GEMCITABINE 2 g Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Gemcitabine Accord, 200 mg, powder for solution for infusion
3. Gemcitabine Accord, 1 g, powder for solution for infusion
4. Gemcitabine Accord, 2 g, powder for solution for infusion
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet:
5. What is Gemcitabine Accord and what is it used for
6. Important information before using Gemcitabine Accord
   1. When not to use Gemcitabine Accord
   2. Warnings and precautions
   3. You should inform your doctor:
   4. Children and adolescents
   5. Gemcitabine Accord and other medicines
   6. Pregnancy
   7. Fertility
   8. Breastfeeding
   9. Driving and using machines
   10. Gemcitabine Accord contains
7. How to use Gemcitabine Accord
8. Possible side effects
   1. If you experience any of the following symptoms, contact your doctor immediately:
   2. Other possible side effects of Gemcitabine Accord:
   3. Very common side effects (may affect more than 1 in 10 people):
   4. Common side effects (may affect up to 1 in 10 people)
   5. Uncommon side effects (may affect up to 1 in 100 people)
   6. Rare side effects (may affect up to 1 in 1,000 people)
   7. Very rare side effects (may affect up to 1 in 10,000 people)
   8. Side effects with unknown frequency
   9. Reporting side effects
9. How to store Gemcitabine Accord
10. Contents of the pack and other information
    1. What Gemcitabine Accord contains
    2. What Gemcitabine Accord looks like and contents of the pack
    3. Marketing authorization holder and manufacturer:
    4. This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
    5. Date of last revision of the leaflet: December 2023
    6. The following information is intended for healthcare professionals only:
    7. Instructions for preparation, administration of the medicine, and disposal of its residues
    8. Precautions for preparation and administration of the medicine:
    9. Disposal of residues of the medicine

Leaflet accompanying the packaging: information for the user

Gemcitabine Accord, 200 mg, powder for solution for infusion

Gemcitabine Accord, 1 g, powder for solution for infusion

Gemcitabine Accord, 2 g, powder for solution for infusion

Gemcitabine

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• 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 symptoms are the same as yours.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

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

Gemcitabine Accord belongs to a group of cytotoxic medicines, which work by destroying dividing cells, including cancer cells.
Gemcitabine Accord can be used alone or in combination with other anti-cancer medicines, depending on the type of cancer.
Gemcitabine Accord is used to treat the following types of cancer:

• as monotherapy or in combination with cisplatin for the treatment of non-small cell lung cancer (NSCLC),
• for the treatment of pancreatic cancer,
• in combination with paclitaxel for the treatment of breast cancer,
• in combination with carboplatin for the treatment of ovarian cancer,
• in combination with cisplatin for the treatment of bladder cancer.

2. Important information before using Gemcitabine Accord

When not to use Gemcitabine Accord

• if you are allergic to gemcitabine or any of the other ingredients of this medicine (listed in section 6),
• if you are breastfeeding.

Warnings and precautions

Before the first infusion, medical staff will take blood samples from you to assess whether your kidney and liver function is sufficient. Before each infusion, medical staff will take blood samples from you to assess whether you have enough blood cells to receive Gemcitabine Accord. Depending on your general condition and in case of excessive reduction of blood cell count, your doctor may change the dose or postpone the administration of Gemcitabine Accord. Periodically, blood samples will be taken from you to assess kidney and liver function.

You should inform your doctor:

• if you have ever had a severe skin rash or blistering of the skin after taking gemcitabine,
• if you have or have had liver, heart, vascular, or kidney disease, as gemcitabine may be contraindicated,
• if you have been or are going to be exposed to radiation therapy, as early or late radiation reactions may occur with gemcitabine,
• if you have been recently vaccinated, as this may interfere with the effect of gemcitabine,
• if you experience difficulty breathing or weakness and pallor of the skin (which may be signs of kidney or lung failure).
• if you experience generalized edema, shortness of breath, or weight gain, as these may be signs of fluid leakage from small blood vessels into tissues, a serious condition called capillary leak syndrome.
• if you experience headaches with vision disturbances, confusion, seizures, or changes in vision, you should contact your doctor immediately. These may be signs of a very rare side effect affecting the nervous system, called reversible posterior leukoencephalopathy syndrome.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP) have been reported with gemcitabine. If you experience any of the symptoms related to these severe skin reactions described in section 4, you should contact your doctor immediately.

Children and adolescents

This medicine should not be used in children and adolescents under 18 years of age, as there is limited data on the safety and efficacy of gemcitabine in this age group.

Gemcitabine Accord and other medicines

Tell your doctor or hospital pharmacist about all the medicines you are taking or have recently taken, including vaccines and medicines obtained without a prescription.

