Vincristine teva

Vincristine Teva, 1 mg/ml, solution for injection
vincristini sulfas

Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed strictly for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Vincristine Teva is and what it is used for

Vincristine sulfate belongs to a group of medicines known as antimicrotubule cytostatic agents.
These medicines inhibit the growth of cancer cells.
Vincristine Teva is usually used in combination with other medicines for the treatment of:

• Acute lymphoblastic leukemia, a rapidly progressing cancer in which the body produces large numbers of immature white blood cells.
• Hodgkin's disease, a malignant disorder of the lymphatic system.
• Non-Hodgkin's lymphomas, cancers of the lymph nodes not caused by Hodgkin's disease.
• Small cell lung cancer.
• Rhabdomyosarcoma, a cancer of the skeletal muscles.
• Ewing's sarcoma, a type of bone cancer.
• Bleeding (internal hemorrhage) associated with low platelet count (idiopathic thrombocytopenic purpura).
• Adrenal cortical carcinoma (a tumor of the adrenal gland).
• Primitive neuroectodermal tumors, cancers of parts of the nervous system.
• Wilms' tumor, a type of kidney cancer.
• Metastatic breast cancer (breast cancer that has spread to other parts of the body).
• Multiple myeloma, a cancer of immune system cells.
• Retinoblastoma, a type of eye cancer.

2. Important information before using Vincristine Teva

When NOT TO USE Vincristine Teva:

• if the patient has hypersensitivity to vincristine sulfate or any of the other ingredients of this medicine (listed in section 6)
• if the patient has neuromuscular disorders known as Charcot-Marie-Tooth disease
• if the patient has severe liver function impairment
• if the patient has constipation or risk of intestinal obstruction (bowel blockage), especially in children
• if the patient is receiving radiotherapy involving the liver.

Warnings and precautions
Vincristine Teva should be administered only under strict supervision of physicians experienced in the use of cytostatic agents (medicines used in cancer treatment).
Vincristine Teva must be administered intravenously only (into a vein) and must not be given by any other route. Other routes of administration may result in patient death.
Care must be taken to avoid leakage into surrounding tissues (extravasation), as this may cause significant irritation. The infusion should be stopped immediately if this occurs.
Avoid contact of vincristine sulfate with the eyes. In case of contact with the eyes, rinse immediately with copious amounts of water. If irritation persists, consult a physician.
In case of accidental skin contact, wash thoroughly with large amounts of water, followed by mild soap and then rinse again thoroughly.
Before starting treatment with Vincristine Teva, discuss with your doctor if the patient:

• has disorders of the nervous system
• has liver function disorders; see also section “How to use Vincristine Teva”
• is taking medicines which may have harmful effects on the nervous system; the doctor will closely monitor the patient during treatment
• develops constipation during treatment; the doctor will take preventive measures, e.g. dietary adjustments or agents improving intestinal motility (laxatives, especially lactulose)
• has heart diseases, including ischaemic conditions (diseases related to heart and circulation)
• has an infection or develops an infection during treatment; inform the doctor
• is sexually active; during treatment and for 6 months after its completion, both the patient and their partner should use effective contraception.

The doctor will perform tests to monitor liver and kidney function, blood cell counts, and neurological function before starting treatment, during treatment, and before each treatment cycle. Based on the results, it may be necessary to reduce the dose or suspend or discontinue treatment.

Vincristine Teva and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Interactions may occur when this medicine is used concomitantly with:

• certain medicines that inhibit liver enzyme activity, e.g. ritonavir (used in HIV treatment), nelfinavir (used in HIV treatment), ketoconazole (used to treat fungal infections), itraconazole (used to treat fungal infections), erythromycin (used to treat infections), and nefazodone (used to treat depression);
  concomitant use of these medicines with vincristine may lead to premature and/or increased muscle disorders

• certain medicines used to treat high blood pressure, e.g. nifedipine; these may increase vincristine blood levels, potentially increasing the risk of adverse effects

• certain medicines used to treat epilepsy, e.g. phenytoin, fosphenytoin; vincristine may reduce blood levels of phenytoin

• certain anticancer medicines and other agents that suppress bone marrow function, such as doxorubicin (especially in combination with prednisone); there is a possibility of enhanced effects, adverse reactions, and bone marrow suppression

• certain medicines with neurotoxic effects, such as isoniazid (used to treat tuberculosis), L-asparaginase (used to treat blood cancers), and cyclosporine A (an immunosuppressant); these may potentially enhance the neurotoxic effects of vincristine

• vaccines (vaccinations); vincristine suppresses immune function and may affect the body’s ability to respond to vaccines

• digoxin (used to treat heart failure and cardiac arrhythmias); vincristine may reduce the effectiveness of digoxin

• mitomycin C (used to treat certain cancers); concomitant administration with vincristine may cause respiratory disturbances

• radiotherapy (treatment of diseases with radiation); radiotherapy may enhance the neurotoxic adverse effects of vincristine

