Gemcitabinum Accord

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

Gemcitabinum Accord belongs to a group of cytotoxic medicines which work by killing dividing cells, including cancer cells. Gemcitabinum Accord can be used alone or in combination with other anti-cancer medicines, depending on the type of cancer being treated. Gemcitabinum 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 you use Gemcitabinum Accord

When not to use Gemcitabinum Accord

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

Warnings and precautions

Before you start using Gemcitabinum Accord, talk to your doctor, pharmacist, or nurse. Before the first infusion, your medical team will take blood samples to check if your kidneys and liver are working properly. Before each infusion, your medical team will take blood samples to check if you have enough blood cells to receive Gemcitabinum Accord. Depending on your general condition and if you have a reduced number of blood cells, your doctor may change the dose or delay the treatment. Blood samples will be taken periodically to check your kidney and liver function. You should tell your doctor:

• if you have ever had a severe skin rash or blistering of the skin after receiving gemcitabine,
• if you have or have had liver, heart, or vascular problems, or kidney problems,
• if you have received or are going to receive radiation therapy, as radiation recall reactions can occur,
• if you have recently been vaccinated or plan to be vaccinated, as gemcitabine may interfere with the effect of the vaccine. If you experience symptoms such as headache, confusion, seizures, or vision disturbances while receiving gemcitabine, contact your doctor immediately, as these may be symptoms of a rare side effect affecting the nervous system called reversible posterior leukoencephalopathy syndrome.
• if you experience difficulty breathing or weakness and pale skin (which may be signs of lung or kidney problems),
• if you have a history of alcoholism, as this product contains ethanol (alcohol)
• if you have epilepsy, as this product contains ethanol (alcohol)
• if you have capillary leak syndrome, which can cause swelling, low blood pressure, and thickening of the blood.
• if you have reversible posterior leukoencephalopathy syndrome (PRES), which can cause loss of consciousness, seizures, headache, vision disturbances, and high blood pressure.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP) have been reported with gemcitabine use. If you experience any symptoms of severe skin reactions, contact your doctor immediately.

Children and adolescents

Due to the lack of data on safety and efficacy, Gemcitabinum Accord is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Gemcitabinum Accord

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any vaccines you have received or plan to receive.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. You should not use Gemcitabinum Accord during pregnancy. Your doctor will discuss the potential risks with you. Women of childbearing potential must use effective contraception during treatment with Gemcitabinum Accord and for 6 months after the last dose. You should not breast-feed while using Gemcitabinum Accord.

Fertility

Men are advised not to father a child during treatment with Gemcitabinum Accord and for up to 3 months after the last dose. Men are advised to use effective contraception during treatment and for 3 months after the last dose. If you plan to have a child after treatment with Gemcitabinum Accord, consult your doctor or pharmacist for advice. Before starting treatment, patients may consult a fertility preservation centre.

Driving and using machines

Gemcitabinum Accord may cause drowsiness, especially when taken with alcohol. The ethanol content in this product may impair your ability to drive or use machines. You should not drive or operate machinery until you know how Gemcitabinum Accord affects you.

Gemcitabinum Accord contains ethanol (alcohol)

• -it is harmful to individuals with alcohol dependence
• -it should be taken into account in pregnant or breast-feeding women, children, and high-risk groups such as patients with liver disease or epilepsy
• the alcohol content in this product may interact with other medicines
• the alcohol content in this product may impair your ability to drive or use machines

Gemcitabinum Accord contains sodium

This should be taken into account for patients on a controlled sodium diet.

3. How to use Gemcitabinum Accord

The recommended dose of Gemcitabinum Accord is 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 adjusted according to the calculated body surface area. The dose may be adjusted or delayed based on the results of blood tests and the patient's overall condition. The frequency of Gemcitabinum Accord infusion depends on the type of cancer being treated. Before administration, the hospital pharmacist or doctor will dilute the concentrate. Gemcitabinum Accord is always given by intravenous infusion, which takes about 30 minutes. Gemcitabinum Accord is not recommended for use in children under 18 years of age. If you have any questions, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Gemcitabinum Accord can cause side effects, although not everybody gets them. If you experience any of the following symptoms, contact your doctor immediately:

