PLATICEPT 50 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

PlatiCept 50 mg powder for solution for injection EFG

cisplatin

Read all of this leaflet carefully before you start 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 only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is PlatiCept and what is it used for

Cisplatin belongs to a group of medicines called antineoplastics, indicated in the treatment of certain diseases localized in the ovary, testicles, lung, head and neck, and bladder where cell growth is altered.

Ask your doctor what PlatiCept has been prescribed for.

2. What you need to know before you use PlatiCept

Do not use PlatiCept

• If you are allergic to cisplatin or other platinum-containing agents or to any other component of the medicine (listed in section 6)
• If you have severe kidney failure
• If you have hearing impairment
• If you have severe bone marrow suppression
• If you have neuropathy caused by cisplatin
• If you are breastfeeding.
• In combination with certain types of vaccines such as the yellow fever vaccine and phenytoin (a medicine used to prevent seizures) (see the section "Using PlatiCept with other medicines").

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with PlatiCept

• If you receive prolonged treatment, a decrease in the number of red blood cells in the blood (anemia) may occur, and a transfusion may be necessary. Neurological, kidney, and hearing alterations may also occur.
• Receiving PlatiCept may cause you nausea and vomiting. Your doctor will give you a medicine to prevent them before administering PlatiCept.
• PlatiCept may cause allergic reactions that require specific treatment.
• Before, during, and after therapy with PlatiCept, you will undergo frequent blood tests, as well as kidney, liver, and brain function tests.
• If you wish to have children (see the section "Pregnancy, breastfeeding, and fertility"). You should use an effective contraceptive method during and for at least 6 months after treatment with cisplatin.
• In case of cisplatin spillage, the contaminated skin should be washed immediately with water and soap. If cisplatin is injected outside the blood vessels, administration should be stopped immediately. Cisplatin on the skin can cause tissue damage (cellulitis, fibrosis, and necrosis).

Using PlatiCept with other medicines

Note that these statements may also apply to products used in the past or in the future.

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

• The simultaneous use of medicines that inhibit bone marrow function or radiation may enhance the adverse reactions of cisplatin in the bone marrow.
• The toxicity of cisplatin may increase when administered simultaneously with other cytostatics (cancer treatment medicines), such as bleomycin and methotrexate.
• Medicines for treating high blood pressure (antihypertensives containing furosemide, hydralazine, diazoxide, and propranolol) may increase the toxic effect of cisplatin on the kidneys.
• The toxicity of cisplatin may severely affect the kidneys if administered simultaneously with medicines that can cause adverse effects on the kidneys, such as those indicated for the prevention/treatment of certain infections (antibiotics: cephalosporins, aminoglycosides, and/or amphotericin B) and contrast agents.
• The toxicity of cisplatin may affect hearing if administered simultaneously with medicines that can have adverse effects on the ear, such as aminoglycoside antibiotics.
• If you use medicines for gout during treatment with cisplatin, the dose of these medicines should be adjusted (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone).
• The administration of medicines that increase urine excretion (loop diuretics) combined with cisplatin (cisplatin dose: more than 60 mg/m2, urine excretion: less than 1,000 ml in 24 hours) may cause toxic effects on the kidneys and ear.
• The first signs of hearing damage (dizziness and/or tinnitus) may be masked if, during treatment with cisplatin, you also receive medicines for treating hypersensitivity (antihistamines, such as buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes, and/or trimetobenzamides).
• Cisplatin administered in combination with bleomycin and vinblastine may cause paleness or bluish discoloration of the fingers and toes (Raynaud's phenomenon).
• The administration of cisplatin before treatment with paclitaxel or in combination with docetaxel may cause severe nerve damage.
• The combined use of cisplatin with bleomycin and etoposide may reduce lithium levels in the blood. Therefore, lithium levels should be periodically checked.
• Cisplatin reduces the effects of phenytoin in the treatment of epilepsy.
• Penicillamine and other agents called chelating agents may reduce the efficacy of cisplatin.
• Cisplatin may have an adverse effect on the effectiveness of medicines that prevent blood clotting (anticoagulants). Therefore, coagulation should be checked more frequently during combined use.
• The concomitant use of cisplatin with cyclosporin may weaken the immune system, with the risk of increased production of white blood cells (lymphocytes).
• You should not receive any vaccine containing live, attenuated virus in the 3 months following the end of treatment with cisplatin.
• During treatment with cisplatin, you should not receive yellow fever vaccines (see also "Do not use PlatiCept").

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor, pharmacist, or nurse for advice before using this medicine.

PlatiCept should not be used in pregnant women unless clearly indicated by your doctor. If you become pregnant during treatment with PlatiCept, inform your doctor immediately.

