Peringatan Keamanan

Minimum lethal dose in rat: 500 mg/kg.
Maximum asymptomatic dose in non human primate: 40 mg/kg.

Lymphatic, immune system, bone marrow and erythroid cell toxicity was seen in animal studies involving rate and monkeys. Doses used in these studies ranged from 1mg/kg/day to 10mg/kg/day, over a duration of 6 weeks to 6 months. Lymphopenia, neutropenia, and anemia is seen in human subjects and may call for an interruption or discontinuation of therapy if severe.

Reduced female fertility in rats was seen at exposures 17 times the maximum recommended human dose. Fertility may be impaired in human females and harm may be caused to unborn child.
Carcinogenic potential is seen, however evidence for dose dependency is lacking.

Because the janus kinase pathway plays a role in stimulating the production of red blood cells and is involved in immune cell function, inhibition of this pathway leads to increased risk of anemia, neutropenia, lymphopenia, cancer and infection.

Lymphopenia, neutropenia, and anemia in human subjects may call for an interruption or discontinuation of therapy if severe.

Role of JAK inhibition in the development of gastrointestinal perforation is not known.

Tofacitinib

DB08895

small molecule approved investigational

Deskripsi

Tofacitinib is an inhibitor of Janus kinases, a group of intracellular enzymes involved in signalling pathways that affect hematopoiesis and immune cell function. It is approved by the FDA for treatment of moderate to severe rheumatoid arthritis that responds inadequately to methotrexate or in those who are intolerant to methotrexate.
Besides rheumatoid arthritis, tofacitinib has also been studied in clinical trials for the prevention of organ transplant rejection, and is currently under investigation for the treatment of psoriasis. Known adverse effects include nausea and headache as well as more serious immunologic and hematological adverse effects. Tofacitinib is marketed under the brand name Xeljanz by Pfizer.

Struktur Molekul 2D

Berat 312.3696
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) ~3 hours
Volume Distribusi Vd= 87L after intravenous administration. Distribution is equal between red blood cells and plasma.
Klirens (Clearance) -

Absorpsi

74% oral absorption (absolute bioavailability), with peak plasma concentrations (T max) achieved in 0.5-1 hour. Administration with fatty meals does not alter AUC but reduces Cmax by 32%.

Metabolisme

Metabolized in the liver by CYP3A4 and CYP2C19. Metabolites produced are inactive.

Rute Eliminasi

70% metabolized in the liver by CYP3A4 (major) and CYP2C19 (minor). Metabolites produced are inactive. 30% renally eliminated as unchanged drug.

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Dose adjustments are required when administering CYP3A4 inhibitors (grapefruit) and CYP2C19 inhibitors with tofacitinib.
  • 2. Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of tofacitinib and may reduce its serum concentration.
  • 3. Take with or without food.

