Peringatan Keamanan

Based on findings in animals and mechanism of action, capivasertib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of capivasertib in pregnant women. In an animal reproduction study, oral administration of capivasertib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality and reduced fetal weights at maternal exposures 0.7 times the human exposure (AUC) at the recommended dose of 400 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.L48691

Carcinogenicity studies have not been conducted with capivasertib. Capivasertib was genotoxic in the in vivo rat bone marrow micronucleus assay through an aneugenic mechanism. Capivasertib was not mutagenic in vitro in a bacterial reverse mutation (Ames) assay or mouse lymphoma gene mutation assay.L48691

In repeat-dose toxicity studies up to 26 weeks duration in rats and 39 weeks duration in dogs, tubular degeneration in the testes and cellular debris in the epididymides were observed at oral capivasertib doses of 100 mg/kg/day in rats and 15 mg/kg/day in dogs (approximately 1 time the human exposure at the recommended dose of 400 mg twice daily based on AUC). In a male fertility study, capivasertib had no effect on fertility in male rats at oral doses up to 100 mg/kg/day following 10 weeks of treatment. Effects
of capivasertib on female fertility have not been studied in animals.L48691

Capivasertib

DB12218

small molecule approved investigational

Deskripsi

Hormone receptor (HR) positive, especially estrogen receptor-positive, HER2-negative breast cancer is the most common subtype of metastatic breast cancer, resulting in more than 400,000 deaths annually. Although endocrine-based therapy is the first line of treatment, resistance eventually emerges, leaving chemotherapy the only but often ineffective treatment left. Therefore, significant research has been put into developing genetically targeted treatments.A262021

The PIK3/AKT pathway is one of the most commonly activated pathways in breast cancer, mainly through the constitutively active mutation in AKT1, loss of function mutation in PTEN, a negative regulator of the PIK3/AKT pathway, or PIK3CA mutations. Therefore, targeting the PIK3/AKT pathway presents a promising approach for the treatment of breast cancer, leading to the development of capivasertib, a pan-AKT kinase inhibitor.A262021,A262026,A262031

On November 17th, 2023, capivasertib, under the brand name TRUQAP, was approved by the FDA for the treatment of adult patients HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more alterations in PIK3CA/AKT1/PTEN gene(s) in combination with fulvestrant. This approval is based on favorable results obtained from the CAPItello-291 trial, where the combination of capivasertib and fulvestrant reduced the risk of disease progression or death by 50% versus fulvestrant alone.L48706

Struktur Molekul 2D

Berat 428.915
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half-life of capivasertib is 8.3 hours.[L48691]
Volume Distribusi The steady-state oral volume of distribution is 1,847 L (36%).[L48691]
Klirens (Clearance) The steady-state oral clearance of capivasertib is 50 L/h (37% CV), and renal clearance was 21% of total clearance.[L48691]

Absorpsi

The capivasertib steady-state AUC is 8,069 h·ng/mL (37%) and Cmax is 1,371 ng/mL (30%). Steady-state concentrations are predicted to be attained on the 3rd and 4th dosing day of each week, starting week 2.L48691 Capivasertib plasma concentrations are approximately 0.5% to 15% of the steady-state Cmax during the off-dosing days.L48691 Capivasertib AUC and Cmax are proportional with doses over a range of 80 to 800 mg (0.2 to 2 times the approved recommended dosage).L48691 Tmax is approximately 1-2 hours. The absolute bioavailability is 29%.L48691 No clinically meaningful differences in capivasertib pharmacokinetics were observed following the administration of capivasertib with a high-fat meal (approximately 1,000 kcal; fat 60%) or a low-fat meal (approximately 400 kcal; fat 26%).L48691

Metabolisme

Capivasertib is primarily metabolized by CYP3A4 and UGT2B7.L48691

Rute Eliminasi

Following a single radiolabeled oral dose of 400 mg, the mean total recovery was 45% from urine and 50% from feces.L48691