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. You should avoid taking Gemcitabine Accord during pregnancy. Your doctor will inform you about the risks associated with taking Gemcitabine Accord during pregnancy. Women of childbearing age must use effective contraception during treatment with Gemcitabine Accord and for 6 months after the last dose.

Fertility

It is recommended that men do not attempt to father a child during treatment with Gemcitabine Accord and for up to 3 months after the end of treatment. It is recommended that men use effective contraception during treatment and for 3 months after the end of treatment. Men should seek advice from their doctor or pharmacist if they wish to have a child during or within 3 months of treatment. Before starting treatment, patients may seek advice from a sperm bank.

Breastfeeding

Women who are breastfeeding should inform their doctor.
During treatment with Gemcitabine Accord, breastfeeding should be discontinued.

Driving and using machines

Gemcitabine Accord may cause drowsiness, especially if you drink alcohol.
Patients should not drive or operate machinery until it is established that Gemcitabine Accord does not cause drowsiness.

Gemcitabine Accord contains

3.5 mg (<1mmol) of sodium per 200 mg vial, 17.5 mg (<1mmol) of sodium per 1 g vial, and 35 mg (1.52 mmol) of sodium per 2 g vial. This should be taken into account for patients on a controlled sodium diet.

3. How to use Gemcitabine Accord

The usual dose of gemcitabine is from 1000 mg to 1250 mg per square meter of body surface area. The body surface area is calculated based on the patient's height and weight. The dose is determined based on the calculated body surface area. The dose may be adjusted or treatment delayed depending on blood test results and the patient's general condition.
The frequency of Gemcitabine Accord infusion depends on the type of cancer being treated.
Before administration, the hospital pharmacist or doctor will dissolve the powder.
Gemcitabine Accord is always administered by intravenous infusion. The infusion lasts about 30 minutes.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

If you experience any of the following symptoms, contact your doctor immediately:

• A temperature of 38°C or higher, sweating, or other signs of infection (due to the possibility of a decrease in white blood cell count with fever, known as febrile neutropenia, which occurs frequently).
• Irregular heart rhythm (arrhythmia) (not very common).
• Pain, redness, swelling, or ulcers in the mouth (stomatitis) (common).
• Allergic reactions: mild to moderate skin rash (very common) and/or itching (common), or fever (very common).
• Feeling tired, fainting, rapid onset of shortness of breath, or pallor of the skin (due to the possibility of a decrease in hemoglobin levels, which occurs very commonly).
• Bleeding from the gums, nose, or mouth, or other bleeding that cannot be stopped, red or pink urine, unexpected bruising of the skin (due to the possibility of a decrease in platelet count, which occurs very commonly).
• Difficulty breathing (very common in the short term after administration of Gemcitabine Accord, mild respiratory disorders may occur, which usually resolve quickly. Less common or rare, more serious pulmonary complications may occur).
• Generalized edema, shortness of breath, or weight gain, as these may be signs of fluid leakage from blood vessels into tissues (capillary leak syndrome) (very rare).
• Headache with vision disturbances, confusion, seizures, or changes in vision, you should contact your doctor immediately. These may be signs of a very rare side effect affecting the nervous system, called reversible posterior leukoencephalopathy syndrome.
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity/allergic reaction with severe skin rash, including redness and itching of the skin, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and feeling of fainting (anaphylactic reaction) (very rare).
• Severe skin rash with itching, blistering, or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Extreme fatigue and weakness, petechiae or small areas of bleeding on the skin (purpura), acute kidney failure (low urine production or absence of urine), and signs of infection. These may be signs of thrombotic microangiopathy (formation of blood clots in small blood vessels) and hemolytic-uremic syndrome, which can be fatal (not very common).
• Red, peeling, widespread rash with blisters under the skin (including skin folds, torso, and upper limbs) and blisters with fever - acute generalized exanthematous pustulosis (AGEP - frequency not known).

