Vincristine Eg

Package leaflet: Information for the patient

VINCRISTINA EG 1 mg/ml injection solution for intravenous use

Vincristine sulfate
Please read this leaflet carefully before you are given 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 side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What VINCRISTINA EG is and what it is used for

VINCRISTINA EG contains the active substance vincristine, which belongs to a group of medicines known as antineoplastic agents (anticancer drugs that work by inhibiting the growth of tumour cells). It is administered alone or in combination with other anticancer medicines.

VINCRISTINA EG is used in adults and children to treat:

• acute leukaemias, cancers that develop in blood cells and progress rapidly;
• malignant lymphomas (including Hodgkin's lymphoma, a cancer of the lymphatic system);
• lymphosarcoma, a malignant tumour originating from lymphatic vessels;
• reticulosarcoma, a malignant tumour originating from reticular cells, usually affecting lymph glands;
• neuroblastoma, a malignant tumour arising from immature nerve cells;
• Wilms' tumour, a type of kidney cancer;
• rhabdomyosarcoma, a cancer of the muscles.

2. What you need to know before you are given VINCRISTINA EG

Do not receive VINCRISTINA EG

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• during pregnancy and breastfeeding;
• if you suffer from a neuromuscular disease (nerve and muscle disorder), particularly a form called Charcot-Marie-Tooth syndrome;
• if you have severe liver disease;
• if you suffer from constipation or are at risk of intestinal blockage (ileus), especially in children;
• if you are undergoing radiotherapy involving the liver;
• if you have a bacterial infection.

Warnings and precautions
Since VINCRISTINA EG is an anticancer medicine, it will be administered to you only in a specialized unit and under the supervision of a physician experienced in the use of such medicines. The staff of the unit will explain to you the special precautions you should take before, during, and after treatment. This

The patient information leaflet will help you remember this.

VINCRISTINA EG must be administered only by intravenous route (directly into a vein), not by any other route.
Administration by other routes may result in patient death, as occurs with intrathecal administration.
Before each administration, blood samples will be taken to check whether you have sufficient blood cells to receive VINCRISTINA EG.
Your doctor may decide to adjust the dose or interrupt treatment depending on your general condition and if blood tests show inadequate results.
Before VINCRISTINA EG is administered to you, inform your doctor

• if you have or have had liver or heart problems;
• if you have recently undergone or are scheduled to undergo radiotherapy involving the liver;
• if you have or develop an infection. Generally, your doctor will treat your infection before administering vincristine to you.

You should be aware that treatment with VINCRISTINA EG may cause side effects such as

• constipation; therefore, your doctor may recommend an appropriate diet and preventive treatment with laxatives (particularly lactulose);
• hair loss.

Other medicines and VINCRISTINA EG
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
The following medicines may affect and/or increase the toxicity of VINCRISTINA EG, and vice versa:

• digoxin and nifedipine (used to treat certain heart conditions);
• certain antibiotics (e.g. erythromycin, bleomycin, mitomycin C);
• medicines for epilepsy (e.g. phenytoin);
• ketoconazole (used to treat fungal infections and Cushing's syndrome, a condition characterized by excessive production of the hormone cortisol);
• azole antifungals (a group of medicines used to treat fungal infections such as itraconazole, posaconazole, fluconazole, isavuconazole, or voriconazole);
• other medicines used to treat cancer (e.g. doxorubicin, dactinomycin);
• other neurotoxic medicines such as isoniazid, L-asparaginase, and cyclosporine A;
• cyclosporine and tacrolimus (used to prevent organ transplant rejection);
• vaccines;
• radiotherapy.

Pregnancy, breastfeeding and fertility
Pregnancy
Vincristine must not be used if you are pregnant. If treatment with vincristine is essential for you, your doctor will evaluate the potential risks to the unborn child.
If you are a woman of childbearing age, you must avoid becoming pregnant during treatment and for 6 months after stopping therapy with VINCRISTINA EG.
Male and female patients of reproductive age must use an effective method of contraception during treatment and for at least 6 months after its completion.
If you become pregnant during this period, inform your doctor immediately.
Breastfeeding
Do not breastfeed during treatment with VINCRISTINA EG.
Fertility
Vincristine may reduce fertility in both men and women.
Since VINCRISTINA EG may cause permanent infertility, before starting treatment, your doctor will inform male patients about the possibility of sperm preservation.
Driving and use of machines
Given the possible adverse effects on the nervous system, such as reduced reflexes, muscle weakness, and visual disturbances, this medicine may affect your ability to drive vehicles or operate machinery.
VINCRISTINA EG contains methyl parahydroxybenzoate and propyl parahydroxybenzoate
These may cause allergic reactions (including delayed reactions) and, rarely, bronchospasm.
VINCRISTINA EG contains sodium
This medicine contains 10.37 mg of sodium (a component of common table salt) per vial.
This corresponds to 0.52% of the maximum daily recommended dietary intake for an adult.

