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mitoxantrone (Novantrone, Mitozantrone)
Indications:
1) non-Hodgkin's lymphoma
2) leukemia
a) FDA approved for acute non-lymphocytic leukemia
b) active against other leukemias as well
3) advanced or recurrent breast cancer
4) ovarian cancer
5) prostate cancer [7]
6) pediatric sarcomas
7) severe, progressive multiple sclerosis [3]
Contraindications:
- avoid in patients with pre-existing myelosuppression
- pregnancy
Dosage:
1) solid tumors:
a) 12 mg/m2 IV every 4 weeks
b) 5 mg/m2 IV weekly for 3 weeks
2) leukemia: 10-12 mg/m2/day for 3-5 days
3) multiple sclerosis: every 3 month dosing for maximum of 8-12 doses [3]
Stability:
1) incompatible with heparin
2) 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:
1) 95% is bound to plasma proteins
2) retained in tissue
3) metabolized by liver
4) most is eliminated in the bile
5) elimination 1/2life is 40 hours
Monitor:
- left-ventricular ejection fraction prior to each dose [5]
- complete blood count (CBC)
Adverse effects:
1) 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
2) less common (1-10%)
- hypotension, seizures, pruritus, skin desquamation, conjunctivitis, renal failure, jaundice, congestive heart failure
3) uncommon (< 1%)
- pain at site of injection
4) other
- emetic potential moderate (31-72%)
- myelosuppression
- WBC & platelets mild
- onset 7-10 days
- nadir 14 days
- recovery 21 days
- 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
5) black box warnings
- cardiotoxicity
- acute myeloid leukemia [6]
Toxicity: no known antidote
Test interactions: increases serum K+
Mechanism of action:
1) antitumor antibiotic
2) inhibits topoisomerase 2
3) inhibits DNA synthesis
4) not cell cycle-specific
General
antineoplastic agent (chemotherapeutic agent)
enzyme inhibitor
Properties
MISC-INFO: elimination route LIVER
1/2life 1 HOUR
elimination by hemodialysis -
pregnancy-category D
Database Correlations
PUBCHEM correlations
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
- Prescriber's Letter 7(12):71 2000
- FDA MedWatch
http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Novantrone
- FDA MedWatch
http://www.fda.gov/medwatch/safety/2008/safety08.htm#Mitoxantrone
- Medical Knowledge Self Assessment Program (MKSAP) 16, 17.
American College of Physicians, Philadelphia 2012, 2015
- Deprecated Reference