THE MOST IMPORTANT FORM OF TOXICITY ASSOCIATED WITH THE USE OF MITHRACIN (plicamycin) CONSISTS OF A BLEEDING SYNDROME WHICH USUALLY BEGINS WITH AN EPISODE OF EPISTAXIS. This bleeding tendency may only consist of a single or several episodes of epistaxis and progress no further. However, in some cases, this hemorrhagic syndrome can start with an episode of hematemesis which may progress to more widespread hemorrhage in the gastrointestinal tract or to a more generalized bleeding tendency. This hemorrhagic diathesis is most likely due to abnormalities in multiple clotting factors.
A detailed analysis of the clinical data in 1,160 patients treated with Mithracin (plicamycin) indicates that the hemorrhagic syndrome is dose related. With doses of 30 mcg/kg/day or less for 10 or fewer doses, the incidence of bleeding episodes has been 5.4% with an associated drug-related mortality rate of 1.6%. With doses greater than 30 mcg/kg/day and/or for more than 10 doses, a significantly larger number of bleeding episodes occurred (11.9%) and the associated drug-related mortality rate was also significantly higher (5.7%).
The most common side effects reported with the use of Mithracin (plicamycin) consist of gastrointestinal symptoms: anorexia, nausea, vomiting, diarrhea, and stomatitis. Other less frequently reported side effects include fever, drowsiness, weakness, lethargy, malaise, headache, depression, phlebitis, facial flushing, and skin rash.
The following laboratory abnormalities have been reported during therapy with Mithracin (plicamycin) and in most instances were reversible following cessation of treatment:
Hematologic Abnormalities: Depression of platelet count, white count, hemoglobin and prothrombin content; elevation of clotting time and bleeding time; abnormal clot retraction.
Thrombocytopenia may be rapid in onset and may occur at any time during therapy or within several days following the last dose. With the occurrence of severe thrombocytopenia, the infusion of platelet concentrates of platelet-rich plasma may be helpful in elevating the platelet count.
The occurrence of leukopenia with the use of Mithracin (plicamycin) is relatively uncommon, occurring only in approximately 6% of patients.
It has been uncommon for abnormalities in clotting time or clot retraction to be demonstrated prior to the onset of an overt bleeding episode noted in some patients treated with Mithracin (plicamycin) . Nevertheless, the performance of these tests periodically is recommended because in a few instances, an abnormality in one of these studies may have served as a warning to terminate therapy because of impending serious toxicity.
Abnormal Liver Function Tests: Increased levels of serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase, alkaline phosphatase, serum bilirubin, ornithine carbamyl transferase, isocitric dehydrogenase, and increased retention of bromsulphalein.
Abnormal Renal Function Tests: Increased blood urea nitrogen and serum creatinine; proteinuria.
Abnormalities in Electrolyte Concentrations: Depression of serum calcium, phosphorus, and potassium.
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