3. How VINCRISTINA EG is administered

EXCLUSIVELY FOR INTRAVENOUS USE. POTENTIALLY FATAL IF
ADMINISTERED BY OTHER ROUTES.
VINCRISTINA EG will be administered exclusively intravenously (into a vein) and only by personnel
experienced in the administration of vincristine.
VINCRISTINA EG will be administered once a week. The injection will take approximately 1 minute.
The amount of medicine to be administered will depend on your age, body size, and general medical
condition. It will also depend on which other treatments you have received for cancer therapy.
Your height and weight will be measured to calculate your body surface area. Your doctor will use this
body surface area in square meters (m²) to calculate the correct dose for you.
The recommended initial dose is:
Adults: a single dose of 1.4 mg/m².
Children: a single dose of 2 mg/m². In children weighing equal to or less than 10 kg, the initial dose is
0.05 mg/kg.
Patients with impaired liver function
If your liver is not functioning properly, your doctor will halve the recommended dose. In more severe cases,
your doctor may decide not to administer VINCRISTINA EG.
If you receive more VINCRISTINA EG than you should or if a dose of VINCRISTINA EG is missed
Since VINCRISTINA EG is administered by a doctor or nurse, it is unlikely that too much will be given or that
a dose will be missed.
If you suspect that you have received an excessive dose of VINCRISTINA EG, contact your doctor or
nurse immediately.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Your doctor will explain these side effects to you and will discuss the risks and benefits associated with using this medicine. Most of the side effects are reversible and depend on the dose of medicine taken.

Very common: may affect more than 1 in 10 people:

• Hair loss (resolves within 6 weeks after stopping treatment).

Common: may affect up to 1 in 10 people:

• Sudden onset of breathlessness and difficulty breathing due to spasms of the airway muscles (bronchospasm), particularly if the medicine is used concomitantly with mitomycin C;
• Transient increase in platelets (thrombocytosis);
• Peripheral neuropathy, which includes damage to the peripheral nervous system, nerves that carry electrical signals from the brain and spinal cord to the rest of the body and vice versa. This may affect movement, sensation, and bodily functions; symptoms may include sensory disturbances, tingling, itching, or prickling sensations without apparent cause, nerve pain (including in the jaw/mandible or testicles), movement problems, loss of certain reflexes (deep tendon reflexes), paralysis, or muscle weakness in the feet (foot drop), muscle weakness, coordination problems (e.g., walking as if intoxicated), and paralysis. Cranial nerves may be affected, which can result in paralysis of certain muscles, laryngeal muscle weakness, hoarseness, vocal cord paralysis, weakness of the external eye muscles, drooping eyelids (ptosis), double vision, eye nerve disorders, disorders of the external eye nerves, and transient blindness;
• Nausea, vomiting, constipation, intestinal obstruction, abdominal pain;
• Male infertility, absence of sperm in semen (azoospermia);
• Irritation at the injection site.

Uncommon: may affect up to 1 in 100 people:

• Seizures (often associated with high blood pressure in adults and followed by coma in children), depression, agitation, insomnia, confusion, hallucinations;
• Loss of appetite, weight loss, diarrhoea, oral ulceration, paralytic ileus (a condition in which the intestine stops functioning and peristalsis ceases);
• Production of large amounts of urine (polyuria), difficulty urinating (dysuria), urinary retention, kidney damage due to high concentrations of uric acid;
• Heart problems, heart attack;
• Severe suppression of bone marrow function, anaemia, reduction in white blood cells (leucopenia) and platelets (thrombocytopenia);
• Deafness;
• Absence of menstruation in women;
• Fever, inflammation of a vein (phlebitis), pain and changes at the injection site.

