Vincasar PFS

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Vincristine is cancer medication that interferes with the growth of cancer cells and slows their spread in the body.

Vincristine is used to treat leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, rhabdomyosarcoma (soft tissue tumors), neuroblastoma (cancer that forms in nerve tissue), and Wilms' tumor.

Vincristine is sometimes used in combination with other cancer medications.

Vincristine may also be used for other purposes not listed in this medication guide.

Vincristine is injected into a vein through an IV. A healthcare provider will give you this injection.

Vincristine is usually given once per week. Follow your doctor's instructions.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when the medicine is injected.

Vincristine can cause severe constipation. You may be given medication to prevent constipation while you are receiving this medicine. Use all medications as directed by your doctor.

You may need frequent medical tests to be sure this medication is not causing harmful effects. Your cancer treatments may be delayed based on the results of these tests.

Get emergency medical help if you have any signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• bronchospasm (wheezing, chest tightness, trouble breathing);

• signs of infection such as fever, chills, sore throat, swollen gums, painful mouth sores, cold or flu symptoms;

• problems with vision, hearing, speech, swallowing, walking, or daily activities;

• numbness, burning, pain, or tingly feeling; or

• severe constipation, severe bloating or stomach pain, bloody or tarry stools.

Common side effects may include:

• temporary hair loss;

• decreased weight with loss of muscle tissue;

• diarrhea, nausea, vomiting, loss of appetite; or

• weight loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Vincristine belongs to the group of medicines known as antineoplastic agents. It is used to treat some kinds of cancer as well as some noncancerous conditions.

Vincristine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by vincristine, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, such as hair loss, may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with vincristine, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Vincristine is to be administered only by or under the immediate supervision of your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

This medicine has been tested in children and has not been shown to cause different side effects or problems than it does in adults.

Geriatric

Nervous system effects may be more likely to occur in the elderly, who are usually more sensitive to the effects of vincristine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Boceprevir

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Asparaginase
• Atazanavir
• Azithromycin
• Captopril
• Carbamazepine
• Carvedilol
• Ceritinib
• Clarithromycin
• Cobicistat
• Conivaptan
• Cyclosporine
• Darunavir
• Dasabuvir
• Diltiazem
• Dronedarone
• Eliglustat
• Erythromycin
• Felodipine
• Filgrastim
• Fluconazole
• Fosphenytoin
• Idelalisib
• Indinavir
• Itraconazole
• Ketoconazole
• Lopinavir
• Nefazodone
• Nelfinavir
• Netupitant
• Nilotinib
• Phenytoin
• Posaconazole
• Quercetin
• Quinidine
• Quinupristin
• Ranolazine
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Saquinavir
• Sargramostim
• Simeprevir
• St John's Wort
• Telaprevir
• Telithromycin
• Ticagrelor
• Tolvaptan
• Valspodar
• Verapamil
• Voriconazole
• Warfarin
• Zidovudine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Nifedipine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)—Risk of severe disease affecting other parts of the body

• Gout (history of) or
• Kidney stones (history of)—Vincristine may increase levels of uric acid in the body, which can cause gout or kidney stones

• Infection—Vincristine can reduce immunity to infection

• Liver disease—Effects may be increased because of slower removal of vincristine from the body

• Nerve or muscle disease—May be worsened

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.
• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

The mechanisms of action of vincristine sulfate remain under investigation. The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage.

Central nervous system leukemia has been reported in patients undergoing otherwise successful therapy with vincristine sulfate. This suggests that vincristine does not penetrate well into the cerebrospinal fluid.

Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, and 85 hours respectively; however, the range of the terminal half-life in humans is from 19 to 155 hours. The liver is the major excretory organ in humans and animals. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes (see PRECAUTIONS). About 80% of an injected dose of vincristine sulfate appears in the feces and 10% to 20% can be found in the urine. Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.

Current principles of cancer chemotherapy involve the simultaneous use of several agents. Generally, each agent used has a unique toxicity and mechanism of action so that therapeutic enhancement occurs without additive toxicity. It is rarely possible to achieve equally good results with single-agent methods of treatment. Thus, vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone-marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy). See DOSAGE AND ADMINISTRATION section for possible increased toxicity when used in combination therapy.

