Dosing and uses of Doxorubicin (Adriamycin, Caelyx, Rubex)
Adult dosage forms and strengths
injectable solution
- 2mg/mL
powder for injection
- 10mg
- 20mg
- 50mg
Cancers
Cancer of breast, ovary, prostate, stomach, thyroid; small cell cancer of lung, liver; squamous cell cancer of head and neck; multiple myeloma, Hodgkin's disease, lymphomas, ALL, AML
60-75 mg/m² IV q21Days Or
60 mg/m² IV q14Days Or
40-60 mg/m² IV q21-28Days Or
20 mg/m²/dose qweek
Hepatocellular Carcinoma (Orphan)
Orphan indication sponsor
- Delcath Systems, Inc; Rockefeller Center, 23rd Floor; New York, NY 10020
Renal Impairment
Dose adjustment not necessary
Hepatic Impairment
Serum bilirubin <1.2 mg/dL: Dose adjustment not necessary
Serum bilirubin 1.2-3 mg/dL [20.5-51.3 micromoles/L]: Give 50% dose
Serum bilirubin: 3.1-5 mg/dL [53-85.5 micromoles/L]: Give 25% dose
Severe hepatic impairment: Contraindicated
Administration
Limit lifetime cumulative dose to <550 mg/m² to reduce risk of cardiotox
Monitor: CBC, cardiac function, LFTs
Pediatric dosage forms and strengths
injectable solution
- 2mg/mL
powder for injection
- 10mg
- 20mg
- 50mg
Cancers
Cancer of stomach, neuroblastoma, thyroid; liver; squamous cell cancer of head and neck; multiple myeloma, Hodgkin's disease, lymphomas, ALL, AML
35-75 mg/m² IV q21Days Or
20-30 mg/m²/dose qweek
60-90 mg/m² IV over 96 hr q3-4weeks Or
Doxorubicin (Adriamycin, Caelyx, Rubex) adverse (side) effects
>10%
Neutropenia (52%)
Anemia (52%)
Leukopenia (42%)
Pruritus (37%)
Nausea (37%)
Stomatitis (37%)
Fatigue (33%)
CHF (30%)
Thrombocytopenia (24%)
Vomiting (22%)
Rash (21%)
Alopecia (15%)
Anorexia (12%)
Constipation (12%)
Diarrhea (10%)
1-10%
Cardiomyopathy (0.5-9%)
Frequency not defined
Photosensitivity
Cardiac dysrhythmia
Necrotizing colitis
Myelosuppression
Hyperuricemia
Red urine
Hyperpigmentation of previously radiated areas
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Cumulative dose-related cardiotoxicity may occur. Potentially fatal CHF may occur months to years after completion of therapy. The risk of developing CHF increases with increasing total cumulative doses of doxorubicin in excess of 450 mg/m².
Delayed cardiotoxicity may occur in patients with prior mediastinal irradiation, in those on concurrent cyclophosphamide therapy, or in those with preexisting heart disease. Toxicity may also occur at a lower cumulative dose in patients
For IV administration only. Severe local tissue damage will occur in extravasation. Do not administer IM or SC
Development of secondary acute myelogenous leukemia and myelodysplastic syndrome reported
Severe myelosuppression may occur
Reduce dose in hepatic dysfunction
Contraindications
Hypersensitivity
Active infection
Severe hepatic impairment
Baseline neutrophil count <1500/mm³
Recent MI or severe myocardial insufficiency
Prior treatment max dose of doxorubicin, daunorubicin, idarubicin, or other anthracyclines
Cardiomyopathy, CHF, impaired cardiac function
IM/SC administration
Cautions
Vesicant
Risk of cardiotoxicity (cardiomyopathy, CHF)- may manifest months or even years after discontinuation
Risk of infusion reactions, myelosuppression
May cause tumor lysis syndrome and hyperuricemia
Secondary oral cancers, primarily squamous cell carcinoma, reported with long-term (ie, >1 yr)
Pediatric patients, elderly, liver impairment, concomitant radiotherapy
Not effective in malignant melanoma, kidney CA, bowel CA, brain tumors, CNS metastasis
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: Enters breast milk/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Doxorubicin (Adriamycin, Caelyx, Rubex)
Mechanism of action
Anthracycline; intercalates between DNA base pairs, impairs topoisomerase II function and inhibits replication & transcription
Distribution
Protein Bound: 75%
Vd: 20-30 L/kg (700-1214 L/m²)
Metabolism
Predominantly liver
Metabolites: DoxorubicinoL
Elimination
Half-Life: 1-3 hr
Clearance: 8-20 mL/min/kg
Excretion: Feces (40-50%); urine (5-12%)
Administration
IV Incompatibilities
Additive: aminophylline, dacarbazine/ondansetron(?), diazepam, fluorouraciL
Syringe: cisplatin/mitomycin(?), fluorouracil (at high concs of both), furosemide, heparin
Y-site: allopurinol, amphotericin B cholesteryl sulfate, cefepime, furosemide(?), ganciclovir, heparin(?), piperacillin/tazobactam, propofoL
IV Preparation
Reconstitute with NS to a final concentration of 2 mg/mL
Protect from light
Reconstituted soln stable for 7 d at room temp if protected from light & 15 d at 2-8°C
IV Administration
Administered into the tubing of a freely running intravenous infusion of NS or D5W
Administer over 3-5 min with frequent checks of IV patency via visible blood return
Monitor for local erythematous streaking (flare rxn) along vein &/or facial flushing (may indicate too rapid administration)
Extravasation Management
Terminate injection or infusion immediately & aspirate back as much as possible
Apply cold pack w/ circulating ice water, ice pack or cryogel pack to extravasation site for 15-20 min QID x 24-48 hr
Elevate site for 48 hr, then resume normal activity
Extravasation of <1-2 mL often heal spontaneously. If >3 mL, ulceration may occur.
Protect site from heat & sunlight
Varied results in studies using 99% DMSO to treat extravasation, follow institutional policy
If pain, erythema, &/or swelling persist beyond 48 hr, refer pt immediately to plastic surgeon for consultation & possible debridement
See also Totect
Storage
Store intact vials of solution under refrigeration at 2-8°C
Protect from light
Store intact vials of lyophilized powder at room temp(15-30°C)
