DBL Vincristine Sulfate Overdosage

Signs and symptoms: Overdosage with vincristine produces adverse reactions that are mainly extensions of the common adverse effects as these are dose related. As no antidote for vincristine has been found to date, treatment is purely supportive and symptomatic.
In children under 13 years of age, death has occurred following doses of vincristine that were ten 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).
Treatment: Anticonvulsants such as phenobarbitone may be beneficial in controlling seizures. If profound 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 hypersecretion of antidiuretic hormone. Enemas or cathartics may be used to prevent ileus (in some cases decompression of the GI tract may be necessary). Routine monitoring of the cardiovascular system is also recommended together with daily blood counts as an indicator for transfusion requirements.
Folinic acid has been observed to have a protective effect in normal mice which were administered lethal doses of vincristine sulfate. Isolated reports suggest that folinic acid may be helpful in treating humans who have received an overdose of vincristine. A suggested schedule is to administer 15 mg of folinic acid 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 can be expected to remain significantly elevated for at least 72 hours. Treatment with folinic acid does not eliminate the need for the previously-mentioned supportive measures.
Most of the intravenous dose of vincristine sulfate is excreted into the bile after rapid tissue binding (see Pharmacology: Pharmacokinetics under Actions). Because only very small amounts of the drug appear in dialysate, haemodialysis is not likely to be helpful in cases of overdosage. An increase in the severity of side effects may be experienced in patients with liver disease with diminished biliary excretion.
Enhanced faecal excretion of parenterally administered vincristine has been demonstrated in dogs pretreated with cholestyramine. There are no published clinical data on the use of cholestyramine as an antidote in humans. Nor is there published clinical data on the consequences of oral ingestion of vincristine. Should oral ingestion occur the stomach should be evacuated, and activated charcoal administered orally.