Gemcitabine Accord

Package leaflet: Information for the user

Gemcitabine Accord 100 mg/ml Concentrate for Solution for Infusion

Generic medicine
Please 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 questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1 What Gemcitabine Accord is and what it is used for
Gemcitabine Accord belongs to a group of medicines called "cytotoxic agents".
These medicines kill dividing cells, including cancer cells.
Gemcitabine Accord may be given alone or in combination with other anticancer medicines, depending on the type of cancer being treated.
Gemcitabine Accord 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 taking Gemcitabine Accord

Do not take Gemcitabine Accord

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Gemcitabine Accord.
Before your first infusion, blood samples will be taken to assess whether your kidney and liver function are adequate. Before each infusion, blood samples will be taken to evaluate whether your blood cell count is sufficient to receive Gemcitabine Accord. Your doctor may decide to adjust the dose or delay your treatment depending on your general condition and if your blood cell count is too low. Periodically, blood samples will be taken to monitor your kidney and liver function.
Inform your doctor if:

• you have or have previously had any liver, heart, vascular disease, or kidney problems.
• you have recently received or are about to receive radiotherapy, as there may be an early or delayed radiation reaction with gemcitabine.
• you have recently been vaccinated, as this could potentially cause harmful effects with gemcitabine.
• during treatment with this medicine, you experience symptoms such as headache with confusion, seizures (fits), or changes in vision, contact your doctor immediately. This could be a very rare nervous system side effect called reversible posterior encephalopathy syndrome.
• you develop breathing difficulties or feel very weak and look very pale (this may be a sign of lung or kidney problems).
• you suffer from alcoholism, because this medicine contains ethanol (alcohol).
• you have epilepsy, because this medicine contains ethanol (alcohol).
• capillary leak syndrome (CLS) occurs, which is when fluids from your small blood vessels leak into the tissues. Symptoms may include swelling of the legs, face, and arms, weight gain, hypoalbuminemia (a mild disorder also known as low blood protein), severe hypotension (low blood pressure), acute kidney failure, and pulmonary edema (fluid in the lungs).
• reversible posterior encephalopathy syndrome (PRES) occurs. Symptoms include altered consciousness, seizure activity, headache, visual disturbances, focal neurological signs, and high blood pressure.

For athletes
For individuals engaged in sports, the use of medicines containing ethyl alcohol may result in positive anti-doping tests, depending on the blood alcohol concentration limits specified by certain sports federations.

Children and adolescents
The use of this medicine is not recommended in children under 18 years of age, as there is insufficient safety and efficacy data.

Other medicines and Gemcitabine Accord
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including vaccines.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor. The use of Gemcitabine Accord should be avoided during pregnancy. Your doctor will inform you of the potential risks of taking Gemcitabine Accord during pregnancy.
You must stop breastfeeding during treatment with Gemcitabine Accord.

Fertility
Men are advised not to father a child during treatment and for up to 6 months after treatment with Gemcitabine Accord. If you wish to conceive a child during or within 6 months after treatment, consult your doctor or pharmacist. You may ask about sperm preservation options before starting therapy.

Driving and using machines
Gemcitabine Accord may cause drowsiness, especially if you consume alcoholic beverages. The amount of alcohol contained in this medicine may impair your ability to drive or operate machinery. Do not drive or operate machinery until you are certain that treatment with Gemcitabine Accord does not make you drowsy.

Gemcitabine Accord contains 44% w/v anhydrous ethanol, up to 9.9 g per maximum daily dose (2,250 mg), equivalent to 250 ml of beer or 100 ml of wine per dose.

• Dangerous for individuals with alcoholism.
• Should be taken into consideration in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.
• The amount of alcohol in this medicine may alter the effects of other medicines.
• The amount of alcohol in this medicine may impair your ability to drive or operate machinery.

Gemcitabine Accord contains 206 mg (9.0 mmol) of sodium per maximum daily dose (2,250 mg).

• Should be taken into consideration in patients on a low-sodium diet.

