Peringatan Keamanan

Oral, mouse: LD50 = 7330 mg/kg; Oral, rat: LD50 = 5760 mg/kg

Hydroxyurea can cause fetal harm based on findings from animal studies and the drug’s mechanism of action. There are no studies on the use of Hydroxyurea in pregnant women and limited available data on SIKLOS use during pregnancy are insufficient to inform drug-associated risks. Drugs that affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents. In animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m² basis. In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae. Embryotoxicity was characterized by decreased fetal viability, reduced live
litter sizes, and developmental delays. Advise pregnant women of the potential risk to a fetus.L49181

Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed. In patients with sickle cell anemia, neutropenia was reported in isolated cases of hydroxyurea overdose (1.43 times and 8.57 times the maximum recommended dose of 35 mg/kg b.w./day). Monitor blood counts weekly until recovery. Treatment of overdose consists of gastric lavage, followed by symptomatic treatment and control of bone marrow function.L49181

Conventional long-term studies to evaluate the carcinogenic potential of hydroxyurea have not been performed. However, hydroxyurea is presumed to be a transspecies carcinogen. Intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months in female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype.L49181

Hydroxyurea administered to male rats at 60 mg/kg /day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females.L49181

Hydroxyurea

DB01005

small molecule approved

Deskripsi

Hydroxyurea is a non-alkylating antineoplastic agent that was first synthesized in 1869 but was not characterized biologically until 1928.A262596 It was first approved by the FDA in 1998 for the treatment of sickle cell anemia in adults.A262601 Although clinical evidence on the efficacy of hydroxyurea in certain conditions exists, hydroxyurea is used sparingly in clinical settings, largely due to lack of knowledge and adherence, the need for therapeutic monitoring, and serious side effects of secondary cancer and birth defects.A262606

Struktur Molekul 2D

Berat 76.0547
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) In adult cancer patients, hydroxyurea was eliminated with a half-life of approximately 2-3 hours. In a single-dose study in children with Sickle Cell Disease, the mean half-life was reported to be 1.7 hours.[L47137]
Volume Distribusi Hydroxyurea distributes rapidly throughout the human body, enters the cerebrospinal fluid, appears in peritoneal fluid and ascites, and concentrates in leukocytes and erythrocytes. The estimated volume of distribution of hydroxycarbamide approximates total body water. The volume of distribution following oral dosing of hydroxycarbamide is approximately equal to total body water: adult values of 0.48 – 0.90 L/kg have been reported, whilst in children a population estimate of 0.7 L/kg has been reported.[L47137]
Klirens (Clearance) The total body clearance of hydroxyurea in adult patients with Sickle Cell Disease is 0.17 L/h/kg. The respective value in children was similar, 0.22 L/h/kg.[L47137]

Absorpsi

After oral administration hydroxyurea is readily absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 2 hours and by 24 hours the serum concentrations are virtually zero. Bioavailability is complete or nearly complete in cancer patients.L47137 After oral administration of 20 mg/kg of hydroxyurea, a rapid absorption is observed with peak plasma levels of about 30 mg/L occurring after 0.75 and 1.2 h in children and adult patients with sickle cell syndrome, respectively. The total exposure up to 24 h post-dose is 124 mg.h/L in children and adolescents and 135 mg.h/L in adult patients. The oral bioavailability of hydroxyurea is almost complete as assessed in indications other than sickle cell syndrome.L47143 In a comparative bioavailability study in healthy adult volunteers (n=28), 500 mg of hydroxyurea oral solution was demonstrated to be bioequivalent to the reference 500 mg capsule, with respect to both the peak concentration and area under the curve. There was a statistically significant reduction in time to peak concentration with hydroxyurea oral solution compared to the reference 500 mg capsule (0.5 versus 0.75 hours, p = 0.0467), indicating a faster rate of absorption.[L47137 In a study of children with Sickle Cell Disease, liquid and capsule formulations resulted in similar area under the curve, peak concentrations, and half-life. The largest difference in the pharmacokinetic profile was a trend towards a shorter time to peak concentration following ingestion of the liquid compared with the capsule, but that difference did not reach statistical significance (0.74 versus 0.97 hours, p = 0.14).L47137

Metabolisme

Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation to acetohydroxamic acid by urease found in intestinal bacteria.L47112,L47142

Rute Eliminasi

A significant fraction of hydroxycarbamide is eliminated by nonrenal (mainly hepatic) mechanisms. In adults, the urinary recovery of unchanged drug is reported to be approximately 37% of the oral dose when renal function is normal. In children, the fraction of hydroxyurea excreted unchanged into the urine comprised about 50%.L47137

Interaksi Makanan

1 Data
  • 1. Drink plenty of fluids. Drinking extra fluids will help pass more urine to prevent kidney problems and keep the kidneys working well.

