Description

Simple

A medication used to treat various cancers and a skin condition seen in some AIDS patients.

Clinical

A medication used to treat various cancers and Kaposi's Sarcoma.

Overview

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Doxorubicin binds to nucleic acids, presumably by specific intercalation of the planar anthracycline nucleus with the DNA double helix.

Pharmacology

Indication

Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gas... Read more

Pharmacodynamic

Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of... Read more

Mechanism of action

Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion... Read more

Absorption

Information currently not available.

Protein binding

Doxorubicin and its major metabolite, doxorubicinol, is 74-76% bound to plasma protein. The extent to binding is independent of plasma concentration up to 1.1 mcg/mL. Doxorubicin does not cross the blood brain barrier.

Volume of distribution

The distributive half-life is 5 minutes, which suggests that doxorubicin is rapidly taken up by tissue.Steady state volume of distribution = 809 to 1214 L/m2

Clearance

324-809 mL/min/m2 [by metabolism and biliary excretion]1088 mL/min/m2 [Men]433 mL/min/m2 [Women]1540 mL/min/m2 [children greater than 2 years of age receiving administration of 10 to 75 mg/m2 doses]813 mL/min/m2 [infants younger than 2 years of age receiving administration of 10 to 75 mg/m2 doses]

Half life

Terminal half life = 20 - 48 hours.

Route of elimination

40% of the dose appears in bile in 5 days. 5-12% of the drug and its metabolites appears in urine during the same time period.

Toxicity

LD50=21800 ug/kg (rat, subcutaneous)

Adverse Effects

Contraindications

  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Severe Hepatic Impairment
      • Drugbank Id: DBCOND0070791
      • Modification Of:
        • Base:
          • Name: Heptic Impairment
          • Drugbank Id: DBCOND0072269
        • Severity:
          • Includes:
            • severe
  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Recent Myocardial Infarction
      • Drugbank Id: DBCOND0043731
  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Severe persistent drug-induced myelosuppression
      • Drugbank Id: DBCOND0108146
  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Severe myocardial insuffiency
      • Drugbank Id: DBCOND0108145

Food Interactions

  • Drink plenty of fluids. Increased fluid intake increases urine output and the excretion of uric acid.

Interactions

Type in a drug name to check for interaction with Doxorubicin
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Doxorubicin.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Doxorubicin.
2-Methoxyethanol
The risk or severity of adverse effects can be increased when Doxorubicin is combined with 2-Methoxyethanol.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Doxorubicin.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Doxorubicin.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Doxorubicin.
9-(N-methyl-L-isoleucine)-cyclosporin A
The risk or severity of adverse effects can be increased when Doxorubicin is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Doxorubicin.
Abatacept
The risk or severity of adverse effects can be increased when Doxorubicin is combined with Abatacept.
Abciximab
The risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin.
Abemaciclib
The serum concentration of Doxorubicin can be increased when it is combined with Abemaciclib.
Abetimus
The risk or severity of adverse effects can be increased when Doxorubicin is combined with Abetimus.
Acebutolol
The serum concentration of Acebutolol can be increased when it is combined with Doxorubicin.
Acenocoumarol
The serum concentration of Acenocoumarol can be increased when it is combined with Doxorubicin.
Acetaminophen
The serum concentration of Doxorubicin can be increased when it is combined with Acetaminophen.
Acetyldigitoxin
Acetyldigitoxin may decrease the cardiotoxic activities of Doxorubicin.
Acetyldigoxin
Doxorubicin may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acid
The serum concentration of Doxorubicin can be decreased when it is combined with Acetylsalicylic acid.
Acteoside
The risk or severity of adverse effects can be increased when Doxorubicin is combined with Acteoside.
Adalimumab
The risk or severity of adverse effects can be increased when Adalimumab is combined with Doxorubicin.
7 References
  1. 1 . Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86.PubMed: 1462166
  2. 2 . Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA: Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53.PubMed: 4290058
  3. 3 . Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101-10.PubMed: 5365804
  4. 4 . Di Marco A, Gaetani M, Scarpinato B: Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969 Feb;53(1):33-7.PubMed: 5772652
  5. 5 . Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR: Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. J Bacteriol. 1999 Jan;181(1):305-18.PubMed: 9864344
  6. 6 . Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72.PubMed: 19442138
  7. 7 . Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8.PubMed: 2555273