Peringatan Keamanan

The most common adverse reactions reported with migalastat (? 10%) during the 6-month placebo-controlled, double-blind phase of its Study 1 clinical studies were headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia FDA Label, F1107.

In case of overdose, general medical care is recommended FDA Label, F1107. Headache and dizziness were the most common adverse reactions reported at doses of migalastat of up to 1250 mg and 2000 mg, respectively FDA Label, F1107.

Migalastat

DB05018

small molecule approved investigational

Deskripsi

Fabry disease is a rare, progressive genetic disorder characterized by a defective GLA gene that causes a deficiency in the enzyme alpha-Galactosidase A (alpha-Gal A). This enzyme is responsible for breaking down glycosphingolipid substrate that, when deficient in patients with Fabry disease, builds up in the blood vessels, the kidneys, the nerves, the heart, and other organs.L47036,L47057,L4274,L4278 In the U.S., it is estimated that more than 3,000 people are living with Fabry disease, and an estimated more than 50 percent of these diagnosed patients are currently untreated.L4274

Migalastat (approved and sold under Amicus Therapeutics' brand name Galafold) is subsequently an oral pharmacological chaperone of alpha-Gal A for the treatment of Fabry disease in adults who have amenable GLA variants.L47036,L47057,L4274,L4278 In these patients, migalastat works by stabilizing the body’s dysfunctional alpha-Gal A enzyme so that it can clear the accumulation of glycosphingolipid disease substrate.L47036,L47057,L4274,L4278 Globally, it is estimated that approximately 35 to 50 percent of Fabry patients may have amenable GLA variants that are treatable with migalastat. L4274

Given the rarity of Fabry disease and the proportion of Fabry disease patients that could benefit from migalastat therapy, Amicus Therapeutics' brand name Galafold was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is an unmet medical need and where a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients.L47036,L47057,L4274,L4278 A further study is required to verify and describe the clinical benefits of Galafold, and the sponsor will be conducting a confirmatory clinical trial of Galafold in adults with Fabry disease.L47036,L47057,L4274,L4278

Additionally, Galafold was also granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months of application filing where the agency determines that the drug if approved, would provide a significant improvement in treating, diagnosing or preventing a serious condition over available therapies.L47036,L47057 Galafold also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.L47036,L47057

As of August 2018, migalastat under Amicus Therapeutics' brand name Galafold is currently approved in Australia, Canada, European Union, Israel, Japan, South Korea, Switzerland, and the United States.L4274

Struktur Molekul 2D

Berat 163.1717
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean elimination half-life (t1/2) of migalastat ranges from approximately 3 to 5 hours for a single oral dose of 150 mg.[L47057] For the dose of 123 mg, the mean elimination half-life was estimated to be 4 hours.[L47036]
Volume Distribusi In healthy volunteers, the volume of distribution (Vz/F) of migalastat following ascending single oral doses (25-675 mg migalastat HCl) ranged from 77 to 133 L, indicating it is well distributed into tissues and greater than total body water (42 liters).[L47057]
Klirens (Clearance) Following ascending single oral doses (25-675 mg migalastat hydrochloride), no trends were found for clearance (CL/F). At the 150 mg dose, CL/F was approximately 11 to 14 L/hr, while at 123 mg, the apparent clearance was calculated to be 12.5 L/hr.[L47057,L47036]

Absorpsi

With absorption occurring largely in the gut, the absolute bioavailability (AUC) for a single oral 150 mg migalastat hydrochloride dose or a single 2-hour 150 mg intravenous infusion was approximately 75% and Tmax was approximately 3 hours.L4263,L47057 Plasma migalastat exposure (AUC0-?) and Cmax demonstrated dose-proportional increases at migalastat hydrochloride oral doses from 50 mg to 1,250 mg (doses from 0.5 to 8.3-fold of the approved recommended dosage).L47036,L47057 Migalastat administered with a high-fat meal (850 calories; 56% from fat), or 1 hour before a high-fat or light meal (507 calories; 30% from fat), or 1 hour after a light meal, resulted in significant reductions of 37% to 42% in mean total migalastat exposure (AUC0-?) and reductions of 15% to 39% in mean peak migalastat exposure (Cmax) compared with the fasting state.L47036

Metabolisme

Based upon in vivo data, migalastat is a substrate for uridine diphosphate glucuronosyltransferase (otherwise known as UGT or UDPGT), being a minor elimination pathway.L47036

