Doxorubicin


Description

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.

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Pharmacology

Indication

Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphobla... Read more

Pharmacodynamic

Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this cla... Read more

Mechanism of action

Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action... Read more

Absorption

Information currently not available.

Protein binding

Doxorubicin and its major metabolite, doxorubicinol, is 74-76% bound to plasma protein. The extent t... Read more

Volume of distribution

The distributive half-life is 5 minutes, which suggests that doxorubicin is rapidly taken up by tiss... Read more

Clearance

324-809 mL/min/m2 [by metabolism and biliary excretion]1088 mL/min/m2 [Men]433 mL/min/m2 [Women]1540... Read more

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 du... Read more

Toxicity

LD50=21800 ug/kg (rat, subcutaneous)


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Alopecia US
  • Kind: experimental
    • Percent: 92%
  • Kind: comparator
    • Percent: 71%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 46%
  • Kind: comparator
    • Percent: 63%
  • Clinical Trial
    Thrombocytopenia US
  • Kind: experimental
    • Percent: 61%
  • Clinical Trial
    Anemia US
  • Kind: experimental
    • Percent: 55%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 40%
  • Kind: comparator
    • Percent: 52%
  • Clinical Trial
    Hand-foot Syndrome US
  • Kind: experimental
    • Percent: 51%
  • Kind: comparator
    • Percent: 0.9%
  • Clinical Trial
    Hand-foot Syndrome US
  • Kind: experimental
    • Percent: 51%
  • Kind: comparator
    • Percent: 0.9%
  • Clinical Trial
    Neutropenia US
  • Kind: experimental
    • Percent: 49%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 48%
  • Kind: comparator
    • Percent: 40%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 46%
  • Kind: comparator
    • Percent: 39%
  • Clinical Trial
    Peripheral neuropathy US
  • Kind: experimental
    • Percent: 42%
  • Kind: comparator
    • Percent: 45%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 33%
  • Kind: comparator
    • Percent: 44%
  • Clinical Trial
    Stomatitis US
  • Kind: experimental
    • Percent: 41%
  • Kind: comparator
    • Percent: 15%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 37%
  • Kind: comparator
    • Percent: 25%
  • Clinical Trial
    Neutropenia US
  • Kind: experimental
    • Percent: 36%
  • Kind: comparator
    • Percent: 22%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 36%
  • Kind: comparator
    • Percent: 28%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 21%
  • Kind: comparator
    • Percent: 35%
  • Clinical Trial
    Thrombocytopenia US
  • Kind: experimental
    • Percent: 33%
  • Kind: comparator
    • Percent: 28%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 32%
  • Kind: comparator
    • Percent: 22%
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 31%
  • Kind: comparator
    • Percent: 31%
  • Clinical Trial
    Pyrexia US
  • Kind: experimental
    • Percent: 31%
  • Kind: comparator
    • Percent: 22%
  • Clinical Trial
    Fever US
  • Kind: experimental
    • Percent: 21%
  • Kind: comparator
    • Percent: 31%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 29%
  • Kind: comparator
    • Percent: 12%
  • Clinical Trial
    Anemia US
  • Kind: experimental
    • Percent: 25%
  • Kind: comparator
    • Percent: 21%
  • Clinical Trial
    Anemia US
  • Kind: experimental
    • Percent: 5%
  • Kind: comparator
    • Percent: 25%
  • Clinical Trial
    Dyspnea US
  • Kind: experimental
    • Percent: 15%
  • Kind: comparator
    • Percent: 23%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 22%
  • Kind: comparator
    • Percent: 18%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 22%
  • Kind: comparator
    • Percent: 18%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 20%
  • Kind: comparator
    • Percent: 22%
  • Clinical Trial
    Neuralgia US
  • Kind: experimental
    • Percent: 17%
  • Kind: comparator
    • Percent: 20%
  • Clinical Trial
    Stomatitis US
  • Kind: experimental
    • Percent: 20%
  • Kind: comparator
    • Percent: 5%
  • Clinical Trial
    Mucositis US
  • Kind: experimental
    • Percent: 20%
  • Kind: comparator
    • Percent: 5%
  • Clinical Trial
    Cardiomyopathy US
  • Kind: experimental
    • Percent: 1-20%
  • Varying Reports
    Pericarditis US
  • Kind: experimental
    • Percent: 1-20%
  • Varying Reports
    Congestive Heart Failure US
  • Kind: experimental
    • Percent: 1-20%
  • Varying Reports
    Left Ventricular Ejection Fraction US
  • Kind: experimental
    • Percent: 1-20%
  • Varying Reports
    Myocarditis US
  • Kind: experimental
    • Percent: 1-20%
  • Varying Reports
    Anorexia US
  • Kind: experimental
    • Percent: 19%
  • Kind: comparator
    • Percent: 14%
  • Clinical Trial
    Hand-foot Syndrome US
  • Kind: experimental
    • Percent: 19%
  • Kind: comparator
    • Percent: <1%
  • Clinical Trial
    Cough US
  • Kind: experimental
    • Percent: 18%
  • Kind: comparator
    • Percent: 12%
  • Clinical Trial
    Pharyngitis US
  • Kind: experimental
    • Percent: 16%
  • Kind: comparator
    • Percent: 18%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 17%
  • Clinical Trial
    Thrombocytopenia US
  • Kind: experimental
    • Percent: 1.3%
  • Kind: comparator
    • Percent: 17%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 11%
  • Kind: comparator
    • Percent: 15%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 12%
  • Kind: comparator
    • Percent: 14%
  • Clinical Trial
    Neutropenia US
  • Kind: experimental
    • Percent: 8%
  • Kind: comparator
    • Percent: 14%
  • Clinical Trial
    Mucous membrane disorder US
  • Kind: experimental
    • Percent: 14%
  • Kind: comparator
    • Percent: 3.4%
  • Clinical Trial
    Dysthesia US
  • Kind: experimental
    • Percent: 13%
  • Kind: comparator
    • Percent: 10%
  • Clinical Trial
    Paresthesia US
  • Kind: experimental
    • Percent: 13%
  • Kind: comparator
    • Percent: 10%
  • Clinical Trial
    Weight decreased US
  • Kind: experimental
    • Percent: 12%
  • Kind: comparator
    • Percent: 4%
  • Clinical Trial

