Cisplatin Accord 1 mg/ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Cisplatino Accord 1 mg/ml concentrate for solution for infusion EFG

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Leaflet contents

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

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

Cisplatino Accord contains the active substance cisplatin, which belongs to a group of medicines called cytostatics used in the treatment of cancer. Cisplatin may be used alone, but it is most commonly used in combination with other cytostatic agents.

Cisplatin is capable of destroying cells in your body that can cause certain types of cancer (testicular tumour, ovarian tumour, bladder tumour, head and neck epithelial tumour, lung cancer, and cervical cancer when used in combination with radiotherapy).

Your doctor can provide you with further information.

You should speak with a doctor if you do not feel better or if you feel worse.

2. What you need to know before using Cisplatin Accord

Do not use cisplatin

• if you are allergic to cisplatin, to similar anticancer medicines, to other platinum-containing compounds, or to any of the other ingredients of this medicine (listed in section 6)
• if you have a very low blood cell count (called myelosuppression) (your doctor will monitor this with a blood test)
• if you are breastfeeding
• if you have severe kidney disease
• if you have hearing problems
• if you are dehydrated
• if you need to be vaccinated against "yellow fever"

Inform your doctor if any of the above apply to you before using this medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Cisplatin Accord:

• If you have any symptoms of nerve damage (peripheral neuropathy), such as tingling, numbness, or reduced sense of touch. You will be examined periodically for these symptoms, and treatment may be interrupted if necessary.
• If you have previously received radiation therapy to the head

Your doctor will carry out tests to determine your blood levels of calcium, sodium, potassium, and magnesium, as well as to check your blood count, liver and kidney function, and neurological function.

Cisplatin may affect the bone marrow, causing changes in blood cell production. Inform your doctor if you experience unusual bleeding or bruising. Do not take aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or other medications without informing your doctor. Your doctor will perform frequent blood tests and monitor for signs of infection.

Cisplatin may cause hearing problems (ototoxicity) and kidney problems (nephrotoxicity). Kidney function and hearing will be monitored before and during treatment. If you notice any changes in your hearing, inform your doctor.

Inform your doctor if you plan to be vaccinated during treatment with Cisplatin. Some live vaccines should be avoided, as they may cause serious infections, and your response to other types of vaccines (inactivated) may be reduced.

Other medicines and Cisplatin Accord

Contact your doctor, pharmacist, or nurse if you are using, have recently used, or might need to use any other medicines, for example:

• Certain antibiotics such as cephalosporins, aminoglycosides, and amphotericin B, and certain substances used for medical imaging may worsen the adverse effects of cisplatin, particularly kidney problems
• Certain diuretic tablets called loop diuretics, antibiotics called aminoglycosides, and an anticancer medicine called ifosfamide may worsen the adverse effect of hearing loss
• Bleomycin (an anticancer medicine), methotrexate (an anticancer or arthritis medicine), and paclitaxel (an anticancer medicine) may cause more adverse effects when used together with cisplatin
• Cisplatin may reduce the effectiveness of anticonvulsants (used to treat epilepsy); monitoring of blood phenytoin levels may be necessary
• The effectiveness of oral anticoagulants (e.g., warfarin) may be affected. Your doctor will monitor you with blood tests
• Buclizine, cyclizine, and meclozine (antihistamine medicines), loxapine, phenothiazines and thioxanthenes (medicines used to treat psychiatric disorders), or trimethobenzamides (medicines used to prevent nausea and vomiting) may mask symptoms of balance disturbances (such as dizziness or tinnitus)
• Cisplatin may worsen the adverse effects of the anticancer medicine ifosfamide
• Pyridoxine (vitamin B6) and altretamine (an anticancer medicine), when used in combination with cisplatin for the treatment of advanced ovarian cancer, may reduce recovery time. Your doctor will discuss this with you
• Bleomycin and etoposide (anticancer medicines) used in combination with cisplatin, and lithium (used to treat mental illnesses), may reduce blood lithium levels. Monitoring of lithium levels is recommended
• The yellow fever vaccine must not be used at the same time as treatment with cisplatin due to the risk of death resulting from vaccination. An inactivated vaccine is recommended
• Antigout medicines such as allopurinol, colchicine, probenecid, or sulfinpyrazone reduce blood uric acid levels. Your doctor may need to adjust your dose of Cisplatin Injection.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Due to the possible risk of birth defects, male and female patients must use contraception during treatment with cisplatin and for at least six months after treatment ends.

