Overview
DESCRIPTION Mitoxantrone injection, USP (concentrate) is a synthetic antineoplastic anthracenedione for intravenous use. It is supplied as a concentrate that MUST BE DILUTED PRIOR TO INJECTION. The concentrate is a sterile, nonpyrogenic, dark blue aqueous solution containing mitoxantrone hydrochloride, USP equivalent to 2 mg per mL mitoxantrone free base, with sodium chloride (0.
Mechanism of Action
CLINICAL PHARMACOLOGY Mechanism of Action Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. Mitoxantrone injection has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFα, and IL-2.
Indications
- INDICATIONS AND USAGE Mitoxantrone injection, USP (concentrate) is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Mitoxantrone injection, USP (concentrate) is not indicated in the treatment of patients with primary progressive multiple sclerosis.
Common Doses
- 12 mg
- 140 mg
- 14 mg
- 100 mg
Dosage
DOSAGE AND ADMINISTRATION (See also WARNINGS .) Multiple Sclerosis The recommended dosage of mitoxantrone injection (concentrate) is 12 mg/m 2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months. Left ventricular ejection fraction (LVEF) should be evaluated by echocardiogram or MUGA prior to administration of the initial dose of mitoxantrone injection (concentrate) and all subsequent doses.
Black Box Warning
WARNING Mitoxantrone injection (concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents. Mitoxantrone injection (concentrate) should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration (see ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions ). NOT FOR INTRATHECAL USE.
Contraindications
- CONTRAINDICATIONS Mitoxantrone injection (concentrate) is contraindicated in patients who have demonstrated prior hypersensitivity to it.
Side Effects
- ADVERSE REACTIONS Multiple Sclerosis Mitoxantrone injection has been administered to 149 patients with multiple sclerosis in two randomized clinical trials, including 21 patients who received mitoxantrone injection in combination with corticosteroids. In Study 1, the proportion of patients who discontinued treatment due to an adverse event was 9.7% (n = 6) in the 12 mg/m 2 mitoxantrone injection arm (leukopenia, depression, decreased LV function, bone pain and emesis, renal failure, and one discontinuation to prevent future complications from repeated urinary tract infections) compared to 3.
Interactions
- Drug Interactions Mitoxantrone and its metabolites are excreted in bile and urine, but it is not known whether the metabolic or excretory pathways are saturable, may be inhibited or induced, or if mitoxantrone and its metabolites undergo enterohepatic circulation. To date, postmarketing experience has not revealed any significant drug interactions in patients who have received mitoxantrone injection for treatment of cancer. Information on drug interactions in patients with multiple sclerosis is limited.