VCR

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,rhabdomyosarcoma,neuroblastoma,and Wilms’ tumor.

Anti Cancer

Vincristine Sulfate is the salt of an alkaloid obtained from the periwinkle plant (Vinca rasea Linn). Vincristine sulfate is a white or slightly yellow, hygroscopic, amorphous or crystalline powder and is freely soluble in water and slightly soluble in alcohol. 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; about 80% of an injected dose of vincristine sulfate appears in the faeces 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.

This preparation is for intravenous use only . 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. 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. The drug is administered intravenously at weekly intervals.

Allopurinol may increase the incidence of cytotoxic induced bone-marrow depression. The mechanism for this potentiation has not been fully classified. The neurotoxicity of vincristine may be additive with that of asparaginase isoniazid and other drugs acting on the peripheral nervous system. The concurrent use of doxorubicin with vincristine and prednisone may produce increased myelosuppression; it is recommended that the combination be avoided. Vincristine appears to increase the cellular uptake of methotrexate by malignant cells and this principle has been applied in high-dose methotrexate therapy.

Patients with the demyelinating form of Charcot?Marie?Tooth syndrome should not be given vincristine sulfate injection.

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.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

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.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. becoming pregnant.

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.

Store in a refrigerator at 2°C - 8°C. Do not freeze. Protect from light. Keep out of the reach of children.

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