Vincristine Sulfate Injection, USP is the salt of an alkaloid obtained from a common flowering herb, the periwinkle plant (Vinca rosea Linn). Originally known as leurocristine, it has also been referred to as LCR and VCR. The molecular formula for Vincristine Sulfate, USP is C₄₆H₅₆N₄O₁₀•H₂SO₄. It has a molecular weight of 923.04.

The structural formula is as follows:

Vincristine Sulfate, USP is a white to off-white powder. It is soluble in methanol, freely soluble in water, but only slightly soluble in 95% ethanol. In 98% ethanol, Vincristine Sulfate, USP has an ultraviolet spectrum with maxima at 221 nm (ε¸+47,100).

Vincristine Sulfate Injection, USP is a sterile, preservative-free, single use only solution available for intravenous use in 2 mL (1 mg and 2 mg) vials. Each mL contains 1 mg Vincristine Sulfate, USP, 100 mg mannitol and Water for Injection, USP q.s. Sulfuric acid or sodium hydroxide have been added for pH control. The pH of Vincristine Sulfate Injection, USP ranges from 4.0 to 5.0. At the time of manufacture, the air in the containers is replaced by nitrogen.

Vincristine sulfate injection is indicated in acute leukemia.

Vincristine sulfate injection has also been shown to be useful in combination with other oncolytic agents in Hodgkin's disease, non-Hodgkin's malignant lymphomas (lymphocytic, mixed cell, histiocytic, undifferentiated, nodular and diffuse types), rhabdomyosarcoma, neuroblastoma, and Wilms' tumor.

This preparation is for intravenous use only (see WARNINGS).

Neurotoxicity appears to be dose related. Extreme care must be used in calculating and administering the dose of Vincristine Sulfate Injection, USP since overdosage may have a very serious or fatal outcome.

Special Dispensing Information: WHEN DISPENSING VINCRISTINE SULFATE INJECTION, USP IN OTHER THAN THE ORIGINAL CONTAINER, IT IS IMPERATIVE THAT IT BE PACKAGED IN THE PROVIDED OVERWRAP WHICH BEARS THE FOLLOWING STATEMENT: “DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY” (see WARNINGS). A syringe containing a specific dose must be labeled, using the auxiliary sticker provided, to state: “FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.”

The concentration of Vincristine Sulfate Injection, USP is 1 mg/mL. Do not add extra fluid to the vial prior to removal of the dose. Withdraw the solution of Vincristine Sulfate Injection, USP into an accurate dry syringe, measuring the dose carefully. Do not add extra fluid to the vial in an attempt to empty it completely.

Caution: It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration of Vincristine Sulfate Injection, USP may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage will help disperse the drug and may minimize discomfort and the possibility of cellulitis.

Vincristine Sulfate Injection, USP must be administered via an intact, free-flowing intravenous needle or catheter. Care should be taken that there is no leakage or swelling occurring during administration (see BOXED WARNINGS).

The solution may be injected either directly into a vein or into the tubing of a running intravenous infusion (see Drug Interactions below). Injection of Vincristine Sulfate Injection, USP should be accomplished within 1 minute.

The drug is administered intravenously at weekly intervals.

The usual dose of Vincristine Sulfate Injection, USP for pediatric patients is 1.5-2 mg/m². For pediatric patients weighing 10 kg or less, the starting dose should be 0.05 mg/kg, administered once a week. The usual dose of Vincristine Sulfate Injection, USP for adults is 1.4 mg/m². A 50% reduction in the dose of Vincristine Sulfate Injection, USP is recommended for patients having a direct serum bilirubin value above 3 mg/100 mL.

Vincristine Sulfate Injection, USP should not be given to patients while they are receiving radiation therapy through ports that include the liver. When Vincristine Sulfate Injection, USP is used in combination with L-asparaginase, Vincristine Sulfate Injection, USP should be given 12 to 24 hours before administration of the enzyme in order to minimize toxicity; administering L-asparaginase before Vincristine Sulfate Injection, USP may reduce hepatic clearance of vincristine.

