Peringatan Keamanan

No information regarding the acute toxicity profile and LD50 of deucravacitinib is available. There is no experience regarding human overdosage with deucravacitinib. There is no known antidote for deucravacitinib overdose and hemodialysis is unlikely to be effective, as the extent of deucravacitinib elimination by hemodialysis is small (5.4% of dose per dialysis treatment).L43150

Deucravacitinib

DB16650

small molecule approved investigational

Deskripsi

Deucravacitinib is a novel oral selective tyrosine kinase 2 (TYK2) inhibitor. Unlike other Janus kinase 1/2/3 inhibitors that bind to the conserved active domain of these non-receptor tyrosine kinases, deucravacitinib binds to the regulatory domain of TYK2 with high selectivity to this therapeutic target.A246938, A246943 This selectivity towards TYK2 may lead to an improved safety profile of deucravacitinib, as nonselective JAK inhibitors are associated with a range of adverse effects such as altered cholesterol and triglyceride levels and liver and kidney dysfunction.A246943

Deucravacitinib was first approved by the FDA in September 2022 to treat moderate-to-severe plaque psoriasis.L43150 It was later approved by Health Canada in November 2022 L44216 and by the European Medicines Agency in March 2023.L45788

Struktur Molekul 2D

Berat 425.467
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 deucravacitinib was 10 hours.[L43150]
Volume Distribusi The volume of distribution of deucravacitinib at steady state is 140 L.[L43150]
Klirens (Clearance) The renal clearance of deucravacitinib ranged from 27 to 54 mL/minute.[L43150]

Absorpsi

Following oral administration, deucravacitinib plasma Cmax and AUC increased proportionally over a dose range from 3 mg to 36 mg (0.5 to 6 times the approved recommended dosage) in healthy subjects. The steady state Cmax and AUC24 of deucravacitinib following administration of 6 mg once daily were 45 ng/mL and 473 ng x hr/mL, respectively. The steady state Cmax and AUC24 of the active deucravacitinib metabolite, BMT-153261, following administration of 6 mg once daily were 5 ng/mL and 95 ng x hr/mL, respectively. The absolute oral bioavailability of deucravacitinib was 99% and the median Tmax ranged from two to three hours.L43150 A high-fat, high-calorie meal decreased Cmax and AUC of deucravacitinib by 24% and 11%, respectively, and prolonged Tmax by one hour; however, this has clinically significant effects on drug absorption and exposure.L43150

Metabolisme

Deucravacitinib undergoes N-demethylation mediated by cytochrome P-450 (CYP) 1A2 to form major metabolite BMT-153261, which has a comparable pharmacological activity to the parent drug. However, the circulating exposure of BMT-153261 accounts for approximately 20% of the systemic exposure of the total drug-related components. Deucravacitinib is also metabolized by CYP2B6, CYP2D6, carboxylesterase (CES) 2, and uridine glucuronyl transferase (UGT) 1A9.L43150

Rute Eliminasi

After a single dose of radiolabeled deucravacitinib, approximately 13% and 26% of the dose was recovered as unchanged in urine and feces, respectively. Approximately 6% and 12% of the dose was detected as BMT-153261 in urine and feces, respectively.L43150

