Gemcitabine accord

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Package leaflet: Information for the user

Gemcitabinum Accord, 100 mg/ml, concentrate for solution for infusion
Gemcitabine
Please read all of this leaflet before use, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• Ask your doctor, pharmacist, or nurse if you have any further questions.
• If any side effect worsens or if you experience any side effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Gemcitabinum Accord is and what it is used for
Gemcitabinum Accord belongs to a group of medicines called cytotoxic agents that work by destroying dividing cells, including cancer cells.
Gemcitabinum Accord may be used alone or in combination with other anticancer medicines, depending on the type of cancer.
Gemcitabinum Accord is used in the treatment of the following types of cancer:

• Non-small cell lung cancer (NSCLC), either as monotherapy 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. Important information before using 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 breastfeeding.

Warnings and precautions
Before starting treatment with Gemcitabinum Accord, speak to your doctor, pharmacist, or nurse.
Before the first infusion, medical staff will take blood samples to assess whether your kidney and liver function are sufficient. Before each infusion, blood samples will be taken to check whether your blood cell count is adequate for administration of Gemcitabinum Accord. Depending on your overall condition and if your blood cell counts are too low, your doctor may adjust the dose or delay treatment. Blood samples will be taken periodically to monitor kidney and liver function.

Inform your doctor:

• If you have ever experienced severe skin rash, skin peeling, blistering, or oral mucositis after receiving gemcitabine,
• If you have or have had liver, heart, or vascular diseases, or kidney problems,
• If you have undergone or will undergo radiotherapy (ionizing radiation), as early or delayed radiation reactions may occur,
• If you have recently been vaccinated, as gemcitabine may cause adverse effects. If during treatment with this medicine you experience symptoms such as headache, confusion, seizures, or visual disturbances, contact your doctor immediately. These may be symptoms of a very rare neurological side effect called posterior reversible encephalopathy syndrome (PRES).
• If you develop breathing difficulties or skin pallor and weakness (which may indicate lung or kidney problems),
• If you suffer from alcoholism, as this product contains ethanol (alcohol),
• If you have epilepsy, as this product contains ethanol (alcohol),
• If you have capillary leak syndrome leading to fluid leakage from small blood vessels into cells. Symptoms may include swelling of the legs, face, and arms, weight gain, hypoalbuminemia (low albumin levels in plasma), hypotension, acute kidney failure, or pulmonary edema.
• If you have posterior reversible encephalopathy syndrome (PRES), characterized by loss of consciousness, epileptic seizures, headache, visual disturbances, focal neurological signs, and acute hypertension.

Serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP), have occurred during gemcitabine treatment. If you experience any symptoms related to serious skin reactions described in section 4, contact your doctor immediately.

Children and adolescents
Due to insufficient data on safety and efficacy, this medicine 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 currently taking, have recently taken, plan to take, and about any vaccinations.

Pregnancy, breastfeeding, and fertility
Do not use Gemcitabinum Accord during pregnancy unless clearly necessary. Consult your doctor before using this medicine if you are pregnant, suspect you may be pregnant, or are planning to become pregnant. Your doctor will inform you about the risks associated with using Gemcitabinum Accord during pregnancy. Women of childbearing potential must use effective contraception during treatment with Gemcitabinum Accord and for 6 months after the last dose. Breastfeeding must be discontinued during treatment with Gemcitabinum Accord.

Fertility
Men are advised not to father a child during treatment with Gemcitabinum Accord and for 3 months after treatment ends. Men should use effective contraception during treatment and for 3 months after treatment completion. Men who wish to have children during or within 3 months after treatment should consult their doctor or pharmacist. Patients may consider seeking advice from a facility specializing in sperm storage before starting treatment.

Driving and using machines
Gemcitabinum Accord may cause drowsiness, especially if alcohol is consumed. The alcohol content in this medicine may impair the ability to drive or operate machinery. Patients should not drive or operate machinery until they know whether Gemcitabinum Accord causes drowsiness in them.

Gemcitabinum Accord contains 44% v/v anhydrous ethanol, up to 9.9 g in the maximum daily dose (2250 mg), equivalent to 250 ml of beer or 100 ml of wine per dose

• It is harmful for individuals with alcohol-related disorders,
• This should be considered in pregnant and breastfeeding women, children, and patients at high risk, such as those with liver disease or epilepsy,
• The alcohol content in this medicine may affect the action of other medicines,
• The alcohol content in this medicine may impair the ability to drive or operate machinery.

Gemcitabinum Accord contains 206 mg (9.0 mmol) of sodium in the maximum daily dose (2250 mg)
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 metre of the patient's body surface area. The body surface area is calculated based on the patient's height and weight measurements. The dose is determined according to 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 Gemcitabinum Accord infusion depends on the type of tumour for which the patient is being treated.