Drug Interactions - Vincristine Sulfate Injection, USP should not be diluted in solutions that raise or lower the pH outside the range of 3.5 to 5.5. It should not be mixed with anything other than normal saline or glucose in water.

Whenever solution and container permit, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Handling and Disposal - Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Vincristine Sulfate Injection, USP, preservative free solution.

NDC 61703-309-06 1 mg, 1 mg/1 mL (single use), flip-top vial (blue cap)
NDC 61703-309-16 2 mg, 2 mg/2 mL (single use), flip-top vial (blue cap)

This product should be refrigerated between 2°-8°C (36°-46°F). Discard unused solution. Protect from light.

Store Upright.

REFERENCES

1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs, NIH Publication No. 83-2621. For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.

2. AMA Council Report, Guidelines for Handling Parenteral Antineoplastics, JAMA, 1985; 253 (11): 1590-1592.

3. National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.

4. Clinical Oncological Society of Australia, Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia, 1983; 1:426-428.

5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: Report from the Mount Sinai Medical Center. CA - A Cancer Journal of Clinicians, 1983; (Sept/Oct) 258-263.

6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J. Hosp. Pharm, 1990; 47:1033-1049.

7. OSHA Work-Practice Guidelines for Personnel Dealing with Cytotoxic (Antineoplastic) Drugs. Am J Hosp Pharm, 1986; 43: 1193-1204.

Hospira, Inc., Lake Forest, IL 60045. Product of Australia. Revision December 2007. FDA rev date: 10/28/2003

Prior to the use of this drug, patients and/or their parents/guardian should be advised of the possibility of untoward symptoms.

In general, adverse reactions are reversible and are related to dosage. The most common adverse reaction is hair loss; the most troublesome adverse reactions are neuromuscular in origin.

When single, weekly doses of the drug are employed, the adverse reactions of leukopenia, neuritic pain, and constipation occur but are usually of short duration (ie., less than 7 days). When the dosage is reduced, these reactions may lessen or disappear. The severity of such reactions seems to increase when the calculated amount of drug is given in divided doses. Other adverse reactions, such as hair loss, sensory loss, paresthesia, difficulty in walking, slapping gait, loss of deep-tendon reflexes, and muscle wasting, may persist for at least as long as therapy is continued. Generalized sensorimotor dysfunction may become progressively more severe with continued treatment. Although most such symptoms usually disappear by about the sixth week after discontinuance of treatment, some neuromuscular difficulties may persist for prolonged periods in some patients. Regrowth of hair may occur while maintenance therapy walking, slapping gait, loss of deep-tendon reflexes, and muscle wasting, may persist for at least as long as therapy is continued. Generalized sensorimotor dysfunction may become progressively more severe with continued treatment.

Although most such symptoms usually disappear by about the sixth week after discontinuance of treatment, some neuromuscular difficulties may persist for prolonged periods in some patients. Regrowth of hair may occur while maintenance therapy continues.

The following adverse reactions have been reported:

Hepatic veno-occlusive disease has been reported in patients receiving vincristine, particularly in pediatric patients, as part of standard combination chemotherapy regimens. Some of the patients had fatal outcomes; some who survived had undergone liver transplantation.

Hypersensitivity - Rare cases of allergic-type reactions, such as anaphylaxis, rash and edema, that are temporally related to vincristine therapy have been reported in patients receiving vincristine as a part of multidrug chemotherapy regimens.

Gastrointestinal - Constipation, abdominal cramps, weight loss, nausea, vomiting, oral ulceration, diarrhea, paralytic ileus, intestinal necrosis and/or perforation, and anorexia have occurred. Constipation may take the form of upper-colon impaction, and, on physical examination, the rectum may be empty. Colicky abdominal pain coupled with an empty rectum may mislead the physician. A flat film of the abdomen is useful in demonstrating this condition. All cases have responded to high enemas and laxatives. A routine prophylactic regimen against constipation is recommended for all patients receiving vincristine sulfate injection. Paralytic ileus (which mimics the “surgical abdomen”) may occur, particularly in young pediatric patients. The ileus will reverse itself with temporary discontinuance of vincristine sulfate injection and with symptomatic care.