Interaksi Obat

848 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tofacitinib.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Tofacitinib.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Tofacitinib.
Hydroxychloroquine The risk or severity of adverse effects can be increased when Hydroxychloroquine is combined with Tofacitinib.
Natalizumab The risk or severity of immunosuppression can be increased when Tofacitinib is combined with Natalizumab.
Pimecrolimus The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Tofacitinib.
Roflumilast Roflumilast may increase the immunosuppressive activities of Tofacitinib.
Sipuleucel-T The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Tofacitinib.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Tofacitinib.
Rituximab Rituximab may increase the immunosuppressive activities of Tofacitinib.
Ceritinib Tofacitinib may increase the bradycardic activities of Ceritinib.
Ivabradine Tofacitinib may increase the bradycardic activities of Ivabradine.
Fluconazole The metabolism of Tofacitinib can be decreased when combined with Fluconazole.
Clozapine The metabolism of Tofacitinib can be decreased when combined with Clozapine.
Aldesleukin The metabolism of Tofacitinib can be decreased when combined with Aldesleukin.
Octreotide The metabolism of Tofacitinib can be decreased when combined with Octreotide.
Fluvoxamine The metabolism of Tofacitinib can be decreased when combined with Fluvoxamine.
Erythromycin The metabolism of Tofacitinib can be decreased when combined with Erythromycin.
Citalopram The metabolism of Tofacitinib can be decreased when combined with Citalopram.
Nelfinavir The metabolism of Tofacitinib can be decreased when combined with Nelfinavir.
Indinavir The metabolism of Tofacitinib can be decreased when combined with Indinavir.
Ziprasidone The metabolism of Tofacitinib can be decreased when combined with Ziprasidone.
Cabergoline The metabolism of Tofacitinib can be decreased when combined with Cabergoline.
Diethylstilbestrol The metabolism of Tofacitinib can be decreased when combined with Diethylstilbestrol.
Isradipine The metabolism of Tofacitinib can be decreased when combined with Isradipine.
Valproic acid The metabolism of Tofacitinib can be decreased when combined with Valproic acid.
Acetaminophen The metabolism of Tofacitinib can be decreased when combined with Acetaminophen.
Dihydroergotamine The metabolism of Tofacitinib can be decreased when combined with Dihydroergotamine.
Methadone The metabolism of Tofacitinib can be decreased when combined with Methadone.
Terfenadine The metabolism of Tofacitinib can be decreased when combined with Terfenadine.
Diltiazem The metabolism of Tofacitinib can be decreased when combined with Diltiazem.
Methylergometrine The metabolism of Tofacitinib can be decreased when combined with Methylergometrine.
Mefloquine The metabolism of Tofacitinib can be decreased when combined with Mefloquine.
Mirtazapine The metabolism of Tofacitinib can be decreased when combined with Mirtazapine.
Sorafenib The metabolism of Tofacitinib can be decreased when combined with Sorafenib.
Nitric Oxide The metabolism of Tofacitinib can be decreased when combined with Nitric Oxide.
Cerivastatin The metabolism of Tofacitinib can be decreased when combined with Cerivastatin.
Teniposide The metabolism of Tofacitinib can be decreased when combined with Teniposide.
Chloramphenicol The metabolism of Tofacitinib can be decreased when combined with Chloramphenicol.
Lansoprazole The metabolism of Tofacitinib can be decreased when combined with Lansoprazole.
Quinine The metabolism of Tofacitinib can be decreased when combined with Quinine.
Raloxifene The metabolism of Tofacitinib can be decreased when combined with Raloxifene.
Cimetidine The metabolism of Tofacitinib can be decreased when combined with Cimetidine.
Haloperidol The metabolism of Tofacitinib can be decreased when combined with Haloperidol.
Ritonavir The metabolism of Tofacitinib can be decreased when combined with Ritonavir.
Erlotinib The metabolism of Tofacitinib can be decreased when combined with Erlotinib.
Ciprofloxacin The metabolism of Tofacitinib can be decreased when combined with Ciprofloxacin.
Zafirlukast The metabolism of Tofacitinib can be decreased when combined with Zafirlukast.
Vinblastine The metabolism of Tofacitinib can be decreased when combined with Vinblastine.
Fluticasone propionate The metabolism of Tofacitinib can be decreased when combined with Fluticasone propionate.
Thiopental The metabolism of Tofacitinib can be decreased when combined with Thiopental.
Imatinib The metabolism of Tofacitinib can be decreased when combined with Imatinib.
Nicardipine The metabolism of Tofacitinib can be decreased when combined with Nicardipine.
Efavirenz The metabolism of Tofacitinib can be decreased when combined with Efavirenz.
Astemizole The metabolism of Tofacitinib can be decreased when combined with Astemizole.
Dextropropoxyphene The metabolism of Tofacitinib can be decreased when combined with Dextropropoxyphene.
Verapamil The metabolism of Tofacitinib can be decreased when combined with Verapamil.
Epinephrine The metabolism of Tofacitinib can be decreased when combined with Epinephrine.
Aprepitant The metabolism of Tofacitinib can be decreased when combined with Aprepitant.
Tamoxifen The metabolism of Tofacitinib can be decreased when combined with Tamoxifen.
Midazolam The metabolism of Tofacitinib can be decreased when combined with Midazolam.
Daunorubicin The metabolism of Tofacitinib can be decreased when combined with Daunorubicin.
Ergotamine The metabolism of Tofacitinib can be decreased when combined with Ergotamine.
Amprenavir The metabolism of Tofacitinib can be decreased when combined with Amprenavir.
Delavirdine The metabolism of Tofacitinib can be decreased when combined with Delavirdine.
Paroxetine The metabolism of Tofacitinib can be decreased when combined with Paroxetine.
Tranylcypromine The metabolism of Tofacitinib can be decreased when combined with Tranylcypromine.
Tetracycline The metabolism of Tofacitinib can be decreased when combined with Tetracycline.
Methimazole The metabolism of Tofacitinib can be decreased when combined with Methimazole.
Roxithromycin The metabolism of Tofacitinib can be decreased when combined with Roxithromycin.
Phenelzine The metabolism of Tofacitinib can be decreased when combined with Phenelzine.
Propofol The metabolism of Tofacitinib can be decreased when combined with Propofol.
Acetazolamide The metabolism of Tofacitinib can be decreased when combined with Acetazolamide.
Diazepam The metabolism of Tofacitinib can be decreased when combined with Diazepam.
Mifepristone The metabolism of Tofacitinib can be decreased when combined with Mifepristone.
Loperamide Loperamide may increase the bradycardic activities of Tofacitinib.
Clofazimine The metabolism of Tofacitinib can be decreased when combined with Clofazimine.
Tacrolimus The metabolism of Tofacitinib can be decreased when combined with Tacrolimus.
Conivaptan The metabolism of Tofacitinib can be decreased when combined with Conivaptan.
Ethanol The metabolism of Tofacitinib can be decreased when combined with Ethanol.
Quinidine The metabolism of Tofacitinib can be decreased when combined with Quinidine.
Metronidazole The metabolism of Tofacitinib can be decreased when combined with Metronidazole.
Buprenorphine The metabolism of Tofacitinib can be decreased when combined with Buprenorphine.
Tipranavir The metabolism of Tofacitinib can be decreased when combined with Tipranavir.
Isoniazid The metabolism of Tofacitinib can be decreased when combined with Isoniazid.
Dirithromycin The metabolism of Tofacitinib can be decreased when combined with Dirithromycin.
Telithromycin The metabolism of Tofacitinib can be decreased when combined with Telithromycin.
Doxorubicin The metabolism of Tofacitinib can be decreased when combined with Doxorubicin.
Metyrapone The metabolism of Tofacitinib can be decreased when combined with Metyrapone.
Glyburide The metabolism of Tofacitinib can be decreased when combined with Glyburide.
Ketoconazole The metabolism of Tofacitinib can be decreased when combined with Ketoconazole.
Irbesartan The metabolism of Tofacitinib can be decreased when combined with Irbesartan.
Topotecan The metabolism of Tofacitinib can be decreased when combined with Topotecan.
Norfloxacin The metabolism of Tofacitinib can be decreased when combined with Norfloxacin.
Oxybutynin The metabolism of Tofacitinib can be decreased when combined with Oxybutynin.
Mequitazine The metabolism of Tofacitinib can be decreased when combined with Mequitazine.
Atazanavir The metabolism of Tofacitinib can be decreased when combined with Atazanavir.
Primaquine The metabolism of Tofacitinib can be decreased when combined with Primaquine.
Dimethyl sulfoxide The metabolism of Tofacitinib can be decreased when combined with Dimethyl sulfoxide.
Fluvastatin The metabolism of Tofacitinib can be decreased when combined with Fluvastatin.

