Peringatan Keamanan

Intraperitoneal LD50 is 150 mg/kg in mice.L50698

High doses of cladribine have been associated with irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia, and thrombocytopenia.L50693 Lymphopenia may also occur, which is known to be dose-dependent.L50688 There is no known antidote to cladribine overdosage; thus, treatment of overdosage consists of drug discontinuation, careful observation, and appropriate supportive measures.L50693 Although it is not known whether cladribine can be removed from the circulation by dialysis or hemofiltration, because of its rapid and extensive intracellular and tissue distribution, hemodialysis is unlikely to eliminate cladribine to a significant extent.L50688

Cladribine

DB00242

small molecule approved investigational

Deskripsi

Cladribine is a purine analogue or a chlorinated derivative of adenine A263733 that causes apoptosis of B and T lymphocytes.A350 Cladribine was first approved in the United States in 1993 A263713 initially as a treatment for a number of hematological malignancies; currently, it is approved for the treatment of hairy cell leukemia.A263733 In 2017 in Europe and in 2019 in the United States, cladribine was also approved for the treatment multiple sclerosis.A263718

Struktur Molekul 2D

Berat 285.687
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Cladribine plasma concentration after intravenous administration declines multi-exponentially with an average half-life of 6.7 +/- 2.5 hours.[L50693] Following oral administration, the terminal half-life is approximately one day.[L50688] The intracellular half-life is 15 hours for Cd-AMP and 10 hours for Cd-ATP.[L50688]
Volume Distribusi In general, the apparent volume of distribution of cladribine is approximately 9 L/kg, indicating an extensive distribution in body tissues.[L50693] In patients with hematologic malignancies who received a two-hour infusion of cladribine injection at a dose of 0.12 mg/kg, the mean steady-state volume of distribution was 4.5 ± 2.8 L/kg.[L50693] Following oral administration, the mean apparent volume of distribution ranges from 480 to 490 L.[L50688] Cladribine penetrates into cerebrospinal fluid. One report indicates that concentrations are approximately 25% of those in plasma.[L50693] A cerebrospinal fluid:plasma concentration ratio of approximately 0.25 was observed in cancer patients.[L50688]
Klirens (Clearance) In patients with hematologic malignancies who received a two-hour infusion of cladribine injection at a dose of 0.12 mg/kg, the mean clearance was 978 ± 422 mL/h/kg.[L50693]

Absorpsi

Oral bioavailability is approximately 40%.L50688 Following the oral administration of 10 mg cladribine, the mean maximum concentration (Cmax) was in the range of 22 to 29 ng/ mL, and the corresponding mean AUC was in the range of 80 to 101 ng x h/mL.L50688 The Cmax and AUC of cladribine increased proportionally across a dose range from 3 to 20 mg.L50688 Under fasted conditions, the median time to maximum concentration (Tmax) was 0.5 h (range 0.5 to 1.5 hours).L50688 A high-fat meal decreased Cmax by 29% and delayed Tmax to 1.5 hours (range one to three hours), but this difference is not expected to be clinically significant.L50688 Following a cladribine injection given by continuous infusion over seven days, the mean steady-state serum concentration was estimated to be 5.7 ng/mL.L50693

Metabolisme

Cladribine is a prodrug that is phosphorylated to cladribine monophosphate (Cd-AMP, 2-chlorodeoxyadenosine monophosphate) by deoxycytidine kinase and mitochondrial deoxyguanosine kinase in lymphocytes. Cd-AMP is further phosphorylated to cladribine diphosphate (Cd-ADP, 2-chlorodeoxyadenosine diphosphate) and the active moiety Cd-ATP. The dephosphorylation and deactivation of Cd-AMP is catalyzed by cytoplasmic 5’-nucleotidase (5’-NTase). The metabolism of cladribine in whole blood has not been fully characterized; however, extensive whole blood and negligible hepatic enzyme metabolism was observed, in vitro.L50688