Genitourinary-Polyuria, dysuria, and urinary retention due to bladder atony have occurred. Other drugs known to cause urinary retention (particularly in the elderly) should, if possible, be discontinued for the first few days following administration of vincristine sulfate injection.

Cardiovascular - Hypertension and hypotension have occurred. Chemotherapy combinations that have included vincristine sulfate, when given to patients previously treated with mediastinal radiation, have been associated with coronary artery disease and myocardial infarction. Causality has not been established.

Neurologic - Frequently, there is a sequence to the development of neuromuscular side effects. Initially, only sensory impairment and paresthesia may be encountered. With continued treatment, neuritic pain and, later, motor difficulties may occur. There have been no reports of any agent that can reverse the neuromuscular manifestations that may accompany therapy with vincristine sulfate.

Loss of deep-tendon reflexes, foot drop, ataxia, and paralysis have been reported with continued administration. Cranial nerve manifestations, such as isolated paresis and/or paralysis of muscles controlled by cranial motor nerves including potentially life-threatening bilateral vocal cord paralysis, may occur in the absence of motor impairment elsewhere; extraocular and laryngeal muscles are those most commonly involved. Jaw pain, pharyngeal pain, parotid gland pain, bone pain, back pain, limb pain, and myalgias have been reported; pain in these areas may be severe. Convulsions, frequently with hypertension, have been reported in a few patients receiving vincristine sulfate. Several instances of convulsions followed by coma have been reported in pediatric patients. Transient cortical blindness and optic atrophy with blindness have been reported. Treatment with vinca alkaloids has resulted in both vestibular and auditory damage to the eighth cranial nerve. Manifestations include partial or total deafness which may be temporary or permanent, and difficulties with balance including dizziness, nystagmus, and vertigo. Particular caution is warranted when vincristine is used in combination with other agents known to be ototoxic such as the platinum-containing oncolytics.

Pulmonary - See PRECAUTIONS.

Endocrine - Rare occurrences of a syndrome attributable to inappropriate antidiuretic hormone secretion have been observed in patients treated with vincristine sulfate. This syndrome is characterized by high urinary sodium excretion in the presence of hyponatremia; renal or adrenal disease, hypotension, dehydration, azotemia, and clinical edema are absent. With fluid deprivation, improvement occurs in the hyponatremia and in the renal loss of sodium.

Hematologic - Vincristine sulfate injection does not appear to have any constant or significant effect on platelets or red blood cells. Serious bone-marrow depression is usually not a major dose-limiting event. However, anemia, leukopenia, and thrombocytopenia have been reported. Thrombocytopenia, if present when therapy with vincristine sulfate injection is begun, may actually improve before the appearance of bone marrow remission.

Skin - Alopecia and rash have been reported.

Other - Fever and headache have occurred.

The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vincristine sulfate to this interaction is not certain. The interaction may result from reduced absorption of phenytoin and an increase in the rate of its metabolism and elimination.

Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vincristine sulfate with itraconazole (a known inhibitor of the metabolic pathway) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side effects (see ADVERSE REACTIONS). This interaction is presumed to be related to inhibition of the metabolism of vincristine.

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 child-bearing potential should be advised to avoid becoming pregnant.

General - Acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with vincristine sulfate. In the presence of leukopenia or a complicating infection, administration of the next dose of vincristine sulfate injection warrants careful consideration.

If central nervous system leukemia is diagnosed, additional agents may be required, because vincristine does not appear to cross the blood-brain barrier in adequate amounts.

Particular attention should be given to dosage and neurologic side effects if vincristine sulfate injection is administered to patients with preexisting neuromuscular disease and when other drugs with neurotoxic potential are also being used.

