No

Antidote; Antineoplastic Agent, Antibiotic

Malignant testicular tumors, in the treatment of hypercalcemia and hypercalciuria of malignancy not responsive to conventional treatment; Paget's disease

X

Thrombocytopenia, bleeding diatheses, coagulation disorders; bone marrow function impairment; or hypocalcemia

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Use with caution in patients with hepatic or renal impairment; reduce dosage in patients with renal impairment; discontinue if bleeding or epistaxis occurs. Plicamycin may cause permanent sterility and may cause birth defects.

>10%: Gastrointestinal: Anorexia, stomatitis, nausea, vomiting, diarrhea

Nausea and vomiting occur in almost 100% of patients within the first 6 hours after treatment; incidence increases with rapid injection; stomatitis has also occurred

Time course for nausea/vomiting: Onset 4-6 hours; Duration: 4-24 hours

1% to 10%:

Cardiovascular: Facial flushing

Central nervous system: Fever, headache, depression, drowsiness

Endocrine & metabolic: Hypocalcemia

Hematologic: Myelosuppressive: Mild leukopenia and thrombocytopenia

WBC: Moderate, but uncommon

Platelets: Moderate, rapid onset

Onset (days): 7-10

Nadir (days): 14

Recovery (days): 21

Clotting disorders: May also depress hepatic synthesis of clotting factors, leading to a form of coagulopathy; petechiae, prolonged PT, epistaxis, and thrombocytopenia may be seen and may require discontinuation of the drug. Epistaxis is frequently the first sign of this bleeding disorder.

Hepatic: Hepatotoxicity

Local: Pain at injection site

Extravasation: Is an irritant; may produce local tissue irritation or cellulitis if infiltrated; if extravasation occurs, follow hospital procedure, discontinue I.V., and apply ice for 24 hours

Irritant chemotherapy

Renal: Azotemia, nephrotoxicity

Miscellaneous: Hemorrhagic diathesis

Symptoms of overdose include bone marrow suppression, bleeding syndrome, thrombocytopenia

Supportive therapy; treatment of hemorrhagic episodes should include transfusion of fresh whole blood or packed red blood cells and fresh frozen plasma, vitamin K, and corticosteroids

Increased toxicity: Calcitonin, etidronate, glucagon, additive hypoglycemic effects

Store intact vials under refrigeration (2°C to 8°C); vials are stable at room temperature (<25°C) for up to 3 months. Dilute powder in 4.9 mL SWI to result in a concentration of 500 mcg/mL which is stable for 24 hours at room temperature (25°C) and 48 hours under refrigeration (4°C). Further dilution in 1000 mL D₅W or NS is stable for 24 hours at room temperature.

Potent osteoclast inhibitor; may inhibit parathyroid hormone effect on osteoclasts; inhibits bone resorption; forms a complex with DNA in the presence of magnesium or other divalent cations inhibiting DNA-directed RNA synthesis

Decreasing calcium levels:

Onset of action: Within 24 hours

Peak effect: 48-72 hours

Duration: 5-15 days

Distribution: Crosses blood-brain barrier in low concentrations

Protein binding: 0%

Half-life, plasma: 1 hour

Elimination: 90% of dose excreted in urine within the first 24 hours

Refer to individual protocols. Dose should be diluted in 1 L of D₅W or NS and administered over 4-6 hours. Dosage should be based on the patient's body weight. If a patient has abnormal fluid retention (ie, edema, hydrothorax or ascites), the patient's ideal weight rather than actual body weight should be used to calculate the dose.

Testicular cancer: 25-30 mcg/kg/day for 8-10 days

Blastic chronic granulocytic leukemia: 25 mcg/kg over 2-4 hours every other day for 3 weeks

Paget's disease: 15 mcg/kg/day once daily for 10 days

Hypercalcemia:

25 mcg/kg single dose which may be repeated in 48 hours if no response occurs

OR 25 mcg/kg/day for 3-4 days

OR 25-50 mcg/kg/dose every other day for 3-8 doses

Dosing adjustment in renal impairment:

Cl_cr 10-50 mL/minute: Decrease dosage to 75% of normal dose

Cl_cr <10 mL/minute: Decrease dosage to 50% of normal dose

Hemodialysis: Unknown

CAPD effects: Unknown

CAVH effects: Unknown

Dosing in hepatic impairment: In the treatment of hypercalcemia in patients with hepatic dysfunction: Reduce dose to 12.5 mcg/kg/day

Hepatic and renal function tests, CBC, platelet count, prothrombin time, serum electrolytes

May cause drowsiness or depression

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. and frequent blood tests will be necessary to monitor effects of the drug. Report pain, swelling, or irritation at infusion site. Do not take alcohol, and prescription or OTC medications containing aspirin or ibuprofen without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Maintain good oral hygiene (use soft toothbrush or cotton applicators several times a day and rinse mouth frequently). You will be susceptible to infection; avoid crowds and infected persons and do not receive any vaccinations unless approved by prescriber. Report persistent fever or chills, unhealed sores, oral or vaginal sores, foul-smelling urine, easy bruising or bleeding, yellowing of eyes or skin, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication - use appropriate barrier contraceptive measures. Breast-feeding is not recommended.

Rapid I.V. infusion has been associated with an increased incidence of nausea and vomiting; an antiemetic given prior to and during plicamycin infusion may be helpful. Avoid extravasation since plicamycin is a strong vesicant.

Powder for injection: 2.5 mg

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Mutch RS, Hutson PR, and Lewinsky DB, "Plicamycin: Bolus or Infusion?" DICP, 1990, 24(9):885-6.

Ritch PS, "Treatment of Cancer-Related Hypercalcemia," Semin Oncol, 1990, 17(2 Suppl 5):26-33.

Stumpf JL, "Pharmacologic Management of Paget's Disease," Clin Pharm, 1989, 8(7):485-95.