Monograph: |
Vindesine Sulfate
Adverse Effects, Treatment, and Precautions
As for Vinblastine Sulfate,see vinblastine sulphate monograph.
The main dose-limiting effect of vindesine is granulocytopenia, with the nadir of the white cell count usually occurring 3 to 5 days after a dose and recovery after a further 4 to 5 days. Although neurotoxicity occurs it may be less severe than that seen with vincristine .Alopecia is the most common adverse effect.
Folinic acid has been suggested for the treatment of overdosage by analogy with vincristine.
Vindesine should not be given by the intrathecal route, as this may produce fatal toxicity. Care should be taken if acute abdominal pain occurs: further doses may result in paralytic ileus.
Administration error.
Inadvertent intrathecal doses of vinca alkaloids result in ascending paralysis and death. In a 10-year-old child accidentally given an intrathecal injection of vindesine, treatment with folinic acid and dexamethasone produced transient recovery but symptoms subsequently recurred and the patient died of progressive ascending paralysis.The CNS showed changes at necropsy similar to those seen after intrathecal vincristine. For reference to the successful treatment of inadvertent intrathecal dosage of vincristine, and UK recommendations on dilution of vinca alkaloids to avoid intrathecal use.
Interactions
As for Vinblastine Sulfate, see vinblastine sulfate monograph.
Pharmacokinetics
The pharmacokinetics of vindesine are similar to those of the other vinca alkaloids. After intravenous doses elimination from the blood is triphasic; the drug is rapidly distributed to body tissues. The terminal half-life is reported to be about 20 hours. It is metabolised primarily in the liver and excreted in bile and urine.
Uses and Administration
Vindesine sulfate is an antineoplastic agent derived from vinblastine like the other vinca alkaloids it causes mitotic arrest in metaphase by binding to microtubular protein. It is used in the treatment of refractory acute lymphoblastic or chronic myeloid leukaemias, and malignant melanoma. It has also been tried in malignant neoplasms of the breast, and lung. See also the cross references given below.
Vindesine sulfate is given weekly by intravenous injection. It may be given as a solution containing 1 mg/mL in sodium chloride injection 0.9%. However, UK guidelines recommend that for patients over the age of 10 years, solutions of vindesine should generally be diluted to a volume of at least 20 mL to avoid inadvertent intrathecal use; higher concentrations can be used for children under 10 years of age. Care should be taken to avoid extravasation and it may be given into a fast-running infusion of sodium chloride, glucose 5%, or glucose-saline injection. The usual starting dose for adults is 3 mg/m2 which may be raised by increments of 500 micrograms/m2 weekly providing that the granulocyte and platelet counts do not fall below acceptable levels (see also Bone-marrow Depression in vinblastine monograph), and acute abdominal pain is not experienced; weekly doses are usually between 3 and 4 mg/m2. Children may be given 4 mg/m2 initially, with weekly doses usually ranging between 4 and 5 mg/m2. An alternative regimen for children with leukaemia is 2 mg/m2 daily for 2 consecutive days, repeated after an interval of 5 to 7 days. Blood counts should be made before each injection. It may be necessary to reduce initial doses in patients with significantly impaired hepatic function.
Malignant neoplasms.
Vindesine has been tried in refractory metastatic melanoma, childhood acute lymphoblastic leukaemia , chronic myeloid leukaemia in blastic crisis, and neuroblastoma . It is also under investigation in lung cancer, particularly non-small cell lung cancer and responses have been reported in advanced breast cancer.
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