Peringatan Keamanan

The most common side effects with Elonva (seen in between 1 and 10 patients in 100) include a headache, nausea, fatigue, pelvic pain and/or discomfort, breast tenderness and ovarian hyperstimulation syndrome (OHSS). This syndrome occurs when the ovaries have a heightened response to therapy, leading to abdominal swelling and pain, nausea and diarrhea L2270.

More than one injection of Elonva within one treatment cycle or an excessively high dose of Elonva and/or (rec)FSH can increase the risk of ovarian hyperstimulation syndrome L2270, which may cause swollen or painful ovaries, abdominal bloating, nausea, and a weight gain of up to 3kg L2275.

In severe cases, ovarian hyperstimulation syndrome may cause rapid weight gain ranging from 15 to 20 kilograms in 5-10 days. Severe abdominal pain, severe, persistent nausea, and vomiting, decreased urination, and abdominal bloating, as well as other generalized symptoms, may occur L2275. About 1 - 2 % of women undergoing ovarian stimulation develop a severe form of ovarian hyperstimulation syndrome (OHSS). Severe OHSS can be life-threatening. Complications may include: ascites, pulmonary edema, electrolyte disturbances (sodium, potassium, others), thrombosis in large vessels, usually in the lower extremities, renal failure, ovarian torsion, rupture of ovarian cysts. Some of these conditions can lead to hemorrhage, respiratory failure, spontaneous miscarriage or pregnancy termination due to complications, resulting in death L2270.

Corifollitropin alfa

DB09066

biotech approved investigational

Deskripsi

Corifollitropin alfa, also known as Elonva is used in women undergoing fertility treatment to stimulate the development of more than one mature egg (oocyte) at a time in the ovaries. This drug used together with a gonadotropin-releasing hormone (GnRH) antagonist, a type of medicine also used in fertility treatments. Elonva is available only by prescription L2270.

In July 2014, Merck announced the receipt of a Complete Response Letter (CRL) from the U.S. FDA for its New Drug Application for this drug. Corifollitropin alfa is marketed as Elonva in more than 75 countries L2272.

Corifollitropin alfa is produced by a method known as ‘recombinant DNA technology’. This means that it is made by cells into which a DNA has been introduced that makes them able to produce corifollitropin alfa L2270.

Multiple studies and a meta-analysis suggest that corifollitropin alfa is as efficacious as recombinant FSH in terms of live birth rate, ongoing pregnancy rate, as well as clinical pregnancy rate. The increased in the number of eggs retrieved under corifollitropin alfa regimen represents the elevated effectiveness of this drug, however, warns at the same time against the possibility of an increased risk of ovarian hyperstimulation in the high responder study group of women L2276, A32526.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing [A32516]. Corifollitropin alfa has an elimination half-life of 70 hours (59-82 hours) [L2270].
Volume Distribusi Distribution, metabolism and elimination of corifollitropin alfa are very similar to other gonadotropins, such as FSH, hCG and LH [L2273]. After absorption into the blood, corifollitropin alfa is distributed mainly to the ovaries and the kidneys. The steady-state volume of distribution is 9.2 L [L2273]. Exposure to corifollitropin alfa increases in a linear fashion with the dose within a range of 60 micrograms - 240 micrograms [L2270].
Klirens (Clearance) 0.13 L/h (0.10-0.18 L/h1) [L2270]

Absorpsi

After one single subcutaneous injection of this drug, the maximal serum concentration is 4.24 ng/mL (2.49-7.21 ng/mL1) and is reached 44 hours (35-57 h) post-dose administration. Its absolute bioavailability is 58% (48-70%) L2270.

Metabolisme

The metabolic fate of corifollitropin alfa highly resembles that of endogenous glycoprotein hormones, which predominantly is comprised of kidney clearance and the urinary excretion of the intact protein in parallel to kidney catabolism A32519.

Rute Eliminasi

Radioactivity labeling showed that the drug was mainly (86%) excreted in the urine. 90% of the radioactivity in serum was identified as (125)Icorifollitropin alfa, but only 7-15% of the radioactivity in urine was identified as (125)Icorifollitropin alfa and its dissociation products, the alpha- and beta-subunits (including its CTP part) A32519. Elimination of corifollitropin alfa mainly occurs via the kidneys. The elimination rate of this drug may be reduced in patients with renal insufficiency. Hepatic metabolism contributes to a minor extent to the elimination of corifollitropin alfa L2270.

Interaksi Obat

733 Data
Leuprolide The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Leuprolide.
Goserelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Goserelin.
Gonadorelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Gonadorelin.
Nafarelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Nafarelin.
Buserelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Buserelin.
Histrelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Histrelin.
Triptorelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Triptorelin.
Deslorelin The therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Deslorelin.
Cyclosporine Cyclosporine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Flurbiprofen Flurbiprofen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Meloxicam Meloxicam may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Carprofen Carprofen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Tacrolimus Tacrolimus may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Atazanavir Atazanavir may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Tiaprofenic acid Tiaprofenic acid may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Lopinavir Lopinavir may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Etoricoxib Etoricoxib may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Hydrolyzed Cephalothin Hydrolyzed Cephalothin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Cephalothin Group Cephalothin Group may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Oxyphenbutazone Oxyphenbutazone may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Latamoxef Latamoxef may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.
Nimesulide Nimesulide may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.

Target Protein

Follicle-stimulating hormone receptor FSHR

Referensi & Sumber

Artikel (PubMed)
  • PMID: 19337959
    Loutradis D, Drakakis P, Vlismas A, Antsaklis A: Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility. Curr Opin Investig Drugs. 2009 Apr;10(4):372-80.
  • PMID: 21850281
    de Lartigue J: Corifollitropin alfa: a new option to treat female infertility. Drugs Today (Barc). 2011 Aug;47(8):583-90. doi: 10.1358/dot.2011.47.8.1635872.
  • PMID: 20110752
    van Schanke A, van de Wetering-Krebbers SF, Bos E, Sloot WN: Absorption, distribution, metabolism and excretion of corifollitropin alfa, a recombinant hormone with a sustained follicle-stimulating activity. Pharmacology. 2010;85(2):77-87. doi: 10.1159/000276546. Epub 2010 Jan 21.
  • PMID: 28368800
    Benchabane M, Santulli P, Maignien C, Bourdon M, De Ziegler D, Chapron C, Gayet V: Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for oocyte donors. Gynecol Obstet Fertil Senol. 2017 Feb;45(2):83-88. doi: 10.1016/j.gofs.2016.12.022. Epub 2017 Feb 16.

Contoh Produk & Brand

Produk: 2 • International brands: 0
Produk
  • Elonva
    Injection, solution • 100 micrograms • Subcutaneous • EU • Approved
  • Elonva
    Injection, solution • 150 micrograms • Subcutaneous • EU • Approved

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