3. How to take Gemcitabine Accord

The recommended dose of Gemcitabine Accord is 1,000–1,250 mg per square
meter of body surface area. Your height and weight will be measured to
calculate your body surface area. Your doctor will use this body surface area to determine the correct dose to be administered to you. This
dose may be adjusted, or treatment may be delayed, depending on your blood counts and your overall condition.
The frequency with which you receive Gemcitabine Accord depends on the type of cancer for which you are being treated.
A hospital pharmacist or doctor will dilute the gemcitabine concentrate before administering the infusion to you.
You will always receive gemcitabine as an intravenous infusion. The infusion will last approximately
30 minutes.
This medicine is not recommended for use in children under 18 years
of age.
Please consult your doctor or pharmacist if you have any further questions about the use of this
product.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although
not everyone gets them.
You must inform your doctor immediately if you notice any of the following side
effects:

• Bleeding from gums, nose or mouth, or any bleeding that does not stop, reddish or pinkish urine, unexpected bruising (because your platelet count may be lower than normal, which is very common).
• Tiredness, feeling faint, shortness of breath or paleness (because you may have less haemoglobin than normal, which is very common).
• Mild to 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 (because your white blood cell count may be lower than normal and accompanied also by fever, a condition known as febrile neutropenia) (common).
• Pain, redness, swelling or ulcers in the mouth (common).
• Irregular heartbeat (arrhythmia) (frequency not known).
• Extreme tiredness and weakness, purpura or small areas of bleeding in the skin (bruising), acute kidney failure (low urine output/no urine output) and signs of infection (haemolytic-uraemic syndrome). This may be fatal (uncommon).
• Breathing difficulties (it is very common to have mild breathing difficulty shortly after gemcitabine infusion, which soon disappears; however, more serious lung problems may occur in uncommon or rare cases).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity / allergic reaction with severe skin rash including redness of the skin with itching, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), shortness of breath, increased heart rate and feeling faint (anaphylactic reaction) (very rare).
• Generalised swelling, shortness of breath or weight gain, because you may have 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 skin rash with itching, blistering or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).

Other side effects with Gemcitabina Accord may include:
Very common (may affect more than 1 in 10 people)

• Low white blood cells
• Low platelets
• Breathing difficulties
• Vomiting
• Nausea
• Hair loss
• Liver problems: detected through abnormal blood test results
• Blood in urine
• Abnormal urine tests: protein in urine
• Flu-like symptoms, including fever
• Oedema (swelling of ankles, fingers, feet, face)

Common (may affect up to 1 in 10 people)

• • Anorexia (loss of appetite)
• Headache
• Insomnia
• Drowsiness
• Cough
• Runny nose
• Constipation
• Diarrhoea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills

Uncommon (may affect up to 1 in 100 people)

• Interstitial pneumonia (scarring in lung alveoli)
• Respiratory tract spasm (shortness of breath)
• Abnormal chest X-ray/ultrasound (scarring in lungs)
• Heart failure
• Stroke
• Serious liver damage, including liver failure
• Kidney failure

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

• Low blood pressure

• Skin peeling, ulceration or blistering

• Reactions at injection site

• Gangrene of fingers or toes

• Fluid in the lungs

• Adult respiratory distress syndrome (severe lung inflammation causing respiratory failure)

• Skin rash called “radiation recall” (similar to severe sunburn) which may occur on skin previously exposed to radiotherapy

• Radiation toxicity: scarring in lung alveoli associated with radiotherapy

• Inflammation of blood vessels (peripheral vasculitis)

• Skin peeling/severe blistering

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

• Increased platelets
• Ischaemic colitis (inflammation of the colon lining caused by reduced blood supply)

Low levels of haemoglobin (anaemia), white blood cell count and platelet count will be detected through blood tests.
You may experience any of these symptoms and/or conditions. Inform your doctor immediately if you start experiencing any of these side effects.
Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gemcitabine Accord

Keep this medicinal product out of the sight and reach of children.
This medicinal product requires no special storage conditions.
After opening prior to dilution:
Each vial is for single use only and must be used immediately after opening.
If not used immediately, the user is responsible for the duration and conditions of in-use storage.
After dilution:
Chemical and physical in-use stability after dilution in 0.9% sodium chloride solution has been demonstrated for 60 days at 25°C and at 2-8°C.
From a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2-8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.
Do not use this medicinal product after the expiry date stated on the carton or vial after EXP. The expiry date refers to the last day of that month.
The medicine will be prepared and administered by healthcare personnel. Any unused medicinal product must be disposed of by healthcare personnel.

