#高警訊藥品

急慢性白血球過多症、硬瘤、淋巴瘤、軟纖維性肉瘤、交感神經母細胞瘤、乳癌、肺癌
Breast cancer: Treatment component of adjuvant therapy (multi-agent) in women with evidence of axillary lymph node involvement following resection of primary breast cancer.
Other cancers: Treatment of acute lymphoblastic leukemia, acute myeloid leukemia, bladder cancer (transitional cell, metastatic), bone sarcoma (metastatic), breast cancer (metastatic), bronchogenic carcinoma, (metastatic), gastric cancer (metastatic), Hodgkin lymphoma, non-Hodgkin lymphomas, neuroblastoma (metastatic), ovarian cancer (metastatic), soft tissue sarcoma (metastatic), thyroid carcinoma (metastatic), Wilms tumor (metastatic).

#仿單變更2021

Anthracycline Antineoplastic Agent; Topoisomerase II Inhibitor
Doxorubicin inhibits DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II 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. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.

Distribution:
1. Vd: 809 to 1,214 L/m2; does not cross the blood-brain barrier <20210323>
2. Protein binding, plasma: ~75%
Metabolism:
1. Primarily hepatic to doxorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides
2. Half-life elimination: (Distribution) 5 minutes; (Terminal) 20-48 hours
Excretion:
1. Feces (~40% as unchanged drug); urine (5-12% as unchanged drug and metabolites)
2. Clearance: (Children <2 years) 813 mL/min/m²; (Children >2 years) 1,540 mL/minute/m²; (Adults) 324-809 mL/minutes/m²

1. Severe hypersensitivity (including anaphylaxis) to doxorubicin or any component of the formulation
2. Recent myocardial infarction (within past 4 to 6 weeks), severe myocardial insufficiency
3. Severe persistent drug-induced myelosuppression
4. Severe hepatic impairment (Child-Pugh class C or bilirubin >5 mg/dL)

1. Cardiovascular: Cardiotoxicity
2. CNS: Malaise
3. Dermatologic: Alopecia, discoloration of sweat, pruritus, skin photosensitivity, skin rash
4. Endocrine & metabolic: Amenorrhea, dehydration, hyperuricemia
5. GI: Abdominal pain, anorexia, diarrhea, discoloration of saliva, gastrointestinal ulcer, mucositis, nausea, vomiting
6. GU: Urine discoloration, infertility (may be temporary)
7. Hematologic & oncologic: Leukopenia, neutropenia, anemia, thrombocytopenia
8. Local: Post-injection flare
9. Neuromuscular & skeletal: Weakness
10. Ophthalmic: Discoloration of tears
11. Miscellaneous: Necrosis (colon), radiation recall phenomenon

Breast cancer:
1. AC regimen (Adriamycin and Cyclophosphamide):
60-75 mg/m² on day 1 every 21 days for 4 cycles
2. ddAC followed by T regimen (Adriamycin, Cyclophosphamide, and Filgrastim, then followed by Paclitaxel):
60 mg/m² on day 1 every 14 days for 4 cycles
3. FAC regimen (Adriamycin, Fluorouracil, and Cyclophosphamide):
50 mg/m² on day 1 (or administered as a 72-hour continuous infusion) every 21 days for 6 cycles
4. TAC regimen (Adriamycin, Docetaxel, and Cyclophosphamide):
50 mg/m² on day 1 every 21 days for 6 cycles
Soft tissue sarcoma:
1. AD regimen (Adriamycin and Dacarbazine):
60 mg/m² on day 1 every 21 days
2. Single-agent regimen:
75 mg/m² on day 1 every 21 days until disease progression or unacceptable toxicity
Metastatic solid tumors, leukemia, or lymphoma:
1. Single-agent therapy: 60-75 mg/m² every 21 days
2. Combination therapy: 40-75 mg/m² every 21 to 28 days

No dosage adjustments provided in the manufacturer's labeling; however, adjustments are likely not necessary given limited renal excretion.

1. Serum bilirubin 1.2-3 mg/dL (20-50umol/L): Administer 50% of dose.
2. Serum bilirubin 3.1-5 mg/dL (>50umol/L): Administer 25% of dose.
3. Severe hepatic impairment (Child-Pugh class C or bilirubin >5 mg/dL): Use is contraindicated.