Acute shortness of breath and severe broncospasm have been reported following the administration of vinca alkaloids. These reactions have been encountered most frequently when the vinca alkaloid was used in combination with mitomycin-C and may require aggressive treatment, particularly when there is preexisting pulmonary dysfunction. The onset of these reactions may occur minutes to several hours after the vinca alkaloid is injected and may occur up to 2 weeks following the dose of mitomycin. Progressive dyspnea requiring chronic therapy may occur. Vincristine sulfate should not be readministered.

Care must be taken to avoid contamination of the eye with concentration of vincristine sulfate injection used clinically. If accidental contamination occurs severe irritation (or, if the drug was delivered under pressure, even corneal ulceration) may result. The eye should be washed immediately and thoroughly.

Laboratory Tests - Because dose-limiting clinical toxicity is manifested as neurotoxicity clinical evaluation (e.g., history, physical examination) is necessary to detect the need for dosage modification. Following administration of vincristine sulfate injection, some individuals may have a fall in the white blood cell count or platelet count, particularly when previous therapy or the disease itself has reduced bone-marrow function. Therefore, a complete blood count should be done before administration of each dose. Acute elevation of serum uric acid may also occur during induction of remission in acute leukemia; thus, such levels should be determined frequently during the first 3 to 4 weeks of treatment or appropriate measures taken to prevent uric acid nephropathy. The laboratory performing these tests should be consulted for its range of normal values.

Carcinogenesis, Mutagenesis, Impairment of Fertility- Neither in vivo nor in vitro laboratory tests have conclusively demonstrated the mutagenicity of this product. Fertility following treatment with vincristine sulfate alone for malignant disease has not been studied in humans. Clinical reports of both male and female patients who received multiple-agent chemotherapy that included vincristine sulfate indicate that azoospermia and amenorrhea can occur in postpubertal patients. Recovery occurred many months after completion of chemotherapy in some but not all patients. When the same treatment is administered to prepubertal patients, permanent azoospermia and amenorrhea are much less likely.

Patients who received chemotherapy with vincristine sulfate in combination with anti-cancer drugs known to be carcinogenic have developed second malignancies. The contributing role of vincristine sulfate in this development has not been determined. No evidence of carcinogenicity was found following intraperitoneal administration of vincristine sulfate in rats and mice, although this study was limited.

Usage in Pregnancy - Pregnancy Category D. See WARNINGS.

Nursing Mothers- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions due to vincristine sulfate in nursing infants, a decision should be made either to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Pediatric Use - See DOSAGE AND ADMINISTRATION section.

Side effects following the use of vincristine sulfate injection 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.

Patients with the demyelinating form of Charcot-Marie-Tooth syndrome should not be given vincristine sulfate injection. Careful attention should be given to those conditions listed under Warning and Precautions.

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.

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

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

VINCRISTINE - INJECTION

(vin-CRISS-teen)

COMMON BRAND NAME(S): Oncovin, Vincasar

WARNING: This drug is to be given only into a vein (IV). It must not be injected into the spine. Fatal reactions occur if vincristine is injected into the spine.

If vincristine leaks out of the vein into the surrounding area, it may cause serious skin and tissue damage. Tell your health care professional immediately if you experience pain, irritation, redness, or swelling at the injection site. Prompt treatment of the leakage will help reduce discomfort and possible skin damage.

USES: Vincristine is used to treat various types of cancer. It is a cancer chemotherapy drug that is usually used with other chemotherapy drugs to slow or stop cancer cell growth.

HOW TO USE: See also Warning section.

This medication is given by injection only into a vein by a health care professional. It is given on a schedule usually at weekly intervals or as directed by your doctor. Health care professionals must follow all the manufacturer's instructions for properly mixing and giving this drug. If you have any questions about the use of this medication, consult your doctor or pharmacist.

The dosage is based on your medical condition, body size, and response to treatment. In small children, dosage is also based on weight. Many dosing regimens recommend that a single dose be limited to no more than 2 milligrams.

