Peringatan Keamanan

Doxorubicin hydrochloride treatment can increase the risk of secondary malignancies based on postmarketing reports. Doxorubicin hydrochloride was mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay.L45231

Doxorubicin hydrochloride decreased fertility in female rats at doses of 0.05 and 0.2 mg/kg/day (approximately 0.005 and 0.02 times the recommended human dose, based on body surface area).L45231 In females of reproductive potential, Doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment.L45231

A single intravenous dose of 0.1 mg/kg doxorubicin hydrochloride (approximately 0.01 times the recommended human dose based on body surface area) was toxic to male reproductive organs in animal studies, producing testicular atrophy, diffuse degeneration of the seminiferous tubules, and oligospermia/hypospermia in rats. Doxorubicin hydrochloride induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice.L45231

Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection/for Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection/for Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2. Advise pregnant women of the potential risk to a fetus.L45231

Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride. Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually
temporary.L45231

Doxorubicin

DB00997

small molecule approved investigational

Deskripsi

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius along side with daunorubicin, another cytotoxic agent, in 1970.A1575,A257709,A257614 Although they both have aglyconic and sugar moieties, doxorubicin's side chain terminates with a primary alcohol group compared to the methyl group of daunorubicin.A257709 Although its detailed molecular mechanisms have yet to be understood, doxorubicin is generally thought to exert its effect through DNA intercalation, which eventually leads to DNA damage and the generation of reactive oxygen species.A257614 Thanks to its efficacy and broad effect, doxorubicin was approved by the FDA in 1974 to treat a variety of cancer, including but not limited to breast, lung, gastric, ovarian, thyroid, non-Hodgkin’s and Hodgkin’s lymphoma, multiple myeloma, sarcoma, and pediatric cancers.A1573,A257614,L45231 However, one of the major side effects of doxorubicin is cardiotoxicity, which excludes patients with poor heart function and requires treatment termination once the maximally tolerated cumulative dose is reached.A257719

Struktur Molekul 2D

Berat 543.5193
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life of doxorubicin ranges from 20 hours to 48 hours.[L45231] The distribution half-life of doxorubicin is approximately 5 minutes.[L45231] For the liposomal formulation, the first-phase and second-phase half-lives were calculated to be 4.7 ± 1.1 and 52.3 ± 5.6 hours respectively for a 10 mg/m<sup>2</sup> of doxorubicin in patients with AIDS-Related Kaposi’s Sarcoma.[L45226]
Volume Distribusi The steady-state distribution volume of doxorubicin ranges from 809 L/m<sup>2</sup> to 1214 L/m<sup>2</sup>.[L45231]
Klirens (Clearance) The plasma clearance of doxorubicin ranges from 324 mL/min/m2 to 809 mL/min/m<sup>2</sup> by metabolism and biliary excretion.[L45231] Sexual differences in doxorubicin were also observed, with men having a higher clearance compared to women (1088 mL/min/m<sup>2</sup> versus 433 mL/min/m<sup>2</sup>).[L45231] Following the administration of doses ranging from 10 mg/m2 to 75 mg/m<sup>2</sup> of doxorubicin hydrochloride, the plasma clearance was estimated to be 1540 mL/min/m<sup>2</sup> in children greater than 2 years of age and 813 mL/min/m<sup>2</sup> in infants younger than 2 years of age.[L45231]

Absorpsi

Following a 10 mg/m2 administration of liposomal doxorubicin in patients with AIDS-related Kaposi's Sarcoma, the Cmax and AUC values were calculated to be 4.12 ± 0.215 ?g/mL and 277 ± 32.9 ?g/mL•h respectively.L45226