Interaksi Makanan

1 Data
  • 1. Take with or without food.

Interaksi Obat

383 Data
Succinic acid The excretion of Succinic acid can be decreased when combined with Capivasertib.
Citrulline The excretion of Citrulline can be decreased when combined with Capivasertib.
Pravastatin The excretion of Pravastatin can be decreased when combined with Capivasertib.
Oseltamivir The excretion of Oseltamivir can be decreased when combined with Capivasertib.
Cefotiam The excretion of Cefotiam can be decreased when combined with Capivasertib.
Conjugated estrogens The excretion of Conjugated estrogens can be decreased when combined with Capivasertib.
Tenofovir disoproxil The excretion of Tenofovir disoproxil can be decreased when combined with Capivasertib.
Valproic acid The excretion of Valproic acid can be decreased when combined with Capivasertib.
Piperacillin The excretion of Piperacillin can be decreased when combined with Capivasertib.
Indomethacin The excretion of Indomethacin can be decreased when combined with Capivasertib.
Aminohippuric acid The excretion of Aminohippuric acid can be decreased when combined with Capivasertib.
Trifluridine The excretion of Trifluridine can be decreased when combined with Capivasertib.
Allopurinol The excretion of Allopurinol can be decreased when combined with Capivasertib.
Zidovudine The excretion of Zidovudine can be decreased when combined with Capivasertib.
Cimetidine The excretion of Cimetidine can be decreased when combined with Capivasertib.
Cefdinir The excretion of Cefdinir can be decreased when combined with Capivasertib.
Methotrexate The excretion of Methotrexate can be decreased when combined with Capivasertib.
Cephalexin The excretion of Cephalexin can be decreased when combined with Capivasertib.
Valaciclovir The excretion of Valaciclovir can be decreased when combined with Capivasertib.
Levocarnitine The excretion of Levocarnitine can be decreased when combined with Capivasertib.
Oxytetracycline The excretion of Oxytetracycline can be decreased when combined with Capivasertib.
Pemetrexed Capivasertib may decrease the excretion rate of Pemetrexed which could result in a higher serum level.
Leucovorin The excretion of Leucovorin can be decreased when combined with Capivasertib.
Fluorescein The excretion of Fluorescein can be decreased when combined with Capivasertib.
Hydrocortisone The excretion of Hydrocortisone can be decreased when combined with Capivasertib.
Tetracycline The excretion of Tetracycline can be decreased when combined with Capivasertib.
Estradiol The excretion of Estradiol can be decreased when combined with Capivasertib.
Acyclovir The excretion of Acyclovir can be decreased when combined with Capivasertib.
Cefaclor The excretion of Cefaclor can be decreased when combined with Capivasertib.
Ranitidine The excretion of Ranitidine can be decreased when combined with Capivasertib.
Quinapril The excretion of Quinapril can be decreased when combined with Capivasertib.
Bumetanide The excretion of Bumetanide can be decreased when combined with Capivasertib.
Dinoprostone The excretion of Dinoprostone can be decreased when combined with Capivasertib.
Famotidine The excretion of Famotidine can be decreased when combined with Capivasertib.
Fexofenadine The excretion of Fexofenadine can be decreased when combined with Capivasertib.
Hydrochlorothiazide The excretion of Hydrochlorothiazide can be decreased when combined with Capivasertib.
Mercaptopurine The excretion of Mercaptopurine can be decreased when combined with Capivasertib.
Benzylpenicillin The excretion of Benzylpenicillin can be decreased when combined with Capivasertib.
Rosuvastatin The excretion of Rosuvastatin can be decreased when combined with Capivasertib.
Captopril The excretion of Captopril can be decreased when combined with Capivasertib.
Dexamethasone The serum concentration of Capivasertib can be decreased when it is combined with Dexamethasone.
Sitagliptin The excretion of Sitagliptin can be decreased when combined with Capivasertib.
Polythiazide The excretion of Polythiazide can be decreased when combined with Capivasertib.
Cefazolin The excretion of Cefazolin can be decreased when combined with Capivasertib.
Ceftizoxime The excretion of Ceftizoxime can be decreased when combined with Capivasertib.
Cefacetrile The excretion of Cefacetrile can be decreased when combined with Capivasertib.
Ceftibuten The excretion of Ceftibuten can be decreased when combined with Capivasertib.
Tazobactam The excretion of Tazobactam can be decreased when combined with Capivasertib.
Cyclic adenosine monophosphate The excretion of Cyclic adenosine monophosphate can be decreased when combined with Capivasertib.
Cholic Acid The excretion of Cholic Acid can be decreased when combined with Capivasertib.
Glutaric Acid The excretion of Glutaric Acid can be decreased when combined with Capivasertib.
