Prospect: information for the patient

Vincristine Pfizer 1 mg/ml injectable solution EFG

Vincristine sulfate

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only to you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

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

2.What you need to know before starting to use Vincristine Pfizer

3.How to use Vincristine Pfizer

4.Possible adverse effects

5.Storage of Vincristine Pfizer

6.Contents of the package and additional information

Vincristina Pfizer belongs to a group of medications known as antineoplastic drugs, which are used to treat cancer.

Vincristina Pfizeris a medication that is used alone or in combination with otherantineoplastic medications, in the treatment of:

• Acute leukemia.
• Malignant lymphomas, including: Hodgkin's disease, non-Hodgkin lymphoma of lymphocytic, mixed cell, histiocytic, undifferentiated, nodular, and diffuse types.
• Rhabdomyosarcoma.
• Neuroblastoma.
• Wilms' tumor.
• Osteogenic sarcoma.
• Mycosis fungoides.
• Ewing's sarcoma.
• Breast cancer.
• Malignant melanoma.
• Small cell lung carcinoma.
• Gynecologic tumors in children.
• True idiopathic thrombocytopenic purpura in patients who do not respond to splenectomy (removal of the spleen) and short-term treatment with adrenocortical steroids.

No use Vincristina Pfizer

• If you are allergic to vincristine sulfate or any of the other components of this medication (listed in section 6).
• Administered intrathecally, its use by this route may be fatal.
• If you have the demyelinating form of Charcot-Marie-Tooth syndrome.
• If you are receiving radiation therapy in areas near the liver.
• If you are pregnant.
• During breastfeeding.

Warnings and precautions

Vincristine Pfizer must be administered EXCLUSIVELYthrough a vein, either by slow intravenous injection (IV) or infusion (IV)..

Vincristine Pfizermust not be administeredby intramuscular injection, subcutaneous injection, or spinal canal injection (intrathecal injection).

The intrathecal administration of vincristine may be fatal.

Consult your doctor or pharmacist before starting to use Vincristine Pfizer.

Be especially careful with Vincristine Pfizer:

• If you have a leukemia that affects the central nervous system, as additional antitumor medications will be required.
• If you are using other neurotoxic medications (medications that cause damage to the nervous system), have had radiation therapy to the spinal cord, or have a neurological disease, as the adverse effects of vincristine on the nervous system may be increased. In these situations, a periodic clinical evaluation is required to determine if a dose adjustment is necessary.
• If the blood tests that you must undergo before each dose of vincristine show low white blood cell or platelet counts, as this should be taken into account before continuing with the administration of that dose.
• If you have symptoms of infection, as this situation should be considered before administering the next dose of vincristine.
• If you are using other medications that may cause urinary retention, particularly if you are elderly, in which case your doctor should consider suspending that treatment during the first days of vincristine administration.
• If you have impaired liver function, as this may increase the severity of the adverse effects caused by vincristine, requiring a dose adjustment.
• If you are being treated with mitomycin-C (a medication used to treat certain types of cancer) and have lung damage, as this increases the risk of severe respiratory problems. In the event of these reactions, vincristine sulfate should not be administered again.
• If you are using other ototoxic medications.

Since this medication may cause constipation, your doctor will recommend a treatment to prevent this problem.

During the first three or four weeks of treatment, you will need to undergo blood tests to determine your uric acid levels, as they may rise during treatment and cause kidney damage. The way to reduce these effects will be through adequate fluid intake, urine alkalization, and/or administration of a medication called allopurinol.

Use of Vincristine Pfizer with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Certain medications, such as allopurinol (a medication used to treat gout and high uric acid levels), L-asparaginase (a medication used to treat certain types of cancer), mitomycin-C (a medication used to treat certain types of cancer), itraconazole and fluconazole (medications used to treat fungal infections), voriconazole (a medication used to treat severe fungal infections), and other medications that affect the cytochrome P450 enzyme, neurotoxic medications (medications that cause damage to the nervous system), and ototoxic medications (toxic to the ear), may increase the adverse effects of vincristine.

Azole antifungals (a group of medications used to treat fungal infections such as itraconazole, posaconazole, fluconazole, isavuconazole, or voriconazole).

Ketoconazole (used to treat Cushing's syndrome, a disease characterized by excessive cortisol production).

St. John's Wort should be administered with caution (also known as "Hypericum perforatum", a natural remedy or plant-based remedy used to treat mild depression).

Vincristine may also modify the action of other medications, such as phenytoin (a medication used to treat epilepsy).

If you are receiving radiation therapy, do not administer vincristine until the treatment is completed.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Vincristine Pfizer is contraindicated during pregnancy.

If you become pregnant during treatment, you should consult your doctor, who will inform you of the potential risks to the fetus.

Breastfeeding

Vincristine Pfizer is contraindicated during breastfeeding.

The excretion of vincristine sulfate in breast milk is unknown. Due to the adverse reactions that it may cause in the infant, breastfeeding should be suspended during treatment and at least one month after the last dose.

