Vincristine Teva

Patient Information Leaflet: User Manual

Vincristine Teva, 1 mg/ml, Solution for Injection

Vincristine sulfate

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

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

Vincristine sulfate belongs to a group of medicines called antimicrotubular cytostatic agents.
These medicines inhibit the growth of cancer cells.
Vincristine Teva is usually used in combination with other medicines to treat:

• acute lymphocytic leukemia, which is a rapidly progressing cancer in which the body produces large amounts of immature white blood cells.
• Hodgkin's disease, which is a malignant tumor of the lymphatic system.
• non-Hodgkin's lymphoma, which are tumors of the lymph nodes not caused by Hodgkin's disease.
• lung cancer (small cell).
• rhabdomyosarcoma, which is a tumor of the muscles.
• Ewing's sarcoma, which is a type of bone cancer.
• hemorrhages (internal bleeding) with decreased platelet count (idiopathic thrombocytopenic purpura).
• adrenal gland cancer (part of the adrenal gland).
• primary neuroectodermal tumors, which are tumors of part of the nervous system
• Wilms tumor, which is a type of kidney cancer.
• breast cancer with metastases to other parts of the body.
• multiple myeloma, which is a cancer of immune system cells.
• retinoblastoma, which is a type of eye cancer.

2. Important information before using Vincristine Teva

When NOT to use Vincristine Teva:

• if the patient has been diagnosed with an allergy to vincristine sulfate or any of the other ingredients of this medicine (listed in section 6)
• if the patient has neuromuscular disordersknown as Charcot-Marie-Tooth disease
• if the patient has severe liver dysfunction
• if the patient has constipationor risk of intestinal obstruction, especially in children
• if the patient is receiving radiation therapyinvolving the liver.

Warnings and precautions

Vincristine Teva should only be used under the strict supervision of doctors experienced in the treatment of cytostatic agents (cancer medicines).
Vincristine Teva should be administered only intravenously(into a vein) and cannot be administered by any other route. Other methods of administration may lead to the patient's death.
Caution should be exercised to avoid leakage into surrounding tissue (extravasation), as this may cause significant irritation. The injection should be stopped immediately.
Eye contact with vincristine sulfate should be avoided. If eye contact occurs, the eyes should be flushed immediately with a large amount of water. If irritation persists, a doctor should be consulted.
In case of accidental skin contact, rinse with a large amount of water, then with mild soap and rinse thoroughly again.
Before starting treatment with Vincristine Teva, the patient should discuss it with their doctor

• if the patient has nerve disorders
• if the patient has liver dysfunction, see also "How to use Vincristine Teva"
• if the patient is taking medicines that may have a harmful effect on the nervous system; the doctor will closely monitor the patient during treatment
• if constipationoccurs as a result of treatment; the doctor will use measures to prevent constipation, such as adjusting the diet or using laxatives (e.g. lactulose)
• if the patient has heart disease, including ischemic conditions(heart and circulation-related diseases)
• if the patient has an infection or develops an infection during treatment, they should inform their doctor
• if the patient is sexually active; during treatment and for 6 months after its completion, both the patient and their partner should use contraception.

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

Vincristine Teva and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
An interaction may occur when this medicine is used with:

• certain medicines that inhibit the activity of liver enzymes, such as ritonavir (used to treat HIV), nelfinavir (used to treat HIV), ketoconazole (used to treat fungal infections), itraconazole (used to treat fungal infections), erythromycin (used to treat infections), and nefazodone (used to treat depression);

concomitant administration of these medicines with vincristine may lead to premature and/or enhanced neuromuscular disturbances

