Vincristine Kalbe®
Composition
Each ml contains:
Vincristine Sulphate B.P. …………………………………………. 1 mg
Pharmacology
The precise mechanism of action of Vincristine Kalbe® is not clearly understood. It appears to bind or crystallize critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerisation and causing metaphase arrest. In high concentrations, Vincristine Kalbe® may also inhibit nucleic acid and protein synthesis.
After injection, Vincristine Kalbe® is rapidly distributed to body tissues and bound to the formed blood elements (especially red blood cells and platelets). Vincristine Kalbe ® does not enter the C.N.S. in appreciable amounts.
Vincristine Kalbe® is believed to be extensively metabolised in the liver and excreted mainly via the bite. One-third of an administered dose may be found in the faeces within 24 hours and two-thirds within 72 hours. Only a small percentage of the dose is excreted in the urine. In both faeces and urine, approximately half oh the drug is recovered in the form of metabolites.
The precise mechanism of action of Vincristine Kalbe® is not clearly understood. It appears to bind or crystallize critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerisation and causing metaphase arrest. In high concentrations, Vincristine Kalbe® may also inhibit nucleic acid and protein synthesis.
After injection, Vincristine Kalbe® is rapidly distributed to body tissues and bound to the formed blood elements (especially red blood cells and platelets). Vincristine Kalbe ® does not enter the C.N.S. in appreciable amounts.
Vincristine Kalbe® is believed to be extensively metabolised in the liver and excreted mainly via the bite. One-third of an administered dose may be found in the faeces within 24 hours and two-thirds within 72 hours. Only a small percentage of the dose is excreted in the urine. In both faeces and urine, approximately half oh the drug is recovered in the form of metabolites.
Indication
Vincristine Kalbe® is used primarily as a component of various chemotherapeutic regiments for the treatment of acute leukaemia. It has also been used in conjunctions with other oncolytic drugs in the treatment of Hodgkin’s disease, non-Hodgkin’s malignant lymphomas, neuroblastoma, rhabdomyosarcoma, osteogenic sarcoma Ewing’s sarcoma, mycosis fungoides, Wilms’s tumour and carcinomas of the breast, cervix and lung.
Vincristine Kalbe® has been used with some success in the treatment of ldiopathic thrombocytopenic purpura refractory to corticosteroids and splenectomy, however, its value compared to other drugs such as vinblastine, azathioprine or cyclophosphamide has not been determined.
Vincristine Kalbe® is used primarily as a component of various chemotherapeutic regiments for the treatment of acute leukaemia. It has also been used in conjunctions with other oncolytic drugs in the treatment of Hodgkin’s disease, non-Hodgkin’s malignant lymphomas, neuroblastoma, rhabdomyosarcoma, osteogenic sarcoma Ewing’s sarcoma, mycosis fungoides, Wilms’s tumour and carcinomas of the breast, cervix and lung.
Vincristine Kalbe® has been used with some success in the treatment of ldiopathic thrombocytopenic purpura refractory to corticosteroids and splenectomy, however, its value compared to other drugs such as vinblastine, azathioprine or cyclophosphamide has not been determined.
Contra Indication
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 Kalbe ® may be additive with that of other drugs acting on the peripheral nervous system. .
Vincristine Kalbe ® appears to increase the cellular uptake of methotrexate by malignant cells and this principal has been applied in high-dose methotrexate therapy. .
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 Kalbe ® may be additive with that of other drugs acting on the peripheral nervous system. .
Vincristine Kalbe ® appears to increase the cellular uptake of methotrexate by malignant cells and this principal has been applied in high-dose methotrexate therapy. .
Warning
Vincristine Kalbe ® should be used only by physicians experienced in cytotoxic chemotherapy. .
The drug is very irritating and should not be given intramuscularly of subcutaneously. Intra-thecal administration of Vincristine Kalbe ® is usually fatal. Vincristine Kalbe ® is a vesicant and may cause a severe local reaction o extravasations. If leakage into the surrounding tissue should occur during I.V. administration of Vincristine Kalbe ®, the injection should be discontinued immediately and any remaining portion of the dose should be introduced into another vein. Local injection of hyaluronidase with the application of heat has been used to disperse the drug in order to minimize discomfort and the possibility of tissue damage. .