• cyclosporine, tacrolimus; when used concomitantly, they may impair the immune system’s ability to protect the body against disease (immunosuppression) and increase the risk of certain cell proliferation (lymphoproliferation)

• GM-CSF and G-CSF (medicines used to stimulate blood cell growth after chemotherapy); concomitant use with vincristine may cause nerve disease (neuropathy)

• dactinomycin; in patients with kidney cancer (Wilms' tumour), cases of severe liver damage have been reported

• bleomycin; this combination may cause impaired blood flow to the extremities, including fingers and toes, nose and ears, especially when exposed to temperature changes or stress (Raynaud's syndrome)

• azole antifungal medicines (a group of medicines used to treat fungal infections, e.g. itraconazole, posaconazole, fluconazole, isavuconazole, or voriconazole); adverse effects of vincristine may be worsened

• ketoconazole (used to treat Cushing's syndrome, a condition characterized by excessive cortisol hormone secretion); adverse effects of vincristine may be worsened.

Pregnancy, breastfeeding and fertility

If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy

• Use of vincristine during pregnancy is not recommended.
• Both women and men should use effective contraception during treatment and for six months after its completion.
• Female patients who suspect they are pregnant or plan to become pregnant should contact their doctor.
• There are insufficient data on the use of vincristine sulfate in human pregnancy to assess potential adverse effects. Animal studies have shown harmful effects of the drug.

Breastfeeding

• DO NOT breastfeed during treatment with Vincristine Teva.

Fertility

• Vincristine may cause infertility, which may be irreversible. Male patients are advised to avoid fathering a child during treatment and for 6 months after its completion, and to seek advice regarding the possibility of sperm storage (sperm banking) before treatment begins.

Driving and using machines
Treatment with Vincristine Teva may occasionally cause adverse effects affecting the nervous system, such as reduced reflexes, muscle weakness, and visual disturbances, as well as gastrointestinal adverse effects (see “Possible side effects”). Patients experiencing any of these adverse effects MUST NOT drive or operate machinery requiring heightened attention.

Vincristine Teva contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use Vincristine Teva

Vincristine Teva must always be used exactly as directed by the doctor. In case of doubt,
contact your doctor or pharmacist again.
If you feel that Vincristine Teva is too strong or not effective enough,
contact your doctor.

Vincristine must be administered intravenously only:
The recommended dose is:

• Adults The usual dose in adult patients is 1.4 mg per square metre of body surface area (body size) (maximum 2 mg) once weekly.
• Children In children weighing more than 10 kg, the usual dose is 1.5 to 2.0 mg per square metre of body surface area once weekly. For children weighing 10 kg or less, the initial dose is 0.05 mg per kilogram of body weight once weekly. Important: In infants, the dose is calculated based on individual body weight (not body surface area).
• Patients with impaired liver function In patients with impaired liver function, the doctor will adjust the dose as necessary.

Method of administration
Vincristine Teva is administered by intravenous infusion or slow injection via an intravenous line. Vincristine must be administered only under the strict supervision of physicians experienced in the use of cytotoxic agents.

Use of a higher than recommended dose of Vincristine Teva
If a patient suspects that an overdose of Vincristine Teva has been administered, contact a doctor or pharmacist immediately.
If an overdose of Vincristine Teva is administered, the described adverse reactions may occur with increased severity or have more serious consequences.
There is no effective treatment for vincristine overdose. In case of overdose, the doctor will provide supportive treatment and closely monitor the patient.

Missed dose of Vincristine Teva
The doctor will decide when the patient should receive the medicine. If a patient suspects that a dose has been missed, they should contact their doctor as soon as possible.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Adverse effects may be more pronounced in patients with impaired liver function.
The following adverse effects may occur with the following frequencies:
Very common: (may affect more than 1 in 10 people)
Common: (may affect up to 1 in 10 people)
Uncommon: (may affect up to 1 in 100 people)
Rare: (may affect up to 1 in 1,000 people)
Very rare: (may affect up to 1 in 10,000 people)
Frequency not known: frequency cannot be estimated from the available data.

Immune system

• Rare: Hypersensitivity reaction associated with a significant drop in blood pressure, pallor, anxiety, rapid or slowed heart rate, moist skin, and disturbances in consciousness (anaphylaxis), rash, and fluid retention.

Blood

• Common: Transient increase in platelet count; patients may experience headache, dizziness, tingling in the hands, fingers, or feet, nosebleeds, bruising, or bleeding gums.
• Uncommon: Bone marrow suppression, blood disorders such as anaemia (which may manifest as weakness, fatigue, and/or general malaise), leukopenia (associated with increased risk of infections), and thrombocytopenia (manifesting as a tendency to bruise and bleed).

