Doxorubicin

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

Introduction

• Doxorubicin HCl.

• Tradenames: Adriamycin PFS, Adriamycin RDF, Rubex.

Indications

• solid tumors

• ovarian
• breast
• bladder
• gastric
• hepatic
• lung

• leukemias & lymphomas ( Hodgkin's & non-Hogkin's)
• soft tissue sarcomas

• neuroblastoma
• osteosarcoma
• Kaposi's sarcoma in patients with AIDS (liposomal)

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

• complete blood count ( CBC)
• echocardiogram
• liver function tests ( LFTs)

Adverse-effects

• common (> 10%)

• alopecia
• gastrointestinal

• nausea/vomiting (21-55%)
• mucositis, ulceration & necrosis of colon
• diarrhea

• 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
• congestive heart failure

• uncommon (< 1%)

• allergic reaction, anaphylaxis, fever/ chills, urticaria, conjunctivitis

• others:

• red colored urine
• stomatitis

• complications

• therapy induced leukemia ( acute myeloid leukemia)
• genetic aberrations of chromosome 11
  
• drug adverse effects of anthracyclines

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

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

• anthracycline
• antineoplastic agent (chemotherapeutic agent)

Additional Terms

• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Internet Database

PubChem: 31703
PubChem: 1691
PubChem: 3160
PubChem: 443939

References

1. Kaiser Permanente Northern California Regional Drug Formulary, 1998
2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 680
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
5. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: [1] (subscription needed) [2]

doxorubicin (Adriamycin, Rubex)