Peringatan Keamanan

Data regarding the toxicity of acalabrutinib is not readily available.L10241

Acalabrutinib

DB11703

small molecule approved investigational

Deskripsi

To date, acalabrutinib has been used in trials studying the treatment of B-All, myelofibrosis, ovarian cancer, multiple myeloma, and Hodgkin lymphoma, among others.

As of October 31, 2017 the FDA approved Astra Zeneca's orally administered Calquence (acalabrutinib, capsules). This Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, and in adult patients with Mantle cell lymphoma (MCL) who have already received at least one prior therapy.L10241 In August 2022, the FDA approved a new tablet formulation of Calquence, enabling the co-administration of this drug with proton pump inhibitors (PPIs).L42795,L42800 Unlike Calquence capsules, the co-administration of Calquence tablets and PPIs does not have an effect in the pharmacokinetics of acalabrutinib.L10241,L42795

Also known as ACP-196, acalabrutinib is also considered a second generation BTK inhibitor because it was rationally designed to be more potent and selective than ibrutinib, theoretically expected to demonstrate fewer adverse effects owing to minimized bystander effects on targets other than BTK.

Nevertheless, acalabrutinib was approved under the FDA's accelerated approval pathway, which is based upon overall response rate and faciliates earlier approval of medicines that treat serious conditions or/and that fill an unmet medical need based on a surrogate endpoint. Continued approval for acalabrutinib's currently accepted indication may subsequently be contingent upon ongoing verification and description of clinical benefit in confimatory trials.

Furthermore, the FDA granted this medication Priority Review and Breakthrough Therapy designations. It also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. At this time, more than 35 clinical trials across 40 countries with more than 2500 patients are underway or have been completed with regards to further research into better understanding and expanding the therapeutic uses of acalabrutinib L1009.

Struktur Molekul 2D

Berat 465.517
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) After administering a single oral dose of 100 mg acalabrutinib, the median terminal elimination half-life of the drug was found to be 0.9 (with a range of 0.6 to 2.8) hours.[L10241] The half-life of the active metabolite, ACP-5862, is about 6.9 hours.[L10241]
Volume Distribusi The mean steady-state volume of distribution is approximately 34 L.[L10241]
Klirens (Clearance) Acalabrutinib's mean apparent oral clearance (CL/F) is observed to be 159 L/hr with similar PK between patients and healthy subjects, based on population PK analysis.[L10241]

Absorpsi

The geometric mean absolute bioavailability of acalabrutinib is 25% with a median time to peak plasma concentrations (Tmax) of 0.75 hours.L10241

Metabolisme

Acalabrutinib is mainly metabolized by CYP3A enzymes. ACP-5862 is identified to be the major active metabolite in plasma with a geometric mean exposure (AUC) that is about 2-3 times greater than the exposure of acalabrutinib. ACP-5862 is about 50% less potent than acalabrutinib in regards to the inhibition of BTK.L10241

Rute Eliminasi

After administration of a single 100 mg radiolabelled acalabrutinib dose in healthy subjects, 84% of the dose was recovered in the feces and 12% of the dose was recovered in the urine.L10241 An irradiated dose of acalabrutinib was 34.7% recovered as the metabolite ACP-5862; 8.6% was recovered as unchanged acalabrutinub; 10.8 was recovered as a mixture of the M7, M8, M9, M10, and M11 metabolites; 5.9% was the M25 metabolite; 2.5% was recovered as the M3 metabolite.A188027

Interaksi Makanan

5 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of acalabrutinib. Dose adjustment may be necessary if co-administered.
  • 2. Exercise caution with St. John's Wort. The official product labeling recommends avoiding strong CYP3A4 inducers. This herb induces CYP3A metabolism and may reduce serum levels of acalabrutinib.
  • 3. Take separate from antacids. Take at least 2 hours before or after antacids.
  • 4. Take with a full glass of water.
  • 5. Take with or without food.