Rute Eliminasi

In a mass balance study in healthy male subjects, following oral administration of 123 mg 14C-migalastat, approximately 77% of the total radiolabeled dose was recovered in urine and 20% of the total radiolabeled dose was recovered in feces with an overall total recovery of 98% within 96 hours post-dose. In urine, unchanged migalastat accounted for 80% of the radioactivity, which equates to 62% of the administered dose. In feces, unchanged migalastat was the only drug-related component. In plasma, unchanged migalastat accounted for approximately 77% of the plasma radioactivity, and three dehydrogenated O-glucuronide conjugated metabolites, M1 to M3, together accounted for approximately 13% of the plasma radioactivity, none of which comprised more than 6% of the radiolabeled dose. Approximately 9% of the total radioactivity in plasma was unassigned.L47036

Interaksi Makanan

3 Data
  • 1. Avoid caffeine. Co-administration of GALAFOLD with caffeine decreases migalastat AUC and Cmax which may reduce its efficacy.
  • 2. Take at the same time every day.
  • 3. Take on an empty stomach. Avoid eating for at least two hours before and after taking migalastat.

Interaksi Obat

729 Data
Lamotrigine Lamotrigine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Testosterone propionate Testosterone propionate may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cyclosporine Cyclosporine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Migalastat which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Migalastat which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Migalastat which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Migalastat which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Migalastat which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Migalastat which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Migalastat which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Migalastat which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Migalastat which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Migalastat which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Migalastat which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Migalastat which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Migalastat which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Migalastat which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Migalastat which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Migalastat which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Migalastat which could result in a higher serum level.
Meloxicam Meloxicam may decrease the excretion rate of Migalastat which could result in a higher serum level.
Carprofen Carprofen may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Migalastat which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Migalastat which could result in a higher serum level.
Tacrolimus Tacrolimus may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Migalastat which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Migalastat which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Migalastat which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Migalastat which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Migalastat which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Migalastat which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Migalastat which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Migalastat which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Migalastat which could result in a higher serum level.
Tiaprofenic acid Tiaprofenic acid may decrease the excretion rate of Migalastat which could result in a higher serum level.
Lopinavir Lopinavir may decrease the excretion rate of Migalastat which could result in a higher serum level.
Etoricoxib Etoricoxib may decrease the excretion rate of Migalastat which could result in a higher serum level.
Hydrolyzed Cephalothin Hydrolyzed Cephalothin may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cephalothin Group Cephalothin Group may decrease the excretion rate of Migalastat which could result in a higher serum level.
Oxyphenbutazone Oxyphenbutazone may decrease the excretion rate of Migalastat which could result in a higher serum level.
Latamoxef Latamoxef may decrease the excretion rate of Migalastat which could result in a higher serum level.
Nimesulide Nimesulide may decrease the excretion rate of Migalastat which could result in a higher serum level.
Benoxaprofen Benoxaprofen may decrease the excretion rate of Migalastat which could result in a higher serum level.
Metamizole Metamizole may decrease the excretion rate of Migalastat which could result in a higher serum level.
Zomepirac Zomepirac may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceftobiprole Ceftobiprole may decrease the excretion rate of Migalastat which could result in a higher serum level.
Cimicoxib Cimicoxib may decrease the excretion rate of Migalastat which could result in a higher serum level.
Ceftaroline fosamil Ceftaroline fosamil may decrease the excretion rate of Migalastat which could result in a higher serum level.
Lornoxicam Lornoxicam may decrease the excretion rate of Migalastat which could result in a higher serum level.
Aceclofenac Aceclofenac may decrease the excretion rate of Migalastat which could result in a higher serum level.
Zaltoprofen Zaltoprofen may decrease the excretion rate of Migalastat which could result in a higher serum level.

Target Protein

Alpha-galactosidase A GLA

Referensi & Sumber

Synthesis reference: Patent US20180208955A1: Process for the microbial synthesis of migalastat (https://patents.google.com/patent/US20180208955A1/en)
Artikel (PubMed)
  • PMID: 26252393
    Warnock DG, Bichet DG, Holida M, Goker-Alpan O, Nicholls K, Thomas M, Eyskens F, Shankar S, Adera M, Sitaraman S, Khanna R, Flanagan JJ, Wustman BA, Barth J, Barlow C, Valenzano KJ, Lockhart DJ, Boudes P, Johnson FK: Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active alpha-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase. PLoS One. 2015 Aug 7;10(8):e0134341. doi: 10.1371/journal.pone.0134341. eCollection 2015.

Contoh Produk & Brand

Produk: 3 • International brands: 1
Produk
  • Galafold
    Capsule • 123 mg • Oral • Canada • Approved
  • Galafold
    Capsule • 123 mg/1 • Oral • US • Approved
  • Galafold
    Capsule • 123 mg • Oral • EU • Approved
International Brands
  • Amigal

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