Unless your doctor instructs you otherwise, drink plenty of fluids while using this medication. This helps to reduce some of the side effects to the kidneys.

SIDE EFFECTS: See also Warning section.

Nausea, vomiting, weight loss, diarrhea, bloating, stomach/abdominal pain or cramps, mouth sores, dizziness, or headache may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Vincristine may also affect the nerves in the intestines, causing gut movement to slow down. This effect can result in constipation, which in some cases may become serious. Consult your doctor or pharmacist about how you can prevent constipation (e.g., maintain a diet adequate in fiber, drink plenty of water, exercise, choose the right type of laxative with a stool softener, avoid bulk-forming laxatives). Tell your doctor or pharmacist promptly if you develop constipation.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Many people using this medication have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

This medication commonly affects the nerves and muscles in your body. Most of these side effects go away after this medication is stopped, however some effects may persist for a long time. Tell your doctor immediately if any of these serious side effects occur: painful/difficult urination, change in the amount of urine, pain (e.g., in the joints, back, muscles, jaw), numbness/tingling/pain of the arms/legs, weakness, difficulty walking, loss of coordination/balance, inability to move your muscles (e.g., muscles of the face, other parts of your body), drooping eyelids, hoarseness, trouble speaking, mental/mood changes (e.g., depression, hallucinations, confusion).

Tell your doctor immediately if any of these rare but very serious side effects occur: vision/hearing changes, seizures, unusual bleeding/bruising.

This medication can lower the body's ability to fight an infection. Tell your doctor promptly if you develop any signs of an infection such as fever, chills, or persistent sore throat.

Trouble breathing may infrequently occur with vincristine treatment, especially when it is given with another chemotherapy drug, mitomycin-C. Patients with lung problems may be more sensitive to this side effect. Long-term treatment of this side effect may be required if it worsens. This effect may occur within minutes to several hours after vincristine is given and up to 2 weeks after the dose of mitomycin-C. Seek immediate medical attention if you have shortness of breath or coughing. If you have this reaction, you should not receive vincristine again.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using vincristine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a certain type of nerve/muscle disease (demyelinating form of Charcot-Marie-Tooth syndrome), radiation treatment to the liver.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other nerve/muscle problems (neuromuscular disease, neuropathy), liver disease, decreased bone marrow function, blood disorders, current infections.

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received polio vaccine by mouth or flu vaccine inhaled through the nose.

Since this medication can increase your risk of developing serious infections, wash your hands well to prevent the spread of infections. Avoid contact with people who have illnesses that may spread to others (e.g., flu, chickenpox).

To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like safety razors and nail cutters, and avoid activities such as contact sports.

Children may be more sensitive to the effects of this drug, especially slowed movement of the gut that may cause vomiting and constipation.

Elderly patients who also take drugs that may cause difficult urination as a side effect may be more sensitive to the effects of this drug on the kidneys (urinary retention). Consult your doctor for more details. See also Drug Interactions.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details and to discuss reliable forms of birth control. It is recommended that men and women use 2 effective forms of birth control (e.g., condoms, birth control pills) while using this medication and for some time afterwards. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: digoxin, phenytoin, drugs that may cause nerve damage to the ear (e.g., chemotherapy drugs that contain platinum), drugs affecting liver enzymes that remove vincristine from your body (such as aprepitant, cimetidine, St. John's wort, azole antifungals including itraconazole, macrolide antibiotics including erythromycin, rifamycins including rifabutin, certain anti-seizure medicines including carbamazepine), drugs that may cause difficult urination (e.g., belladonna alkaloids, anticholinergic drugs such as atropine, antispasmodics such as dicyclomine, drugs to treat an overactive bladder such as oxybutynin).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Laboratory and/or medical tests (e.g., complete blood count, uric acid blood levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: It is important that you receive each dose of this medication as scheduled. If you miss a dose, contact your doctor to establish a new dosing schedule.

STORAGE: Store the medication in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light. Consult your pharmacist for information about how long this drug may be stored.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.