Interaksi Makanan

1 Data
  • 1. Take with or without food. Food has no clinically significant effect on drug absorption and exposure.

Interaksi Obat

378 Data
Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Deucravacitinib.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Deucravacitinib.
Salmon calcitonin The therapeutic efficacy of Salmon calcitonin can be decreased when used in combination with Deucravacitinib.
Thyrotropin alfa The therapeutic efficacy of Thyrotropin alfa can be decreased when used in combination with Deucravacitinib.
Follitropin The therapeutic efficacy of Follitropin can be decreased when used in combination with Deucravacitinib.
Liothyronine The therapeutic efficacy of Liothyronine can be decreased when used in combination with Deucravacitinib.
Carbimazole The therapeutic efficacy of Carbimazole can be decreased when used in combination with Deucravacitinib.
Levothyroxine The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Deucravacitinib.
Propylthiouracil The therapeutic efficacy of Propylthiouracil can be decreased when used in combination with Deucravacitinib.
Methimazole The therapeutic efficacy of Methimazole can be decreased when used in combination with Deucravacitinib.
Liotrix The therapeutic efficacy of Liotrix can be decreased when used in combination with Deucravacitinib.
3,5-Diiodotyrosine The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Deucravacitinib.
Tiratricol The therapeutic efficacy of Tiratricol can be decreased when used in combination with Deucravacitinib.
Parathyroid hormone The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Deucravacitinib.
Teriparatide The therapeutic efficacy of Teriparatide can be decreased when used in combination with Deucravacitinib.
Potassium Iodide The therapeutic efficacy of Potassium Iodide can be decreased when used in combination with Deucravacitinib.
Dibromotyrosine The therapeutic efficacy of Dibromotyrosine can be decreased when used in combination with Deucravacitinib.
Thyroid, porcine The therapeutic efficacy of Thyroid, porcine can be decreased when used in combination with Deucravacitinib.
Potassium perchlorate The therapeutic efficacy of Potassium perchlorate can be decreased when used in combination with Deucravacitinib.
Protirelin The therapeutic efficacy of Protirelin can be decreased when used in combination with Deucravacitinib.
3,5-diiodothyropropionic acid The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Deucravacitinib.
Methylthiouracil The therapeutic efficacy of Methylthiouracil can be decreased when used in combination with Deucravacitinib.
Elcatonin The therapeutic efficacy of Elcatonin can be decreased when used in combination with Deucravacitinib.
Benzylthiouracil The therapeutic efficacy of Benzylthiouracil can be decreased when used in combination with Deucravacitinib.
Thyrotropin The therapeutic efficacy of Thyrotropin can be decreased when used in combination with Deucravacitinib.
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Deucravacitinib.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Deucravacitinib.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Deucravacitinib.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Deucravacitinib.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Deucravacitinib.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Deucravacitinib.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Deucravacitinib.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Deucravacitinib.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Deucravacitinib.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Deucravacitinib.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Deucravacitinib.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Deucravacitinib.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Deucravacitinib.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Deucravacitinib.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Deucravacitinib.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Deucravacitinib.
Trastuzumab The risk or severity of neutropenia can be increased when Trastuzumab is combined with Deucravacitinib.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Deucravacitinib.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Deucravacitinib.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Deucravacitinib.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Deucravacitinib.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Deucravacitinib.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Deucravacitinib.
Cyclosporine Deucravacitinib may increase the immunosuppressive activities of Cyclosporine.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Deucravacitinib.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Deucravacitinib.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Deucravacitinib.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Deucravacitinib.
Natalizumab The risk or severity of immunosuppression can be increased when Deucravacitinib is combined with Natalizumab.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Deucravacitinib.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Deucravacitinib.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Deucravacitinib.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Deucravacitinib.
Cladribine Deucravacitinib may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Deucravacitinib.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Deucravacitinib.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Deucravacitinib.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Deucravacitinib.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Deucravacitinib.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Deucravacitinib.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Deucravacitinib.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Deucravacitinib.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Deucravacitinib.
Fluorometholone The risk or severity of adverse effects can be increased when Fluorometholone is combined with Deucravacitinib.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Deucravacitinib.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Deucravacitinib.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Deucravacitinib.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Deucravacitinib.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Deucravacitinib.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Deucravacitinib.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Deucravacitinib.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Deucravacitinib.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Deucravacitinib.
Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Deucravacitinib.
Teniposide The risk or severity of adverse effects can be increased when Teniposide is combined with Deucravacitinib.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Deucravacitinib.
Chloramphenicol The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Deucravacitinib.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Deucravacitinib.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Deucravacitinib.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Deucravacitinib.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Deucravacitinib.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Deucravacitinib.
Cyclophosphamide The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Deucravacitinib.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Deucravacitinib.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Deucravacitinib.
Desoximetasone The risk or severity of adverse effects can be increased when Desoximetasone is combined with Deucravacitinib.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Deucravacitinib.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Deucravacitinib.
Carbamazepine The risk or severity of adverse effects can be increased when Carbamazepine is combined with Deucravacitinib.
Vinblastine The risk or severity of adverse effects can be increased when Vinblastine is combined with Deucravacitinib.
Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Deucravacitinib.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Deucravacitinib.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Deucravacitinib.
Imatinib The risk or severity of adverse effects can be increased when Imatinib is combined with Deucravacitinib.
Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Deucravacitinib.

Target Protein

Non-receptor tyrosine-protein kinase TYK2 TYK2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 35241426
    Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, Kim J, Singhal S, Nowak M, Banerjee S: Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022 Mar 3. pii: annrheumdis-2021-221664. doi: 10.1136/annrheumdis-2021-221664.
  • PMID: 34471993
    Chimalakonda A, Burke J, Cheng L, Catlett I, Tagen M, Zhao Q, Patel A, Shen J, Girgis IG, Banerjee S, Throup J: Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors. Dermatol Ther (Heidelb). 2021 Oct;11(5):1763-1776. doi: 10.1007/s13555-021-00596-8. Epub 2021 Aug 30.
  • PMID: 34767869
    Catlett IM, Hu Y, Gao L, Banerjee S, Gordon K, Krueger JG: Molecular and clinical effects of selective tyrosine kinase 2 inhibition with deucravacitinib in psoriasis. J Allergy Clin Immunol. 2021 Nov 10. pii: S0091-6749(21)01690-0. doi: 10.1016/j.jaci.2021.11.001.
  • PMID: 35960487
    Le AM, Puig L, Torres T: Deucravacitinib for the Treatment of Psoriatic Disease. Am J Clin Dermatol. 2022 Aug 12. pii: 10.1007/s40257-022-00720-0. doi: 10.1007/s40257-022-00720-0.

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