6. Package contents and other information

What Gemcitabina Accord contains

• The active substance is gemcitabine. Each ml of concentrate for solution for infusion 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 excipients are macrogol 300, propylene glycol, anhydrous ethanol, sodium hydroxide (for pH adjustment), concentrated hydrochloric acid (for pH adjustment).

Description of the appearance of Gemcitabina Accord and contents of the pack
Gemcitabina Accord concentrate for solution for infusion is a clear, colourless to slightly yellow solution.
Gemcitabina Accord is contained in clear glass vials closed with a rubber stopper and sealed with an aluminium flip-off cap.
Packs
1 vial of 2 ml
1 vial of 10 ml
1 vial of 15 ml
1 vial of 20 ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona,
s/n, Edifici Est 6ª planta,
08039 Barcelona,
Spain
Manufacturer
Accord Healthcare Limited
Sage House, 319 Pinner Road,
North Harrow, Middlesex, HA1 4HF,
United Kingdom

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

The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling, and disposal

Gemcitabine Accord must be appropriately diluted before use. The

concentration of gemcitabine in Gemcitabine Accord differs from other gemcitabine-containing products.
The concentration must be documented (100 mg/ml); otherwise, a life-threatening overdose may occur.
Gemcitabine Accord must be diluted before administration.

• Use aseptic techniques when preparing gemcitabine for intravenous infusion.
• Gemcitabine concentrate for solution for infusion is a clear, colourless to slightly yellow solution with a concentration of 100 mg/ml of gemcitabine. The total amount of Gemcitabine Accord required for a single patient must be diluted with sterile sodium chloride solution 9 mg/ml (0.9%). Further dilution with the same diluent may be performed to achieve a final concentration between 0.1 and 9 mg/ml. The diluted solution is a clear, colourless to slightly yellow solution.
• DEHP (di-(2-ethylhexyl)phthalate) may leach from plasticized polyvinyl chloride (PVC) containers during storage of the diluted solution of Gemcitabine concentrate for infusion. Therefore, preparation, storage, and administration of the diluted solution must be carried out using non-PVC-containing sets.
• Special storage precautions

After opening, prior to dilution:
Each vial is for single use only and must be used immediately after opening. If not used immediately, the user is responsible for the storage conditions and duration of storage in use.
After dilution:
Chemical and physical in-use stability after dilution in 0.9% sodium chloride solution has been demonstrated for 60 days at 25°C and at 2–8°C.
From a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless the dilution was performed under controlled and validated aseptic conditions.

Preparation of the infusion solution
Gemcitabine Accord contains 100 mg of gemcitabine per ml of concentrate for solution. The concentrate for solution must be diluted before administration.

• If vials have been stored in the refrigerator, allow the required number of Gemcitabine Accord packages to reach below 25°C for 5 minutes before use. More than one vial of Gemcitabine Accord may be needed to achieve the required patient dose.
• Aseptically withdraw the required amount of Gemcitabine Accord using a calibrated syringe.
• Inject the required volume of Gemcitabine Accord into an infusion bag containing 0.9% sodium chloride solution (9 mg/ml).
• Mix the infusion bag manually by gentle agitation. Further dilution with the same diluent may be performed to achieve a final concentration of approximately 0.1–9 mg/ml. Considering the maximum dose of approximately 2.25 g of Gemcitabine Accord, concentrations of 4.5 mg/ml (achieved with 500 ml diluent) and 9 mg/ml (achieved with 250 ml diluent) correspond approximately to an osmolarity of 1,000 mOsmol/kg to 1,700 mOsmol/kg.
• As with all parenteral medications, visually inspect the gemcitabine infusion solution before administration to ensure there are no particles or discoloration. Do not administer if particles are observed.

Preparation and precautions for administration
Standard safety precautions for cytotoxic agents must be observed during preparation and disposal of the infusion solution. Handling of the infusion solution must be performed in a safety cabinet, and protective gowns and gloves must be worn. If a safety cabinet is not available, equipment must be supplemented with a face mask and protective goggles.
If the solution comes into contact with the eyes, it may cause severe irritation. Immediately rinse the eyes thoroughly with abundant water. If irritation persists, consult a physician. If the solution spills onto the skin, wash the skin thoroughly with abundant water.

Disposal
Unused medicine must be disposed of in accordance with local regulations.