Metabolisme

Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged.A1578 The two-electron reduction is the major metabolic pathway of doxorubicin.A1578 In this pathway, doxorubicin is reduced to doxorubicinol, a secondary alcohol, by various enzymes, including Alcohol dehydrogenase NADP(+), Carbonyl reductase NADPH 1, Carbonyl reductase NADPH 3, and Aldo-keto reductase family 1 member C3.A18032,A257574,A1578,A18033,A18034 The one-electron reduction is facilitated by several oxidoreductase, both cytosolic and mitochondrial, to form a doxirubicin-semiquinone radical.A1579 These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases.A18035,A18042,A18407,A257579,A18037,A18038 This semiquinone metabolite can be re-oxidized to doxorubicin, although with the concurrent formation of reactive oxygen species (ROS) and hydrogen peroxide.A257584 It is the ROS generating through this pathway that contributes most to the doxorubicin-related adverse effects, particularly cardiotoxicity, rather than through doxorubicin semiquinone formation.A257589 Deglycosidation is a minor metabolic pathway, since it only accounts for 1 to 2% of doxorubicin metabolism.A1578, A257514 Under the catalysis of cytoplasmic NADPH quinone dehydrogenase, xanthine oxidase, NADPH-cytochrome P450 reductase, doxorubicin can either be reduced to doxorubicin deoxyaglycone or hydrolyzed to doxorubicin hydroxyaglycone.A257569,A18036,A18043

Rute Eliminasi

Approximately 40% of the dose appears in the bile in 5 days, while only 5% to 12% of the drug and its metabolites appear in the urine during the same time period. In urine, <3% of the dose was recovered as doxorubicinol over 7 days.L45231

Farmakogenomik

3 Varian
RARG (rs2229774)

Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.

SLC28A3 (rs7853758)

Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.

UGT1A6 (rs17863783)

Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.

Interaksi Makanan

2 Data
  • 1. Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of doxorubicin.
  • 2. Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of doxorubicin.

Interaksi Obat

1290 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Doxorubicin.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Doxorubicin.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Doxorubicin.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Doxorubicin.
Peginterferon alfa-2b The serum concentration of Doxorubicin can be increased when it is combined with Peginterferon alfa-2b.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Doxorubicin.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Doxorubicin.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Doxorubicin.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Doxorubicin.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Doxorubicin.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Doxorubicin.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Doxorubicin.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Doxorubicin.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Doxorubicin.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Doxorubicin.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Doxorubicin.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Doxorubicin.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Doxorubicin.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Doxorubicin.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Doxorubicin.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Doxorubicin.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Doxorubicin.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Doxorubicin.
Cladribine Doxorubicin may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Doxorubicin.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Doxorubicin.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Doxorubicin.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Doxorubicin.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Doxorubicin.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Doxorubicin.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Doxorubicin.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Doxorubicin.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Doxorubicin.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Doxorubicin.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Doxorubicin.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Doxorubicin.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Doxorubicin.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Doxorubicin.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Doxorubicin.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Doxorubicin.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Doxorubicin.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Doxorubicin.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Doxorubicin.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Doxorubicin.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Doxorubicin.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Doxorubicin.
Tretinoin The risk or severity of cardiotoxicity can be increased when Tretinoin is combined with Doxorubicin.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Doxorubicin.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Doxorubicin.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Doxorubicin.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Doxorubicin.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Doxorubicin.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Doxorubicin.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Doxorubicin.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Doxorubicin.
Hydroxyurea The serum concentration of Doxorubicin can be increased when it is combined with Hydroxyurea.
Mycophenolic acid The risk or severity of adverse effects can be increased when Doxorubicin is combined with Mycophenolic acid.
Thalidomide The serum concentration of Doxorubicin can be decreased when it is combined with Thalidomide.
Melphalan The risk or severity of adverse effects can be increased when Doxorubicin is combined with Melphalan.
Fludarabine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Fludarabine.
Flucytosine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Flucytosine.
Capecitabine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Capecitabine.
Procarbazine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Procarbazine.
Idarubicin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Idarubicin.
Lomustine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Lomustine.
Eculizumab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Eculizumab.
Decitabine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Decitabine.
Nelarabine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Nelarabine.
Ciclesonide The risk or severity of adverse effects can be increased when Doxorubicin is combined with Ciclesonide.
Stepronin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Stepronin.
Castanospermine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Castanospermine.
Vorinostat The risk or severity of adverse effects can be increased when Doxorubicin is combined with Vorinostat.
2-Methoxyethanol The risk or severity of adverse effects can be increased when Doxorubicin is combined with 2-Methoxyethanol.
Brequinar The risk or severity of adverse effects can be increased when Doxorubicin is combined with Brequinar.
Pirfenidone The risk or severity of adverse effects can be increased when Doxorubicin is combined with Pirfenidone.
Interferon alfa The risk or severity of adverse effects can be increased when Doxorubicin is combined with Interferon alfa.
Glatiramer The risk or severity of adverse effects can be increased when Doxorubicin is combined with Glatiramer.
Briakinumab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Briakinumab.
Human interferon omega-1 The risk or severity of adverse effects can be increased when Doxorubicin is combined with Human interferon omega-1.
Mepolizumab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Mepolizumab.
Abetimus The risk or severity of adverse effects can be increased when Doxorubicin is combined with Abetimus.
Belatacept The risk or severity of adverse effects can be increased when Doxorubicin is combined with Belatacept.
Bendamustine The risk or severity of adverse effects can be increased when Doxorubicin is combined with Bendamustine.
Pralatrexate The risk or severity of adverse effects can be increased when Doxorubicin is combined with Pralatrexate.
Wortmannin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Wortmannin.
Eribulin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Eribulin.
Belimumab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Belimumab.
Teriflunomide The risk or severity of adverse effects can be increased when Doxorubicin is combined with Teriflunomide.
Dimethyl fumarate The risk or severity of adverse effects can be increased when Doxorubicin is combined with Dimethyl fumarate.
Obinutuzumab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Obinutuzumab.
Vedolizumab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Vedolizumab.
Blinatumomab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Blinatumomab.
Dinutuximab The risk or severity of adverse effects can be increased when Doxorubicin is combined with Dinutuximab.
Vilanterol The risk or severity of adverse effects can be increased when Doxorubicin is combined with Vilanterol.
Tixocortol The risk or severity of adverse effects can be increased when Doxorubicin is combined with Tixocortol.
Peginterferon beta-1a The risk or severity of adverse effects can be increased when Doxorubicin is combined with Peginterferon beta-1a.
Antilymphocyte immunoglobulin (horse) The risk or severity of adverse effects can be increased when Doxorubicin is combined with Antilymphocyte immunoglobulin (horse).
Fluprednisolone The risk or severity of adverse effects can be increased when Doxorubicin is combined with Fluprednisolone.
Tepoxalin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Tepoxalin.
Melengestrol The risk or severity of adverse effects can be increased when Doxorubicin is combined with Melengestrol.