Oxalic Acid The excretion of Oxalic Acid can be decreased when combined with Capivasertib.
Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Capivasertib.
Doripenem The excretion of Doripenem can be decreased when combined with Capivasertib.
Saxagliptin The excretion of Saxagliptin can be decreased when combined with Capivasertib.
Ellagic acid The excretion of Ellagic acid can be decreased when combined with Capivasertib.
Cefaloridine The excretion of Cefaloridine can be decreased when combined with Capivasertib.
Avibactam The excretion of Avibactam can be decreased when combined with Capivasertib.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Capivasertib.
Silibinin The excretion of Silibinin can be decreased when combined with Capivasertib.
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Capivasertib.
Baricitinib The serum concentration of Baricitinib can be increased when it is combined with Capivasertib.
Vadadustat The serum concentration of Vadadustat can be increased when it is combined with Capivasertib.
Relebactam The excretion of Relebactam can be decreased when combined with Capivasertib.
Tenofovir The excretion of Tenofovir can be decreased when combined with Capivasertib.
Prednisolone phosphate The excretion of Prednisolone phosphate can be decreased when combined with Capivasertib.
Dexamethasone acetate The serum concentration of Capivasertib can be decreased when it is combined with Dexamethasone acetate.
Phenytoin The serum concentration of Capivasertib can be decreased when it is combined with Phenytoin.
Pentobarbital The serum concentration of Capivasertib can be decreased when it is combined with Pentobarbital.
Carbamazepine The serum concentration of Capivasertib can be decreased when it is combined with Carbamazepine.
Mitotane The serum concentration of Capivasertib can be decreased when it is combined with Mitotane.
Primidone The serum concentration of Capivasertib can be decreased when it is combined with Primidone.
Rifampin The serum concentration of Capivasertib can be decreased when it is combined with Rifampicin.
Phenobarbital The serum concentration of Capivasertib can be decreased when it is combined with Phenobarbital.
Rifapentine The serum concentration of Capivasertib can be decreased when it is combined with Rifapentine.
Fosphenytoin The serum concentration of Capivasertib can be decreased when it is combined with Fosphenytoin.
St. John's Wort The serum concentration of Capivasertib can be decreased when it is combined with St. John's Wort.
Midostaurin The serum concentration of Capivasertib can be increased when it is combined with Midostaurin.
Enzalutamide The serum concentration of Capivasertib can be decreased when it is combined with Enzalutamide.
Lumacaftor The serum concentration of Capivasertib can be decreased when it is combined with Lumacaftor.
Apalutamide The serum concentration of Capivasertib can be decreased when it is combined with Apalutamide.
Cyclosporine The serum concentration of Capivasertib can be increased when it is combined with Cyclosporine.
Fluvoxamine The serum concentration of Capivasertib can be increased when it is combined with Fluvoxamine.
Fluconazole The serum concentration of Capivasertib can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Capivasertib can be increased when it is combined with Erythromycin.
Ziprasidone The serum concentration of Capivasertib can be increased when it is combined with Ziprasidone.
Isradipine The serum concentration of Capivasertib can be increased when it is combined with Isradipine.
Diltiazem The serum concentration of Capivasertib can be increased when it is combined with Diltiazem.
Clozapine The serum concentration of Capivasertib can be increased when it is combined with Clozapine.
Haloperidol The serum concentration of Haloperidol can be increased when it is combined with Capivasertib.
Ciprofloxacin The serum concentration of Capivasertib can be increased when it is combined with Ciprofloxacin.
Voriconazole The serum concentration of Capivasertib can be increased when it is combined with Voriconazole.
Nicardipine The serum concentration of Capivasertib can be increased when it is combined with Nicardipine.
Verapamil The serum concentration of Capivasertib can be increased when it is combined with Verapamil.
Aprepitant The serum concentration of Capivasertib can be increased when it is combined with Aprepitant.
Isoniazid The serum concentration of Capivasertib can be increased when it is combined with Isoniazid.
Primaquine The serum concentration of Capivasertib can be increased when it is combined with Primaquine.
Miconazole The serum concentration of Capivasertib can be increased when it is combined with Miconazole.
Danazol The serum concentration of Capivasertib can be increased when it is combined with Danazol.
Fusidic acid The serum concentration of Capivasertib can be increased when it is combined with Fusidic acid.