Before administration, the hospital pharmacist or doctor will dilute the concentrate. Gemcitabinum Accord is always administered as an intravenous infusion over approximately 30 minutes.

Gemcitabinum Accord is not recommended for use in children under 18 years of age.

If you have any doubts, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following symptoms occur, you should immediately inform your
doctor:

• Bleeding from the gums, nose or mouth, or other bleeding that cannot be stopped, red or pink discoloration of the urine, unexpected bruising of the skin (which may be due to a reduced number of platelets, a very common occurrence).
• Feeling of fatigue, faintness, rapid onset of breathlessness or paleness of the skin (which may be due to reduced hemoglobin levels, a very common occurrence).
• Mild to moderate skin rash (very common), itching (common), or fever (very common) (allergic reactions).
• Fever of 38ºC or higher, sweating, or other signs of infection (which may be due to a reduced white blood cell count with accompanying fever, known as febrile neutropenia, a common occurrence).
• Pain, redness, swelling, or ulceration in the mouth (oral mucositis) (common).
• Irregular heartbeat (arrhythmia) (uncommon).
• Extreme fatigue and weakness, small spots or petechiae on the skin (bruising), acute kidney failure (low urine output or anuria), and signs of infection (hemolytic-uremic syndrome, which may be fatal) (uncommon).
• Difficulty breathing (very commonly, mild respiratory disturbances may occur shortly after administration of Gemcitabinum Accord and resolve quickly. More severe pulmonary complications may occur uncommonly or rarely).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity reactions / allergic reactions including severe skin rash, red itchy skin, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), wheezing, rapid heartbeat, feeling of faintness (anaphylactic reaction) (very rare).
• Generalized swelling, shortness of breath, or weight gain caused by leakage of fluid from small blood vessels into tissues (capillary leak syndrome) (very rare).
• Headache accompanied by visual disturbances, confusion, seizures or convulsions (reversible posterior encephalopathy syndrome) (very rare).
• Severe skin rash with accompanying itching, blistering, and peeling of the outer layer of skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Extreme fatigue and weakness, small spots or petechiae on the skin (bruising), acute kidney failure (low urine output or anuria), and signs of infection. These may be symptoms indicating thrombotic microangiopathy (formation of clots in small blood vessels) and hemolytic-uremic syndrome, which may lead to death.
• Red, scaly, widespread rash with blisters under swollen skin (including in skin folds, trunk, and upper limbs), and blisters with concurrent fever—acute generalized exanthematous pustulosis (AGEP—frequency unknown).

Other adverse reactions that may occur after administration of Gemcitabinum Accord include:
Very common adverse reactions (may occur in more than 1 in 10 patients):

• Low white blood cell count
• Difficulty breathing
• Vomiting
• Nausea
• Hair loss
• Liver function abnormalities, indicated by abnormal blood test results
• Presence of blood in urine
• Abnormal urine test results: presence of protein in urine
• Flu-like symptoms, including fever
• Swelling of the ankles, fingers, feet, and face

Common adverse reactions (may occur in 1 to 10 patients out of 100):

• Loss of appetite (anorexia)
• Headache
• Insomnia
• Drowsiness
• Cough
• Nasal congestion
• Constipation
• Diarrhea
• Itching
• Excessive sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Uncommon adverse reactions (may occur in 1 to 100 patients):

• Changes in lung alveoli (interstitial pneumonitis)
• Noisy breathing (bronchospasm)
• Lung changes (abnormal chest X-ray findings)
• Heart failure, stroke
• Severe liver damage, including liver failure
• Kidney failure

Rare adverse reactions (may occur in 1 in 1,000 patients):

• Low blood pressure
• Skin peeling, blistering, or ulceration
• Reactions at the injection site
• Formation of large blisters and oozing
• Gangrene of fingers and toes
• Fluid accumulation in the lungs
• Severe pneumonia causing breathing difficulties (adult respiratory distress syndrome)
• Sunburn-like skin rash that may appear in areas previously irradiated (radiation recall reaction)
• Radiation-induced lung damage (radiation-induced toxicity)
• Peripheral vasculitis
• Increased liver enzyme activity (GGT)

Very rare adverse reactions (may occur in 1 in 10,000 patients):

• Increased platelet count
• Ischemic colitis (inflammation of the colon mucosa due to reduced blood flow)
• Thrombotic microangiopathy (formation of clots in small blood vessels)

Low hemoglobin levels (anemia), low white blood cell count, and low platelet count will be detected in blood tests.

