Amonafide
Pronunciation
(a MON a fide)
Synonyms
Amonafide Hydrochloride; Benzisoquinolinedione; BIDA; M-FA-142; Nafidimide; NSC-308847
Generic Available
No
Use - Unlabeled/Investigational
Has shown some activity against breast, prostate, renal cell, ovarian, pancreatic, and nonsmall cell lung cancers
Contraindications
Hypersensitivity to amonafide or any component of the formulation; pregnancy
Warnings/Precautions
Amonafide should be used cautiously in bone marrow transplant patients and patients with existing bone marrow suppression, hepatic dysfunction, arrhythmias, conduction problems, congestive heart failure, or seizures or other neurological disorders. Amonafide toxicity, particularly hematologic, correlates with the patient's acetylator status. If possible, determination of acetylator type (fast vs slow) should be considered prior to beginning therapy.
Adverse Reactions
>10%:
Gastrointestinal: Nausea and vomiting (mild)
Hematologic: Granulocytopenia, possibly dose-limiting; nadir occurs at days 12-15, recovery by day 21
1% to 10%:
Cardiovascular: Chest pain
Central nervous system: Dizziness, fatigue, headache
Dermatologic: Skin rash, exfoliative dermatitis, alopecia
Local: Inflammatory reactions
Otic: Tinnitus
Neuromuscular & skeletal: Myoclonic jerking, weakness
<1%: CHF, hypotension, taste alteration, thrombocytopenia
Stability
Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F). Vials may be reconstituted with SWFI or 0.9% sodium chloride. Reconstituted vials and solutions of 0.25 mg/mL for infusion are stable for up to 14 days at room temperature or under refrigeration.
Compatibility
Incompatible:
Dextrose solutions
Mechanism of Action
Amonafide acts as a DNA intercalator, stabilizing DNA to thermal denaturation and producing single-strand DNA breaks.
Pharmacodynamics/Kinetics
Distribution: Vd: 370-530 L/m
2
Protein binding: High
Half-life:
Elimination: 3.5-11 hours
Terminal: 3-6 hours
Metabolism: Hepatic, primarily by oxidation and N-acetylation. N-acetylamonafide (active) and amonafide-N'-oxide are the major metabolites. Clearance depends on whether the patient is a fast or slow acetylator. Fast acetylators may experience greater toxicity from the drug.
Excretion: Urine (3% to 22% as unchanged drug)
Dosage
Adults (refer to individual protocols):
Breast cancer: 800 mg/m
2
over 3 hours every 28 days
Renal cell, ovarian, pancreatic cancer: Up to 450 mg/m
2
over 1 hour on days 1-5 every 21 days
Nonsmall cell lung cancer: 1600 mg/m
2
by continuous infusion over 24 hours every 21 days
Dosage adjustment in hepatic impairment:
May be required but specific guidelines have not been established.
Administration
May be administered by short (1-3 hours) infusion or continuous 24-hour infusion.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness and sedation
Mental Health: Effects on Psychiatric Treatment
Granulocytopenia is common; use caution with clozapine; monitor
Oncology: Emetic Potential
Moderate (30% to 60%)
Oncology: Vesicant
No
Dosage Forms
Powder for injection, lyophilized: 500 mg
References
Kornek G, Raderer M, Depisch D, et al, "Amonafide as First-Line Chemotherapy for Metastatic Breast Cancer,"
Eur J Cancer
, 1994, 30A(3):398-400.
Kreis W, Chan K, Budman DR, et al, "Clinical Pharmacokinetics of Amonafide (NSC-308847) in 62 Patients,"
Cancer Invest
, 1996, 14(4):320-7.
Leaf AN, Neuberg D, Schwartz EL, et al, "An ECOG Phase II Study of Amonafide in Unresectable or Recurrent Carcinoma of the Head and Neck (PB390). Eastern Cooperative Oncology Group,"
Invest New Drugs
, 1997, 15(2):165-72.
Marshall ME, Blumenstein B, Crawford ED, et al, "Phase II Trial of Amonafide for the Treatment of Advanced, Hormonally Refractory Carcinoma of the Prostate,"
Am J Clin Oncol
, 1994, 17(6):514-5.
Ratain MJ, Rosner G, Allen SL, et al, "Population Pharmacodynamic Study of Amonafide: A Cancer and Leukemia Group B Study,"
J Clin Oncol
, 1995, 13(3):741-7.
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