Target Protein

RAC-alpha serine/threonine-protein kinase AKT1
RAC-beta serine/threonine-protein kinase AKT2
RAC-gamma serine/threonine-protein kinase AKT3

Referensi & Sumber

Artikel (PubMed)
  • PMID: 32312891
    Smyth LM, Tamura K, Oliveira M, Ciruelos EM, Mayer IA, Sablin MP, Biganzoli L, Ambrose HJ, Ashton J, Barnicle A, Cashell DD, Corcoran C, de Bruin EC, Foxley A, Hauser J, Lindemann JPO, Maudsley R, McEwen R, Moschetta M, Pass M, Rowlands V, Schiavon G, Banerji U, Scaltriti M, Taylor BS, Chandarlapaty S, Baselga J, Hyman DM: Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1 (E17K)-Mutant, ER-Positive Metastatic Breast Cancer. Clin Cancer Res. 2020 Aug 1;26(15):3947-3957. doi: 10.1158/1078-0432.CCR-19-3953. Epub 2020 Apr 20.
  • PMID: 33863913
    Smyth LM, Batist G, Meric-Bernstam F, Kabos P, Spanggaard I, Lluch A, Jhaveri K, Varga A, Wong A, Schram AM, Ambrose H, Carr TH, de Bruin EC, Salinas-Souza C, Foxley A, Hauser J, Lindemann JPO, Maudsley R, McEwen R, Moschetta M, Nikolaou M, Schiavon G, Razavi P, Banerji U, Baselga J, Hyman DM, Chandarlapaty S: Selective AKT kinase inhibitor capivasertib in combination with fulvestrant in PTEN-mutant ER-positive metastatic breast cancer. NPJ Breast Cancer. 2021 Apr 16;7(1):44. doi: 10.1038/s41523-021-00251-7.
  • PMID: 35398754
    Andrikopoulou A, Chatzinikolaou S, Panourgias E, Kaparelou M, Liontos M, Dimopoulos MA, Zagouri F: "The emerging role of capivasertib in breast cancer". Breast. 2022 Jun;63:157-167. doi: 10.1016/j.breast.2022.03.018. Epub 2022 Apr 1.

Contoh Produk & Brand

Produk: 6 • International brands: 0
Produk
  • Truqap
    Tablet, film coated • 160 mg • Oral • EU • Approved
  • Truqap
    Tablet, film coated • 200 mg • Oral • EU • Approved
  • Truqap
    Tablet • 160 mg • Oral • Canada • Approved
  • Truqap
    Tablet • 200 mg • Oral • Canada • Approved
  • Truqap
    Tablet, film coated • 160 mg/1 • Oral • US • Approved
  • Truqap
    Tablet, film coated • 200 mg/1 • Oral • US • Approved

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