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

• Sepsis (a condition in which bacteria and their toxins circulate in the blood and begin to damage organs)
• Pseudoscleroderma (skin redness and swelling resembling scleroderma)

If any of the above adverse reactions occur, you should immediately inform your doctor.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the 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 conditions.
Vial after opening, prior to 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 period and storage conditions.
Concentrate after dilution: chemical and physical in-use stability of the diluted solution in 0.9% sodium chloride solution has been demonstrated for 60 days at 25°C and at temperatures between 2°C and 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 period and conditions prior to use. In such cases, the solution should not be stored for longer than 24 hours at temperatures between 2°C and 8°C, except when dilution has been carried out under controlled and validated aseptic conditions.
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 the specified month.
This medicine will be prepared and administered to the patient by healthcare professionals.
Any unused medicine or waste material must be disposed of by healthcare professionals.

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), concentrated hydrochloric acid (for pH adjustment).

What Gemcitabinum Accord looks like and contents of the pack
Gemcitabinum Accord, concentrate for solution for infusion, is a clear, colourless to slightly yellow solution.
Gemcitabinum Accord is packed in vials made of colourless type I glass, closed with a rubber stopper and an aluminium seal with a "flip-off" cap, and placed 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 Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer / Importer
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Accord Healthcare Single Member S.A.
64th Km National Road Athens
32009 Lamia
Greece

This medicinal product is authorised in the European Economic Area countries under the following names:

Information intended exclusively for medical professionals:

Instructions for preparation, administration and disposal of the medicinal product

Gemcitabinum Accord requires appropriate dilution prior to administration.
The concentration of gemcitabine in Gemcitabinum Accord differs from other available medicinal products containing gemcitabine.
Caution must be exercised, as the solution is a concentrate (100 mg/ml); administration in undiluted form may result in life-threatening overdose.
The Gemcitabinum Accord concentrate for infusion solution must be diluted prior to administration.

• Preparation of the gemcitabine infusion solution must be carried out under aseptic conditions.
• The Gemcitabinum Accord concentrate for infusion is a clear, colourless to slightly yellow solution with a concentration of 100 mg/ml gemcitabine. The total amount of gemcitabine concentrate required for an individual patient should be diluted with sterile sodium chloride 9 mg/ml (0.9%) solution to achieve a final concentration between 0.1 and 9 mg/ml. The diluted solution is also a clear, colourless to slightly yellow solution.
• DEHP (di-(2-ethylhexyl) phthalate), a component of PVC, may leach out during storage of the diluted gemcitabine solution in PVC containers. Therefore, preparation, storage and administration of the diluted solution should be performed using equipment free of PVC.
• Storage precautions

Vial after opening, prior to dilution: each vial is for single use only; its contents should be used immediately after opening. If the product is not used immediately, the user is responsible for storage conditions and duration.
Concentrate after dilution: Chemical and physical stability of the solution diluted in 0.9% sodium chloride solution has been demonstrated for 60 days at 25°C and at temperatures between 2°C and 8°C. From a microbiological standpoint, the infusion solution should be used immediately after preparation. If the product is not used immediately, the user is responsible for storage conditions and duration. In such cases, the solution should not be stored for longer than 24 hours at temperatures between 2°C and 8°C, except when dilution has been performed under controlled and validated aseptic conditions.

Preparation of the infusion solution
The Gemcitabinum Accord concentrate for infusion contains 100 mg of gemcitabine in 1 ml of concentrate solution. Dilution should be performed immediately before administration.
If vials have been stored in the refrigerator, the required number of concentrate packages should be allowed to equilibrate for 5 minutes at below 25°C before use. More than one vial may be required to achieve the required dose for a single patient.
The gemcitabine solution should be withdrawn under aseptic conditions using a calibrated syringe.
The required volume of gemcitabine concentrate should be administered into an infusion bag containing 0.9% sodium chloride solution.
The contents of the bag should be mixed manually by gentle agitation prior to administration. Further dilution using the same diluent may be performed to achieve a final concentration between approximately 0.1 and 9 mg/ml. Considering the maximum dose of gemcitabine (approximately 2.25 g), concentrations of 4.5 mg/ml (achieved using 500 ml diluent) to 9 mg/ml (achieved using 250 ml diluent) correspond to osmolarities ranging from 1000 mOsmol/kg to 1700 mOsmol/kg, respectively.
As with all parenteral medicinal products, the gemcitabine solution should be visually inspected for particulate matter and discoloration prior to infusion. If particulate matter is observed, the solution must not be administered to the patient.

Special precautions for preparation and administration
Standard safety procedures for handling cytotoxic medicinal products must be observed during preparation and disposal of the infusion solution. Preparation should be performed in a safety cabinet using protective clothing and gloves. If a safety cabinet is not available, a protective mask and safety goggles should also be used.
In case of contact with the eyes, the solution may cause severe irritation. Eyes should be immediately and thoroughly rinsed with water. If irritation persists, medical advice should be sought. In case of spillage and skin contact, the skin should be thoroughly washed with water.

Disposal of unused medicinal product and waste
Any unused medicinal product and waste materials should be disposed of in accordance with local regulations.