Breastfeeding

PlatiCept is excreted in breast milk. If you are breastfeeding, you should stop breastfeeding your child during treatment with PlatiCept.

Fertility

Measures should be taken to avoid conception during and for at least 6 months after treatment with PlatiCept; this rule applies to patients of both sexes. If patients wish to have children after completing treatment, genetic counseling is recommended.

Driving and using machines

Cisplatin may cause drowsiness and/or vomiting. It is not recommended to drive vehicles or use machinery during treatment with PlatiCept.

PlatiCept contains sodium

Patients on low-sodium diets should note that this medicine contains 177 mg (7.7 mmol) of sodium per vial.

3. How to use PlatiCept

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, ask your doctor or pharmacist.

PlatiCept should only be administered intravenously after reconstitution and by specialized healthcare personnel, and under medical supervision.

Your doctor will calculate the dose based on your needs. It is usually administered as an injection every 3 or 4 weeks, but this schedule may be subject to changes as your doctor considers necessary in each case. Your doctor will adjust the dose at the start of treatment or later, depending on your physical condition.

In elderly patients, when determining the appropriate dose, your doctor should take into account that kidney function is often decreased.

Your doctor will indicate the duration of your treatment with PlatiCept. Do not stop treatment without talking to your doctor first.

If you think the action of PlatiCept is too strong or too weak, tell your doctor or pharmacist.

Cisplatin should not come into contact with materials containing aluminum.

If you receive more PlatiCept than you should

Your doctor will ensure that you are given the correct dose. In case of overdose, you may experience increased side effects, which can include kidney failure, liver failure, deafness, changes in vision, decreased blood cell production, and conditions such as feeling sick, being sick, and nerve inflammation. Your doctor may give you symptomatic treatment for these side effects.

If you think you may have received too much PlatiCept, contact your doctor immediately.

There is no known antidote for PlatiCept overdose. The first complications from overdose are expected to be related to bone marrow suppression, as well as liver and kidney function alterations. Administration of doses higher than recommended for PlatiCept has been associated with loss of vision and hearing. If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

If you forget to use PlatiCept

Talk to your doctor. The doctor will determine what actions to take.

4. Possible side effects

Like all medicines, PlatiCept can cause side effects, although not everybody gets them.

If you experience any side effect, it is important that you inform your doctor before the next treatment.

Adverse reactions depend on the dose used and may have cumulative effects.

Tell your doctor immediately if you experience any of the following:

• Persistent or severe diarrhea or vomiting
• Stomatitis/mucositis (sore lips or mouth ulcers)
• Inflammation of the face, lips, mouth, or throat
• Unexpected respiratory symptoms such as dry cough, difficulty breathing, or wheezing
• Difficulty swallowing
• Numbness or tingling in the fingers of the hands or feet
• Extreme fatigue
• Unusual bruising or bleeding
• Signs of infection, such as sore throat and fever
• Feeling unwell near or at the injection site during infusion

Other side effects may occur:

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

• Depression of the bone marrow characterized by a significant decrease in the number of white blood cells, which increases the risk of infection (leucopenia), reduction of blood platelets (thrombocytopenia), which increases the risk of bruising and bleeding, as well as reduction in the number of red blood cells, which can cause paleness of the skin and weakness or difficulty breathing (anemia).
• Reduction of electrolyte levels (sodium).
• Hearing loss (ototoxicity).
• Vomiting, nausea, anorexia, and diarrhea.
• Acute kidney failure, kidney failure (increased BUN, increased creatinine, increased serum uric acid, and reduced creatinine clearance), disorders of the renal tubules.

Common (may affect up to 1 in 10 people)

• Blood infection (sepsis).
• Alteration of the nervous system (neurotoxicity).
• Deafness and vestibular toxicity combined with vertigo.
• Arrhythmia, including reduced heart rate (bradycardia) and increased heart rate (tachycardia).
• Inflammation of the veins (phlebitis).
• Difficulty breathing (dyspnea), inflammation of the lungs (pneumonia), respiratory failure.
• Liver dysfunction with elevated serum transaminases and bilirubin that is reversible.
• Redness and inflammation of the skin (erythema, skin ulcer) at the injection site, swelling (edema), pain at the injection site.
• Severe side effects

Contact your doctor as soon as possible if:

You experience severe pain or inflammation in any of your legs, chest pain, or difficulty breathing (which may indicate harmful blood clots in a vein).

Uncommon (may affect up to 1 in 100 people)

• Severe allergic reactions (anaphylactic), including skin rash, itching eczema, and hives, redness and inflammation of the skin (erythema) or itching (pruritus) and fever, low blood pressure (hypotension),
• Reduction of electrolyte levels (magnesium).
• Metallic discoloration of the gums.
• Hair loss (alopecia).
• Alterations in sperm and egg production and painful abnormal development of the breasts in men (gynecomastia).