Target Protein

Tyrosine-protein kinase JAK1 JAK1
Tyrosine-protein kinase JAK2 JAK2
Tyrosine-protein kinase JAK3 JAK3
Non-receptor tyrosine-protein kinase TYK2 TYK2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 26899199
    Papp KA, Krueger JG, Feldman SR, Langley RG, Thaci D, Torii H, Tyring S, Wolk R, Gardner A, Mebus C, Tan H, Luo Y, Gupta P, Mallbris L, Tatulych S: Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. J Am Acad Dermatol. 2016 May;74(5):841-850. doi: 10.1016/j.jaad.2016.01.013. Epub 2016 Feb 19.

Contoh Produk & Brand

Produk: 38 • International brands: 0
Produk
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    Tablet • 5 mg • Oral • Canada • Generic • Approved
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    Tablet • 10 mg • Oral • Canada • Generic • Approved
  • Auro-tofacitinib
    Tablet • 10 mg • Oral • Canada • Generic • Approved
  • Auro-tofacitinib
    Tablet • 5 mg • Oral • Canada • Generic • Approved
  • Jamp Tofacitinib
    Tablet • 5 mg • Oral • Canada • Generic • Approved
  • PMS-tofacitinib
    Tablet • 5 mg • Oral • Canada • Generic • Approved
  • Sandoz Tofacitinib
    Tablet • 5 mg • Oral • Canada • Generic • Approved
  • Sandoz Tofacitinib
    Tablet • 10 mg • Oral • Canada • Generic • Approved
Menampilkan 8 dari 38 produk.

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