Patients with the demyelinating form of Charcot-Marie-Tooth syndrome should not be given Vincasar PFS. Careful attention should be given to those conditions listed under WARNINGS and PRECAUTIONS.

WARNINGS

This preparation is for intravenous use only. It should be administered by individuals experienced in the administration of vincristine sulfate injection. The intrathecal administration of Vincasar PFS (vincristine sulfate injection) usually results in death.

To reduce the potential for fatal medication errors due to incorrect route of administration, Vincasar PFS should be diluted in a flexible plastic container and prominently labeled as indicated for intravenous use only.

Syringes containing this product must be labeled, using the auxiliary sticker provided, to state “FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES.”

Extemporaneously prepared syringes containing this product must be packaged in an overwrap which is labeled “do not remove covering until moment of injection. For intravenous use only – fatal if given by other routes.”

See OVERDOSAGE section for the treatment of patients given intrathecal Vincasar PFS.

Pregnancy Category D

Vincristine sulfate can cause fetal harm when administered to a pregnant woman. When pregnant mice and hamsters were given doses of vincristine sulfate that caused resorption of 23% to 85% of fetuses, fetal malformations were produced in those that survived. Five monkeys were given single doses of vincristine sulfate between days 27 and 34 of their pregnancies; 3 of the fetuses were normal at term, and 2 viable fetuses had grossly evident malformations at term. In several animal species, vincristine sulfate can induce teratogenesis as well as embryo death at doses that are nontoxic to the pregnant animal. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Side effects following the use of Vincasar PFS are dose related. In pediatric patients under 13 years of age, death has occurred following doses of vincristine sulfate that were 10 times those recommended for therapy. Severe symptoms may occur in this patient group following dosages of 3 to 4 mg/m2. Adults can be expected to experience severe symptoms after single doses of 3 mg/m2 or more (see ADVERSE REACTIONS). Therefore, following administration of doses higher than those recommended, patients can be expected to experience exaggerated side effects. Supportive care should include the following: (1) prevention of side effects resulting from the syndrome of inappropriate antidiuretic hormone secretion (preventive treatment would include restriction of fluid intake and perhaps the administration of a diuretic affecting the function of Henle’s loop and the distal tubule); (2) administration of anticonvulsants; (3) use of enemas or cathartics to prevent ileus (in some instances, decompression of the gastrointestinal tract may be necessary); (4) monitoring the cardiovascular system; (5) determining daily blood counts for guidance in transfusion requirements.

Folinic acid has been observed to have a protective effect in normal mice that were administered lethal doses of vincristine sulfate (Cancer Res 1963;23:1390). Isolated case reports suggest that folinic acid may be helpful in treating humans who have received an overdose of vincristine sulfate. It is suggested that 100 mg of folinic acid be administered intravenously every 3 hours for 24 hours and then every 6 hours for at least 48 hours. Theoretically (based on pharmacokinetic data), tissue levels of vincristine sulfate can be expected to remain significantly elevated for at least 72 hours. Treatment with folinic acid does not eliminate the need for the above-mentioned supportive measures.

Most of an intravenous dose of vincristine is excreted into the bile after rapid tissue binding (see CLINICAL PHARMACOLOGY). Because only very small amounts of the drug appear in dialysate, hemodialysis is not likely to be helpful in cases of overdosage. An increase in the severity of side effects may be experienced by patients with liver disease that is severe enough to decrease biliary excretion.

Enhanced fecal excretion of parenterally administered vincristine has been demonstrated in dogs pretreated with cholestyramine. There are no published clinical data on the use of cholestyramine as an antidote in humans.

There are no published clinical data on the consequences of oral ingestion of vincristine. Should oral ingestion occur, the stomach should be evacuated. Evacuation should be followed by oral administration of activated charcoal and a cathartic.

Treatment of patients following intrathecal administration of vincristine sulfate injection has included immediate removal of spinal fluid and flushing with Lactated Ringer’s, as well as other solutions and has not prevented ascending paralysis and death. In one case, progressive paralysis in an adult was arrested by the following treatment initiated immediately after the intrathecal injection: