VINCRISTINE PFIZER 1 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Vincristine Pfizer 1 mg/ml Solution for Injection EFG

Vincristine Sulfate

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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Vincristine Pfizer and what is it used for
2. What you need to know before you use Vincristine Pfizer
3. How to use Vincristine Pfizer
4. Possible side effects
5. Storage of Vincristine Pfizer
6. Contents of the pack and other information

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

Vincristine Pfizer belongs to a group of medicines called antineoplastic drugs, which are used to treat cancer.

Vincristine Pfizer is a medicine used alone or in combination with other anticancer medicines 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 cancer.
• Gynecological tumors of childhood.
• Idiopathic thrombocytopenic purpura in patients who do not respond to splenectomy and short-term treatment with adrenocorticosteroids.

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

Do not use Vincristine Pfizer

• If you are allergic to vincristine sulfate or any of the other ingredients of this medicine (listed in section 6).
• By the intrathecal route, its use by this route can be fatal.
• If you have the demyelinating form of Charcot-Marie-Tooth syndrome.
• If you are receiving radiation therapy in areas close to the liver.
• If you are pregnant.
• During breastfeeding.

Warnings and precautions

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

Vincristine Pfizershould not be administeredby intramuscular injection, subcutaneous injection, or intrathecal injection.

Intrathecal administration of vincristine can be fatal.

Consult your doctor or pharmacist before starting treatment with Vincristine Pfizer.

Be careful with Vincristine Pfizer:

• If you have leukemia that affects the central nervous system, as additional administration of other anticancer medicines may be necessary.
• If you are using other neurotoxic medicines (medicines that damage the nervous system), have irradiated the spinal cord, or have a neurological disease, as the adverse effects of vincristine on the nervous system may be increased. In these situations, periodic clinical evaluation is necessary to determine if a dose adjustment is necessary.
• If the results of blood tests to be performed before each dose of vincristine administration 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 medicines that may cause urinary retention, particularly if you are elderly, in which case your doctor should consider the possibility of suspending such treatment during the first days of vincristine administration.
• If you have altered liver function, as in this situation the severity of the adverse effects caused by vincristine may increase, and a dose adjustment may be necessary.
• If you are being treated with mitomycin-C (a medicine used to treat some types of cancer) and have lung impairment, as the risk of severe respiratory disorders increases. In case of suffering any of these reactions, vincristine sulfate will not be administered again.
• If you are using other medicines toxic to the ear.

Since this medicine can cause constipation, your doctor will recommend treatment to prevent this problem.

During the first three or four weeks of treatment, controls should be performed to determine the levels of uric acid in the blood, as they may increase during treatment and cause kidney damage. The way to reduce these effects will be through adequate fluid intake, alkalization of the urine, and/or administration of a medicine called allopurinol.

Using Vincristine Pfizer with other medicines

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

It is possible that certain medicines, such as allopurinol (a medicine used to treat gout and high uric acid levels), L-asparaginase (a medicine used to treat some types of cancer), mitomycin-C (a medicine used to treat some types of cancer), itraconazole, and fluconazole (medicines used to treat fungal infections), voriconazole (a medicine used to treat severe fungal infections), and other medicines with action on cytochrome P450, neurotoxic medicines (medicines that damage the nervous system), as well as ototoxic medicines (toxic to the ear), may increase the adverse effects of vincristine.

Azole antifungals (a group of medicines 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 production of the cortisol hormone).

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

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

If you are receiving radiation therapy, vincristine should not be administered until such treatment is completed.

Vaccines known as "live microbe" vaccines. Vincristine sulfate decreases immune defenses, and in case of concomitant administration with this type of vaccine, severe infections may occur. It is necessary to wait between 3 months and 1 year after suspension of the medicine for the ability to respond to the vaccine to recover.

Medicines for the treatment of low white blood cell count (granulocyte colony-stimulating factors [G-CSF]). Concomitant administration with vincristine sulfate may decrease blood cell production in the bone marrow (myelosuppression).

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 medicine.

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.

It is not known whether vincristine sulfate is excreted in breast milk. Due to the adverse reactions that it could cause in the breastfed child, breastfeeding should be discontinued during treatment and at least one month after the last dose.

Fertility

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

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

Contraceptive measures 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 using machines

It is not recommended to drive or use machines after administration of this medicine.

Vincristine Pfizer contains sodium

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

3. How to use Vincristine Pfizer

This product should be administered EXCLUSIVELY through a vein, either by slow intravenous injection (IV) or perfusion (IV), by personnel with experience in the use of chemotherapy. If administered by the intrathecal route, it is fatal.

The dose will depend on your weight and general 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 form of administration for you, according to your condition and response to treatment.