• certain medicines used to treat high blood pressure, such as nifedipine; they may cause an increase in vincristine levels in the blood, which in turn may lead to an increase in side effects
• certain medicines used to treat epilepsy, such as phenytoin, fosphenytoin; vincristine may decrease phenytoin levels in the blood
• certain medicines used to treat cancer and other medicines that suppress bone marrow function, such as doxorubicin (especially in combination with prednisone); there is a possibility of enhanced effects, side effects, and bone marrow suppression
• certain medicineswith harmful effects on the nervous system, such as isoniazid (a medicine used to treat tuberculosis), L-asparaginase (a medicine used to treat blood cancers), and cyclosporine A (a medicine that suppresses the immune system); these medicines may likely enhance the harmful effects of vincristine on the nervous system
• vaccines( vaccinations); vincristine suppresses the immune system and may affect the body's ability to respond to the vaccine
• digoxin(a medicine used to treat reduced heart function and heart rhythm disorders); vincristine may weaken the effect of digoxin
• mitomycin C(a medicine used to treat certain cancers); concomitant administration with vincristine may cause respiratory disorders
• radiation therapy(treatment of diseases using radiation); radiation therapy may enhance the side effects of vincristine on the nervous system
• cyclosporine, tacrolimus; used at the same time, they may prevent the immune system from protecting the body against disease (immunosuppression) and cause a risk of growth of certain cells (lymphoproliferation)
• GM-CSF and G-CSF(medicines used to stimulate the growth of blood cells after chemotherapy); used concomitantly with vincristine, they may cause nerve disease (neuropathy)
• dactinomycin;in patients with kidney cancer (Wilms tumor), cases of severe liver damage have been reported
• bleomycin;such a combination may cause disorders of blood flow to the extremities, including fingers and toes, nose, and ears, 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); the side effects of vincristine may worsen.
• ketoconazole(used to treat Cushing's syndrome, a disease characterized by excessive secretion of cortisol hormone); the side effects of vincristine may worsen.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.

Pregnancy

• The use of vincristine during pregnancy is not recommended.
• Both men and women should use contraception during treatment and for six months after its completion.
• Pregnant patients or those planning to become pregnant should contact their doctor.
• There is insufficient data on the use of vincristine sulfate during pregnancy in humans to assess possible side effects. Animal studies have shown harmful effects of the medicine.

Breastfeeding

• Do not breastfeedduring 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 consult about the possibility of storing sperm (sperm bank) before treatment.

Driving and using machines

Treatment with Vincristine Teva may sometimes cause side effects related to the nervous system, such as decreased reflexes, muscle weakness, and vision disturbances, as well as gastrointestinal side effects (see "Possible side effects"). Patients who experience any of these side effects MUST NOTdrive or operate machines that require increased attention.

Vincristine Teva contains sodium

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

3. How to use Vincristine Teva

Vincristine Teva should always be used according to the doctor's instructions. In case of doubts
the patient should consult their doctor or pharmacist again.
If the patient feels that Vincristine Teva is working too strongly or its effect is too weak
they should consult their doctor.

Vincristine should be administered only intravenously:

The recommended dose is:

• AdultsThe usual dose for adult patients is 1.4 mg per square meter of body surface area (maximum 2 mg) once a week.
• ChildrenIn children weighing more than 10 kg, the usual dose is 1.5 to 2.0 mg per square meter of body surface area once a week. In children weighing 10 kg or less, the initial dose is 0.05 mg per kilogram of body weight once a week. Important: In infants, the dose is calculated based on individual body weight (not body surface area).
• Patients with liver dysfunctionIn case of liver dysfunction, the doctor will adjust the dose of the medicine if necessary.

Method of administration
Vincristine Teva is administered through an infusion or slow injection through an attached infusion line into a vein (intravenously). Vincristine should be used only under the strict supervision of doctors experienced in the treatment of cytotoxic agents.

Using a higher dose of Vincristine Teva than recommended

If the patient suspects that they have received too high a dose of Vincristine Teva, they should immediately consult their doctor or pharmacist.
In case of overdose of Vincristine Teva, the described side effects may occur with greater intensity or have more serious consequences.
There is no effective treatment for vincristine overdose. In case of overdose, the doctor will use supportive treatment and closely monitor the patient.

Missing a dose of Vincristine Teva

The doctor will decide when the patient will receive the medicine. If the patient suspects that a dose of the medicine has been missed, they should contact their doctor as soon as possible.
In case of any further doubts about the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects may be more pronounced in patients with liver dysfunction.
The following side effects may occur with similar frequency:
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

• RareHypersensitivity reaction with a significant drop in blood pressure, paleness, anxiety, rapid, slow pulse, sweaty skin, and changes in consciousness (anaphylaxis), rash, and fluid retention.

Blood

• CommonTransient increase in platelet count; patients may experience headache, dizziness, tingling in hands, fingers, or toes, nosebleeds, or bruising.
• UncommonBone marrow suppression, blood disorders, such as anemia (may manifest as weakness, fatigue, and/or general malaise), decreased white blood cell count (associated with increased risk of infection), and decreased platelet count (manifested by a tendency to bruise and bleed).

