doxorubicin (Adriamycin, Rubex)
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Introduction
Doxorubicin HCl.
Tradenames: Adriamycin PFS, Adriamycin RDF, Rubex.
Indications
- solid tumors
- leukemias & lymphomas (Hodgkin's disease & non-Hodgkin's lymphoma)
- soft tissue sarcomas
- neuroblastoma, Wilm's tumor
- osteosarcoma
- Kaposi's sarcoma in patients with AIDS (liposomal)
- carcinoid syndrome[6]
Dosage
- 60-75 mg/m2 once every 3-4 weeks, or
- continuous infusion over 2-4 days
- adjustment for liver function (total bilirubin):
- total bilirubin 1.2-3.0 mg/dL: 50% of dose
- total bilirubin > 3.0 mg/dL: 25% of dose
Injection: 2 mg/mL (5, 10, 25, 100 mL)
Doxorubicin liposomal
Pharmacokinetics
- widely distributed
- does not penetrate blood brain barrier
- metabolized in liver by cyt P450 3A4 to multiple metabolites
- most is eliminated in the bile
- 1/2life is 20-30 hours
elimination via liver
1/2life = 20-30 hours
Monitor
* no indication for continued surveillance with echocardiography or cardiac magnetic resonance imaging if LV systolic function normal 6 months after completion of therapy, & no signs or symptoms of heart failure[7]
Adverse effects
- common (> 10%)
- alopecia
- gastrointestinal
- myelosuppression
- 60-80% will have leukopenia
- onset 7 days
- nadir 10-14 days
- recovery 21-28 days
- radiation recall
- in patients with prior irradiation
- warmth, erythema & dermatitis in radiation port
- may progress to severe desquamation & ulceration
- extravasation: severe inflammation, tissue necrosis, ulceration
- less common (1-10%)
- erythematous streaking along vein if administered too rapidly
- cardiac toxicity
- maximum lifetime dose 450-550 mg/m2
- arrhythmias, heart block
- pericarditis/myocarditis
- dilated cardiomyopathy, congestive heart failure (1.6-5%)
- uncommon (< 1%)
- others:
- red colored urine
- stomatitis
- hand & foot syndrome[7]
- complications
Drug interactions
- any drug that inhibits cyt P450 3A4 may increase levels of doxorubicin
- any drug that induces cyt P450 3A4 may diminish levels of doxorubicin
- digoxin, cyclophosphamide, mercaptopurine, hydrocortisone, aminophylline, heparin, cephalothin, dexamethasone, 5-fluorouracil
- drug interaction(s) of antibiotics with warfarin
- drug interaction(s) of atorvastatin with anthracycline
Mechanism of action
- genotoxic
- transported out of cells by ABCB5
- exogenous expression of LANCL2 in a sarcoma cell line decreases the expression of ABCB1 (P-glycoprotein 1) & increases cellular sensitivity to adriamycin
More general terms
Additional terms
Component of
- cyclophosphamide/dexamethasone/doxorubicin/vincristine; cyclophosphamide/vincristine/adriamycin/dexamethasone (CVAD)
- thalidomide, dexamethasone & pegylated liposomal doxorubicin (ThADD)
- brentuximab vedotin/doxorubicin/vinblastine/dacarbazine (A+AVD)
- rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/dexamethasone (R-CVAD)
- rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (R-CHOP)
- doxorubicin (Adriamycin)/bleomycin/vinblastine/dacarbazine (ABVD)
- cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (CHOP)
- cyclophosphamide/doxorubicin (Adriamycin)/vincristine (VAC)
- cyclophosphamide/doxorubicin (Adriamycin)/5-fluorouracil (CAF)
- doxorubicin (Adriamycin) & cyclophosphamide (AC)
- doxorubicin (Adriamycin)/paclitaxel (Taxol)
- doxorubicin (Adriamycin)/docetaxel (Taxotere)
Components
References
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 680
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Deprecated Reference
- ↑ 7.0 7.1 7.2 7.3 7.4 Medical Knowledge Self Assessment Program (MKSAP) 17, 19. American College of Physicians, Philadelphia 2015, 2023
- ↑ 8.0 8.1 Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003 Jun 1;97(11):2869-79. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12767102
- ↑ Perez EA, Suman VJ, Davidson NE et al Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008 Mar 10;26(8):1231-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18250349