Target Protein

DNA topoisomerase 2-alpha TOP2A
Telomerase reverse transcriptase TERT
DNA
DNA topoisomerase 1 TOP1
DNA topoisomerase 2-beta TOP2B
Nucleolar and coiled-body phosphoprotein 1 NOLC1

Referensi & Sumber

Synthesis reference: Gian P. Vicario, Sergio Penco, Federico Arcamone, "Daunorubicin and doxorubicin labelled with .sup.14 C at the 14-position and processes for their preparation." U.S. Patent US4211864, issued March, 1976.
Artikel (PubMed)
  • PMID: 1462166
    Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86.
  • PMID: 4290058
    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.
  • PMID: 5365804
    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.
  • PMID: 5772652
    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.
  • PMID: 9864344
    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.
  • PMID: 19442138
    Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72.
  • PMID: 2555273
    Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8.
  • PMID: 18559761
    Quereux G, Marques S, Nguyen JM, Bedane C, D'incan M, Dereure O, Puzenat E, Claudy A, Martin L, Joly P, Delaunay M, Beylot-Barry M, Vabres P, Celerier P, Sasolas B, Grange F, Khammari A, Dreno B: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sezary syndrome. Arch Dermatol. 2008 Jun;144(6):727-33. doi: 10.1001/archderm.144.6.727.
Menampilkan 8 dari 40 artikel.

Contoh Produk & Brand

Produk: 172 • International brands: 2
Produk
  • Adriamycin
    Injection, solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, powder, lyophilized, for solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, powder, lyophilized, for solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, powder, lyophilized, for solution • 2 mg/1mL • Intravenous • US • Generic • Approved
  • Adriamycin
    Injection, solution • 2 mg/1mL • Intravenous • US • Generic • Approved
Menampilkan 8 dari 172 produk.
International Brands
  • Adriablastina — Pfizer
  • Adriblastin — Actavis

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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