Leucopenia is less likely following therapy with Vincristine Kalbe ® than is the case with other oncolytic agents. However, because of its possibility both physician and patient should remain alert for signs of any complicating infection. If leucopenia of a complicating infection is present, the administration of the next dose of Vincristine Kalbe ® warrants careful consideration. .
Acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with Vincristine Kalbe ®..
As Vincristine Kalbe ® penetrates the blood-brain barrier poorly, additional agents and route of administration may required for central nervous system leukaemia. The neurotoxic effect of Vincristine Kalbe ® may be additive with other neurotixic agents or increased by spinal cord irradiation and neurological disease. .
Because of the hepatic metabolism and biliary excretion of Vincristine Kalbe ®, a dosage modification may be required in patients with liver disease or jaundice. .
Care should be taken to avoid accidental contamination of the eyes, because Vincristine Kalbe ® is highly irritant and can cause corneal ulceration. .
Safe use of Vincristine Kalbe ® during pregnancy has not been established. There is insufficient information to assess its effect on fertility in humans. It is recommended that the drug not be used in pregnant woman or in individuals with reproductive capabilities unless the expected benefit outweighs the potential risk. .
Although very little information is available regarding excretion of anti-neoplastic agents in breast milk, breast-feeding is not recommended while Vincristine Kalbe ® is being administered because of the risks to the infant. .
Vincristine Kalbe ® should be used only by physicians experienced in cytotoxic chemotherapy. .
The drug is very irritating and should not be given intramuscularly of subcutaneously. Intra-thecal administration of Vincristine Kalbe ® is usually fatal. Vincristine Kalbe ® is a vesicant and may cause a severe local reaction o extravasations. If leakage into the surrounding tissue should occur during I.V. administration of Vincristine Kalbe ®, the injection should be discontinued immediately and any remaining portion of the dose should be introduced into another vein. Local injection of hyaluronidase with the application of heat has been used to disperse the drug in order to minimize discomfort and the possibility of tissue damage. .
Leucopenia is less likely following therapy with Vincristine Kalbe ® than is the case with other oncolytic agents. However, because of its possibility both physician and patient should remain alert for signs of any complicating infection. If leucopenia of a complicating infection is present, the administration of the next dose of Vincristine Kalbe ® warrants careful consideration. .
Acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with Vincristine Kalbe ®..
As Vincristine Kalbe ® penetrates the blood-brain barrier poorly, additional agents and route of administration may required for central nervous system leukaemia. The neurotoxic effect of Vincristine Kalbe ® may be additive with other neurotixic agents or increased by spinal cord irradiation and neurological disease. .
Because of the hepatic metabolism and biliary excretion of Vincristine Kalbe ®, a dosage modification may be required in patients with liver disease or jaundice. .
Care should be taken to avoid accidental contamination of the eyes, because Vincristine Kalbe ® is highly irritant and can cause corneal ulceration. .
Safe use of Vincristine Kalbe ® during pregnancy has not been established. There is insufficient information to assess its effect on fertility in humans. It is recommended that the drug not be used in pregnant woman or in individuals with reproductive capabilities unless the expected benefit outweighs the potential risk. .
Although very little information is available regarding excretion of anti-neoplastic agents in breast milk, breast-feeding is not recommended while Vincristine Kalbe ® is being administered because of the risks to the infant. .
Adverse Reaction
In general, the incidence and severity of side effects of Vincristine Kalbe ® are considered to be related to the total dose and duration of therapy. .
Neurotoxicity is the common dose-limiting toxicity of Vincristine Kalbe ®. It is frequently manifested as peripheral neuropathy. Other symptoms include the loss deep tendon reflexes and peripheral paraesthesias, especially numbness, pain and tingling. At higher or prolonged doses, cranial nerve palsy, atrophy, cramps, ataxia, a slapping gait, foot drop and difficulty in walking or inability to walk may occur. Cranial nerve palsies may account for headaches and jaw pains associated with Vincristine Kalbe ®..
