Drug information of Plicamycin

Plicamycin


Plicamycin is an antineoplastic antibiotic produced by Streptomyces plicatus. It has been used in the treatment of testicular cancer, Paget's disease of bone, and, rarely, the management of hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer

:Dosage Forms & Strengths
Vial 2500 mcg or 2.5 mg » store at refrigerator

Mechanism of effect

Plicamycin is presumed to inhibit cellular and enzymic RNA synthesis by forming a complex with DNA. Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D

Pharmacodynamic

Plicamycin is lethal to Hela cells in 48 hours at concentrations as low as 0.5 micrograms per milliliter of tissue culture medium. Plicamycin has shown significant anti-tumor activity against experimental leukemia in mice when administered intraperitoneally

Pharmacokinetics

:Absorption & Distribution & Metabolism
Not Available

:Elimination
Radioautography studies with 3H-labeled plicamycin in mice show that the greatest concentrations of the isotope are in the Kupffer cells of the liver and cells of the renal tubules. Plicamycin is rapidly cleared from the blood within the first 2 hours and excretion is also rapid. 67% percent of measured excretion occurs within 4 hours, 75% within 8 hours, and 90% is recovered in the first 24 hours after injection

Dosage

The daily dose of Mithracin (plicamycin) is based on the patient's body weight. If a patient has abnormal fluid retention such as edema, hydrothorax or ascites, the patient's ideal weight rather than actual body weight should be used to calculate the dose

Testicular tumors: 25 to 30 mcg (0.025-0.030 mg) per kilogram for a period of 8 to 10 days unless significant side effects or toxicity occur during therapy
A course of therapy consisting of more than 10 daily doses is not recommended. Individual daily doses should not exceed 30 mcg (0.030 mg) per kilogram of body weight

Hypercalcemia and hypercalciuria: 25 mcg (0.025 mg) per kilogram per day for 3 or 4 days
If the desired degree of reversal of hypercalcemia or hypercalciuria is not achieved with the initial course of therapy, additional courses of therapy may then be administered at intervals of one week or more to achieve the desired result or to maintain serum calcium and urinary calcium excretion at normal levels. It may be possible to maintain normal calcium balance with single, weekly doses or with a schedule of 2 or 3 doses per week

Alerts

It is recommended that Plicamycin be administered only to hospitalized patients by or under the supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents, because of the possibility of severe reactions. Facilities for the determination of necessary laboratory studies must be available
Severe thrombocytopenia, a hemorrhagic tendency and even death may result from the use of plicamycin. Although severe toxicity is more APT to occur in patients who have far-advanced disease or are otherwise consideed poor risks for therapy. Serious toxicity may also occasionally occur even in patients who are in relatively good condition
In the treatment of each patient, physician must weigh carefully the possibility of achieving therapeutic benefit versus the risk of toxicity which may occur with plicamycin therapy

Electrolyte imbalance, especially hypocalcemia, hypokalemia, and hypophosphatemia, should be corrected with appropriate electrolyte therapy prior to treatment with plicamycin

Plicamycin should be used with extreme caution in patients with significant impairment of renal or hepatic function.

Plicamycin should not normally be administered to patients who are pregnant or to mothers who are breast feeding

Points of recommendation

:Administration
By IV administration only. The appropriate daily dose of plicamycin should be diluted in one liter of 5% Dextrose Injection or Sodium Chloride Injection and administered by slow intravenous infusion over a period of 4 to 6 hours. Rapid direct intravenous injection of plicamycin should be avoided as it may be associated with a higher incidence and greater severity of gastrointestinal side effects. Extravasation of solutions of plicamycin may cause local irritation and cellulitis at injection sites. Should thrombophlebitis or perivascular cellulitis occur, the infusion should be terminated and reinstituted at another site. The application of moderate heat to the site of extravasation may help to disperse the compound and minimize discomfort and local tissue irritation. The use of antiemetic compounds prior to and during treatment with plicamycin may be helpful in relieving nausea and vomiting

:Most Common Side Effect
Dose-related bleeding syndrome beginning with an episode of epistaxis or hematemesis and somehow progressing to more widespread hemorrhage in the gastrointestinal tract or to a more generalized bleeding tendency. This hemorrhagic diathesis is most likely due to abnormalities in multiple clotting factors
:Other Side Effects
 Gastrointestinal symptoms: anorexia, nausea, vomiting, diarrhea, and stomatitis. Other less frequently reported side effects include fever, drowsiness, weakness, lethargy, malaise, headache, depression, phlebitis, facial flushing, and skin rash
Depression of platelet count, white count, hemoglobin and prothrombin content; elevation of clotting time and bleeding time; abnormal clot retraction
 Increased levels of serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase, alkaline phosphatase, serum bilirubin, ornithine carbamyl transferase, isocitric dehydrogenase, and increased retention of bromsulphalein
Increased blood urea nitrogen and serum creatinine; proteinuria
Depression of serum calcium, phosphorus, and potassium

Drug Interactions: No information provided

:Contraindications
Plicamycin is contraindicated in patients with thrombocytopenia, thrombocytopathy, coagulation disorder or an increased susceptibility to bleeding due to other causes. Plicamycin should not be administered to any patient with impairment of bone marrow function

Plicamycin may cause fetal harm when administered to a pregnant woman. Plicamycin is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus

Pregnancy level

Pregnancy Category: X

Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit

Breast feeding warning

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding

Related drugs

Bleomycin , Daunorubicin


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