GEMCITABINE HIKMA 1000 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Gemcitabine Hikma 200 mg concentrate for solution for infusion

Gemcitabine Hikma 1000 mg concentrate for solution for infusion

Gemcitabine Hikma 2000 mg concentrate for solution for infusion

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.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Gemcitabine Hikma is and what it is used for

Gemcitabine belongs to a group of medicines called “cytotoxics”. These medicines destroy cells that are dividing, including cancer cells.

Gemcitabine Hikma can be given alone or in combination with other anti-cancer medicines (e.g. cisplatin, paclitaxel, carboplatin), depending on the type of cancer.

This medicine is used to treat the following types of cancer:

• non-small cell lung cancer (NSCLC), alone or in combination with cisplatin
• pancreatic cancer
• breast cancer, in combination with paclitaxel
• ovarian cancer, in combination with carboplatin
• bladder cancer, in combination with cisplatin

2. What you need to know before you use Gemcitabine Hikma

Do not use Gemcitabine Hikma:

• If you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• If you are breast-feeding

Warnings and precautions

Before the first infusion, blood samples will be taken to check if your liver and kidney function is correct. Before each infusion, blood samples will be taken to check if you have enough red blood cells to receive treatment with gemcitabine.

Your doctor may decide to change the dose or delay treatment depending on your general health and if your blood cell counts are too low. Blood samples will be taken periodically to check the function of your kidneys and liver.

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

If you have or have had liver, heart, blood vessel or kidney disease, tell your doctor or hospital pharmacist, as you may not be able to receive gemcitabine.

If you have recently received or are going to receive radiotherapy, tell your doctor, as there may be an early or late radiation reaction with gemcitabine.

If you have been vaccinated recently, tell your doctor, as this may cause negative effects with gemcitabine.

If during treatment with this medicine you experience symptoms such as headache with confusion, seizures or changes in vision, call your doctor immediately. This may be a very rare side effect of the nervous system called posterior reversible encephalopathy syndrome.

If you experience difficulty breathing or feel very weak and very pale (this may be a sign of lung or kidney problems).

If you experience swelling, shortness of breath, weight gain, please inform your doctor, as this may be a sign that fluids from your small blood vessels are leaking into tissues.

If you have ever developed a severe skin rash or skin peeling or blisters or sores in the mouth after using gemcitabine.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis (AGEP), have been reported in association with gemcitabine treatment. Seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents

The use of this medicine is not recommended in children under 18 years due to lack of safety and efficacy data in this population.

Other medicines and Gemcitabine Hikma

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines, including vaccines and medicines without a prescription.

Pregnancy, breast-feeding and fertility

Pregnancy

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

The use of gemcitabine should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking gemcitabine during pregnancy.

Breast-feeding

Tell your doctor if you are breast-feeding.

You should stop breast-feeding during treatment with gemcitabine.

Fertility

Men are advised not to father a child during treatment with gemcitabine and for up to 6 months after treatment. If you wish to father a child during treatment or in the 6 months after treatment, seek advice from your doctor or pharmacist. You may want to ask for information on sperm conservation before starting your treatment.

Driving and using machines

This medicine may cause drowsiness, especially if you have consumed alcohol. Avoid driving or using machines until you are sure that treatment with gemcitabine does not make you drowsy.

This medicine contains sodium:

Gemcitabine Hikma 200 mg contains a maximum of 4.9 mg of sodium (<1 mmol) per vial. this medicine contains less than 23 mg of sodium (1 vial; is essentially “sodium-free”.< p>

Gemcitabine Hikma 1000 mg contains a maximum of 24.2 mg (1.05 mmol) of sodium (main component of table/cooking salt) per vial. This is equivalent to 1.2% of the maximum recommended daily sodium intake for an adult.

Gemcitabine Hikma 2000 mg contains a maximum of 48.4 mg (2.10 mmol) of sodium (main component of table/cooking salt) per vial. This is equivalent to 2.4% of the maximum recommended daily sodium intake for an adult.