If you use more Vincristine Pfizer than you should

Although it is unlikely, if higher doses than recommended are administered, it is expected that you will experience adverse effects in an exaggerated manner. Since no specific antidote for vincristine sulfate has been found, treatment of an overdose should include supportive and symptomatic therapy.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, 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:

• Decreased platelet count (thrombocytopenia) and red blood cell count (anemia) in blood.
• Low sodium levels (hyponatremia), decreased appetite.
• Unsteady gait and foot drop (peroneal nerve paralysis), tingling sensation (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 pharynx pain.
• Paralytic ileus, diarrhea.
• Jaw pain.
• Urinary retention.

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

• Coma.

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

• Decreased white blood cell count (granulocytopenia).
• Severe allergic reactions (anaphylaxis), swelling (angioedema).
• High sodium excretion in the urine accompanied by low sodium levels in the blood due to excess antidiuretic hormone (syndrome attributed to inadequate secretion of antidiuretic hormone).
• Dehydration, increased uric acid levels in the blood (hyperuricemia).
• Paralysis, seizures, paralysis of the cranial nerves that particularly affect the eye and larynx muscles, loss of sensitivity, loss of reflexes (areflexia), nerve pain (neuralgia), salivary gland pain, nerve damage, involuntary eye movements (nystagmus), lack of coordination (ataxia), balance disorder, gait disturbance, dizziness, headache.
• Transient blindness, optic nerve atrophy.
• Deafness, vertigo.
• Myocardial infarction, disease of the arteries that supply blood to the heart.
• Low blood pressure (hypotension), high blood pressure (hypertension).
• Respiratory distress (acute respiratory distress syndrome), bronchospasm.
• Intestinal perforation, death of intestinal tissue (gastrointestinal necrosis), mouth sores (oral ulceration).
• Liver disease due to venous obstruction, especially in children.
• Rash.
• Muscle atrophy, limb pain, back pain.
• Kidney disease caused by excess uric acid (uric acid nephropathy), excessive urine production (polyuria), painful urination (dysuria), inability to empty the urinary bladder properly (urinary bladder atony).
• Fever, reaction at the injection site.

In clinical reports of men and women undergoing treatment with multiple anticancer medicines, including vincristine, it has been observed that azoospermia (absence of sperm) and amenorrhea (absence of menstruation) may occur.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es/. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Vincristine Pfizer

Keep out of sight and reach of children.

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

Do not freeze.

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Vincristine Pfizer does not contain any preservative. The vials are for single use, and the unused portion should be discarded.

Do not use any packaging that is damaged or open.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and medicines you no longer need in the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Container Contents and Additional Information

Vincristine Pfizer Composition

• The active ingredient is vincristine sulfate. Each ml 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 Container Contents

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

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)

Manufacturer

Pfizer Service Company BV

Hoge Wei 10

1930 Zaventem

Belgium

Date of Last Revision of this Leaflet:March 2025.

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

This information is intended exclusively for healthcare professionals:

Method of Administration

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

Slow Intravenous Injection

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

Intravenous Perfusion

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

It is recommended to administer the solution over 5 to 10 minutes after dilution in a 50 ml perfusion bag (50 ml of sodium chloride or other compatible diluent).

After administration, the vein should be thoroughly flushed. Care should be taken to avoid extravasation, as this can cause local ulcers.

Instructions for Preparation and Use

The administration of Vincristine Pfizer should be performed by personnel experienced 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 flexible plastic container instead of a syringe. The minibag should be visibly labeled as follows: “FOR INTRAVENOUS USE ONLY – FATAL IF ADMINISTERED BY OTHER ROUTES” (see sections 4.3 and 4.4). Syringes with vincristine sulfate should be labeled to indicate: “FOR INTRAVENOUS USE ONLY – FATAL IF ADMINISTERED BY OTHER ROUTES”.

Extemporaneously 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 INTRAVENOUS USE ONLY – 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, started immediately after the intrathecal injection.

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

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

1. As soon as frozen plasma was available, 25 ml was administered diluted in 1 liter of Ringer lactate solution, through the catheter placed in the lateral cerebral ventricle with a flow rate of 75 ml/hour, removing cerebrospinal fluid through 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 was administered intravenously over 24 hours, followed by 500 mg three times a day orally for 1 month or until neurological dysfunction stabilized. The role of glutamic acid in this treatment is not defined and may not be essential.

Protective Measures

Vincristine sulfate is a cytotoxic drug and adequate safety measures should be taken during its handling:

• It is recommended that pregnant women do not handle cytotoxic drugs, such as vincristine sulfate.
• As with other cytotoxic drugs, the dilution of vincristine sulfate should be performed by trained healthcare personnel. It should be performed in a designated area (preferably in a cytotoxic laminar flow 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 ulcers. In case of accidental contact with the eyes, they should be washed immediately with plenty of water.

Spill Procedure

Personnel involved in the preparation, transportation, and administration of cytotoxic products should be perfectly familiar with the procedures for handling spills. Therefore, it is imperative to have a validated spill handling protocol in all places where cytotoxics are handled. 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. Utensils used to dilute vincristine sulfate or materials in contact with the drug should be placed in a doubly sealed polyethylene bag and incinerated at 1,100 °C.