Interaksi Obat

566 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Hydroxyurea.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Hydroxyurea.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Hydroxyurea.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Hydroxyurea.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Hydroxyurea.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Hydroxyurea.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Hydroxyurea.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Hydroxyurea.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Hydroxyurea.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Hydroxyurea.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Hydroxyurea.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Hydroxyurea.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Hydroxyurea.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Hydroxyurea.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Hydroxyurea.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Hydroxyurea.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Hydroxyurea.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Hydroxyurea.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Hydroxyurea.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Hydroxyurea.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Hydroxyurea.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Hydroxyurea.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Hydroxyurea.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Hydroxyurea.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Hydroxyurea.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Hydroxyurea.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Hydroxyurea.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Hydroxyurea.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Hydroxyurea.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Hydroxyurea.
Cladribine Hydroxyurea may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Hydroxyurea.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Hydroxyurea.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Hydroxyurea.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Hydroxyurea.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Hydroxyurea.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Hydroxyurea.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Hydroxyurea.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Hydroxyurea.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Hydroxyurea.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Hydroxyurea.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Hydroxyurea.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Hydroxyurea.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Hydroxyurea.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Hydroxyurea.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Hydroxyurea.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Hydroxyurea.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Hydroxyurea.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Hydroxyurea.
Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Hydroxyurea.
Teniposide The risk or severity of adverse effects can be increased when Teniposide is combined with Hydroxyurea.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Hydroxyurea.
Chloramphenicol The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Hydroxyurea.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Hydroxyurea.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Hydroxyurea.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Hydroxyurea.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Hydroxyurea.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Hydroxyurea.
Cyclophosphamide The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Hydroxyurea.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Hydroxyurea.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Hydroxyurea.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Hydroxyurea.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Hydroxyurea.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Hydroxyurea.
Carbamazepine The risk or severity of adverse effects can be increased when Carbamazepine is combined with Hydroxyurea.
Vinblastine The risk or severity of adverse effects can be increased when Vinblastine is combined with Hydroxyurea.
Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Hydroxyurea.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Hydroxyurea.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Hydroxyurea.
Imatinib The risk or severity of adverse effects can be increased when Imatinib is combined with Hydroxyurea.
Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Hydroxyurea.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Hydroxyurea.
Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Hydroxyurea.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Hydroxyurea.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Hydroxyurea.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Hydroxyurea.
Daunorubicin The risk or severity of adverse effects can be increased when Daunorubicin is combined with Hydroxyurea.
Irinotecan The risk or severity of adverse effects can be increased when Irinotecan is combined with Hydroxyurea.
Methimazole The risk or severity of adverse effects can be increased when Methimazole is combined with Hydroxyurea.
Etoposide The risk or severity of adverse effects can be increased when Etoposide is combined with Hydroxyurea.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Hydroxyurea.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Hydroxyurea.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Hydroxyurea.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Hydroxyurea.
Prednisolone The risk or severity of adverse effects can be increased when Prednisolone is combined with Hydroxyurea.
Sirolimus The risk or severity of adverse effects can be increased when Sirolimus is combined with Hydroxyurea.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Hydroxyurea.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Hydroxyurea.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Hydroxyurea.
Methylprednisolone The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Hydroxyurea.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Hydroxyurea.
Cytarabine The risk or severity of adverse effects can be increased when Cytarabine is combined with Hydroxyurea.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Hydroxyurea.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Hydroxyurea.
Busulfan The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Busulfan.
Mycophenolic acid The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Mycophenolic acid.
Topotecan The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Topotecan.
Mercaptopurine The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Mercaptopurine.
Thalidomide The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Thalidomide.
Melphalan The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Melphalan.

Target Protein

Ribonucleoside-diphosphate reductase large subunit RRM1
Ribonucleoside-diphosphate reductase subunit M2 RRM2

Referensi & Sumber

Synthesis reference: Dee W. Brooks, Andrew O. Stewart, Richard A. Craig, "Substituted aryl- and heteroarylalkenyl-N-hydroxyurea inhibitors of leukotriene biosynthesis." U.S. Patent US5506261, issued October, 1990.
Artikel (PubMed)
  • PMID: 31123026
    Ferrari A, Carobbio A, Masciulli A, Ghirardi A, Finazzi G, De Stefano V, Vannucchi AM, Barbui T: Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis. Haematologica. 2019 Dec;104(12):2391-2399. doi: 10.3324/haematol.2019.221234. Epub 2019 May 23.
  • PMID: 7700286
    Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T: Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. doi: 10.1056/NEJM199504273321704.
  • PMID: 23346322
    Kim MS, Yu DW, Jung YJ, Kim SW, Chang CH, Kim OL: Long-term follow-up result of hydroxyurea chemotherapy for recurrent meningiomas. J Korean Neurosurg Soc. 2012 Dec;52(6):517-22. doi: 10.3340/jkns.2012.52.6.517. Epub 2012 Dec 31.
  • PMID: 30504328
    Klion A: Hypereosinophilic syndrome: approach to treatment in the era of precision medicine. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):326-331. doi: 10.1182/asheducation-2018.1.326.
  • PMID: 27869662
    Singh A, Xu YJ: The Cell Killing Mechanisms of Hydroxyurea. Genes (Basel). 2016 Nov 17;7(11):99. doi: 10.3390/genes7110099.
  • PMID: 19047254
    Strouse JJ, Lanzkron S, Beach MC, Haywood C, Park H, Witkop C, Wilson RF, Bass EB, Segal JB: Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children. Pediatrics. 2008 Dec;122(6):1332-42. doi: 10.1542/peds.2008-0441.
  • PMID: 20008183
    Ware RE, Aygun B: Advances in the use of hydroxyurea. Hematology Am Soc Hematol Educ Program. 2009:62-9. doi: 10.1182/asheducation-2009.1.62.

Contoh Produk & Brand

Produk: 39 • International brands: 2
Produk
  • Apo-hydroxyurea
    Capsule • 500 mg • Oral • Canada • Generic • Approved
  • Droxia
    Capsule • 300 mg/1 • Oral • US • Approved
  • Droxia
    Capsule • 200 mg/1 • Oral • US • Approved
  • Droxia
    Capsule • 400 mg/1 • Oral • US • Approved
  • Droxia
    Capsule • 300 mg/1 • Oral • US • Approved
  • Droxia
    Capsule • 200 mg/1 • Oral • US • Approved
  • Droxia
    Capsule • 400 mg/1 • Oral • US • Approved
  • Eugia-hydroxyurea
    Capsule • 500 mg • Oral • Canada • Approved
Menampilkan 8 dari 39 produk.
International Brands
  • Litalir — Bristol-Myers Squibb
  • Onco-Carbide — Teofarma

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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