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plicamycin (Mithramycin)

Tradename: Mithramycin. Indications: 1) testicular cancer 2) hypercalcemia of malignancy -> reserved for volume-repleted patients who have failed pamidronate & calcitonin 3) chronic myelogenous leukemia (CML) blast crisis 4) Paget's disease Contraindications: 1) thrombocytopenia 2) bleeding diatheses 3) coagulation disorders 4) bone marrow suppression 5) hypocalcemia Dosage: 1) testicular cancer: 20-30 ug/kg/day IV for 4-5 days, repeated every 4 weeks 2) hypercalcemia of malignancy: 25 ug/kg/day in 500 mL D5W or normal saline infused IV over 4-6 hours 2-3 times weekly 3) dosage adjustment in renal failure: a) 25% reduction for moderate renal failure b) 50% reduction for severe renal failure Powder for injection: 2.5 mg. Pharmacokinetics: 1) well distributed to tissues 2) highest concentrations in liver, kidney, CSF & bone 3) 1/2life is 2 hours 4) 40% is eliminated in the urine Adverse effects: 1) common (> 10%) - nausea/vomiting (100% within the 1st 6 hours) 2) less common (1-10%) - hypocalcemia, weakness, hemorrhagic diathesis*, clotting disorder*, extravasation - myelosuppression - WBC & platelets: moderate - onset 7-10 days - nadir 14 days - recovery 21 days 3) other - thrombocytopenia & platelet dysfunction (hemorrhage)* - coagulation factor deficiency* - renal failure - hepatic dysfunction - stomatitis - phlebitis - fever - headache - depression - drowsiness - facial flushing * may supress hepatic synthesis of clotting factors; treatment of hemorrhagic diathesis includes packed RBC, fresh frozen plasma, vitamin K & corticosteroids Monitor: - Ca+2, CBC, PT, creatinine, & liver function tests should be obtained every 2-3 days. Drug interactions: 1) aspirin, ticlopidine & warfarin increase incidence of hemorrhagic complications 2) heparin, enoxaparin: increased risk of bleeding 3) calcitonin, etidronate, glucagon Test interactions: 1) increases serum K+ 2) decreases serum Ca+2 Mechanism of action: 1) inhibits bone resorption 2) treatment gradually reduces serum Ca+2 over 2-4 days with effects persisting 5-15 days 3) less effective & less well tolerated than pamidronate 4) inhibits binding of transcription factors

Related

hypercalcemia

General

endocrine agent

Properties

MISC-INFO: elimination route KIDNEY LIVER 1/2life 2 HOURS pregnancy-category D

Database Correlations

PUBCHEM correlations

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 492
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998