• Bleeding from the gums, nose, or mouth, or any other bleeding that does not stop, red or pink urine, unexplained bruising on the skin (which may be due to a reduced number of platelets, a very common side effect).
• Feeling tired, fainting, shortness of breath, or pale skin (which may be due to a reduced number of red blood cells, a very common side effect).
• Mild to moderate skin rash (very common), itching (common), or fever (very common) (allergic reactions),
• Fever above 38°C, sweating, or other signs of infection (which may be due to a reduced number of white blood cells with fever, a common side effect).
• Pain, redness, swelling, or ulcers in the mouth (mouth ulcers) (common).
• Irregular heartbeat (arrhythmia) (uncommon).
• Extreme tiredness and weakness, small spots or bruising on the skin (petechiae), acute kidney failure (low urine output or inability to urinate), and signs of infection (hemolytic uremic syndrome, which can be life-threatening) (uncommon).
• Difficulty breathing (very common in the short term after Gemcitabinum Accord administration, mild breathing difficulties may occur, which usually resolve quickly. Less common or rare, more serious lung complications may occur).
• Severe chest pain (heart attack) (rare).
• Severe allergic reactions, including anaphylaxis, which can cause difficulty breathing or swallowing, swelling of the face, lips, tongue, or throat, hives, and a fast heartbeat (very rare).
• Generalized swelling, shortness of breath, or weight gain due to fluid leakage from small blood vessels (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures, or tremors (reversible posterior leukoencephalopathy syndrome) (very rare).
• Severe skin rash with itching, blistering, and peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Extreme tiredness and weakness, small spots or bruising on the skin (petechiae), acute kidney failure (low urine output or inability to urinate), and signs of infection (which may indicate thrombotic microangiopathy and hemolytic uremic syndrome, which can be life-threatening).
• Red, blistering, widespread rash with blisters under the skin (including in skin folds, on the trunk, and upper limbs) and fever - acute generalized exanthematous pustulosis (AGEP) (frequency not known).

Other side effects that may occur with Gemcitabinum Accord include:

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 abnormalities, which may be indicated by abnormal blood test results
Blood in the urine
Abnormal urine test results: protein in the urine
Flu-like symptoms, including fever
Swelling of the ankles, fingers, feet, and face
Common side effects (may affect up to 1 in 10 people)
Lack of appetite (anorexia)
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)
Lung changes (interstitial lung disease)
Wheezing (bronchospasm)
Lung changes (abnormal chest X-ray)
Heart failure, stroke
Severe liver damage, including liver failure
Kidney failure
Rare side effects (may affect up to 1 in 1000 people)
Low blood pressure
Peeling skin, blistering, or ulcers on the skin
Reactions at the injection site
Large blisters on the skin and leaking of fluid
Gangrene of the fingers and toes
Fluid accumulation in the lungs
Severe lung inflammation causing breathing difficulties (adult respiratory distress syndrome)
Skin rash similar to sunburn, which may occur in areas previously exposed to radiation (radiation recall)
Lung damage related to radiation therapy (radiation toxicity)
Inflammation of blood vessels (vasculitis)
Increased liver enzyme activity (GGT)
Very rare side effects (may affect up to 1 in 10,000 people)
Increased platelet count
Ischemic colitis (inflammation of the colon due to reduced blood flow)
Microangiopathic hemolytic anemia (formation of blood clots in small blood vessels)
Low hemoglobin level and low white blood cell and platelet count, which may be detected in blood tests.
Frequency not known (cannot be estimated from the available data)
Septicemia (bacteria and their toxins in the blood, which can cause organ damage)
Pseudosarcomatous thrombophlebitis (inflammation of the vein wall, which can cause swelling and redness)
If you experience any of the above side effects, contact your doctor immediately.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Further information" section. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gemcitabinum Accord

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage precautions.
Vial after opening, before dilution: each vial is for single use only, and its contents should be used immediately after opening. If the product is not used immediately, the user is responsible for the storage conditions and storage period.
Diluted solution: the chemical and physical stability of the solution after dilution in 0.9% sodium chloride solution has been demonstrated for 60 days at 25°C and at a temperature range of 2°C to 8°C. From a microbiological point of view, the infusion solution should be used immediately after preparation. If the product is not used immediately, the user is responsible for the storage conditions and storage period. In this case, the solution should not be stored for more than 24 hours at a temperature range of 2°C to 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.
Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
This medicine will be prepared and administered to you by healthcare professionals.
Any unused medicine or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Gemcitabinum Accord contains

The active substance is gemcitabine. Each ml of concentrate contains 100 mg of gemcitabine (as gemcitabine hydrochloride). Each vial contains 200 mg, 1000 mg, 1500 mg, or 2000 mg of gemcitabine (as gemcitabine hydrochloride). The other ingredients are macrogol 300, propylene glycol, anhydrous ethanol, sodium hydroxide (for pH adjustment), and hydrochloric acid (for pH adjustment).

