No

Antineoplastic Agent, Antibiotic

Treatment of acute nonlymphocytic leukemia (ANLL) in adults in combination with other agents; very active against various leukemias, lymphoma, and breast cancer, and moderately active against pediatric sarcoma

D

Hypersensitivity to mitoxantrone or any component

The FDA currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Dosage should be reduced in patients with impaired hepatobiliary function; use with caution in patients with pre-existing myelosuppression. Predisposing factors for mitoxantrone-induced cardiotoxicity include prior anthracycline therapy, prior cardiovascular disease, and mediastinal irradiation. The risk of developing cardiotoxicity is <3% when the cumulative doses are <100-120 mg/m² in patients with predisposing factors and <160 mg/m² in patients with no predisposing factors.

>10%:

Central nervous system: Headache

Dermatologic: Alopecia

Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, mucositis, stomatitis, GI bleeding

Emetic potential: Moderate (31% to 72%)

Genitourinary: Discoloration of urine (blue-green)

Hepatic: Abnormal LFTs

Respiratory: Coughing, shortness of breath

1% to 10%:

Cardiac toxicity: Much reduced compared to doxorubicin and has been reported primarily in patients who have received prior anthracycline therapy, congestive heart failure, hypotension

Central nervous system: Seizures, fever

Dermatologic: Pruritus, skin desquamation

Hematologic: Myelosuppressive effects of chemotherapy:

WBC: Mild

Platelets: Mild

Onset (days): 7-10

Nadir (days): 14

Recovery (days): 21

Hepatic: Transient elevation of liver enzymes, jaundice

Ocular: Conjunctivitis

Renal: Renal failure

<1%: Pain or redness at injection site, phlebitis; irritant chemotherapy with blue skin discoloration, tissue necrosis following extravasation; interstitial pneumonitis (has occurred during combination chemotherapy)

Symptoms of overdose include leukopenia, tachycardia, marrow hypoplasia

No known antidote

Patients may experience impaired immune response to vaccines; possible infection after administration of live vaccines in patients receiving immunosuppressants

Store intact vials at room temperature or refrigeration

Dilute in at least 50 mL of NS or D₅W; solution is stable for 7 days at room temperature or refrigeration

Incompatible with heparin and hydrocortisone

Standard I.V. dilution:

IVPB: Dose/100 mL D₅W or NS

Solution is stable for 7 days at room temperature and refrigeration

Analogue of the anthracyclines, but different in mechanism of action, cardiac toxicity, and potential for tissue necrosis; mitoxantrone does intercalate DNA; binds to nucleic acids and inhibits DNA and RNA synthesis by template disordering and steric obstruction; replication is decreased by binding to DNA topoisomerase II (enzyme responsible for DNA helix supercoiling); active throughout entire cell cycle; does not appear to produce free radicals

Absorption: Oral: Poor

Distribution: V_d: 14 L/kg; distributes into pleural fluid, kidney, thyroid, liver, heart, and red blood cells

Protein binding: 78%

Albumin binding: 76%

Metabolism: In the liver

Half-life: Terminal: 23-215 hours; may be prolonged with liver impairment

Elimination: Slowly excreted in urine (6% to 11%) and bile as unchanged drug and metabolites

Refer to individual protocols. I.V. (may dilute in D₅W or NS):

Children less than or equal to 2 years: 0.4 mg/kg/day once daily for 3-5 days

Children >2 years and Adults: 12 mg/m²/day once daily for 3 days; acute leukemia in relapse: 8-12 mg/m²/day once daily for 4-5 days

Solid tumors:

Children: 18-20 mg/m² every 3-4 weeks OR 5-8 mg/m² every week

Adults: 12-14 mg/m² every 3-4 weeks OR 2-4 mg/m²/day for 5 days

Maximum total dose: 80-120 mg/m² in patients with predisposing factor and <160 mg in patients with no predisposing factor

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Dosing adjustment in hepatic impairment: Official dosage adjustment recommendations have not been established

Moderate dysfunction (bilirubin 1.5-3 mg/dL): Some clinicians recommend a 50% dosage reduction

Severe dysfunction (bilirubin >3.0 mg/dL) have a lower total body clearance and may require a dosage adjustment to 8 mg/m²; some clinicians recommend a dosage reduction to 25% of dose

Dose modifications based on degree of leukopenia or thrombocytopenia:

Granulocyte count nadir >2000 cells/mm²; platelet count nadir >150,000 cells/mm²; total bilirubin <1.5 mg/dL: Increase dose by 1 mg/m²

Granulocyte count nadir 1000-2000 cells/mm²; platelet count nadir 75,000-150,000 cells/mm²; total bilirubin <1.5 mg/dL: Maintain same dose

Granulocyte count nadir <1000 cells/mm²; platelet count nadir <75,000 cells/mm²; total bilirubin 1.5-3 mg/dL: Decrease dose by 1 mg/m²

CBC, serum uric acid, liver function tests, ECHO

May cause drowsiness

May cause myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be given I.V. Make note of scheduled return dates. Your urine may turn blue-green for 24 hours after infusion and the whites of your eyes may have a blue-green tinge; this is normal. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition. You may experience rash, skin lesions, or loss of hair. Small frequent meals may help if you experience nausea, vomiting, or loss of appetite. Frequent mouth care will help reduce the incidence of mouth sores. Use caution when driving or engaging in tasks that require alertness because you may experience dizziness, drowsiness, syncope, or blurred vision. Report chest pain or heart palpitations; difficulty breathing or constant cough; swelling of extremities or sudden weight gain; burning, pain, or redness at infusion site; persistent fever or chills; unusual bruising or bleeding; twitching or tremors; or pain on urination. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication. Do not breast-feed.

Vesicant; avoid extravasation

Injection, as base: 2 mg/mL (10 mL, 12.5 mL, 15 mL)

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Faulds D, Balfour JA, Chrisp P, et al, "Mitoxantrone. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in the Chemotherapy of Cancer," Drugs, 1991, 41(3):400-49.

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.

Koeller J and Eble M, "Mitoxantrone: A Novel Anthracycline Derivative," Clin Pharm, 1988, 7(8):574-81.

LeMaistre CF and Herzig R, "Mitoxantrone: Potential for Use in Intensive Therapy," Semin Oncol, 1990, 17(1 Suppl 3):43-8.

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Nathanson L, "Mitoxantrone," Cancer Treat Rev, 1984, 11(4):289-93.

Pratt CB, Vietti TJ, Etcubanas E, et al, "Novantrone® for Childhood Malignant Solid Tumors. A Pediatric Oncology Group Phase II Study," Invest New Drugs, 1986, 4(1):43-8.