Rute Eliminasi

An average of 18% of the administered dose has been reported to be excreted in the urine of patients with solid tumours during a five-day continuous intravenous infusion of 3.5 to 8.1 mg/m2/day of cladribine injection.L50693 Following oral administration of 10 mg cladribine in patients with MS, about 28.5% of the dose was excreted unchanged via the renal route. Renal clearance exceeded the glomerular filtration rate, indicating active renal secretion of cladribine.L50688

Interaksi Makanan

1 Data
  • 1. Take with or without food. When taken with oral tablets of cladribine, food decreases Cmax and prolongs Tmax, but not to a clinically significant extent.

Interaksi Obat

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

Target Protein

Ribonucleoside-diphosphate reductase large subunit RRM1
Adenosine deaminase ADA
Ribonucleoside-diphosphate reductase subunit M2 RRM2
Ribonucleoside-diphosphate reductase subunit M2 B RRM2B
DNA
DNA polymerase alpha catalytic subunit POLA1
DNA polymerase epsilon catalytic subunit A POLE
DNA polymerase epsilon subunit 2 POLE2
DNA polymerase epsilon subunit 3 POLE3
DNA polymerase epsilon subunit 4 POLE4
Purine nucleoside phosphorylase PNP
Poly [ADP-ribose] polymerase 1 PARP1

Referensi & Sumber

Synthesis reference: Szepsel Gerszberg, "Method for the production of 2-chloro-2' -deoxyadenosine (cladribine) and its 3,5-di-O-p-toluoyl derivative." U.S. Patent US20020052491, issued May 02, 2002.
Artikel (PubMed)
  • PMID: 20634380
    Sigal DS, Miller HJ, Schram ED, Saven A: Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010 Oct 21;116(16):2884-96. doi: 10.1182/blood-2010-02-246140. Epub 2010 Jul 15.
  • PMID: 31643872
    Authors unspecified: Cladribine. .
  • PMID: 33975489
    Pfeuffer S, Rolfes L, Hackert J, Kleinschnitz K, Ruck T, Wiendl H, Klotz L, Kleinschnitz C, Meuth SG, Pul R: Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres. Mult Scler. 2022 Feb;28(2):257-268. doi: 10.1177/13524585211012227. Epub 2021 May 12.
  • PMID: 30105527
    Deeks ED: Cladribine Tablets: A Review in Relapsing MS. CNS Drugs. 2018 Aug;32(8):785-796. doi: 10.1007/s40263-018-0562-0.
  • PMID: 29168160
    Giovannoni G: Cladribine to Treat Relapsing Forms of Multiple Sclerosis. Neurotherapeutics. 2017 Oct;14(4):874-887. doi: 10.1007/s13311-017-0573-4.
  • PMID: 35853850
    Pagano L, Criscuolo M, Broccoli A, Piciocchi A, Varettoni M, Galli E, Anastasia A, Cantonetti M, Trentin L, Kovalchuk S, Orsucci L, Frustaci A, Spolzino A, Volpetti S, Annibali O, Storti S, Stelitano C, Marchesi F, Offidani M, Casadei B, Nizzoli ME, De Luca ML, Fianchi L, Motta M, Guarnera L, Simonetti E, Visentin A, Vassallo F, Deodato M, Sarlo C, Olivieri A, Falini B, Pulsoni A, Tiacci E, Zinzani PL: Long-term follow-up of cladribine treatment in hairy cell leukemia: 30-year experience in a multicentric Italian study. Blood Cancer J. 2022 Jul 19;12(7):109. doi: 10.1038/s41408-022-00702-9.

Contoh Produk & Brand

Produk: 25 • International brands: 3
Produk
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection • 1 mg/1mL • Intravenous • US • Generic • Approved
  • Cladribine
    Injection, solution • 1 mg/1mL • Intravenous • US • Generic • Approved
Menampilkan 8 dari 25 produk.
International Brands
  • Litak
  • Movectro
  • Mylinax

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