Nervous system

• CommonPeripheral neuropathy, associated with harmful effects on the peripheral nervous system - nerves that conduct electrical signals from the brain and spinal cord to the rest of the body and back. Possible are motor, sensory, and functional disorders. Patients may experience sensory disturbances, tingling, itching, or stabbing without any reason, neuralgia (including jaw or testicular), problems with movement, loss of some reflexes (decreased deep tendon reflexes), foot drop (weakness or paralysis of the muscles of the foot), muscle weakness, coordination problems (e.g. walking like under the influence of alcohol), and paralysis. The medicine may affect cranial nerves (brain nerves), causing paralysis of some muscles, weakness of laryngeal muscles, hoarseness, paralysis of vocal cords, weakness of extraocular muscles of the eye, ptosis (drooping eyelid), double vision, disturbances of the optic nerve, disturbances of the extraocular muscles of the eye, and transient blindness.
• UncommonSeizures/convulsions, often in combination with increased blood pressure. In a few cases, seizures have been reported in children, followed by coma. Changes in consciousness and mental changes, such as depression, agitation, insomnia, confusion, severe mental illness with loss of control over behavior and actions (psychosis), and perception of non-existent objects (hallucinations).
• Frequency not known

A disease that occurs in the white matter of the brain (leukoencephalopathy). Symptoms include mental and convulsive disorders.
Heart

• UncommonIn some patients treated with vincristine in combination with other anticancer medicines, who were previously treated with radiation to the chest area, circulatory disorders and heart attacks have occurred.
• RareIncreased or decreased blood pressure.

Respiratory system

• CommonSudden onset of shortness of breath and dyspnea due to bronchospasm, especially when the medicine is used concomitantly with mitomycin C.

Gastrointestinal system

• CommonConstipation, abdominal pain, colic in the abdominal area, nausea, vomiting.
• UncommonLoss of appetite, weight loss, diarrhea, intestinal disorders due to paralysis (paralytic ileus), especially in young children.
• RareMouth ulcers, necrosis of the small intestine and/or damage to the intestinal wall.
• Very rarePancreatitis.

Liver and bile ducts

• RareLiver dysfunction due to closure of hepatic veins, especially in children.

Skin

• Very commonHair loss (reversible after treatment ends).

Ears and balance organs

• UncommonDeafness.

Kidneys and urinary tract
In elderly patients, the use of medicines that cause urinary retention should be discontinued shortly after the start of vincristine administration.

• UncommonProblems with urination (pain, frequent urination, or problems with proper urination). Presence of high levels of certain breakdown products (uric acid) in the blood (hyperuricemia).
• RareInappropriate secretion of antidiuretic hormone (ADH), resulting in decreased blood pressure, dehydration, abnormal levels of nitrogen compounds (patients may feel dry mouth, confusion, and fatigue), fluid retention, which may cause swelling, and sodium deficiency (syndrome of inappropriate antidiuretic hormone secretion (SIADH)).

can cause swelling and sodium deficiency (syndrome of inappropriate antidiuretic hormone secretion (SIADH)).

• Very rareUrinary incontinence.

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

• CommonInhibition of sperm production, testicular neuralgia.
• UncommonAmenorrhea (cessation of menstruation).

Other
Treatment-related cancer. In some patients receiving vincristine in combination with other anticancer medicines, another type of cancer developed after treatment.

• CommonIrritation at the injection site.
• UncommonPain and inflammation of the veins and subcutaneous connective tissue during intravenous injection, fever.
• RareHeadache.

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should inform their doctor or pharmacist.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather 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 label of the vial and outer packaging after "Expiry date:" or "EXP:". The expiry date refers to the last day of the specified month.
Do not use Vincristine Teva if the solution is not clear and colorless or slightly yellow.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Vincristine Teva contains

The active substance of the medicine is vincristine sulfate (Vincristini sulfas), 1 mg per ml of injectable solution.
Other ingredients of the medicine 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, colorless 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 authorization holder and manufacturer

Marketing authorization holder

Teva Pharmaceuticals Polska Sp. z o.o.
ul. Emilii Plater 53
00-113 Warsaw
tel.: (22) 345 93 00

Manufacturer

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

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

Date of approval of the leaflet:September 2024