mitoxantrone (Novantrone, Mitozantrone)
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Indications
- non-Hodgkin's lymphoma
- leukemia
- FDA approved for acute non-lymphocytic leukemia
- active against other leukemias as well
- advanced or recurrent breast cancer
- ovarian cancer
- prostate cancer[7]
- pediatric sarcomas
- severe, progressive multiple sclerosis[3]
Contraindications
- avoid in patients with pre-existing myelosuppression
- pregnancy
Dosage
- solid tumors:
- leukemia: 10-12 mg/m2/day for 3-5 days
- multiple sclerosis: every 3 month dosing for maximum of 8-12 doses[3]
Stability:
- incompatible with heparin
- after penetration of stopper, stable for 7 days at room temperature or 14 days refrigerated
Injection: 2 mg/mL (10 mL, 12.5 mL, 15 mL).
Pharmacokinetics
- 95% is bound to plasma proteins
- retained in tissue
- metabolized by liver
- most is eliminated in the bile
- elimination 1/2life is 40 hours
elimination via liver
1/2life = 1 hour
elimination by hemodialysis = -
Monitor
- left-ventricular ejection fraction prior to each dose[5]
- complete blood count (CBC)
Adverse effects
- common (> 10%)
- coughing, shortness of breath, leukopenia, headache, blue-green discoloration of urine & sclera, alopecia nausea/vomiting, diarrhea, abdominal pain, mucositis, increased liver function tests, stomatitis, GI bleeding
- less common (1-10%)
- uncommon (< 1%)
- pain at site of injection
- other
- emetic potential moderate (31-72%)
- myelosuppression
- some alopecia
- cardiomyopathy with cumulative dose[4][5]
- 160 mg/m2 cumulative dose
- 125 mg/m2 in combination with anthracycline therapy
- mediastinal irradiation also increases cardiotoxicity
- less cardiotoxic than anthracyclines
- fever
- secondary acute myelogenous leukemia (AML)[4]
- increased risk of infection
- menstrual irregularities
- black box warnings
Toxicity: no known antidote
Test interactions
increases serum K+
Mechanism of action
- antitumor antibiotic
- inhibits topoisomerase 2
- inhibits DNA synthesis
- not cell cycle-specific
More general terms
References
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 3.0 3.1 3.2 Prescriber's Letter 7(12):71 2000
- ↑ 4.0 4.1 4.2 FDA MedWatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Novantrone
- ↑ 5.0 5.1 5.2 FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Mitoxantrone
- ↑ 6.0 6.1 Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015
- ↑ 7.0 7.1 Deprecated Reference