#高警訊藥品

急性非淋巴性白血病 Acute myeloid leukemia (AML) in adults (in combination with other approved chemotherapy agents)

Antineoplastic Agent, Anthracycline; Topoisomerase II Inhibitor
Idarubicin inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA.

Distribution:
1. Vdss: 1,500 L/m2 ; extensive tissue binding; CSF
2. Protein binding: 94% (idarubicinol) to 97% (idarubicin)
Metabolism:
1. Hepatic to idarubicinol (active metabolite)
2. Half-life elimination: (Adults) 22 hours
Excretion:
Primarily biliary; urine

1. Hypersensitivity to idarubicin, any component of the formulation, or to other anthracyclines or anthracenediones
2. History of severe heart disease, recent myocardial infarction, severe myocardial insufficiency, severe arrhythmia
3. Severe persistent drug-induced myelosuppression; severe hepatic impairment; severe renal impairment

European Society for Medical Oncology (ESMO) suggest utilizing only in the second and third trimester

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.

1. Cardiovascular: Cardiac failure (dose-related), ECG abnormalities
2. Central nervous system: Headache
3. Dermatologic: Alopecia, skin rash, urticaria
4. Gastrointestinal: Vomiting, gastrointestinal hemorrhage, diarrhea, stomatitis, nausea
5. Genitourinary: Urine discoloration
6. Hematologic & oncologic: Anemia, bone marrow suppression, thrombocytopenia
7. Hepatic: Increased serum bilirubin or serum transaminases
8. Miscellaneous: Radiation recall phenomenon

Induction AML:
12 mg/m2/day for 3 days (in combination with cytarabine); second cycle may be administered if necessary
Refractory AML:
10 mg/m2/day for 3 days (in combination with fludarabine, cytarabine, and filgrastim)

Induction AML:
5 mg/m2/day for 4 days on days 0 to 3 in combination with cytarabine, etoposide, thioguanine, and dexamethasone
Consolidation:
(1) 5 mg/m2/day for 4 days on days 0 to 3 in combination with cytarabine, etoposide, thioguanine, and dexamethasone
(2) 12 mg/m2/day for 3 days on days 0 to 2 in combination with cytarabine, fludarabine

1. CrCl >50 mL/minute: No dosage adjustment is necessary.
2. CrCl 10 to 50 mL/minute: Administer 75% of dose.
3. CrCl <10 mL/minute: Administer 50% of dose.
4. Hemodialysis OR Continuous ambulatory peritoneal dialysis (CAPD) : Supplemental dose not needed.

1. Bilirubin 2.6 to 5 mg/dL: Administer 50% of dose
2. Bilirubin >5 mg/dL: Avoid use