Indications
Alone or with other modalities in the treatment of various
solid tumors including: Breast, Ovarian, Bladder,
Bronchogenic carcinoma, Malignant lymphomas and
leukemias.
Action
Inhibits DNA and RNA synthesis by forming a complex
with DNA; action is cell-cycle S-phase–specific. Also
has immunosuppressive properties. Therapeutic
Effects: Death of rapidly replicating cells, particularly
malignant ones.
Pharmacokinetics
Absorption: Administered IV only, resulting in complete
bioavailability.
Distribution: Widely distributed; does not cross the
blood-brain barrier; extensively bound to tissues.
Metabolism and Excretion: Mostly metabolized
by the liver (primarily by CYP2D6 and CYP3A4). Converted
by liver to an active compound. Excreted predominantly
in the bile, 50% as unchanged drug. Less
than 5% eliminated unchanged in the urine.
Half-life: 16.7 hr.
TIME/ACTION PROFILE (effect on blood
counts)
ROUTE ONSET PEAK DURATION
IV 10 days 14 days 21–24 days
Contraindications/Precautions
Contraindicated in: Hypersensitivity; OB, Lactation:
Pregnancy or lactation.
Use Cautiously in: History of cardiac disease or
high cumulative doses of anthracyclines; Depressed
bone marrow reserve; Liver impairment (reduce dose if
serum bilirubin 1.2 m g/dL); Pedi, Geri: Children,
geriatric patients, mediastinal radiation, concurrent cyclophosphamide
(qrisk of cardiotoxicity); Rep: Patients
with childbearing potential.
Adverse Reactions/Side Effects
Resp: recall pneumonitis. CV: CARDIOMYOPATHY,
ECG changes. GI: diarrhea, esophagitis, nausea, stomatitis,
vomiting. GU: red urine. Derm: alopecia,
photosensitivity. Endo: sterility, prepubertal growth
failure with temporary gonadal impairment (children
only). Hemat: anemia, leukopenia, thrombocytopenia.
Local: phlebitis at IV site, tissue necrosis. Metab:
hyperuricemia. Misc: hypersensitivity reactions.
Interactions
Drug-Drug: CYP2D6 inhibitors, CYP3A4 inhibitors,
and P-glycoprotein inhibitors mayqrisk of
toxicity; avoid concurrent use. CYP2D6 inducers,
CYP3A4 inducers, and P-glycoprotein inducers
maypeffect andqrisk of therapeutic failure; avoid
concurrent use.qbone marrow depression with other
antineoplastics or radiation therapy. Pediatric patients
who have received concurrent doxorubicin and
dactinomycin have anqrisk of recall pneumonitis at
variable times following local radiation therapy. Mayq
skin reactions at previous radiation therapy sites. If
paclitaxel is administered first, clearance of doxorubicin
ispand the incidence and severity of neutropenia
and stomatitis areq(problem is diminished if doxorubicin
is administered first). Hematologic toxicity isq
and prolonged by concurrent use of cyclosporine;
risk of coma and seizures is alsoq. Incidence and severity
of neutropenia and thrombocytopenia areqby
concurrent progesterone. Phenobarbital mayq
clearance and decrease effects of doxorubicin. Doxorubicin
maypmetabolism andqeffects of phenytoin.
Streptozocin mayqthe half-life of doxorubicin (dosagepof
doxorubicin recommended). Mayqrisk of
hemorrhagic cystitis from cyclophosphamide. Mayq
risk of hepatotoxicity from mercaptopurine. Cardiac
toxicity may beqby radiation therapy or cyclophosphamide.
qrisk of cardiac toxicity with trastuzumab;
avoid concurrent use. If dexrazoxane is administered
at initiation of doxorubicin-containing regimens, may
qrisk of therapeutic failure and tumor progression.
Maypantibody response to live-virus vaccines and
qrisk of adverse reactions.
Route/Dosage
Other regimens are used.
IV (Adults): 60–75 mg/m2 daily, repeat q 21 days; or
25–30 mg/m2 daily for 2–3 days, repeat q 3–4 wk or
20 mg/m2/wk. Total cumulative dose should not exceed
550 mg/m2 without monitoring of cardiac function or
400 mg/m2 in patients with previous chest radiation or
other cardiotoxic chemotherapy.
IV (Children): 30 mg/m2/day for 3 days every 4 wk.
Hepatic Impairment
IV (Adults): Serum bilirubin 1.2–3mg/dL—50% of
usual dose; serum bilirubin 3.1–5 mg/dL—25% of
usual dose.
Availability (generic available)
Powder for injection: 10 mg/vial, 20 mg/vial, 50 mg/
vial, 150 mg/vial. Solution for injection: 2 mg/mL.
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