Peringatan Keamanan

Currently, an MSDS for diroximel fumarate is unavailable. The MSDS for its bioequivalent counterpart, dimethyl fumarate, indicates an oral LD50 of 2,240 mg/kg in rats.MSDS

There is no information regarding overdose on the FDA label for diroximel fumarate. Cases of overdose with its bioequivalent counterpart, dimethyl fumarate, have been reported in the literature, and symptoms reflect the adverse effects of this drug. These symptoms include nausea, vomiting, diarrhea, and flushing, among others.L9632,L9638 Currently there is no antidote to an overdose with diroximel fumarate or dimethyl fumarate. Symptomatic and supportive management are the only options up to this date if an overdose should occur.L9638

Diroximel fumarate

DB14783

small molecule approved investigational

Deskripsi

Multiple Sclerosis (MS) is a chronic, debilitating neurological disease that can lead to profound cognitive and physical symptoms, severely affecting quality of life.A176474 It is the main cause of neurological disability not caused by trauma in the young adult population of both North America and Europe. Relapsing-remitting forms of MS lead to neurological symptoms that resolve and recur periodically. More than 80% of patients suffering from this disease have relapsing-remitting MS.A187535

Diroximel fumarate is a new drug from the fumarate class formulated to treat various relapsing forms of MS. This drug is bioequivalent to Dimethyl fumarateA187544,L9626(initially manufactured in 2013), but is less likely to cause gastrointestinal side effects, owing to its unique chemical structure. Diroximel fumarate was formulated by Alkermes in collaboration with Biogen, and was approved by the FDA in October 2019L9626 and by the EMA in November 2021.L39225

Struktur Molekul 2D

Berat 255.226
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 monomethyl fumarate (MMF), diroximel fumarate's active metabolite, is estimated to be 1 hour.[A187544,L9623]
Volume Distribusi The apparent volume of distribution ranges from 72L to 83L.[L9623] Monomethyl fumarate (MMF), the active metabolite of diroximel fumarate, crosses the blood brain barrier.[A187529]
Klirens (Clearance) No clearance information is available on the FDA label for diroximel fumarate[L9623], however, clinical study results for its active metabolite, monomethyl fumarate show a mean apparent total clearance from the plasma after oral administration of 1.54 mgL?1.[A187544]

Absorpsi

Diroximel fumarate is rapidly absorbed in the gastrointestinal tract following administration, like its bioequivalent drug, dimethyl fumarate.A187544 The median Tmax of monomethyl fumarate (MMF) after oral administration ranges from 2.5-3 hours with a mean Cmax of 2.11 mg/LL9623. The bioequivalent drug, dimethyl fumarate, administered to healthy volunteers also shows a similar mean Tmax and Cmax.A187544 The average steady state concentration of this metabolite is estimated at 8.32 mg.hr/L after it is administered twice a day in patients with MS.L9623 The mean AUC0–? of the active metabolite is 88mg × min L?1. Food appears to significantly reduce the Cmax of diroximel fumarate's active metabolite, MMF, when compared to administration in the fasted state.A187544,L9623

Metabolisme

Esterases heavily metabolize diroximel fumarate, as well as its bioequivalent drug, dimethyl fumarate, in the liver.A187544 These enzymes are present in high quantities in the gastrointestinal tract, tissues, and blood. Esterase metabolism of this drug produces the active metabolite, mono methyl fumarate (MMF), before it moves to the systemic circulation. In addition, the major inactive metabolite, 2-hydroxyethyl succinimide (HES) is produced along with small amounts of methanol, and another inactive metabolite, RDC-8439.A187532,L9623 Following esterase metabolism, the tricarboxylic acid (TCA)cycle further metabolizes MMF. The major metabolites of MMF in plasma include fumaric acid, citric acid, and glucose.A187544,L9623 It is important that methanol is a major metabolite of dimethyl fumarate metabolism, but a minor metabolite of diroximel fumarate metabolism, conferring its lower risk of gastrointestinal effects.A187532

Rute Eliminasi

Monomethyl fumarate is eliminated as carbon dioxide through expired breath. Negligible amounts, under 0.3% of the ingested dose, are measured in urine.L9623 The inactive metabolite, 2-hydroxyethyl succinimide (HES), representing 58-63% of the ingested dose, is excreted in urine.L9623

Interaksi Makanan

2 Data
  • 1. Avoid alcohol.
  • 2. Take with or without food. If taken with food, the meal/snack should contain no more than 700 calories and no more than 30 g fat. Taking diroximel fumarate with food may reduce the adverse effect of flushing.

