plicamycin

plicamycin /pli·ca·my·cin/ (pli″kah-mi´sin) an antineoplastic antibiotic produced by Streptomyces plicatus; used in the treatment of advanced testicular carcinoma. It also has an inhibiting effect on osteoclasts and is used to treat hypercalcemia and hypercalciuria associated with malignancy.

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plicamycin

[plī′kəmī′sin]

an antineoplastic agent. Formerly called mithramycin.

indications It is prescribed primarily in the treatment of malignant tumors of the testis. It is also prescribed in the treatment of hypercalcemia and hypercalciuria associated with cancer.

contraindications Clotting disorders, thrombocytopenia, kidney or liver dysfunction, bone marrow depression, or known hypersensitivity to this drug prohibits its use.

adverse effects Among the more serious adverse effects are thrombocytopenia and clotting defects. Nausea and stomatitis commonly occur.

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plicamycin

an antineoplastic antibiotic produced by Streptomyces argillaceus and S. tanashiensis; particularly effective in treating the hypercalcemia associated with canine lymphosarcoma. Called also mithramycin.

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plicamycin (mithramycin) Warning - Hazardous drug!

Mithracin

Pharmacologic class: Crystalline compound produced by Streptomyces plicatus

Therapeutic class: Antibiotic antineoplastic

Pregnancy risk category X

FDA Boxed Warning

• Drug is for I.V. use only.
• Due to risk of severe reactions, give only to hospitalized patients under supervision of qualified physician experienced in use of cancer chemotherapy, where laboratory resources are available for necessary tests.
• Severe thrombocytopenia, hemorrhagic tendency, and even death may occur. Severe toxicity is more likely in patients with far-advanced disease or who otherwise are poor risks for therapy. However, serious toxicity also may occur in patients in relatively good condition.
• Before therapy starts, clinician must weigh potential benefits against toxicity risk and thoroughly review data regarding drug use in treating testicular tumors and hypercalcemic or hypercalciuric conditions linked to advanced cancers.

Action

Unknown. Thought to form complex that causes cross-linking of DNA strands, inhibiting cellular RNA and enzymatic RNA synthesis.

Availability

Injection: 2.5-mg vials

⊘Indications and dosages

➣ Testicular cancer

Adults: 25 to 30 mcg/kg/day I.V. over 4 to 6 hours for 8 to 10 days, unless significant adverse effects or toxicity occur. Treatment course exceeding 10 daily doses not recommended.

➣ Hypercalcemia and hypercalciuria related to advanced cancer

Adults: 25 mcg/kg/day I.V. over 4 to 6 hours for 3 to 4 days; may repeat weekly until adequate response occurs

Dosage adjustment

• Renal failure

Contraindications

• Hypersensitivity to drug
• Thrombocytopenia, thrombocytopathy
• Bone marrow depression
• Coagulation disorders or increased risk of bleeding
• Females of childbearing potential
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• renal or hepatic disease, electrolyte imbalances.

Administration

☞ Follow facility policy for preparing, handling, and administering carcinogenic, mutagenic, or teratogenic drugs. Don't let drug touch skin or mucous membranes.
• Give antiemetic before plicamycin, as prescribed, to reduce nausea and vomiting.
• Dilute with 4.9 ml of sterile water for injection. Shake vial to dissolve.
• Further dilute in 1,000 ml of dextrose 5% in water or normal saline solution.
• Infuse I.V. over 4 to 6 hours. Discard unused portion.

Route	Onset	Peak	Duration
I.V.	1-2 days	3 days	3-15 days

Adverse reactions

CNS: headache, malaise, drowsiness, asthenia, lethargy, depression

CV: phlebitis

GI: nausea, vomiting, diarrhea, stomatitis, anorexia

GU: proteinuria

Hematologic: leukopenia, thrombocytopenia, bleeding syndrome

Hepatic: mild and reversible hepatotoxicity

Metabolic: hypokalemia, hypocalcemia, hypophosphatemia

Skin: facial flushing; rash; pain, redness, or swelling at injection site; cellulitis with extravasation

Other: fever

Interactions

Drug-drug. Other antineoplastics: increased plicamycin toxicity

Drug-diagnostic tests. Blood urea nitrogen, creatinine, hepatic enzymes: increased levels

Calcium, phosphate, potassium, platelets, white blood cells (WBCs): decreased levels

Drug-herbs. Anise, arnica, chamomile, clove, dong quai, fenugreek, garlic, ginger, ginkgo, ginseng, licorice: increased risk of bleeding

Chaparral, comfrey, eucalyptus, germander, jin bu huan, kava, pennyroyal, skullcap, valerian: increased risk of hepatotoxicity

Patient monitoring

☞ Watch closely for bleeding syndrome, which usually starts with epistaxis and progresses quickly.
• Monitor liver function tests, electrolyte levels, platelet and WBC counts, and prothrombin time. Notify prescriber of platelet count less than 150,000/mm³, WBC count less than 4,000/mm³, or prothrombin time greater than 4 seconds longer than control.
☞ Assess for indications of sudden drop in calcium level, such as Chvostek's sign, muscle cramps, carpopedal spasm, or tetany.
• Monitor I.V. site closely to avoid extravasation.

Patient teaching

☞ Teach patient to recognize and immediately report easy bruising, bleeding, and hypocalcemia. Inform him that nosebleed may be first sign of a bleeding problem.
• Instruct patient to report unusual pain, redness, swelling, or other changes at infusion site.
• Caution female of childbearing age to avoid pregnancy during therapy. Advise her to report suspected pregnancy right away.
• Instruct patient to avoid herbs, because many herbs increase the risk of liver damage.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.