Peringatan Keamanan

The common adverse reactions (? 2%) reported in clinical trials were headache, nausea, and diarrhea.

Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of plasma derived C1 esterase inhibitor products in patients with risk factors. Risk factors may include the presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility. Monitor patients with known risk factors for TE events during and after administration.

Conestat alfa

DB09228

biotech approved investigational

Deskripsi

C1 Esterase Inhibitor (Recombinant) is a recombinant analogue of endogenous complement component-1 esterase inhibitor (rhC1INH), purified from the milk of transgenic rabbits. The primary function of endogenous C1INH is to regulate the activation of the complement and contact system pathways. It does this through inhibition of several target proteases within these pathways including activated C1s, kallikrein, factor XIIa and factor XIa. C1 esterase inhibitor has also been shown to inhibit the action of thrombin within the coagulation pathway, and tPA and plasmin within the fibrinolytic pathway. Deficiency of C1-inhibitor allows for increased plasma kallikrein activation and subsequent production of bradykinin. Additionally, C4 and C2 cleavage occurs resulting in auto-activation of the complement system. Down-stream effects of the lack of enzyme inhibition by C1 esterase inhibitor results in swelling due to leakage of fluid from blood vessels into connective tissue and consequently the presentation of hereditary angioedema (HAE).

Marketed as the product Ruconest (FDA), this drug is indicated for the treatment of acute attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency in adults. Intravenous replacement of C1 esterase inhibitor results in reversal of acute symptoms of HAE.

Struktur Molekul 2D

Struktur tidak tersedia

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) -
Volume Distribusi -
Klirens (Clearance) Clearance was found to be 1207 ± 414 mL/hr following administration of 50 U/kg.

Absorpsi

Mean Cmax was found to be 1.2 U/mL and Tmax was 0.31 ± 0.10 hr following administration of 50 U/kg.

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Elimination half-life was approximately 2.5 hours.

Interaksi Obat

37 Data
Etonogestrel The risk or severity of thromboembolism can be increased when Etonogestrel is combined with Conestat alfa.
Desogestrel The risk or severity of thromboembolism can be increased when Desogestrel is combined with Conestat alfa.
Megestrol acetate The risk or severity of thromboembolism can be increased when Megestrol acetate is combined with Conestat alfa.
Levonorgestrel The risk or severity of thromboembolism can be increased when Levonorgestrel is combined with Conestat alfa.
Dydrogesterone The risk or severity of thromboembolism can be increased when Dydrogesterone is combined with Conestat alfa.
Progesterone The risk or severity of thromboembolism can be increased when Progesterone is combined with Conestat alfa.
Medroxyprogesterone acetate The risk or severity of thromboembolism can be increased when Medroxyprogesterone acetate is combined with Conestat alfa.
Norethisterone The risk or severity of thromboembolism can be increased when Norethisterone is combined with Conestat alfa.
Ethynodiol diacetate The risk or severity of thromboembolism can be increased when Ethynodiol diacetate is combined with Conestat alfa.
Norgestimate The risk or severity of thromboembolism can be increased when Norgestimate is combined with Conestat alfa.
Drospirenone The risk or severity of thromboembolism can be increased when Drospirenone is combined with Conestat alfa.
Allylestrenol The risk or severity of thromboembolism can be increased when Allylestrenol is combined with Conestat alfa.
Cyproterone acetate The risk or severity of thromboembolism can be increased when Cyproterone acetate is combined with Conestat alfa.
Norelgestromin The risk or severity of thromboembolism can be increased when Norelgestromin is combined with Conestat alfa.
Gestodene The risk or severity of thromboembolism can be increased when Gestodene is combined with Conestat alfa.
Hydroxyprogesterone caproate The risk or severity of thromboembolism can be increased when Hydroxyprogesterone caproate is combined with Conestat alfa.
Dienogest The risk or severity of thromboembolism can be increased when Dienogest is combined with Conestat alfa.
Medrogestone The risk or severity of thromboembolism can be increased when Medrogestone is combined with Conestat alfa.
Norethynodrel The risk or severity of thromboembolism can be increased when Norethynodrel is combined with Conestat alfa.
Norgestrel The risk or severity of thromboembolism can be increased when Norgestrel is combined with Conestat alfa.
Altrenogest The risk or severity of thromboembolism can be increased when Altrenogest is combined with Conestat alfa.
Gestrinone The risk or severity of thromboembolism can be increased when Gestrinone is combined with Conestat alfa.
Nomegestrol The risk or severity of thromboembolism can be increased when Nomegestrol is combined with Conestat alfa.
Lynestrenol The risk or severity of thromboembolism can be increased when Lynestrenol is combined with Conestat alfa.
Gestonorone The risk or severity of thromboembolism can be increased when Gestonorone is combined with Conestat alfa.
Chlormadinone The risk or severity of thromboembolism can be increased when Chlormadinone is combined with Conestat alfa.
Methylestrenolone The risk or severity of thromboembolism can be increased when Methylestrenolone is combined with Conestat alfa.
Norgestrienone The risk or severity of thromboembolism can be increased when Norgestrienone is combined with Conestat alfa.
Promegestone The risk or severity of thromboembolism can be increased when Promegestone is combined with Conestat alfa.
Quingestanol The risk or severity of thromboembolism can be increased when Quingestanol is combined with Conestat alfa.
Demegestone The risk or severity of thromboembolism can be increased when Demegestone is combined with Conestat alfa.
Etynodiol The risk or severity of thromboembolism can be increased when Etynodiol is combined with Conestat alfa.
Nomegestrol acetate The risk or severity of thromboembolism can be increased when Nomegestrol acetate is combined with Conestat alfa.
Hydroxyprogesterone The risk or severity of thromboembolism can be increased when Hydroxyprogesterone is combined with Conestat alfa.
Norethindrone enanthate The risk or severity of thromboembolism can be increased when Norethindrone enanthate is combined with Conestat alfa.
Quingestanol acetate The risk or severity of thromboembolism can be increased when Quingestanol acetate is combined with Conestat alfa.
Algestone acetophenide The risk or severity of thromboembolism can be increased when Algestone acetophenide is combined with Conestat alfa.