Cisplatin must not be used during pregnancy unless clearly indicated by your doctor.

Consult your doctor or pharmacist before taking any medicine.

Breastfeeding

Do not use this medicine if you are breastfeeding.

Fertility

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

Driving and using machines

Do not drive or operate machinery if any adverse effects occur that may impair your ability to do so.

Cisplatin Accord contains sodium

This medicine contains 3.5 mg of sodium (the main component of table salt) per ml. This corresponds to 0.18% of the maximum daily recommended sodium intake for an adult.

This medicine may be prepared with a solution containing sodium. This should be taken into account if you are on a low-salt (sodium) diet.

3. How to use Cisplatino Accord

Posology and method of administration

Cisplatino Accord must only be administered by a specialist experienced in cancer treatment.

The concentrate is diluted with a sodium chloride solution.

Cisplatino is usually administered by intravenous infusion over a period of 6 to 8 hours.

Emergency support equipment for managing anaphylactic reactions must be available.

Cisplatino must not come into contact with any materials containing aluminium.

The recommended dose of Cisplatino Accord depends on your health status, the intended effects of treatment, and whether cisplatin is administered alone (monotherapy) or in combination with other medicines (combination chemotherapy).

Recommended dose

Cisplatino (monotherapy):

The following doses are recommended:

• Single dose of 50 to 120 mg/m² body surface area (BSA), every 3–4 weeks.
• 15 to 20 mg/m²/day for 5 days, every 3–4 weeks.

Cisplatino in combination with other anticancer medicines (combination chemotherapy):

• 20 mg/m² BSA or more, once every 3–4 weeks.

For the treatment of cervical cancer, cisplatin is used in combination with radiotherapy or other chemotherapy medicines.

A typical dose is 40 mg/m² BSA weekly for 6 weeks.

To prevent or reduce kidney problems, you should drink large amounts of fluids during the 24 hours following treatment with Cisplatino Accord.

If you think you have been given more Cisplatino Accord than you should

Your doctor will ensure that you receive the correct dose for your condition. In case of overdose, you may experience more adverse effects. Your doctor will provide symptomatic treatment for these effects. If you think you have been given too much Cisplatino Accord, contact your doctor immediately.

If you have any doubts about how to use this medicine, consult your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Tell your doctor immediately if you notice any of the following symptoms

• Severe allergic reaction; you may experience sudden itchy rash (blisters), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), feeling hot and flushed, and you may feel like you are going to faint
• Severe chest pain possibly radiating to the jaw or arm, with sweating, shortness of breath, and nausea (heart attack)
• Fainting or seizures
• Hearing problems – you may experience ringing in the ears or hearing loss (ototoxicity)
• • Kidney and urinary problems
• • Extreme tiredness and general feeling of being unwell, which could be symptoms of reduced blood cell levels (myelosuppression). This would be confirmed by a blood test.

These are serious adverse effects. You may require urgent medical attention.

Very common: may affect more than 1 in 10 people:

• Reduction in bone marrow function (which may affect blood cell production)
• Reduction in white blood cells, leading to increased risk of infections (leukopenia)
• Reduction in platelets, increasing the risk of bruising and bleeding (thrombocytopenia)
• Reduction in red blood cells, which may cause weakness and pale skin (anemia)
• Reduction in blood sodium levels
• High temperature

Common: may affect up to 1 in 10 people:

• Severe pain or swelling in either leg, chest pain, difficulty breathing (possibly indicating painful blood clots in a vein)
• Fast, irregular, or slow heartbeats
• Sepsis (blood poisoning)

Uncommon: may affect up to 1 in 100 people:

• Severe allergic reaction (see above)
• Hearing problems (ototoxicity)
• Decreased blood magnesium levels
• Abnormal sperm production

