by keeping the vials at room temperature until a clear solution is obtained.
Discard the product if the solution does not become clear after vigorous shaking.
Do not use this medicine after the expiry date stated on the vial and carton after Expiry (EXP). The expiry date refers to the last day of the stated month.
Do not use this medicine if there are any visible signs of deterioration.
All materials used for preparation and administration, or any materials that have come into contact with cisplatin, must be disposed of in accordance with local regulations for cytotoxic waste.
If the solution remains cloudy or the precipitate does not dissolve, the vial must be discarded.

6. Contents of the pack and other information

What Cisplatinum Accord contains
The active substance is cisplatin.
Each millilitre (ml) of solution contains 1 milligram (mg) of cisplatin. The medicine is contained in amber glass vials.

The medicine is available in packages containing single vials (not all vial sizes may be marketed).
The other ingredients are sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid, concentrated (for pH adjustment), water for injections.
What Cisplatinum Accord looks like and contents of the pack
Cisplatinum Accord is a clear, colourless to pale yellow solution, free from solid particles, in an amber glass vial with a transparent flip-off seal.
Each vial containing 10 ml of concentrate contains 10 mg of cisplatin.
Each vial containing 25 ml of concentrate contains 25 mg of cisplatin.
Each vial containing 50 ml of concentrate contains 50 mg of cisplatin.
Each vial containing 100 ml of concentrate contains 100 mg of cisplatin.
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,
Lamia, 32009, Greece
This medicinal product is authorised in the European Economic Area countries under the
following names:
Country Medicinal Product Name
Austria Cisplatin Accord 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Belgium Cisplatin Accord Healthcare 1 mg/ml solution à Diluer pour Perfusion / concentraat voor oplossing voor infusie / Konzentrat zur Herstellung einer Infusionslösung
Bulgaria Cisplatin Accord 1 mg/ml Concentrate for Solution for Infusion
Denmark Cisplatin Accord
Estonia Cisplatin Accord 1 mg/ml
Finland Cisplatin Accord 1 mg/ml infuusiokonsentraatti, Liuosta Varten
Germany Cisplatin Accord 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Hungary Cisplatin Accord 1 mg/ml Concentrate for Solution for Infusion
Ireland Cisplatin 1 mg/ml Concentrate for Solution for Infusion
Italy Cisplatin Accord Healthcare 1 mg/ml concentrato per soluzione per infusione
Latvia Cisplatin Accord
Lithuania Cisplatin Accord 1 mg/ml koncentratas infuziniam tirpalui
Netherlands Cisplatin Accord 1 mg/ml Concentraat voor Oplossing voor Infusie
Norway Cisplatin Accord 1 mg/ml Konsentrat til infusjonsvæske
Poland Cisplatinum Accord
Portugal Cisplatin Accord
Romania Cisplatină Accord 1 mg / ml concentrat pentru soluţie perfuzabilă
Slovenia Cisplatin Accord 1 mg/ml koncentrat za raztopino za infundiranje
Spain Cisplatino Accord 1 mg/ml concentrado para solución para perfusión
Sweden Cisplatin Accord 1 mg/ml Koncentrat till Infusionsvätska, Lösning
United Kingdom (Northern Ireland) Cisplatin 1 mg/ml Concentrate for Solution for Infusion

Medicinal Product. For detailed product information, see the Summary of Product Characteristics (SmPC).

Information intended exclusively for medical professionals or

healthcare personnel
Instructions for preparation and handling of the medicinal product
As with other antineoplastic agents, caution must be exercised when handling cisplatin. Dilution should be performed under sterile conditions by trained personnel in a designated area. Appropriate protective gloves must be worn. Precautions should be taken to avoid contact of the medicinal product with skin and mucous membranes. If contact with skin occurs, the affected area should be immediately washed with soap and water. Skin tingling, burning, and redness have been reported following skin contact. In case of contact with mucous membranes, immediately rinse thoroughly with water. Inhalation of the solution may cause dyspnea, chest pain, throat irritation, and nausea. Pregnant women must avoid contact with cytotoxic drugs. Cisplatin should not be used during pregnancy unless the physician considers the potential risk of administering the medicinal product to be clinically justified.
Extreme caution should be taken when handling excreta and vomit.
If the solution appears cloudy or insoluble precipitate is present, the vial must be discarded.
Damaged vials should be handled with the same care as contaminated waste. Contaminated waste must be stored in appropriately labeled waste containers. See section "Disposal of medicinal product residues".

Preparation for intravenous administration
Withdraw the required volume from the vial and dilute it in at least 1 liter of one of the following solutions:

• 0.9% sodium chloride
• mixture of 0.9% sodium chloride and 5% glucose (1:1) (final concentrations: 0.45% sodium chloride solution, 2.5% glucose solution)
• 0.9% sodium chloride and 1.875% mannitol for injection
• 0.45% sodium chloride, 2.5% glucose and 1.875% mannitol for injection

The solution should always be inspected visually before use. Only clear, particle-free solutions should be used.
If a precipitate or crystals form inside the vial, store the vial at room temperature (20–25°C) until a clear solution is obtained. Protect unopened containers from light. The medicinal product must be discarded if the solution does not become clear after vigorous shaking.
DO NOT ALLOW contact with injectable materials containing aluminium.
DO NOT ADMINISTER in undiluted form.
For microbiological, chemical, and physical stability of undiluted solutions, refer to the section below “Special precautions for storage”.
Although cisplatin is usually administered intravenously, cisplatin has also been administered via intraperitoneal infusion in patients with malignant intraperitoneal tumors (e.g., patients with ovarian tumors). When administered by this route, a significant concentration gradient between intraperitoneal and plasma concentrations can be achieved.

Disposal of medicinal product residues
All materials used in the preparation and administration of cisplatin, or that have come into contact with cisplatin in any way, must be disposed of in accordance with local regulations for cytotoxic waste. Medicinal products must not be disposed of via sewage systems or household waste. Consult a pharmacist on how to dispose of unused medicines. Such practices help protect the environment.

Pharmaceutical incompatibilities
Avoid contact with aluminium. Cisplatin may react with metal (aluminium), forming a black precipitate of platinum. Do not use any materials containing aluminium, such as infusion sets, needles, catheters, or syringes.
Cisplatin degrades in solutions with low chloride concentration. The chloride concentration should be at least equivalent to 0.45% sodium chloride solution.
Due to lack of compatibility studies, cisplatin must not be mixed with other medicinal products.
Antioxidants (such as sodium metabisulfite), bicarbonates (sodium bicarbonate), sulfates, fluorouracil, and paclitaxel may inactivate cisplatin in infusion sets.

Special precautions for storage
Medicinal product in the retail package
Concentrate for solution for infusion, 1 mg/ml
Undiluted solution: Store the container in the outer packaging to protect from light. Do not refrigerate or freeze. Do not use the solution if it appears cloudy or if an insoluble precipitate forms.

Diluted solution
For information on storage conditions after dilution: see below "Concentrate for solution for infusion after dilution":
Do not refrigerate or freeze.

Concentrate for solution for infusion after dilution
After dilution
Chemical and physical stability of Cisplatinum Accord has been demonstrated after dilution in the recommended infusion solutions described in the section “Instructions for preparation and handling of the medicinal product” for 24 hours at room temperature (20–25°C).
From a microbiological standpoint, the diluted solution should be used immediately. If the medicinal product is not used immediately, the responsibility for storage duration and conditions lies with the user. Dilution must be performed under controlled and validated aseptic conditions.