Rare: may affect up to 1 in 1,000 people:

• Allergic reactions such as anaphylaxis, skin rash, and generalized swelling (oedema). These side effects occurred when vincristine was administered in combination with other medicines;
• Inflammation of the mouth, degeneration of intestinal tissue (necrosis) and/or intestinal perforation;
• Increased and decreased blood pressure;
• Liver vein damage (hepatic veno-occlusive disease), particularly in children;
• Severe reduction in blood sodium levels (hyponatraemia), causing low blood pressure, dehydration, and generalized swelling;
• Headache.

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

• Inflammation of the pancreas (pancreatitis);
• Urinary incontinence.

Not known frequency: frequency cannot be estimated from the available data:

• Leucoencephalopathy (brain disease).

Other side effects
Cases of therapy-related malignant tumours have also been reported with vincristine in combination with other anticancer medicines.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you help provide more information on the safety of this medicine.

5. How to store VINCRISTINA EG

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.
The medicine must be stored in the refrigerator (between +2°C and +8°C).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What VINCRISTINA EG contains

• The active substance is vincristine (as vincristine sulfate). One vial contains 1 mg of vincristine.
• The other components are: methyl parahydroxybenzoate and propyl parahydroxybenzoate, mannitol, acetic acid and sodium acetate, water for injections.

Description of the appearance of VINCRISTINA EG and contents of the pack
Clear, colourless solution.
VINCRISTINA EG is available in packs containing 1 mg in 1 glass vial.
Marketing Authorization Holder
EG S.p.A., Via Pavia, 6 – 20136 Milan, Italy
Manufacturer
STADA Arzneimittel AG, Stadastraße 2-18, 61118 Bad Vilbel (Germany)

The following information is intended exclusively for healthcare professionals:

Syringes containing this product, prepared by healthcare personnel, must be labeled with the following statement:
“DO NOT REMOVE THE PROTECTION UNTIL IMMEDIATELY BEFORE INJECTION.
FOR INTRAVENOUS USE ONLY. FATAL IF ADMINISTERED BY OTHER ROUTES.”

As with all antineoplastic agents, VINCRISTINA EG must be handled with care. Dilution of the medicinal product must be carried out under aseptic conditions in a designated area by trained personnel. All necessary precautions must be taken to avoid contact with skin and mucous membranes.

Precautions for preparation and administration:
Standard safety precautions for cytotoxic agents must be observed when preparing and disposing of the infusion solution. Handling of the infusion solution must be performed in a safe environment, and protective clothing and gloves must be worn. If a safe environment is not available, protective equipment must include a face mask and safety goggles. If the solution comes into contact with the eyes, it may cause severe irritation. Eyes must be immediately and thoroughly rinsed with water. If irritation persists, medical advice must be sought. If the solution contacts the skin, wash thoroughly with water.

Dilute exclusively with 0.9% sodium chloride solution or 5% glucose solution.

Prior to administration, parenteral medications must be visually inspected for particulate matter and/or discoloration whenever solution and container permit. Do not add any liquids to the vial contents before withdrawing the exact required dose; draw up the accurately calculated dose using a perfectly dry syringe.

VINCRISTINA EG must not be diluted with solvents that alter the pH of the resulting solution outside the range of 3.5 to 5.5. Solutions must be prepared using either physiological saline or 5% glucose in water.

DO NOT USE OTHER DILUENT SOLUTIONS.

If vincristine is administered in combination with L-asparaginase, vincristine must be administered 12 to 24 hours before the enzyme to minimize acute toxicity.

The dose of VINCRISTINA EG may be injected into the tubing of an ongoing intravenous infusion or administered directly into a vein. The latter method is more suitable for outpatient therapy. It is extremely important that the needle is correctly positioned within the vein before injecting the product.

Inject the dose over approximately one minute, taking all necessary precautions to ensure proper needle placement in the vein and to prevent leakage of the solution, which may cause subcutaneous tissue irritation and phlebitis.

WARNING: Accidental extravasation of VINCRISTINA EG solution may cause severe irritation. Injection must be stopped immediately, and the remaining portion of the solution must be injected into another vein. Dispersal of extravasated drug may be facilitated by applying warm compresses or hyaluronidase. These measures help reduce pain and the risk of local tissue reactions.

Disposal
All devices used in the preparation, administration, or otherwise coming into contact with VINCRISTINA EG must be disposed of in accordance with local guidelines for handling cytotoxic compounds.