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

• Increased risk of acute leukemia
• Seizures
• Fainting, headache, confusion, and loss of vision
• Loss of certain types of brain function, including brain dysfunction characterized by muscle spasms and decreased level of consciousness
• Brain dysfunction (confusion, difficulty speaking, sometimes blindness, memory loss, and paralysis)
• Heart attack
• Inflammation of the mucous membranes of the mouth (stomatitis)
• Peripheral sensory nerve neuropathy, characterized by tingling, itching, or pins and needles without cause, sometimes with loss of taste, touch, vision, and sudden electric shock-like sensations running from the neck down the back and into the legs when bending forward

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

• Cardiac arrest

Frequency not known: frequency cannot be estimated from available data

• Signs of infection such as fever or sore throat
• Hemolytic anemia
• Inappropriate release of vasopressin hormone (ADH), which may lead to low blood sodium levels and fluid retention
• Increased blood amylase (enzyme) levels
• Dehydration
• Decreased levels of calcium, phosphate, and potassium in the blood
• High levels of uric acid in the blood
• Muscle cramps
• Spinal cord disorder that may cause electric shock-like sensations in the limbs
• Brain dysfunction (confusion, incomprehensible speech, sometimes blindness, memory loss, and paralysis)
• Stroke
• Loss of taste
• Vision problems (blurred vision, seeing unusual colors, vision loss, or eye pain)
• Ringing in the ears or deafness
• Heart problems
• Unusually cold or pale hands and feet
• Tingling, numbness, or tremors in hands, feet, arms, or legs
• Persistent headache
• Feeling of nausea
• Loss of appetite, anorexia
• Hiccups
• Diarrhea
• Increased liver enzymes, increased bilirubin
• Difficulty breathing
• Difficulty breathing, chest pain (especially when inhaling), and coughing up blood
• Kidney or urinary problems
• Hair loss
• Rash
• Extreme fatigue and weakness
• Swelling or pain at the injection site
• Cramps or spasms
• Burning or stinging sensation
• Unexpected bleeding or bruising
• Hemolytic uremic syndrome, which may cause changes in the kidneys and blood

Cisplatin Accord may cause problems with your blood, liver, and kidneys. Your doctor will perform blood tests to monitor these issues and check your electrolyte levels.

Reporting of adverse effects:

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cisplatin Accord

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

Store the vial in the outer packaging to protect it from light. Do not refrigerate or freeze.

If precipitate or crystals form as a result of exposure to low temperatures, redissolve by storing the vials at room temperature until a clear solution is obtained.

The product must be discarded if the solution does not become clear after vigorous shaking.

Do not use this medicine after the expiry date stated on the outer carton after “EXP”. The expiry date refers to the last day of the month indicated.

Do not use this medicine if visible signs of deterioration are observed.

All materials used for preparation and administration, or that have come into contact with cisplatin in any way, must be disposed of in accordance with local cytotoxic requirements.

If the solution is cloudy or a deposit is observed that does not dissolve, the vial must be discarded.

6. Contents of the container and other information

Composition of Cisplatin Accord

The active substance is cisplatin.

Each millilitre (ml) of solution contains 1 milligram (mg) of cisplatin. This medicine is presented in amber glass containers called vials.

The other components are sodium chloride, hydrochloric acid (to adjust pH) and/or sodium hydroxide (to adjust pH), and water for injections.

Appearance of Cisplatin Accord and contents of the container

Cisplatin Accord is a clear, colourless to pale yellow solution in an amber glass vial practically free from particles, with a transparent flip-off seal.

Pack containing 1 injection vial of 10 ml containing 10 mg of cisplatin.

Pack containing 1 injection vial of 25 ml containing 25 mg of cisplatin.

Pack containing 1 injection vial of 50 ml containing 50 mg of cisplatin.

Pack containing 1 injection vial of 100 ml containing 100 mg of cisplatin.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona, Spain.