What Gemcitabinum Accord looks like and contents of the pack

Gemcitabinum Accord is a clear, colorless to pale yellow solution for infusion. Gemcitabinum Accord is packaged in colorless glass vials (Type I) with a rubber stopper and an aluminum flip-off seal, in a cardboard box.
Pack sizes:
1 vial of 2 ml
1 vial of 10 ml
1 vial of 15 ml
1 vial of 20 ml

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa 7
02-677 Warsaw
Phone: +48 22 577 28 00
Manufacturer/Importer
Accord Healthcare Polska Sp. z o.o.
Lutomierska 50
95-200 Pabianice
Accord Healthcare Single Member S.A.
64th Km National Road Athens
32009 Lamia
Greece

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

Date of last revision of the leaflet: November 2024

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Information intended for healthcare professionals only:

Instructions for preparation, administration, and disposal of the medicinal product

Gemcitabinum Accord requires proper dilution before administration. The concentration of gemcitabine in Gemcitabinum Accord differs from other available gemcitabine-containing medicines. It is essential to note that the solution is a concentrate (100 mg/ml), and its use in an undiluted form can lead to life-threatening overdose.The Gemcitabinum Accord concentrate for solution for infusion must be diluted before administration.

• Preparation of the infusion solution should be performed under aseptic conditions.
• The Gemcitabinum Accord concentrate for solution for infusion is a clear, colorless to pale yellow solution containing 100 mg of gemcitabine per ml. The required dose for an individual patient should be diluted with sterile 0.9% sodium chloride solution to achieve a final concentration of 0.1 to 9 mg/ml. The diluted solution is also a clear, colorless to pale yellow solution.
• DEHP (di-(2-ethylhexyl) phthalate), a component of PVC, may leach into the diluted gemcitabine solution during storage in PVC containers. Therefore, preparation, storage, and administration of the diluted solution should be performed using non-PVC containers.
• Precautions for storage

Vial after opening, before dilution: each vial is for single use only, and its contents should be used immediately after opening. If the product is not used immediately, the user is responsible for the storage conditions and storage period. Diluted solution: the chemical and physical stability of the solution after dilution in 0.9% sodium chloride solution has been demonstrated for 60 days at 25°C and at a temperature range of 2°C to 8°C. From a microbiological point of view, the infusion solution should be used immediately after preparation. If the product is not used immediately, the user is responsible for the storage conditions and storage period. In this case, the solution should not be stored for more than 24 hours at a temperature range of 2°C to 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

Preparation of the infusion solution

The Gemcitabinum Accord concentrate for solution for infusion contains 100 mg of gemcitabine per ml. Dilution of the concentrate should be performed immediately before administration. If the vials are stored in the refrigerator, the required number of vials should be removed and allowed to stand for 5 minutes below 25°C before use. To achieve the required dose for an individual patient, more than one vial may be necessary. Using a calibrated syringe, the gemcitabine solution should be drawn up under aseptic conditions. The required volume of the concentrate should be added to an infusion bag containing 0.9% sodium chloride solution. The contents of the bag should be mixed manually by shaking. Further dilution using the same diluent can be performed to achieve a final concentration of approximately 0.1 to 9 mg/ml. Considering the maximum dose of gemcitabine (approximately 2.25 g), the concentrations of 4.5 mg/ml (achieved with 500 ml of diluent) and 9 mg/ml (achieved with 250 ml of diluent) correspond to osmolality values ranging from 1000 mOsmol/Kg to 1700 mOsmol/Kg. As with all parenteral drugs, the gemcitabine solution should be inspected visually for particulate matter or discoloration before administration. If particulate matter is observed, the solution should not be administered.

Special precautions for preparation and administration

When preparing and disposing of the infusion solution, standard safety precautions for handling cytotoxic agents should be followed. Preparation of the infusion solution should be performed in a laminar flow cabinet using protective clothing and gloves. If a laminar flow cabinet is not available, a mask and protective glasses should be worn. In case of accidental exposure to the skin or eyes, the affected area should be rinsed immediately with water. If irritation persists, medical attention should be sought. In case of spillage, the skin should be washed immediately with water.

Disposal of the medicinal product

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.