3. How to use Gemcitabine Hikma

The initial dose of gemcitabine will be calculated by your doctor and will depend on the type of cancer you have and your body surface area in square meters (m2).

Your height and weight will be measured to calculate the area of your body. Your doctor will use this body surface area to calculate the correct dose for you. The usual dose is between 1g/m2 and 1.25g/m2.

This dose may be adjusted or treatment delayed depending on your general health and your blood cell counts.

The frequency at which you receive your gemcitabine infusion depends on the type of cancer you are being treated for.

You will always receive gemcitabine by infusion (a slow injection through a drip) into one of your veins. The infusion will take about 30 minutes.

Since gemcitabine will be administered under the supervision of your doctor, it is unlikely that you will receive an incorrect dose. However, if you have any doubts about the dose you received or about the use of this medicine, ask your doctor, nurse or pharmacist.

4. Possible side effects

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

Contact your doctor immediately if you notice any of the following:

• Bleeding from the gums, nose or mouth or any bleeding that does not stop, red or pink urine, unexpected bruising (as you may have fewer platelets than normal, which is very common).
• Tiredness, feeling faint, getting breathless easily or if you are pale (as you may have fewer red blood cells than normal, which is very common).
• Mild or moderate skin rash / itching (very common) / fever (common); (allergic reactions).
• Temperature of 38°C or higher, sweating or other signs of infection (as you may have fewer white blood cells than normal, accompanied by fever, also known as febrile neutropenia) (common).
• Pain, redness, swelling or sores in the mouth (stomatitis) (common).
• Irregular heartbeat (arrhythmia) (frequency not known).

Extreme tiredness and weakness, purpura or small bleeding spots on the skin (petechiae), acute kidney injury (low urine output or absence of urine), and signs of infection. These may be signs of thrombotic microangiopathy (clots forming in small blood vessels) and hemolytic uremic syndrome, which can be fatal.

• Difficulty breathing (it is very common to have mild difficulty breathing immediately after gemcitabine infusion, which passes soon, however, it can rarely be more serious lung problems).
• Severe chest pain (myocardial infarction) (rare).
• Severe allergic reaction with severe skin rash including itching and redness of the skin, swelling of hands, feet, ankles, face, lips, mouth and throat (which can cause difficulty swallowing or breathing), wheezing, rapid heartbeat and you may feel like you are going to faint (anaphylactic reaction) (very rare).
• Generalized swelling, difficulty breathing or weight gain, as you may suffer from fluid leakage from small blood vessels into tissues (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures or fits (posterior reversible encephalopathy syndrome) (very rare).
• Severe rash with itching, blisters or skin peeling (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Generalized red and scaly rash with bumps under the inflamed skin (including skin folds, trunk and upper limbs) and blisters accompanied by fever (Acute Generalized Exanthematous Pustulosis [AGEP]) (frequency not known).

Other side effects of the medicine may include:

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

• Low white blood cell count

• Difficulty breathing
• Vomiting
• Nausea
• Hair loss
• Liver problems: identified through abnormal blood test results
• Blood in the urine
• Abnormal urine tests: protein in the urine
• Pseudo-flu syndrome including fever
• Swelling of ankles, fingers, feet, face (edema)

Common(may affect up to 1 in 10 people)

• Lack of appetite (anorexia)
• Headache
• Insomnia
• Drowsiness
• Cough
• Runny or stuffy nose
• Constipation
• Diarrhea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Uncommon(may affect up to 1 in 100 people)

• Hardening of the walls of the lung air sacs (interstitial pneumonitis)
• Wheezing (bronchospasm)
• Hardening of the walls of the lungs (abnormal chest X-ray/scan)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure
• Stroke (cerebral infarction)

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

• Low blood pressure
• Peeling of the skin, ulcers or blisters
• Peeling of the skin and blisters on the skin.
• Reactions at the injection site
• Severe lung inflammation causing respiratory failure (adult respiratory distress syndrome).
• Severe sunburn-like rash that can occur on skin that has been previously exposed to radiotherapy (late radiation toxicity) Fluid in the lungs
• Hardening of the walls of the lung air sacs associated with radiotherapy (radiation-associated toxicity)
• Gangrene of the toes or fingers
• Inflammation of the blood vessels (peripheral vasculitis).