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,

95-200 Pabianice,

Poland

Accord Healthcare Single Member S. A

64th Km National Road Athens

Lamia, 32009

Greece

This medicinal product is authorised in the EEA Member States under the following names

Member State	Medicinal Product Name
Austria	Cisplatin Accord 1 mg/ml Concentrate for Solution for Infusion
Belgium	Cisplatin Accord Healthcare 1 mg/ml Solution à Diluer pour Perfusion / Concentrate for Solution for Infusion / 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 Concentrate for Solution for Infusion
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	Cisplatin Accord
Portugal	Cisplatin Accord
Romania	Cisplatina Accord 1 mg/ml concentrat pentru solutie perfuzabila
Slovenia	Cisplatin Accord 1 mg/ml koncentrat za raztopino za infundiranje
Spain	Cisplatino Accord 1 mg/ml concentrado para solución para perfusión EFG
Sweden	Cisplatin Accord 1 mg/ml Koncentrat till Infusionsvätska, Lösning
United Kingdom	Cisplatin 1 mg/ml Concentrate for Solution for Infusion

Date of the most recent review of this summary: April 2023

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicinal Products and Medical Devices (AEMPS) http://www.aemps.gob.es/

Information intended exclusively for medical or healthcare professionals:

Preparation and handling of the product

As with all antineoplastic agents, caution is required when handling cisplatin. Dilution must be performed under aseptic conditions by trained personnel in a specifically designated area. Protective gloves must be worn, and extreme care must be taken to avoid contact with the skin and mucous membranes. In case of skin contact, wash immediately with soap and water. Cases of skin contact have reported sensations of tingling, burning, and redness. In case of contact with mucous membranes, they should be thoroughly rinsed with abundant water. Following inhalation, dyspnea, chest pain, throat irritation, and nausea have been reported.

Pregnant women should avoid contact with cytostatic agents. Cisplatin must not be used during pregnancy unless clinicians consider that, for an individual patient, the risk is justified.

Organic waste and vomit must be disposed of carefully.

If the solution is cloudy or if an undissolvable deposit is observed, the vial must be discarded.

Damaged vials must be considered and handled with the same precautions as contaminated waste. Contaminated waste must be placed in specific waste containers designated for this purpose. See section “Disposal”.

Preparation for intravenous administration

Withdraw the required volume from the vial and dilute it with at least 1 L of one of the following solutions:

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

Always inspect the injection before use. Only clear solutions without visible particles should be administered.

If precipitate or crystals are observed in the vial, keep the vial at room temperature (20°C – 25°C) until a clear solution is obtained. Protect unopened packaging from light. The product must be discarded if the solution does not become clear after vigorous shaking.

DO NOT allow contact with injection materials containing aluminum.

DO NOT administer undiluted.

For information on microbiological, chemical, and physical stability during use of undiluted solutions, see section “Special precautions for storage”.

Although cisplatin is usually administered intravenously, it has also been administered via intraperitoneal instillation in patients with malignant intraperitoneal neoplasms (e.g., ovarian tumors). This route of administration allows achieving high concentration gradients between intraperitoneal and plasma levels of the drug.

Disposal

All materials used in the preparation and administration of cisplatin, or that have come into contact with it in any way, must be disposed of in accordance with local regulations for cytotoxic agents. Medicines must not be disposed of via sewage systems or in household waste. Ask your pharmacist how to dispose of medicines you no longer need. This helps protect the environment.

Incompatibilities

Must not come into contact with aluminum. Cisplatin may react with aluminum, leading to the formation of a black precipitate of platinum. Contact must be avoided with any intravenous administration equipment, needles, catheters, and syringes containing aluminum.

Cisplatin decomposes when dissolved in media with low chloride content; the chloride concentration must be at least equivalent to 0.45% sodium chloride.

In the absence of compatibility studies, this medicine 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 systems.

Special precautions for storage

Medicinal product packaged for sale:

Concentrate for perfusion solution 1 mg/mL

Undiluted solution: Store the vial in the outer packaging to protect it from light. Do not refrigerate or freeze. If the solution is not transparent or if insoluble precipitates form, the solution must not be used.

Diluted solution:

For storage conditions of the diluted medicine, see below under:

“Concentrate for perfusion solution after dilution”.

Do not refrigerate or freeze.

Concentrate for perfusion solution after dilution.

After dilution

Chemical and physical in-use stability after dilution with perfusion fluids described in the section “Preparation and handling of the product” indicates that, after dilution with the recommended intravenous fluids, cisplatin injection remains stable for 24 hours at room temperature (20–25°C).

From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, the storage time and conditions prior to use are the responsibility of the user; furthermore, dilution must be carried out under validated and controlled aseptic conditions.