    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

    • Liberal fluid intake to increase urine output and help the excretion of uric acid.

    Interactions

    Type in a drug name to check for interaction with Doxorubicin

    The serum concentration of (R)-warfarin can be increased when it is combined with Doxorubicin.
    The serum concentration of (S)-Warfarin can be increased when it is combined with Doxorubicin.
    The risk or severity of adverse effects can be increased when Doxorubicin is combined with 2-Methoxyethanol.
    The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Doxorubicin.
    The metabolism of 4-hydroxycoumarin can be decreased when combined with Doxorubicin.
    The metabolism of 4-Methoxyamphetamine can be decreased when combined with Doxorubicin.
    The metabolism of 5-androstenedione can be decreased when combined with Doxorubicin.
    The metabolism of Doxorubicin can be decreased when combined with 6-Deoxyerythronolide B.
    The metabolism of 6-O-benzylguanine can be decreased when combined with Doxorubicin.
    The metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Doxorubicin.
    The risk or severity of adverse effects can be increased when Doxorubicin is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
    The metabolism of 9-aminocamptothecin can be decreased when combined with Doxorubicin.
    The metabolism of Doxorubicin can be increased when combined with Abatacept.
    The risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin.
    The serum concentration of Doxorubicin can be increased when it is combined with Abemaciclib.
    The risk or severity of adverse effects can be increased when Doxorubicin is combined with Abetimus.
    The metabolism of Abiraterone can be decreased when combined with Doxorubicin.
    The metabolism of Doxorubicin can be decreased when combined with Acalabrutinib.
    The serum concentration of Acebutolol can be increased when it is combined with Doxorubicin.
    The serum concentration of Acenocoumarol can be increased when it is combined with Doxorubicin.

    References

    • 1 . Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. [PubMed: 1462166]
    • 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 . 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 . 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 . 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 . 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 . Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8. [PubMed: 2555273]

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