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

• Increased platelet count
• Inflammation of the lining of the large intestine, caused by reduced blood supply (ischemic colitis).
• Low hemoglobin levels (anemia), low white blood cell count and low platelet count will be detected by a blood test.
• Thrombotic microangiopathy: clots forming in small blood vessels.

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

• Sepsis: when bacteria and their toxins circulate in your blood and start damaging your organs.
• Pseudo-cellulitis: Redness of the skin with swelling.

You may experience any of these symptoms and/or disorders. You should inform your doctor as soon as possible if you start experiencing any of these side effects.

If you are concerned about any of these side effects, talk to your doctor.

Reporting of side effects

If you experience side effects, talk to your doctor, hospital pharmacist or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Surveillance System for Human Use: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Gemcitabine Hikma

This medicine will be kept and administered by healthcare personnel, who will follow these instructions:

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.
• Store in a refrigerator (between 2°C and 8°C).

6. Container Contents and Additional Information

Composition of Gemcitabina Hikma

• The active ingredient is gemcitabine (as gemcitabine hydrochloride). The concentrated solution has a dose of 38 mg/ml, which means that each milliliter of concentrate contains 38 mg/ml of gemcitabine (as gemcitabine hydrochloride).

• The other components (excipients) are water for injectable preparations, hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment).

Appearance of Gemcitabina Hikma and Container Contents

Transparent, colorless, or slightly yellow solution.

It is packaged in glass vials.

There are 3 container sizes available, containing

200 mg gemcitabine (as hydrochloride) in 5.26 ml of solution

1000 mg gemcitabine (as hydrochloride) in 26.3 ml of solution

2000 mg gemcitabine (as hydrochloride) in 52.6 ml of solution

Each vial is individually packaged in a cardboard box.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó 8, 8A e 8B, Fervença

2705-906 Terrugem SNT

Portugal

Manufacturer

Thymoorgan Pharmazie GmbH

Schiffgraben 23

38690 Goslar

Germany

You can request more information about this medication by contacting the local representative of the Marketing Authorization Holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

Date of the last revision of this prospectus:February 2024

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/The following information is intended only for healthcare professionals:

Instructions for Use, Handling, and Disposal

Shelf Life After Opening:

Chemical and physical stability has been demonstrated for 35 days at 20-25 °C exposed to light and for 35 days at 2-8 °C protected from light.

From a microbiological point of view, unless the opening method excludes the risk of microbial contamination, the product must be used immediately. If it is not used immediately, the storage times and conditions in use are the responsibility of the user.

Use

• Consult the Technical Data Sheet to calculate the dose and the number of vials needed. Dilution of the solution is necessary: An approved diluent for the gemcitabine concentrate is sodium chloride 9 mg/ml (0.9%) injectable solution (without preservatives). Use aseptic techniques during any additional dilution of the gemcitabine concentrate before administration.
• Before administration, parenteral medications should be visually inspected for possible suspended particles and color change. If particles are observed, the medication should not be administered.
• After dilution, chemical and physical stability in use has been demonstrated for:

From a microbiological point of view, prepared solutions should be used immediately. If not used immediately, the storage times and conditions in use and before use are the responsibility of the user and will normally not exceed 24 hours between 2 and 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

Handling

• Normal safety measures for cytostatic agents should be taken into account when preparing and disposing of the infusion solution. Handling of the solution should be performed in a safety cabinet, and protective suits and gloves should be used. If a safety cabinet is not available, the equipment should be supplemented with masks and eye protection.
• If the solution comes into contact with the eyes, it can cause severe irritation. The eyes should be rinsed immediately and thoroughly with plenty of water. If irritation persists, a doctor should be consulted. If the solution spills on the skin, it should be rinsed thoroughly with plenty of water.

Disposal

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.