Interaksi Obat

628 Data
Modafinil The metabolism of Acalabrutinib can be increased when combined with Modafinil.
Armodafinil The metabolism of Acalabrutinib can be increased when combined with Armodafinil.
Lomitapide The metabolism of Lomitapide can be decreased when combined with Acalabrutinib.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Acalabrutinib.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Acalabrutinib.
Cilostazol The metabolism of Cilostazol can be decreased when combined with Acalabrutinib.
Colchicine The metabolism of Colchicine can be decreased when combined with Acalabrutinib.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Acalabrutinib.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Acalabrutinib.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Acalabrutinib.
Vardenafil The metabolism of Vardenafil can be decreased when combined with Acalabrutinib.
Eszopiclone The metabolism of Eszopiclone can be decreased when combined with Acalabrutinib.
Zopiclone The metabolism of Zopiclone can be decreased when combined with Acalabrutinib.
Lovastatin The metabolism of Lovastatin can be decreased when combined with Acalabrutinib.
Metreleptin The metabolism of Acalabrutinib can be increased when combined with Metreleptin.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Acalabrutinib.
Alfuzosin The metabolism of Alfuzosin can be decreased when combined with Acalabrutinib.
Alprazolam The metabolism of Alprazolam can be decreased when combined with Acalabrutinib.
Warfarin The serum concentration of Warfarin can be increased when it is combined with Acalabrutinib.
Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Acalabrutinib.
(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Acalabrutinib.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Acalabrutinib.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Acalabrutinib.
(S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Acalabrutinib.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Acalabrutinib.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Acalabrutinib.
Crizotinib The metabolism of Acalabrutinib can be decreased when combined with Crizotinib.
Atorvastatin The metabolism of Atorvastatin can be decreased when combined with Acalabrutinib.
Pitolisant The serum concentration of Acalabrutinib can be decreased when it is combined with Pitolisant.
Aripiprazole The metabolism of Aripiprazole can be decreased when combined with Acalabrutinib.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be decreased when combined with Acalabrutinib.
Bexarotene The metabolism of Acalabrutinib can be increased when combined with Bexarotene.
Bosentan The metabolism of Acalabrutinib can be increased when combined with Bosentan.
Nafcillin The metabolism of Acalabrutinib can be increased when combined with Nafcillin.
Etravirine The metabolism of Acalabrutinib can be increased when combined with Etravirine.
Avasimibe The metabolism of Acalabrutinib can be increased when combined with Avasimibe.
Echinacea The metabolism of Acalabrutinib can be increased when combined with Echinacea.
Dexamethasone acetate The metabolism of Acalabrutinib can be increased when combined with Dexamethasone acetate.
Asunaprevir The metabolism of Acalabrutinib can be increased when combined with Asunaprevir.
Rufinamide The metabolism of Acalabrutinib can be increased when combined with Rufinamide.
Alpelisib The metabolism of Acalabrutinib can be increased when combined with Alpelisib.
Topiramate The metabolism of Acalabrutinib can be increased when combined with Topiramate.
Rifabutin The metabolism of Acalabrutinib can be increased when combined with Rifabutin.
Felbamate The metabolism of Acalabrutinib can be increased when combined with Felbamate.
Genistein The metabolism of Acalabrutinib can be increased when combined with Genistein.
Oritavancin The metabolism of Acalabrutinib can be increased when combined with Oritavancin.
Glycerol phenylbutyrate The metabolism of Acalabrutinib can be increased when combined with Glycerol phenylbutyrate.
Eslicarbazepine acetate The metabolism of Acalabrutinib can be increased when combined with Eslicarbazepine acetate.
Lesinurad The metabolism of Acalabrutinib can be increased when combined with Lesinurad.
Sarilumab The metabolism of Acalabrutinib can be increased when combined with Sarilumab.
Esketamine The metabolism of Acalabrutinib can be increased when combined with Esketamine.
Isavuconazole The metabolism of Acalabrutinib can be increased when combined with Isavuconazole.
Acetaminophen The metabolism of Acalabrutinib can be increased when combined with Acetaminophen.
Cerivastatin The metabolism of Acalabrutinib can be increased when combined with Cerivastatin.
Quinine The metabolism of Acalabrutinib can be increased when combined with Quinine.
Cyclophosphamide The metabolism of Acalabrutinib can be increased when combined with Cyclophosphamide.
Testosterone The metabolism of Acalabrutinib can be increased when combined with Testosterone.
Tamoxifen The metabolism of Acalabrutinib can be increased when combined with Tamoxifen.
Hydrocortisone The metabolism of Acalabrutinib can be increased when combined with Hydrocortisone.
Mifepristone The metabolism of Acalabrutinib can be increased when combined with Mifepristone.
Nifedipine The metabolism of Nifedipine can be decreased when combined with Acalabrutinib.
Ifosfamide The metabolism of Acalabrutinib can be increased when combined with Ifosfamide.
Perampanel The metabolism of Acalabrutinib can be increased when combined with Perampanel.
Fluticasone furoate The serum concentration of Fluticasone furoate can be increased when it is combined with Acalabrutinib.
Fluticasone The metabolism of Acalabrutinib can be increased when combined with Fluticasone.
Estradiol acetate The metabolism of Acalabrutinib can be increased when combined with Estradiol acetate.
Estradiol benzoate The metabolism of Acalabrutinib can be increased when combined with Estradiol benzoate.
Estradiol cypionate The metabolism of Acalabrutinib can be increased when combined with Estradiol cypionate.
Estradiol dienanthate The metabolism of Acalabrutinib can be increased when combined with Estradiol dienanthate.
Estradiol valerate The metabolism of Acalabrutinib can be increased when combined with Estradiol valerate.
Hydrocortisone acetate The metabolism of Acalabrutinib can be increased when combined with Hydrocortisone acetate.
Chlorpromazine The metabolism of Acalabrutinib can be increased when combined with Chlorpromazine.
Triamcinolone The metabolism of Acalabrutinib can be increased when combined with Triamcinolone.
Fosaprepitant The metabolism of Acalabrutinib can be increased when combined with Fosaprepitant.
Calcitriol The metabolism of Acalabrutinib can be increased when combined with Calcitriol.
Vitamin E The metabolism of Acalabrutinib can be increased when combined with Vitamin E.
Flunisolide The metabolism of Acalabrutinib can be increased when combined with Flunisolide.
Troglitazone The metabolism of Acalabrutinib can be increased when combined with Troglitazone.
Butalbital The metabolism of Acalabrutinib can be increased when combined with Butalbital.
Flucloxacillin The metabolism of Acalabrutinib can be increased when combined with Flucloxacillin.
Clobazam The metabolism of Acalabrutinib can be increased when combined with Clobazam.
Aminoglutethimide The metabolism of Acalabrutinib can be increased when combined with Aminoglutethimide.
Beclomethasone dipropionate The metabolism of Acalabrutinib can be increased when combined with Beclomethasone dipropionate.
Griseofulvin The metabolism of Acalabrutinib can be increased when combined with Griseofulvin.
Secobarbital The metabolism of Acalabrutinib can be increased when combined with Secobarbital.
Betamethasone The metabolism of Acalabrutinib can be increased when combined with Betamethasone.
Dicloxacillin The metabolism of Acalabrutinib can be increased when combined with Dicloxacillin.
Rofecoxib The metabolism of Acalabrutinib can be increased when combined with Rofecoxib.
Vinblastine The metabolism of Acalabrutinib can be increased when combined with Vinblastine.
Fluocinolone acetonide The metabolism of Acalabrutinib can be increased when combined with Fluocinolone acetonide.
Medroxyprogesterone acetate The metabolism of Acalabrutinib can be increased when combined with Medroxyprogesterone acetate.
Clofibrate The metabolism of Acalabrutinib can be increased when combined with Clofibrate.
Hydrocortamate The metabolism of Acalabrutinib can be increased when combined with Hydrocortamate.
Oxcarbazepine The metabolism of Acalabrutinib can be increased when combined with Oxcarbazepine.
Phenylbutazone The metabolism of Acalabrutinib can be increased when combined with Phenylbutazone.
Methylphenobarbital The metabolism of Acalabrutinib can be increased when combined with Methylphenobarbital.
Terbinafine The metabolism of Acalabrutinib can be increased when combined with Terbinafine.
Prednisolone The metabolism of Acalabrutinib can be increased when combined with Prednisolone.
Ethanol The metabolism of Acalabrutinib can be increased when combined with Ethanol.
Norgestimate The metabolism of Acalabrutinib can be increased when combined with Norgestimate.