Other possible side effects of Gemcitabine Accord:

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

• Low white blood cell count
• Difficulty breathing
• Vomiting
• Nausea
• Hair loss
• Liver function disorders, with abnormal blood test results
• Blood in the urine
• Abnormal urine test results: protein in the urine
• Flu-like symptoms, including fever
• Edema (of the ankles, fingers, feet, and face)

Common side effects (may affect up to 1 in 10 people)

• Lack of appetite
• Headache
• Insomnia
• Drowsiness
• Cough
• Rhinitis
• Constipation
• Diarrhea
• Itching
• Excessive sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Uncommon side effects (may affect up to 1 in 100 people)

• Interstitial lung disease (pulmonary fibrosis)
• Bronchospasm (wheezing)
• Abnormal chest X-ray (pulmonary fibrosis)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure.
• Stroke

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

• Low blood pressure
• Peeling of the skin, blistering, or ulcers on the skin
• Formation of large blisters on the skin and leakage from the skin
• Reactions at the injection site
• Severe pneumonia leading to respiratory failure (adult respiratory distress syndrome)
• Skin rash similar to severe sunburn, which may occur on skin previously exposed to radiation
• Fluid in the lungs
• Lung damage associated with radiation therapy (radiation toxicity)
• Gangrene in the fingers and toes
• Vasculitis (peripheral vasculitis)

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

• Increased platelet count
• Inflammation of the large intestine due to reduced blood flow (ischemic colitis)
• Low hemoglobin level and low white blood cell and platelet count detected in blood tests
• Thrombotic microangiopathy: formation of blood clots in small blood vessels

Side effects with unknown frequency

• Sepsis: when bacteria and their toxins circulate in the blood and start damaging organs
• Pseudoscleroderma: redness of the skin with swelling

If you experience any of the above side effects, you should contact your doctor immediately.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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
fax: + 48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gemcitabine Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
Unopened vial: This medicinal product does not require any special storage conditions.
Reconstituted solution: The medicine should be used immediately after preparation. The physical and chemical stability of the gemcitabine solution prepared according to the instructions has been demonstrated for 21 days at 25°C. Medical staff may further dilute the solution.
The prepared solution should not be stored in the refrigerator, as the medicine may crystallize.
The medicine is for single use only. Any unused solution should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Gemcitabine Accord contains

The active substance is gemcitabine. Each vial contains 200 mg, 1 g, or 2 g of gemcitabine (as gemcitabine hydrochloride).
The other excipients are: mannitol (E421), sodium acetate trihydrate, hydrochloric acid, and sodium hydroxide.

What Gemcitabine Accord looks like and contents of the pack

Gemcitabine Accord is a white or almost white powder for solution for infusion in a vial. Each vial contains 200 mg, 1 g, or 2 g of gemcitabine. Each pack contains one vial of Gemcitabine Accord.
The 200 mg, 1 g, and 2 g vials are available in individual packs.

Marketing authorization holder and manufacturer:

Marketing authorization holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa 7
02-677 Warsaw
Tel: + 48 22 577 28 00
Manufacturer and importer
Accord Healthcare Polska Sp. z o.o.
Lutomierska 50
95-200 Pabianice
Accord Healthcare B.V.
Winthontlaan 200
3526 KV Utrecht
Netherlands

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of the leaflet: December 2023

The following information is intended for healthcare professionals only:

Instructions for preparation, administration of the medicine, and disposal of its residues

• 1. Preparation of the gemcitabine solution and further dilution of the solution for intravenous infusion should be carried out under aseptic conditions.
• 2. Calculate the dose and number of Gemcitabine Accord vials required.
• 3. For reconstitution, add 5 ml to the 200 mg vial, 25 ml to the 1000 mg vial, and 50 ml to the 2000 mg vial of sterile sodium chloride solution for injection without preservatives. Shake to dissolve. The total volume after reconstitution is 5.26 ml (200 mg vial), 26.3 ml (1000 mg vial), or 52.6 ml (2000 mg vial). The solution can be further diluted with sterile sodium chloride solution for injection without preservatives. The prepared solution should be clear, colorless, or slightly yellowish.
• 4. Before parenteral administration, the product should be inspected visually for particulate matter and changes in color. If the solution contains visible particles, the medicine should not be administered.
• 5. The reconstituted solution should not be stored in the refrigerator, as the product may crystallize. The chemical and physical stability of the solution has been demonstrated for 21 days at 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the responsibility for the storage time and conditions before use lies with the user. In this case, the solution should not be stored for more than 24 hours at room temperature, unless reconstitution and/or dilution has taken place in controlled and validated aseptic conditions.
• 6. Gemcitabine solutions are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

Precautions for preparation and administration of the medicine:

When preparing and disposing of the infusion solution, standard safety precautions for handling cytotoxic medicines should be followed. Preparation of the infusion solution should be carried out in a safety cabinet using protective clothing and gloves. If a safety cabinet is not available, a mask and protective glasses should be worn.
In case of accidental contact of the solution with the eyes, it may cause serious irritation. The eyes should be rinsed immediately with water. If irritation persists, medical attention should be sought. If the solution comes into contact with the skin, the skin should be washed immediately with water.

Disposal of residues of the medicine

Any unused product should be disposed of in accordance with local requirements.