Fertility

In patients treated with combinations of antitumor medications, including vincristine, fertility may be altered (absence of sperm and absence of menstruation), so you should consult your doctor.

If you want to have children after treatment with vincristine, you should talk to your doctor about your options for preserving fertility before starting treatment.

Contraception in men and women

Women should always use an effective contraceptive method (contraception) during treatment and for at least 7 months after the last dose. Male patients with female partners of childbearing age should always use very effective contraceptive methods to prevent pregnancy during treatment and for at least 4 months after the last dose.

Talk to your doctor about the appropriate contraceptive methods for you and your partner.

Driving and operating machinery

Do not drive or operate machinery after administration of this medication.

Vincristine Pfizer contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per ml; it is essentially "sodium-free".

This product must be administered EXCLUSIVELY through a vein, either by slow intravenous injection (IV injection) or infusion (IV), by experienced personnel in chemotherapy use. Administering it intrathecally is fatal.

The dose will depend on your weight and overall condition. Your doctor will calculate your body surface area in square meters and determine the dose you should receive.

Your doctor will establish the dose and duration of treatment, as well as the most suitable administration method for you, based on your condition and response to treatment.

If you use more Vincristina Pfizer than you should

Although it is unlikely, if you are administered doses higher than recommended, you can expect to experience excessive adverse effects. Since no specific antidote for vincristine sulfate has been found, treatment for an overdose should include supportive and symptomatic therapy.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Generally, side effects are reversible and are related to the dose and cumulative dose. The most common side effect is hair loss (alopecia) and the most problematic are of neuromuscular origin.

The following side effects have been reported:

Very common side effects(may affect more than 1 in 10 patients) are:

• Reduction in the number of platelets (thrombocytopenia) and red blood cells (anemia) in the blood.
• Low sodium levels (hyponatremia), decreased appetite.
• Unsteady gait and fallen foot (peroneal nerve paralysis), sensation of tingling (paresthesia).
• Constipation, abdominal pain, vomiting, nausea.
• Hair loss (alopecia).
• Muscle pain (myalgia), bone pain.
• Weight loss.

Common side effects(may affect up to 1 in 10 people) are:

• Mouth and throat pain.
• Intestinal paralysis (paralytic ileus), diarrhea.
• Jaw pain.
• Urinary retention.

Rare side effects(may affect up to 1 in 100 people) are:

• Coma.

Side effects of unknown frequency(cannot be estimated from available data) are:

• Reduction in the number of white blood cells in the blood (granulocytopenia).
• Severe allergic reactions (anaphylaxis), swelling (angioedema).
• Excessive sodium loss in the urine accompanied by low sodium levels in the blood due to excessive antidiuretic hormone secretion (syndrome attributed to inadequate secretion of antidiuretic hormone).
• Dehydration, elevated uric acid levels in the blood (hyperuricemia).
• Paralysis, convulsions, paralysis of cranial nerves affecting particularly eye and laryngeal muscles, loss of sensation, loss of reflexes (arreflexia), pain along a nerve (neuralgia), salivary gland pain, nerve damage, involuntary eye movements (nystagmus), lack of coordination of movements (ataxia), balance alteration, gait alteration, dizziness, headache.
• Transient blindness, optic nerve atrophy.
• Deafness, vertigo.
• Myocardial infarction, heart disease supplying blood to the heart.
• Low blood pressure (hypotension), high blood pressure (hypertension).
• Difficulty breathing (acute respiratory distress syndrome), bronchospasm.
• Intestinal perforation, gastrointestinal tissue death (gastrointestinal necrosis), mouth ulcers.
• Liver disease due to venous obstruction, especially in children.
• Rash.
• Muscle mass loss (muscular atrophy), limb pain, back pain.
• Uric acid-induced kidney disease (uric acid nephropathy), excessive urine production (polyuria), painful urination (dysuria), inability to empty the urinary bladder correctly (atonic bladder).
• Fever, reaction at the injection site.

In clinical reports of men and women treated with multiple anticancer drugs, including vincristine, it was observed that azoospermia, amenorrhea could be produced.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es/. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep out of the sight and reach of children.

Store in the refrigerator (between 2 °C and 8 °C).

Do not freeze.

Store the vial in the outer packaging to protect it from light.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Vincristina Pfizer does not contain any preservative agents. The vials, therefore, are for single use and the unused portion must be discarded.

Do not use any damaged or open packaging.

Medications should not be thrown down the drain or in the trash.Deposit the containers and medications that you no longer need at the SIGRE collection pointof the pharmacy.Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Vincristine Pfizer Composition

• The active ingredient is vincristine sulfate. Each milliliter of injectable solution contains 1 mg of vincristine sulfate.
• The other components (excipients) are:mannitol, sulfuric acid, sodium hydroxide (to adjust the pH of the solution) and water for injectable preparations.

Product Appearance and Packaging Contents

Vincristine Pfizer is a transparent and colorless solution that is presented in glass vialsof 2 ml of Type I transparent glass, with bromobutyl stoppers, aluminum caps and plastic "flip-off" stoppers.