Target Protein

Complement C1r subcomponent C1R
Complement C1s subcomponent C1S
Plasma kallikrein KLKB1
Coagulation factor XII F12
Prothrombin F2
Coagulation factor XI F11
Tissue-type plasminogen activator PLAT

Referensi & Sumber

Artikel (PubMed)
  • PMID: 16267649
    Cicardi M, Zingale L, Zanichelli A, Pappalardo E, Cicardi B: C1 inhibitor: molecular and clinical aspects. Springer Semin Immunopathol. 2005 Nov;27(3):286-98. Epub 2005 Nov 11.
  • PMID: 123251
    Harpel PC, Cooper NR: Studies on human plasma C1 inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin, and trypsin. J Clin Invest. 1975 Mar;55(3):593-604.
  • PMID: 13734157
    PENSKY J, LEVY LR, LEPOW IH: Partial purification of a serum inhibitor of C'1-esterase. J Biol Chem. 1961 Jun;236:1674-9.
  • PMID: 6184384
    van der Graaf F, Koedam JA, Bouma BN: Inactivation of kallikrein in human plasma. J Clin Invest. 1983 Jan;71(1):149-58.
  • PMID: 6725552
    de Agostini A, Lijnen HR, Pixley RA, Colman RW, Schapira M: Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor. J Clin Invest. 1984 Jun;73(6):1542-9.
  • PMID: 11460008
    Cugno M, Bos I, Lubbers Y, Hack CE, Agostoni A: In vitro interaction of C1-inhibitor with thrombin. Blood Coagul Fibrinolysis. 2001 Jun;12(4):253-60.
  • PMID: 3756141
    Bock SC, Skriver K, Nielsen E, Thogersen HC, Wiman B, Donaldson VH, Eddy RL, Marrinan J, Radziejewska E, Huber R, et al.: Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization. Biochemistry. 1986 Jul 29;25(15):4292-301.

Contoh Produk & Brand

Produk: 6 • International brands: 0
Produk
  • Ruconest
    Injection, powder, for solution • 2100 U/1 • Intravenous • US • Approved
  • Ruconest
    Injection, powder, for solution • 2100 U/1 • Intravenous • US • Approved
  • Ruconest
    Injection, powder, for solution • 2100 U/1 • Intravenous • US • Approved
  • Ruconest
    Injection, powder, for solution • 2100 U/1 • Intravenous • US • Approved
  • Ruconest
    Injection, powder, for solution • 2100 U • Intravenous • EU • Approved
  • Ruconest
    Injection, powder, for solution • 2100 U • Intravenous • EU • Approved

Sekuens Gen/Protein (FASTA)

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