mitoxantrone hydrochloride

mitoxantrone hydrochloride

Novantrone, Onkotrone (UK)

Pharmacologic class: Antibiotic antineoplastic

Therapeutic class: Antineoplastic, immune modifier

Pregnancy risk category D

FDA Box Warning

• Administer slowly into free-flowing I.V. infusion. Never give I.M., subcutaneously, intra-arterially, or intrathecally; severe local tissue damage may occur with extravasation.

• Except in acute nonlymphocytic leukemia, drug generally shouldn't be given to patients with baseline neutrophil counts below 1,500/mm3. Obtain frequent peripheral blood cell counts on all patients to monitor for bone marrow depression.

• Myocardial toxicity, whose severe form manifests as potentially fatal congestive heart failure (CHF), may occur during therapy or months to years afterward. Risk increases with cumulative dose. In cancer patients, risk of symptomatic CHF is about 2.6% for those receiving up to a cumulative dose of 140 mg/m2. Monitor patients for evidence of cardiotoxicity and ask about CHF symptoms before starting therapy. In multiple sclerosis (MS) patients who reach cumulative dose of 100 mg/m2, monitor for evidence of cardiotoxicity before each subsequent dose; they shouldn't receive cumulative dose above 140 mg/m2.

• Active or dormant cardiovascular disease, previous or concomitant radiation to mediastinal or pericardial area, previous anthracycline or anthracenedione therapy, or concurrent use of other cardiotoxic drugs may increase cardiotoxicity risk.

• Secondary acute myelogenous leukemia has occurred in cancer patients and MS patients who received drug. Refractory secondary leukemia is more common when drug is given with DNA-damaging antineoplastics, when patients have been heavily pretreated with cytotoxic drugs, or when dosages have been escalated.

Action

Selectively inhibits DNA synthesis by causing cross-linking of DNA strands and suppressing RNA and protein synthesis, resulting in cell death

Availability

Injection: 2 mg/ml in 10-ml, 12.5-ml, and 15-ml vials

Indications and dosages

Acute nonlymphocytic leukemia (given with other agents)

Adults: For induction-12 mg/m2/day I.V. on days 1 to 3, with 100 mg/m2 of cytosine arabinoside given for 7 days as a continuous I.V. infusion (over 24 hours) on days 1 through 7. If remission doesn't occur, second course may follow, with mitoxantrone given for 2 days and cytosine arabinoside for 5 days at same daily dosages. For consolidation therapy-12 mg/m2/ day mitoxantrone I.V. on days 1 and 2 and 100 mg/m2 cytosine arabinoside I.V. as a continuous infusion over 24 hours on days 1 through 5, given 6 weeks after induction therapy.

Pain in patients with advanced hormone-refractory prostatic cancer (given with corticosteroids)

Adults: 12 to 14 mg/m2 I.V. given over 15 to 30 minutes q 21 days

Multiple sclerosis

Adults: 12 mg/m2 I.V. given over 5 to 15 minutes q 3 months. Maximum cumulative lifetime dosage is 140 mg/m2.

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:
• bone marrow depression, heart failure, chronic debilitating illness, hepatobiliary dysfunction
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

Follow facility policy for handling, administering, and disposing of mutagenic, teratogenic, and carcinogenic drugs.
• Dilute with 50 ml or more of normal saline solution or dextrose 5% in water (D5W). Infuse I.V. over 3 to 5 minutes into running line of normal saline solution or D5W.
• Alternatively, dilute drug further in normal saline solution or D5W and infuse intermittently I.V. over 15 to 30 minutes.

If extravasation occurs, stop infusion immediately.

Avoid contact with skin, mucous membranes, and eyes.
• Be aware that drug isn't indicated for primary progressive multiple sclerosis.

Adverse reactions

CNS: headache, seizures

CV: heart failure, arrhythmias, cardiotoxicity

EENT: conjunctivitis, mucositis

GI: nausea, vomiting, diarrhea, abdominal pain, stomatitis, GI bleeding

GU: urinary tract infection, blue-green urine, renal failure

Hematologic: anemia, bone marrow depression, leukopenia, thrombocytopenia

Hepatic: jaundice, hepatotoxicity

Metabolic: hyperuricemia

Respiratory: cough, dyspnea

Skin: rash, petechiae, bruising, alopecia

Other: fever, infection, hypersensitivity reaction

Interactions

Drug-drug.Anthracycline antineoplastics (daunorubicin, doxorubicin, idarubicin): increased risk of cardiomyopathy

Live-virus vaccines: decreased antibody response to vaccine

Other antineoplastics: additive bone marrow depression

Drug-diagnostic tests.Alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid: increased levels

Patient monitoring

Monitor CBC with white cell differential. Watch for evidence of blood dyscrasias.
• Assess vital signs, ECG, and respiratory and cardiovascular status.
• Monitor kidney and liver function tests. Measure fluid intake and output and evaluate fluid balance.
• Monitor temperature. Stay alert for fever and signs and symptoms of urinary tract and other infections.

Patient teaching

Advise patient to immediately report chest pain, seizure, easy bruising or bleeding, change in urination pattern, yellowing of skin or eyes, or difficulty breathing.
• Instruct patient to limit exposure to infections and to avoid live vaccines.
• Tell patient drug may turn urine blue-green.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Tell female patient to inform prescriber if she is pregnant or breastfeeding.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

mitoxantrone hydrochloride

(mī′tō-zăn′trōn′)
n.
A synthetic antineoplastic drug used intravenously in the treatment of acute myeloid leukemia, advanced prostate cancer, and multiple sclerosis.
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References in periodicals archive ?
Food and Drug Administration has granted final approval for the Company's ANDA for Mitoxantrone Hydrochloride Injection USP, 2 mg/mL.
Intrahepatic Chemotherapy for Liver metastasis - Chemoembolization; Isolated limb perfusion (ILP); Mitoxantrone hydrochloride (Novantrone (R)); Monoclonal Antibody (Mab) Imaging or Radioimmunoscintigraphy - colorectal cancer staging; Photodynamic Therapy; Radiofrequency tumor ablation; Therapeutic phlebotomy; Vaccines to treat various cancers; Cancer-related web sites; Photodynamic Therapy; Vaccines to treat various cancers; Vitamin B12 Injections.