Nervous system

• Common: Peripheral neuropathy, related to harmful effects on the peripheral nervous system – nerves transmitting electrical signals from the brain and spinal cord to the rest of the body and back. Motor, sensory, and functional disturbances may occur. Patients may experience abnormal sensations, tingling, itching, or prickling without any cause, neuralgia (e.g. of the jaw or testicles), difficulty moving, loss of certain reflexes (absent deep tendon reflexes), paralysis, or muscle weakness in the foot (foot drop), muscle weakness, coordination problems (e.g. walking as if under the influence of alcohol), and paralysis. The medicine may affect cranial nerves (brain nerves), causing paralysis of certain muscles, laryngeal muscle weakness, hoarseness, vocal cord paralysis, weakness of the extraocular muscles, drooping eyelids (ptosis), double vision, optic nerve disturbances, disturbances of the extraocular nerves, and transient blindness.
• Uncommon: Seizures, often associated with high blood pressure. In a few cases in children, seizures were followed by coma. Disturbances in consciousness and psychiatric changes such as depression, agitation, insomnia, confusion, severe mental illness with impaired control over behaviour and actions (psychosis), and perception of non-existent objects (hallucinations).
• Frequency not known:
  A disease affecting the white matter of the brain (leukoencephalopathy). Symptoms include
  psychiatric disturbances and seizures.

Heart

• Uncommon: In some patients treated with vincristine in combination with other anticancer medicines, who had previously undergone radiation therapy to the heart area, circulatory disturbances and myocardial infarction have occurred.
• Rare: Increased or decreased blood pressure.

Respiratory system

• Common: Sudden onset of shortness of breath and respiratory arrest due to contraction of the muscles of the airways (bronchospasm), particularly when the medicine is used concomitantly with mitomycin C.

Gastrointestinal system

• Common: Constipation, abdominal pain, cramping abdominal pain caused by spasms, particularly of the intestines and biliary system (organs and ducts – bile ducts, gallbladder, and associated organs – involved in the production and transport of bile) (abdominal colic), nausea, vomiting.
• Uncommon: Loss of appetite, weight loss, diarrhoea, intestinal dysfunction due to paralysis (paralytic ileus, in which intestinal function ceases and intestinal movement is absent), particularly in young children.
• Rare: Inflammation of the mucous membrane of the mouth, necrosis of tissue in the small intestine, and/or damage to the intestinal wall.
• Very rare: Pancreatitis.

Liver and biliary system

• Rare: Liver function disorders due to occlusion of hepatic veins, particularly in children.

Skin

• Very common: Hair loss (reversible after completion of treatment).

Ears and balance organs

• Uncommon: Deafness.

Kidneys and urinary system
In elderly patients, medications causing urinary retention should be discontinued shortly after starting
vincristine administration.

• Uncommon: Problems with urination (pain, frequent urination, or difficulty properly passing urine). Presence of high levels of certain breakdown products (uric acid) in the blood (hyperuricemia).
• Rare: Inappropriate secretion of antidiuretic hormone (ADH), resulting in low blood pressure, dehydration, abnormal concentrations of nitrogen compounds (patients may experience dry mouth, confusion, and fatigue), fluid retention leading to oedema, and hyponatraemia (syndrome of inappropriate antidiuretic hormone secretion (SIADH)).
• Very rare: Urinary incontinence.

Reproductive system
Irreversible infertility occurs more frequently in men than in women.

• Common: Inhibition of semen production, testicular neuralgia.
• Uncommon: Cessation of menstruation.

Other

Secondary malignancy related to treatment. In some patients receiving vincristine in combination with
other anticancer medicines, a different type of cancer has developed after treatment.

• Common: Irritation at the injection site.
• Uncommon: Pain and inflammation of veins and subcutaneous connective tissue during intravenous injection, fever.
• Rare: Headache.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist.
Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions,
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw,
Tel.: +48 22 4921301, Fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Vincristine Teva

Keep out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C).
Store in the outer packaging to protect from light.
Do not use Vincristine Teva after the expiry date stated on the vial label and outer packaging
following the words „Expiry date:” or „EXP:”. The expiry date refers to the last day of the stated month.
Do not use Vincristine Teva if the solution is not clear and colourless or slightly yellow.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Vincristine Teva contains
The active substance is vincristine sulfate (Vincristini sulfas), 1 mg per ml of injectable solution.
Other ingredients are mannitol, sulfuric acid and (or) sodium hydroxide, and water for injections.

What Vincristine Teva looks like and contents of the pack
Vincristine Teva is a clear, colourless or slightly yellow solution, free from particles other than gas bubbles.
Pack sizes:
One 1 ml vial contains 1 mg of vincristine sulfate.
One 2 ml vial contains 2 mg of vincristine sulfate.
One 5 ml vial contains 5 mg of vincristine sulfate.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
Emilii Plater 53 Street
00-113 Warsaw
Tel.: (22) 345 93 00

Manufacturer
Pharmachemie B.V.
Swensweg 5, P.O. Box 552
2003 RN Haarlem, The Netherlands

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