Vincristine Pfizer is available in vials containing 1 ml or 2 ml of injectable solution.

Marketing Authorization Holder

Pfizer, S.L.

Avda. de Europa, 20B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Responsible for Manufacturing

Pfizer Service Company BV

Hoge Wei 10

1930 Zaventem

Belgium

Last Review Date of this Leaflet:August 2024.

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.

This information is intended solely for healthcare professionals:

Administration Form

The calculated dose of vincristine sulfate solution must be administered EXCLUSIVELY through a vein, either by intravenous injection (IV slow injection) or infusion (IV), according to the treatment protocol and under constant supervision to detect signs of extravasation.

Intravenous Slow Injection

The direct injection into the vein (IV slow injection) or through an intravenous catheter/needle can be completed in approximately one minute.

Intravenous Infusion

The injection of diluted vincristine sulfate can be infused through a plastic flexible container (e.g., a perfusion bag) or intravenous continuous infusion of normal saline solution or glucose solution, whichever is more suitable for the patient (see section 6.2).

It is recommended to administer the solution during5 to 10minutes after dilution in a 50ml perfusion bag (50ml of sodium chloride or other compatible diluent).

After administration, the vein must be thoroughly flushed. You must be careful to avoid extravasation, as this can cause local ulcers.

Instructions for Preparation and Use

The administration of Vincristine Pfizer should be performed by experienced personnel in the use of chemotherapy.

To reduce the possibility of fatal medication errors due to incorrect administration route, it is strongly recommended to dilute vincristine sulfate in a plastic flexible container rather than in a syringe. The minibag should be clearly labeled as follows: “FOR EXCLUSIVE INTRAVENOUS USE – FATAL IF ADMINISTERED BY OTHER ROUTES” (see sections 4.3 and 4.4). Syringes containing vincristine sulfate should be labeled to indicate: “FOR EXCLUSIVE INTRAVENOUS USE – FATAL IF ADMINISTERED BY OTHER ROUTES”.

Prepared syringes containing vincristine sulfate should be packaged in a wrapper with the label: “Do not remove the wrapper until the time of injection.FOR EXCLUSIVE INTRAVENOUS USE – FATAL IF ADMINISTERED BY OTHER ROUTES”.

Emergency Treatment for Accidental Intrathecal Administration:The treatment of patients after intrathecal administration of vincristine sulfate has included immediate removal of cerebrospinal fluid and washing with Ringer lactate, as well as with other solutions, which has not prevented ascending paralysis and death. In one case, the progressive paralysis was stopped in an adult following the treatment indicated below, initiated immediately after intrathecal injection.

1. As much cerebrospinal fluid as possible was removed through the lumbar access without putting the patient's life at risk.

1. The subarachnoid space was washed with Ringer lactate solution administered by continuous perfusion through a catheter placed in a lateral cerebral ventricle at a flow rate of 150 ml/hour. Cerebrospinal fluid was removed through the lumbar access.

1. As soon as frozen plasma was available, 25 ml were diluted in 1 liter of Ringer lactate solution and administered through the catheter placed in the lateral cerebral ventricle at a flow rate of 75 ml/hour, with cerebrospinal fluid removal through the lumbar access. The perfusion rate was adjusted to maintain a protein level in the cerebrospinal fluid of 150 mg/dl.

1. 10 g of glutamic acid were administered intravenously over 24 hours, followed by 500 mg three times a day orally for one month or until the neurological dysfunction stabilized. The role of glutamic acid in this treatment is not defined and may not be essential.

Precautions

Vincristine sulfate is a cytotoxic agent and appropriate safety measures must be taken during its handling:

• It is recommended that pregnant women not handle cytotoxic agents, such as vincristine sulfate.
• As with other cytotoxic agents, vincristine sulfate dilution should be performed by trained healthcare personnel. It should be done in a designated area (preferably in a laminar flow cytotoxic cabinet). The work surface should be protected with absorbent, plasticized, and disposable paper.
• While handling vincristine sulfate, protective clothing should be used: protective glasses, gown, gloves, and disposable masks.
• If the solution accidentally comes into contact with the skin or mucous membranes, the affected area should be washed immediately with water and soap.

Avoid accidental contact with the eyes, as vincristine sulfate is highly irritating and can cause corneal ulceration. In the event of accidental contact with the eyes, they should be washed immediately with abundant water.

Spill Procedure

Personnel involved in the preparation, transportation, and administration of cytotoxic agents must be familiar with the spill handling procedures. Therefore, it is essential to have a validated spill handling protocol in all cytotoxic handling areas. The recommended treatment should completely degrade the cytotoxic agent without subsequent release of toxic products. It is recommended to use a 5% sodium hydroxide solution to neutralize vincristine sulfate. Containers used to dilute vincristine sulfate or materials in contact with the drug should be placed in a double-bagged polyethylene bag and incinerated at 1,100 °C.