Geriatric patients and those with underlying neurologic disease may be more susceptible than other patients to the neurotoxic effects of Vincristine Kalbe ®. No agent which can reserve the neurotoxic effects of Vincristine Kalbe ® has been found to date. .
Recovery from neurotoxicity usually begins with discontinuation of therapy. .
Paraesthesias are readily reversible while depressed tendon reflexes return slowly, if at all. Occasionally symptoms may persist for up to several months after the drug has been discontinued. .
Autonomic toxicity such as constipation and paralytic ileus are not uncommon and are frequently associated with abdominal cramps. Stool softeners, mild laxative and enemas may be helpful. A routine prophylactic regimen of laxatives and enemas is usually recommended for patients receiving Vincristine Kalbe ®..
Other autonomic effects may include urinary tract disturbances, orthostatic hypotention, defective sweating and myoclonic jerks. .
C.N.S. toxicity includes depression, agitation, insomnia and hallucinations, convulsions (frequently accompanied by hypertension) and comas have occurred at higher doses. .
Alopecia occurs in a great majority of patients on Vincristine Kalbe ®, however, it is reversible when the drug is discontinued. .
Haematologic toxicity of Vincristine Kalbe ® is less than that of other antineoplastic agent. Occasionally, leucopenia, anaemia and thrombocytopenia occur, but rarely at usual doses. Leucopenia, usually persist for less than 7 days when the drug is given in single weekly doses. .
Hyper secretion of antidiuretic hormone has occurred rarely in patients receiving Vincristine Kalbe ® therapy. In these patients, hyponatraemia associated with increased urinary sodium excretion occurs without evidence of renal or adrenal disease, hypotension, dehydration, azotemia or clinical oedema. .
Nausea, vomiting, diarrhoea, stomatitis and oral ulceration occur occasionally. .
Fever and weight loss at high doses have also been reported. .
In general, the incidence and severity of side effects of Vincristine Kalbe ® are considered to be related to the total dose and duration of therapy. .
Neurotoxicity is the common dose-limiting toxicity of Vincristine Kalbe ®. It is frequently manifested as peripheral neuropathy. Other symptoms include the loss deep tendon reflexes and peripheral paraesthesias, especially numbness, pain and tingling. At higher or prolonged doses, cranial nerve palsy, atrophy, cramps, ataxia, a slapping gait, foot drop and difficulty in walking or inability to walk may occur. Cranial nerve palsies may account for headaches and jaw pains associated with Vincristine Kalbe ®..
Geriatric patients and those with underlying neurologic disease may be more susceptible than other patients to the neurotoxic effects of Vincristine Kalbe ®. No agent which can reserve the neurotoxic effects of Vincristine Kalbe ® has been found to date. .
Recovery from neurotoxicity usually begins with discontinuation of therapy. .
Paraesthesias are readily reversible while depressed tendon reflexes return slowly, if at all. Occasionally symptoms may persist for up to several months after the drug has been discontinued. .
Autonomic toxicity such as constipation and paralytic ileus are not uncommon and are frequently associated with abdominal cramps. Stool softeners, mild laxative and enemas may be helpful. A routine prophylactic regimen of laxatives and enemas is usually recommended for patients receiving Vincristine Kalbe ®..
Other autonomic effects may include urinary tract disturbances, orthostatic hypotention, defective sweating and myoclonic jerks. .
C.N.S. toxicity includes depression, agitation, insomnia and hallucinations, convulsions (frequently accompanied by hypertension) and comas have occurred at higher doses. .
Alopecia occurs in a great majority of patients on Vincristine Kalbe ®, however, it is reversible when the drug is discontinued. .
Haematologic toxicity of Vincristine Kalbe ® is less than that of other antineoplastic agent. Occasionally, leucopenia, anaemia and thrombocytopenia occur, but rarely at usual doses. Leucopenia, usually persist for less than 7 days when the drug is given in single weekly doses. .
Hyper secretion of antidiuretic hormone has occurred rarely in patients receiving Vincristine Kalbe ® therapy. In these patients, hyponatraemia associated with increased urinary sodium excretion occurs without evidence of renal or adrenal disease, hypotension, dehydration, azotemia or clinical oedema. .
