Gemcitabine Hikma 1000 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Gemcitabina Hikma 200 mg concentrate for solution for infusion

Gemcitabina Hikma 1000 mg concentrate for solution for infusion

Gemcitabina Hikma 2000 mg concentrate for solution for infusion

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

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

Contents of the leaflet

1. What Gemcitabina Hikma is and what it is used for
2. What you need to know before using Gemcitabina Hikma
3. How to use Gemcitabina Hikma
4. Possible side effects
5. How to store Gemcitabina 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 "cytotoxic agents". These medicines destroy dividing cells, including cancer cells.

Gemcitabine Hikma may be given alone or in combination with other anticancer 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), either 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 using Gemcitabina Hikma

Do not use Gemcitabina Hikma:

• If you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
• If you are breastfeeding.

Warnings and precautions

Before the first infusion, blood samples will be taken to assess whether your liver and kidney function are normal. Before each infusion, blood samples will be taken to evaluate whether you have enough red blood cells to receive gemcitabine treatment.

Your doctor may decide to adjust the dose or delay treatment depending on your general condition and whether your blood cell counts are too low. Blood samples will be taken periodically to monitor your kidney and liver function.

Consult your doctor, pharmacist, or nurse before starting to use gemcitabine.

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

If you have recently received or are about to receive radiotherapy, consult your doctor, as there may be an early or late radiation reaction when using gemcitabine.

If you have recently been vaccinated, consult your doctor, as this could cause adverse effects with gemcitabine.

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

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

If you experience swelling, shortness of breath, or weight gain, please inform your doctor, as this may indicate leakage of fluid from your small blood vessels into the tissues.

If you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth sores 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 immediate medical attention if you notice any 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 of age due to lack of safety and efficacy data in this population.

Other medicines and Gemcitabina Hikma

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including vaccines and over-the-counter medicines.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

Gemcitabine should be avoided during pregnancy. Your doctor will discuss with you the potential risks of using gemcitabine during pregnancy.

Breastfeeding

Inform your doctor if you are breastfeeding.

Breastfeeding must be discontinued during treatment with gemcitabine.

Fertility

Men are advised not to father a child during treatment with gemcitabine or for 6 months after treatment ends. If you wish to father a child during treatment or within 6 months after treatment, seek advice from your doctor or pharmacist. You may wish to request information about sperm preservation before starting treatment.

Driving and use of machines

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

This medicine contains sodium:

Gemcitabina 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 mmol) per vial; therefore, it is essentially **“**sodium-free.”

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

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

3. How to use Gemcitabine Hikma

Your doctor will determine the initial dose of gemcitabine, which depends 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 your body surface area. Your doctor will use this body surface area to calculate the correct dose for you. The usual dose is between 1 g/m² and 1.25 g/m².

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

The frequency with which you receive gemcitabine infusion depends on the type of cancer being treated.

You will always receive gemcitabine as an infusion (a slow injection given through a drip) into one of your veins. The infusion will last approximately 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 further questions about the dose received or about the use of this medicine, ask your doctor, nurse, or pharmacist.

4. Possible adverse effects

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

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

• Bleeding from gums, nose or mouth, or any bleeding that does not stop; reddish or pink urine; unexpected bruising (as you may have lower than normal platelet count, which is very common).
• Tiredness, feeling faint, shortness of breath, or if you appear pale (as you may have lower than normal hemoglobin levels, which is very common).
• Mild or moderate skin rash (very common), itching (common), or fever (very common); (allergic reactions).
• Temperature of 38°C or higher, sweating, or other signs of infection (as you may have lower than normal white blood cell count, 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 areas of bleeding under the skin (bruising), acute kidney injury (low urine output or absence of urine), and signs of infection. These may be signs of thrombotic microangiopathy (blood clots forming in small blood vessels) and hemolytic uremic syndrome, which can be fatal.