Interaksi Obat

355 Data
Pexidartinib Diroximel fumarate may increase the hepatotoxic activities of Pexidartinib.
Dimethyl fumarate The serum concentration of Monomethyl fumarate, an active metabolite of Diroximel fumarate, can be increased when used in combination with Dimethyl fumarate.
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Diroximel fumarate.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Diroximel fumarate.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Diroximel fumarate.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Diroximel fumarate.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Diroximel fumarate.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Diroximel fumarate.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Diroximel fumarate.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Diroximel fumarate.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Diroximel fumarate.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Diroximel fumarate.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Diroximel fumarate.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Diroximel fumarate.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Diroximel fumarate.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Diroximel fumarate.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Diroximel fumarate.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Diroximel fumarate.
Trastuzumab The risk or severity of neutropenia can be increased when Trastuzumab is combined with Diroximel fumarate.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Diroximel fumarate.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Diroximel fumarate.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Diroximel fumarate.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Diroximel fumarate.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Diroximel fumarate.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Diroximel fumarate.
Cyclosporine Diroximel fumarate may increase the immunosuppressive activities of Cyclosporine.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Diroximel fumarate.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Diroximel fumarate.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Diroximel fumarate.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Diroximel fumarate.
Natalizumab The risk or severity of immunosuppression can be increased when Diroximel fumarate is combined with Natalizumab.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Diroximel fumarate.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Diroximel fumarate.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Diroximel fumarate.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Diroximel fumarate.
Cladribine Diroximel fumarate may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Diroximel fumarate.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Diroximel fumarate.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Diroximel fumarate.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Diroximel fumarate.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Diroximel fumarate.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Diroximel fumarate.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Diroximel fumarate.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Diroximel fumarate.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Diroximel fumarate.
Fluorometholone The risk or severity of adverse effects can be increased when Fluorometholone is combined with Diroximel fumarate.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Diroximel fumarate.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Diroximel fumarate.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Diroximel fumarate.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Diroximel fumarate.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Diroximel fumarate.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Diroximel fumarate.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Diroximel fumarate.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Diroximel fumarate.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Diroximel fumarate.
Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Diroximel fumarate.
Teniposide The risk or severity of adverse effects can be increased when Teniposide is combined with Diroximel fumarate.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Diroximel fumarate.
Chloramphenicol The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Diroximel fumarate.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Diroximel fumarate.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Diroximel fumarate.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Diroximel fumarate.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Diroximel fumarate.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Diroximel fumarate.
Cyclophosphamide The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Diroximel fumarate.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Diroximel fumarate.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Diroximel fumarate.
Desoximetasone The risk or severity of adverse effects can be increased when Desoximetasone is combined with Diroximel fumarate.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Diroximel fumarate.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Diroximel fumarate.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Diroximel fumarate.
Carbamazepine The risk or severity of adverse effects can be increased when Carbamazepine is combined with Diroximel fumarate.
Vinblastine The risk or severity of adverse effects can be increased when Vinblastine is combined with Diroximel fumarate.
Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Diroximel fumarate.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Diroximel fumarate.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Diroximel fumarate.
Imatinib The risk or severity of adverse effects can be increased when Imatinib is combined with Diroximel fumarate.
Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Diroximel fumarate.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Diroximel fumarate.
Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Diroximel fumarate.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Diroximel fumarate.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Diroximel fumarate.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Diroximel fumarate.
Daunorubicin The risk or severity of adverse effects can be increased when Daunorubicin is combined with Diroximel fumarate.
Irinotecan The risk or severity of adverse effects can be increased when Irinotecan is combined with Diroximel fumarate.
Methimazole The risk or severity of adverse effects can be increased when Methimazole is combined with Diroximel fumarate.
Mometasone The risk or severity of adverse effects can be increased when Mometasone is combined with Diroximel fumarate.
Etoposide The risk or severity of adverse effects can be increased when Etoposide is combined with Diroximel fumarate.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Diroximel fumarate.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Diroximel fumarate.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Diroximel fumarate.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Diroximel fumarate.
Prednisolone The risk or severity of adverse effects can be increased when Prednisolone is combined with Diroximel fumarate.
Tacrolimus Tacrolimus may increase the immunosuppressive activities of Diroximel fumarate.
Sirolimus The risk or severity of adverse effects can be increased when Sirolimus is combined with Diroximel fumarate.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Diroximel fumarate.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Diroximel fumarate.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Diroximel fumarate.
Methylprednisolone The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Diroximel fumarate.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Diroximel fumarate.

Target Protein

Neuronal acetylcholine receptor subunit alpha-10 CHRNA10

Referensi & Sumber

Synthesis reference: Adv Ther (2019) 36:3154–3165 https://doi.org/10.1007/s12325-019-01085-3
Artikel (PubMed)
  • PMID: 29410647
    Mills EA, Ogrodnik MA, Plave A, Mao-Draayer Y: Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis. Front Neurol. 2018 Jan 23;9:5. doi: 10.3389/fneur.2018.00005. eCollection 2018.
  • PMID: 31538304
    Palte MJ, Wehr A, Tawa M, Perkin K, Leigh-Pemberton R, Hanna J, Miller C, Penner N: Improving the Gastrointestinal Tolerability of Fumaric Acid Esters: Early Findings on Gastrointestinal Events with Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis from the Phase 3, Open-Label EVOLVE-MS-1 Study. Adv Ther. 2019 Nov;36(11):3154-3165. doi: 10.1007/s12325-019-01085-3. Epub 2019 Sep 19.
  • PMID: 28367411
    Ghasemi N, Razavi S, Nikzad E: Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017 Apr-Jun;19(1):1-10. Epub 2016 Dec 21.
  • PMID: 24722325
    Dutta R, Trapp BD: Relapsing and progressive forms of multiple sclerosis: insights from pathology. Curr Opin Neurol. 2014 Jun;27(3):271-8. doi: 10.1097/WCO.0000000000000094.
  • PMID: 24139424
    Sheikh SI, Nestorov I, Russell H, O'Gorman J, Huang R, Milne GL, Scannevin RH, Novas M, Dawson KT: Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers. Clin Ther. 2013 Oct;35(10):1582-1594.e9. doi: 10.1016/j.clinthera.2013.08.009.
  • PMID: 15373936
    Litjens NH, Burggraaf J, van Strijen E, van Gulpen C, Mattie H, Schoemaker RC, van Dissel JT, Thio HB, Nibbering PH: Pharmacokinetics of oral fumarates in healthy subjects. Br J Clin Pharmacol. 2004 Oct;58(4):429-32. doi: 10.1111/j.1365-2125.2004.02145.x.

Contoh Produk & Brand

Produk: 3 • International brands: 0
Produk
  • Vumerity
    Capsule • 231 mg/1 • Oral • US • Approved
  • Vumerity
    Capsule, delayed release • 231 mg • Oral • EU • Approved
  • Vumerity
    Capsule, delayed release • 231 mg • Oral • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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