Vincristine Sulphate - Serum Institute of India - Marketed Lyophilized Drug Products

ADVERSE REACTIONS
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 are usually of short duration ( i.e. 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
is continued. Generalized sensorimotor dysfunction may become progressively more severe with continued treatment,although such symptoms usually disappear after discontinuation 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:
Hypersensitivity - Rare cases of allergic type reactions, such as anaphylaxis, rash and edema, that are related to VINCRISTINE SULPHATE therapy have been reported in patients receiving VINCRISTINE SULPHATE 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. All cases have responded to high enemas and laxatives. A routine prophylactic regimen against constipation is recommended for all patients receiving VINCRISTINE SULPHATE Paralytic ileus ( which mimics the surgical abdomen ) may occur, particularly in young children. The ileus will reverse itself with temporary discontinuance of VINCRISTINE SULPHATEand with symptomatic care.
Genitourinary - Polyuria, dysuria, and urinary retention due to bladder atony have occured. 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 SULPHATE.
Cardiovascular - Hypertension and hypotension have occurred. Chemotherapy combinations that have included VINCRISTINE SULPHATE, 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 SULPHATE.
Loss of deep-tendon reflexes, foot drop, ataxia, and paralysis have been reported with continued administration. Cranial nerve manifestations, including isolated paresis and /or paralysis of muscles controlled by cranial motor nerves, may occur in the absence of motor impairment elsewhere, extraoccular and laryngeal muscles are most commonly involved. Jaw pain, pharyngeal pain, parotid gland pain, bone pain, back pain, limb pain, and with myalgias have been reported: pain in these areas may be severe. Convulsions, frequently with hypertension have been reported in a few patients receiving VINCRISTINE SULPHATE. Several instances of convulsions followed by coma have been reported in children. Transient cortical blindness and optic atrophy with blindness have been reported.
Pulmonary - See Precautions.
Endocrine - Rare occurrences of a syndrome attributable to inappropriate antidiuretic hormone secretion have been observed in patients treated with VINCRISTINE SULPHATE. This syndrome is characterized by high urinary sodium excretion in the presence of hyponatremia; renal or adrenal disease, hypotension, dehydration azotemia, and and clinical edema are absent.With fluid deprivation, improvement occurs in the renal loss of sodium.
Hematologic - VINCRISTINE SULPHATE 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 SULPHATE is begun, may actually improve before the appearance of marrow remission.
Skin -Alopecia and rash have been reported.
OVERDOSAGE
Side effects following the use of VINCRISTINE SULPHATE are dose related. In children under 13 years of age, death has occurred following doses of VINCRISTINE SULPHATE 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 . Therefore, following adminstration of doses higher than those recommended, patients can be expected to experience exaggerated side effects. Supportive care should include the following
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 loop of Henle and the distal tubule )
Administration of anticonvulsants
Use of enemas or cathartics to prevent ileus ( in some instances, decompression of the gastrointestinal tract may be necessary ) Monitoring the cardiovascular system; and
Determining daily blood counts for guidance in transfusion requirements.
Animal studies conducted have shown that folinic acid has a protective effect in normal mice that were administered lethal doses of VINCRISTINE SULPHATE.
Isolated case reports suggest that folinic acid may be helpful in treating humans who have received an overdosage of VINCRISTINE SULPHATE.
DOSAGE AND ADMINISTRATION
Cautiously calculate and administer VINCRISTINE SULPHATE dose,overdosage may be serious or fatal.
Administer IV only, at weekly intervals. Inject solution either directly into a vein or into the tubing of a running IV infusion . Injection may be completed in about 1 minute.
Adults : 1.4 mg to1.5 / m2 upto a maximum weekly dose of 2 mg / m2 :
For children 2 mg / m2. For children weighing less than 10 kg or less or having a body surface area less than 1 m2 give 0.05 mg/kg once a week.
Hepatic function impairment - A 50% reduction in the dose is recommended for patients having a direct serum bilirubin value > 3 mg/dl.
Extravasation : Properly position the needle in the vein before injecting VINCRISTINE SULPHATE .Leakage into surrounding tissue during IV administration may cause considerable irriation. Discontinue injection immediately; introduce any remaining portion of the dose into another vein. Locally inject hyaluronidase and apply moderate heat to the area to disperse the drug and minimize discomfort and the possibility of cellulitis.
PREPARATION OF SOLUTION
Dissolve contents of the 1mg, 2mg and 5mg vials in 10ml Sodium Chloride Injection B.P. respectively.
Compatibility : Do not dilute in solutions that raise or lower the pH outside the range of 3.5 to 5.5. Do not mix with anything other than normal saline or glucose in water.
HANDLING OF SOLUTION
VINCRISTINE SULPHATE is a toxic compound known to be carcinogenic and mutagenic. Direct contact may cause irritation of skin,eyes and mucous membranes.In case the solution touches skin by accident,the area of contact should be thoroughly washed with soap and water immediately.
Observe all the nessesary routine precautions in handling of cytotoxic drugs in respect of this antineoplastic formulation too.
STORAGE
Store in a refrigerator between 2? to 8?C.
SHELF LIFE
2 years from date of manufacture.
PRESENTATION
VINCRISTINE SULPHATE FOR INJECTION B.P. 1mg : Lyophilised vial supplied with 10 ml ampoule of Sodium Chloride Injection B.P. for reconstitution.
VINCRISTINE SULPHATE FOR INJECTION B.P. 2mg : Lyophilised
VINCRISTINE SULPHATE FOR INJECTION B.P. 5mg : Lyophilised.