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

Other adverse 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: detected through abnormal blood test results
• Blood in urine
• Abnormal urine tests: protein in urine
• Flu-like syndrome including fever
• Swelling of ankles, fingers, feet, face (edema)

Common (may affect up to 1 in 10 people)

• Loss 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 lung alveoli (interstitial pneumonitis)
• Wheezing (spasm of the airways)
• Hardening of lung walls (abnormal chest X-ray/scan)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure
• Cerebral infarction (stroke)

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

• Low blood pressure
• Skin peeling, ulceration, or blistering
• Severe peeling and blistering of the skin
• Reactions at the injection site
• Severe lung inflammation leading to respiratory failure (adult respiratory distress syndrome)
• Skin rash resembling severe sunburn, which may occur in skin previously exposed to radiotherapy (late cutaneous toxicity)
• Fluid in the lungs
• Hardening of lung alveolar walls associated with radiotherapy (radiation-associated toxicity)
• Gangrene of fingers or toes
• Inflammation of blood vessels (peripheral vasculitis)

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

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

Frequency not known (cannot be estimated from available data)

• Sepsis: when bacteria and their toxins circulate in your blood and begin damaging organs
• Pseudocellulitis: skin redness with swelling

You may experience any of these symptoms and/or disorders. You should inform your doctor as soon as possible if you begin to experience any of these adverse effects.

If you are concerned about any of the side effects, consult your doctor.

Reporting of adverse effects

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

5. Storage of Gemcitabine Hikma

This medicine will be handled and administered by healthcare professionals, who must follow the instructions below:

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

6. Contents of the pack and other information

Composition of Gemcitabine Hikma

• The active substance is gemcitabine (as gemcitabine hydrochloride). The concentrate solution has a concentration of 38 mg/mL, meaning that each millilitre of concentrate contains 38 mg of gemcitabine (as gemcitabine hydrochloride).

• The other components (excipients) are water for injections, hydrochloric acid (to adjust pH), and sodium hydroxide (to adjust pH).

Appearance of Gemcitabine Hikma and contents of the pack

Clear, colourless or slightly yellow solution.

It is packaged in glass vials.

Three pack sizes are 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 certain pack sizes may be commercially available.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó 8, 8A and 8B, Fervença
2705-906 Terrugem SNT
Portugal

Manufacturer

Thymoorgan Pharmazie GmbH
Schiffgraben 23
38690 Goslar
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Hikma España, S.L.U.
Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2
28108 - Alcobendas, Madrid
Spain

Date of the most recent revision of this leaflet: February 2024

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/

The following information is intended for healthcare professionals only:

Instructions for use, handling, and disposal

Shelf-life after opening:

Chemical and physical stability has been demonstrated for 35 days at 20–25 °C under light exposure, and for 35 days at 2–8 °C protected from light.

From a microbiological standpoint, unless the opening method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions during use are the responsibility of the user.

Use

• Refer to the Summary of Product Characteristics to calculate the required dose and number of vials. Dilution of the solution is required: An approved diluent for gemcitabine concentrate is sodium chloride 9 mg/mL (0.9%) solution for injection (without preservatives). Use aseptic techniques during any further dilution of the gemcitabine concentrate prior to administration.
• Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, the product must not be administered.
• After dilution, chemical and physical in-use stability has been demonstrated for:

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

Handling

• Standard safety precautions for cytotoxic agents should be observed when preparing and disposing of the infusion solution. The solution should be handled in a safety cabinet, and protective clothing and gloves should be worn. If a safety cabinet is not available, the protective equipment should be supplemented with masks and eye protection.

• If the solution comes into contact with the eyes, it may cause severe irritation. The eyes should be rinsed immediately and thoroughly with abundant water. If irritation persists, medical advice should be sought. If the solution is spilled onto the skin, wash thoroughly with copious amounts of water.

Disposal

Disposal of unused medicinal product and of all materials that have been in contact with it should be carried out in accordance with local regulations.