Nausea, vomiting, diarrhoea, stomatitis and oral ulceration occur occasionally. .
Fever and weight loss at high doses have also been reported. .
Dosage
Vincristine Kalbe ® is administered intravenously
Vincristine Kalbe ® may be injected into the tubing or side-arm of a free flowing I.V. infusion of 0.9% saline or 5% glucose, or directly into a vein over about a one minute period. Care should be taken to avoid extravasations.
Vincristine Kalbe ® has been given by many different dosing schemes and in combination with many other drugs. Because of the narrow range between therapeutic and toxic levels and variations in response, the dosage must always be carefully adjusted according to the needs of the individual. Vincristine Kalbe ® is usually administered at weekly intervals.
Children: the usual dose is 1.5 – 2.0 mg/m¬2 body surface area (b.s.a.) .
Adults: the usual dose is 0.4 – 1.4 mg/m2 b.s.a. .
Elderly patients and those with underlying neurological disease may be more susceptible to the neurotoxic effects of Vincristine Kalbe ®. Dosage modification may also be required in patients with liver disease or jaundice. .
.
Over dosage with Vincristine Kalbe ® produces adverse reactions that are mainly extensions of the common adverse effects as these are dose related. As no antidote for Vincristine Kalbe ® has been found to date, treatment is purely supportive and symptomatic.
Anticonvulsants such as phenobarbitone may be beneficial in controlling seizures. If pro- found neutropenia develops, surveillance for the presence of infection by culture protective isolation and early treatment with antibiotics when infection is suspected may be necessary. Fluid restriction and possibly the use of an appropriate diuretic may have to be instituted to prevent side effects resulting from hyper secretion of antidiuretic hormone. Cathartics may be used to prevent ileus. Routine monitoring of the cardiovascular system is also recommended together with daily blood counts as an indicator for transfusion requirements.
Vincristine Kalbe ® is administered intravenously
Vincristine Kalbe ® may be injected into the tubing or side-arm of a free flowing I.V. infusion of 0.9% saline or 5% glucose, or directly into a vein over about a one minute period. Care should be taken to avoid extravasations.
Vincristine Kalbe ® has been given by many different dosing schemes and in combination with many other drugs. Because of the narrow range between therapeutic and toxic levels and variations in response, the dosage must always be carefully adjusted according to the needs of the individual. Vincristine Kalbe ® is usually administered at weekly intervals.
Children: the usual dose is 1.5 – 2.0 mg/m¬2 body surface area (b.s.a.) .
Adults: the usual dose is 0.4 – 1.4 mg/m2 b.s.a. .
Elderly patients and those with underlying neurological disease may be more susceptible to the neurotoxic effects of Vincristine Kalbe ®. Dosage modification may also be required in patients with liver disease or jaundice. .
.
Over dosage with Vincristine Kalbe ® produces adverse reactions that are mainly extensions of the common adverse effects as these are dose related. As no antidote for Vincristine Kalbe ® has been found to date, treatment is purely supportive and symptomatic.
Anticonvulsants such as phenobarbitone may be beneficial in controlling seizures. If pro- found neutropenia develops, surveillance for the presence of infection by culture protective isolation and early treatment with antibiotics when infection is suspected may be necessary. Fluid restriction and possibly the use of an appropriate diuretic may have to be instituted to prevent side effects resulting from hyper secretion of antidiuretic hormone. Cathartics may be used to prevent ileus. Routine monitoring of the cardiovascular system is also recommended together with daily blood counts as an indicator for transfusion requirements.
Presentation
Vincristine Kalbe ® 1 mg: Box of vial 1 ml Reg. No. .
Vincristine Kalbe ® 2 mg: Box of vial 2 ml Reg. No.
Store below 8oC.
Do not freeze.
Protect from light.
Vincristine Kalbe ® 1 mg: Box of vial 1 ml Reg. No. .
Vincristine Kalbe ® 2 mg: Box of vial 2 ml Reg. No.
Store below 8oC.
Do not freeze.
Protect from light.
Reference
Manufactured by:
Boryung Pharmaceutical Co., Ltd, Korea
Imported, repacked & distributed by :
PT KALBE FARMA TBK
Bekasi
– Indonesia
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