plicamycin
Mithracin

Available forms
Available by prescription only
Injection: 2,500-mcg vials

Indications and dosages
Dosage and indications may vary. Check current literature for recommended protocol.
 Hypercalcemia. Adults: 25 mcg/kg I.V. daily over 4 to 6 hours for 3 to 4 days. Repeat at intervals of 1 week, p.r.n.
 Testicular cancer. Adults: 25 to 30 mcg/kg I.V. daily over 4 to 6 hours for up to 10 days (based on ideal body weight or actual weight, whichever is less).
 Paget’s disease ◇. Adults: 15 mcg/kg I.V. daily over 4 to 6 hours for up to 10 days.

Pharmacodynamics
Antineoplastic action: Exerts cytotoxic activity by intercalating between DNA base pairs and also binding to the outside of the DNA molecule. The result is inhibition of DNA-dependent RNA synthesis.
Hypocalcemic action: Exact mechanism unknown. May block the hypercalcemic effect of vitamin D or may inhibit the effect of parathyroid hormone upon osteoclasts, preventing osteolysis. Both mechanisms reduce serum calcium levels.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Distributed mainly into Kupffer’s cells of liver, into renal tubular cells, and along formed bone surfaces. Crosses blood-brain barrier; achieves appreciable levels in CSF.
Metabolism: Poorly understood.
Excretion: Eliminated primarily through kidneys.

Contraindications and precautions
Contraindicated in patients with thrombocytopenia, bone marrow suppression, or coagulation and bleeding disorders and in women who are or who may become pregnant. Use cautiously in patients with impaired renal or hepatic function.

Interactions
None reported.

Adverse reactions
CNS: drowsiness, weakness, lethargy, headache, malaise, fever.
CV: phlebitis.
GI: nausea, vomiting, anorexia, diarrhea, stomatitis.
GU: renal insufficiency.
Hematologic: leukopenia, thrombocytopenia, bleeding syndrome.
Hepatic: hepatotoxicity.
Skin: facial flushing, rash, cellulitis with extravasation.

Effects on lab test results
• May increase BUN, creatinine, LDH, AST, ALT, and alkaline phosphatase levels. May decrease calcium, potassium, and phosphate levels.
• May decrease WBC and platelet counts.

Overdose and treatment
Toxicity may cause myelosuppression, electrolyte imbalance, and coagulation disorders.
 Treatment includes transfusion of blood components. Patient’s renal and hepatic status should be closely monitored.

Special considerations
• To reconstitute drug, use 4.9 ml of sterile water to give a concentration of 500 mcg/ml. Reconstitute drug immediately before administration, and discard unused solution.
• Drug may be further diluted with normal saline solution or D₅W to a volume of 1,000 ml and administered as an I.V. infusion over 4 to 6 hours.
• To reduce nausea, give antiemetics before administering drug.
• Although drug may be administered by I.V. push injection, this method is discouraged because of the higher risk and greater severity of GI toxicity. Nausea and vomiting are greatly diminished as infusion rate is decreased.
• Infusions of plicamycin in 1,000 ml D₅W are stable for up to 24 hours.
• If I.V. infiltrates, stop infusion immediately and apply ice packs before restarting an I.V. in other arm.
• Therapeutic effect in hypercalcemia may not be seen for 24 to 48 hours; may last 3 to 15 days.
• Avoid drug contact with skin or mucous membranes.
• Monitor LDH, AST, ALT, alkaline phosphatase, BUN, creatinine, potassium, calcium, and phosphorus levels.
• Monitor platelet count and PT before and during therapy.
• Check serum calcium levels. Monitor patient for tetany, carpopedal spasm, Chvostek’s sign, and muscle cramps because a sharp drop in calcium levels is possible.
• Watch for signs of bleeding. Facial flushing may be an early indicator.
• Store lyophilized powder in refrigerator.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Because of potential for serious adverse reactions, mutagenicity, and carcinogenicity in infant, breast-feeding isn’t recommended.

Patient education
• Tell patient to use salicylate-free drugs for pain relief or fever reduction.
• Instruct patient to avoid exposure to people with infections and to call immediately if signs of infection or unusual bleeding occur.
• Inform patient that he and household members shouldn’t receive immunizations during therapy and for several weeks after therapy.
• Advise patient to use contraceptive measures during therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use