Target Protein

Tyrosine-protein kinase BTK BTK

Referensi & Sumber

Artikel (PubMed)
  • PMID: 26957112
    Wu J, Zhang M, Liu D: Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016 Mar 9;9:21. doi: 10.1186/s13045-016-0250-9.
  • PMID: 26755518
    Cheah CY, Seymour JF, Wang ML: Mantle Cell Lymphoma. J Clin Oncol. 2016 Apr 10;34(11):1256-69. doi: 10.1200/JCO.2015.63.5904. Epub 2016 Jan 11.
  • PMID: 30442651
    Podoll T, Pearson PG, Evarts J, Ingallinera T, Bibikova E, Sun H, Gohdes M, Cardinal K, Sanghvi M, Slatter JG: Bioavailability, Biotransformation, and Excretion of the Covalent Bruton Tyrosine Kinase Inhibitor Acalabrutinib in Rats, Dogs, and Humans. Drug Metab Dispos. 2019 Feb;47(2):145-154. doi: 10.1124/dmd.118.084459. Epub 2018 Nov 15.

Contoh Produk & Brand

Produk: 8 • International brands: 0
Produk
  • Calquence
    Tablet, film coated • 100 mg • Oral • EU • Approved
  • Calquence
    Tablet, film coated • 100 mg • Oral • EU • Approved
  • Calquence
    Tablet • 100 mg • Oral • Canada • Approved
  • Calquence
    Capsule • 100 mg • Oral • EU • Approved
  • Calquence
    Capsule • 100 mg • Oral • EU • Approved
  • Calquence
    Tablet, film coated • 100 mg/1 • Oral • US • Approved
  • Calquence
    Capsule • 100 mg • Oral • Canada • Approved
  • Calquence
    Capsule, gelatin coated • 100 mg/1 • Oral • US • Approved

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