ed to be related to inhibition of the metabolism of vincristine.

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. vincasar pfs should not be readministered. care must be taken to avoid contamination of the eye with concentration of vincasar pfs 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.

incasar pfs is 1 mg/ml. do not add extra fluid to the vial prior to removal of the dose. withdraw the solution of vincasar pfs into an accurate dry syringe, measuring the dose carefully. do not add extra fluid to the vial in an attempt to empty it completely. preparation for flexible plastic container vincasar pfs when diluted with 0.9% sodium chloride injection, usp in concentrations from 0.0015 mg/ml to 0.08 mg/ml is stable for up to 24 hours when protected from light or 8 hours under normal light at 25°c. 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 vincasar pfs 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. vincasar pfs 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 diluted vincristine sulfate injection may be infused via a flexible plastic container directly into an intravenous catheter/needle or into a running intravenous infusion (see drug interactions below). patients receiving radiation therapy vincasar pfs should not be given to patients while they are receiving radiation therapy through ports that include the liver. when vincasar pfs is used in combination with l-asparaginase, vincasar pfs should be given 12 to 24 hours before administration of the enzyme in order to minimize toxicity; administering l-asparaginase before vincasar pfs may reduce hepatic clearance of vincristine. drug interactions vincasar pfs 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 0.9% sodium chloride injection, usp. 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 there is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

tinued 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 vincasar pfs. paralytic ileus (which mimics the "surgical abdomen") may occur, particularly in young pediatric patients. the ileus will reverse itself with temporary discontinuance of vincasar pfs 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 vincasar pfs. 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 section. acute respiratory distress syndrome has been reported. 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 vincasar pfs 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 vincasar pfs is begun, may actually improve before the appearance of bone marrow remission. granulocytopenia has been reported. skin alopecia and rash have been reported. other fever, headache, dehydration, and hyperuricemia have occurred.

ed to be related to inhibition of the metabolism of vincristine.

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.

traperitoneal administration of vincristine sulfate in rats and mice, although this study was limited.