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

• Increased risk of leukemia.
• Severe allergic reaction (anaphylaxis), suppression of the immune system (immunosuppression).
• Syndrome of inadequate secretion of antidiuretic hormone.
• High cholesterol levels in the blood (hypercholesterolemia), reduced electrolyte levels (calcium, potassium, phosphate) in the blood with muscle cramps and/or alterations in the electrocardiogram (ECG), involuntary muscle contraction (tetany).
• Seizures, loss of certain brain functions, including dysfunction characterized by spasms and reduced levels of consciousness (leukoencephalopathy), peripheral neuropathy of sensory nerves (sensory neuropathy) characterized by tingling, itching, or numbness without cause and, occasionally, characterized by loss of taste, touch, vision, syndrome of reversible posterior leukoencephalopathy.
• Blurred vision, difficulty perceiving colors, and dysfunction of eye movements, swelling (papilledema), inflammation of the optic nerve combined with pain and reduced nerve function (optic neuritis), blindness due to brain dysfunction.
• Loss of ability to maintain normal conversation.
• Myocardial infarction, hypertension, severe coronary artery disease.
• Inflammation of the mucous membranes of the mouth (stomatitis).
• Reduced serum albumin levels.
• Decreased albumin in the blood.

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

• Inadequate secretion of antidiuretic hormone (ADH).
• Increased iron levels in the blood.
• Seizures.
• Cardiac arrest.
• Dysfunction of blood flow, e.g., in the brain, but also in the fingers and toes (Raynaud's syndrome).

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

• Infections.
• Hemolytic anemia.
• Increased blood amylase.
• Dehydration, excessive uric acid levels in the blood (hyperuricemia).
• Stroke, loss of taste (ageusia), cerebral arteritis, Lhermitte's sign, myelopathy, autonomic neuropathy.
• Retinal pigmentation.
• Ringing in the ears (tinnitus).
• Cardiac disorder.
• Thrombotic microangiopathy (hemolytic-uremic syndrome).
• Pulmonary embolism.
• Hiccups.
• Skin rash, hair loss (alopecia).
• Muscle spasms.
• Fever, weakness (asthenia), malaise, extravasation at the injection site.

Reporting of side effects

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

5. Storage of PlatiCept

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

Do not use this medicine after the expiration date that appears on the label of the vial and on the carton after "EXP". The expiration date is the last day of the month indicated.

The vials of PlatiCept should be stored at room temperature. The recommended storage conditions for the closed vials ensure the stability of the product until the expiration date indicated on the packaging.

The reconstituted solution is stable for 12 hours at room temperature (25°C) in the presence of light. Once reconstituted in the following solutions, the solution should be stored at room temperature:

- Sodium chloride solution for injection 9 mg/ml (0.9%).

- Water for injection.

When the reconstituted solution is refrigerated, a precipitate forms.

Medicines should not be thrown away via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of PlatiCept 50 mg powder for injectable solution EFG

The active ingredient is cisplatin. Each vial contains 50 mg of cisplatin.

The other components are: mannitol (E-421), sodium chloride, and hydrochloric acid.

Patients with low-sodium diets should note that this medicine contains 177 mg (7.7 mmol) of sodium per vial.

Appearance of the Product and Package Contents

PlatiCept is presented in the form of powder for injectable solution.

Package with 1 vial of 50 mg of cisplatin.

After reconstitution, the solution contains 1 mg/ml of cisplatin. Before administration, it is required that the healthcare professional perform another dilution.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

PharmaCept GmbH

Bessemerstr. 82

12103 Berlin

Germany

Local Representative

PRASFARMA, S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

Manufacturer

PRASFARMA, S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of this prospectus: February 2018

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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This information is intended only for healthcare professionals:

Instructions for Use and Handling

Handling

Cisplatin is a cytotoxic agent. Like all medicines of this type, PlatiCept should be handled with caution. Dilutions will be performed by experienced personnel and in a specific area, who should wear protective gloves and take precautions to avoid any contact with the skin and mucous membranes.

In case of skin contact, the affected area should be washed with water and alkaline soap. In case of contact with mucous membranes, they should be thoroughly washed with plenty of water.

Pregnant women should avoid contact with cytotoxic agents.

Preparation for Intravenous Administration

The 50 mg vials should be reconstituted with 50 ml of sodium chloride solution for injection 9 mg/ml (0.9%) or 50 ml of water for injection. Each ml of the resulting solution contains 1 mg of cisplatin. The reconstituted solution should be a clear and colorless solution.

Note: Needles or materials containing aluminum should not be used for preparation or intravenous administration, as aluminum reacts with cisplatin, producing a precipitate and loss of potency.

Elimination

A vial is for single use.

The elimination of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic agents.