plicamycin (Mithramycin)

Introduction

Tradename: Mithramycin.

Indications

• testicular cancer
• hypercalcemia of malignancy
  • reserved for volume-repleted patients who have failed pamidronate & calcitonin
• chronic myelogenous leukemia (CML) blast crisis
• Paget's disease

Contraindications

• thrombocytopenia
• bleeding diatheses
• coagulation disorders
• bone marrow suppression
• hypocalcemia

pregnancy category = d

Dosage

• testicular cancer: 20-30 ug/kg/day IV for 4-5 days, repeated every 4 weeks
• hypercalcemia of malignancy: 25 ug/kg/day in 500 mL D5W or normal saline infused IV over 4-6 hours 2-3 times weekly
• dosage adjustment in renal failure:
  • 25% reduction for moderate renal failure
  • 50% reduction for severe renal failure

Powder for injection: 2.5 mg.

Pharmacokinetics

• well distributed to tissues
• highest concentrations in liver, kidney, CSF & bone
• 1/2life is 2 hours
• 40% is eliminated in the urine

elimination via kidney

elimination via liver

1/2life = 2 hours

Monitor

• Ca+2, CBC, PT, creatinine, & liver function tests should be obtained every 2-3 days.

Adverse effects

• common (> 10%)
  • nausea/vomiting (100% within the 1st 6 hours)
• 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
• 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

Drug interactions

• aspirin, ticlopidine & warfarin increase incidence of hemorrhagic complications
• heparin, enoxaparin: increased risk of bleeding
• calcitonin, etidronate, glucagon

Test interactions

• increases serum K+
• decreases serum Ca+2

Mechanism of action

• inhibits bone resorption
• treatment gradually reduces serum Ca+2 over 2-4 days with effects persisting 5-15 days
• less effective & less well tolerated than pamidronate
• inhibits binding of transcription factors

More general terms

• endocrine agent

Additional terms

• hypercalcemia

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=29051
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=457831
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5284610
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4861
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=230076
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=163659