Identification
- Summary
Conestat alfa is a recombinant C1INH used for the treatment of acute attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency in adults.
- Brand Names
- Ruconest
- Generic Name
- Conestat alfa
- DrugBank Accession Number
- DB09228
- Background
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.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Structure
- Protein Chemical Formula
- Not Available
- Protein Average Weight
- 67000.0 Da
- Sequences
- Not Available
- Synonyms
- C1 Esterase Inhibitor (Recombinant)
- C1 Inhibitor (Recombinant)
- Complement C1 esterase inhibitor
- Conestat alfa
- Human C1-inhibitor (recombinant, rabbit derived)
- Recombinant complement C1 esterase inhibitor
- Recombinant human C1 inhibitor
- Recombinant human C1-inhibitor
- Recombinant human C1-inhibitor rabbit milk derived
Pharmacology
- Indication
For the treatment of acute attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency in adults.
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- Contraindications & Blackbox Warnings
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A dose of 50 U/kg of Ruconest increases plasma C1INH activity levels to greater than 0.7 U/mL (the lower limit of normal) in HAE patients.
- Mechanism of action
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 increased plasma kallikrein activation and subsequent production of bradykinin. Additionally, C4 and C2 cleavage is no longer inhibited allowing 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). Replacement of C1 esterase inhibitor results in a reversal of these effects.
Target Actions Organism AComplement C1r subcomponent inhibitorHumans AComplement C1s subcomponent inhibitorHumans APlasma kallikrein inhibitorHumans ACoagulation factor XII inhibitorHumans AProthrombin inhibitorHumans ACoagulation factor XI inhibitorHumans ATissue-type plasminogen activator inhibitorHumans - Absorption
Mean Cmax was found to be 1.2 U/mL and Tmax was 0.31 ± 0.10 hr following administration of 50 U/kg.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Elimination half-life was approximately 2.5 hours.
- Half-life
Not Available
- Clearance
Clearance was found to be 1207 ± 414 mL/hr following administration of 50 U/kg.
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareCyproterone acetate The risk or severity of thromboembolism can be increased when Cyproterone acetate is combined with Conestat alfa. Desogestrel The risk or severity of thromboembolism can be increased when Desogestrel is combined with Conestat alfa. Dienogest The risk or severity of thromboembolism can be increased when Dienogest is combined with Conestat alfa. Drospirenone The risk or severity of thromboembolism can be increased when Drospirenone is combined with Conestat alfa. Dydrogesterone The risk or severity of thromboembolism can be increased when Dydrogesterone is combined with Conestat alfa. Ethynodiol diacetate The risk or severity of thromboembolism can be increased when Ethynodiol diacetate is combined with Conestat alfa. Etonogestrel The risk or severity of thromboembolism can be increased when Etonogestrel is combined with Conestat alfa. Gestrinone The risk or severity of thromboembolism can be increased when Gestrinone is combined with Conestat alfa. Hydroxyprogesterone caproate The risk or severity of thromboembolism can be increased when Hydroxyprogesterone caproate is combined with Conestat alfa. Levonorgestrel The risk or severity of thromboembolism can be increased when Levonorgestrel is combined with Conestat alfa. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ruconest Injection, powder, for solution 2100 U/1 Intravenous Santarus, Inc. 2014-09-22 2022-01-18 US 
Ruconest Injection, powder, for solution 2100 U/1 Intravenous Tjoapack Netherlands Bv 2016-09-19 Not applicable US Ruconest Injection, powder, for solution 2100 U Intravenous Pharming Group N.V. 2020-12-16 Not applicable EU 
Ruconest Injection, powder, for solution 2100 U/1 Intravenous Pharming Healthcare Inc. 2018-04-01 Not applicable US Ruconest Injection, powder, for solution 2100 U/1 Intravenous Bioconnection B.V. 2014-09-22 Not applicable US Ruconest Injection, powder, for solution 2100 U Intravenous Pharming Group N.V. 2020-12-16 Not applicable EU
Categories
- ATC Codes
- B06AC04 — Conestat alfa
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Angioedemas, Hereditary, drug therapy
- Blood and Blood Forming Organs
- Blood Proteins
- C1 inhibitors
- Complement C1 Inactivator Proteins
- Complement Inactivator Proteins
- Complement System Proteins
- Drugs Used in Hereditary Angioedema
- Enzyme Inhibitors
- Glycoproteins
- Immunoproteins
- Peptides
- Protease Inhibitors
- Proteins
- Serine Protease Inhibitors
- Serpins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 5QS67N4551
- CAS number
- 80295-38-1
References
- General References
- 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. [Article]
- 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. [Article]
- PENSKY J, LEVY LR, LEPOW IH: Partial purification of a serum inhibitor of C'1-esterase. J Biol Chem. 1961 Jun;236:1674-9. [Article]
- van der Graaf F, Koedam JA, Bouma BN: Inactivation of kallikrein in human plasma. J Clin Invest. 1983 Jan;71(1):149-58. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Blood Products: Ruconest C1 Esterase Inhibitor Intravenous Injection [Link]
- External Links
- UniProt
- P05155
- PubChem Substance
- 347910420
- 1599831
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- C1-inhibitor
- FDA label
- Download (5.72 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Post-Viral Disorder (Disorder) / Post-Viral Fatigue Syndrome 1 3 Completed Treatment Angioneurotic Edema / Hereditary Angioedema (HAE) / Hereditary disorder 1 2 Completed Prevention Acute Kidney Injury (AKI) 1 2 Completed Prevention Hereditary Angioedema (HAE) 1 2 Completed Treatment Confirmed Coronavirus Disease / Coronavirus Disease 2019 (COVID‑19) 1 2 Completed Treatment Hereditary Angioedema (HAE) 1 2 Completed Treatment Hereditary Angioedema (HAE) / Hereditary disorder 1 2 Completed Treatment Hereditary disorder 1 2 Recruiting Prevention Acute Ischemic Stroke / Acute Renal Injury 1 2 Recruiting Prevention Non ST Segment Elevation Myocardial Infarction (NSTEMI) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Parenteral 1500 IU Injection, powder, for solution Parenteral Injection, powder, for solution Intravenous 2100 U Injection, powder, for solution Intravenous 2100 U/1 Injection, solution Intravenous - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type peptidase activity
- Specific Function
- C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
- Gene Name
- C1R
- Uniprot ID
- P00736
- Uniprot Name
- Complement C1r subcomponent
- Molecular Weight
- 80118.04 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activat...
- Gene Name
- C1S
- Uniprot ID
- P09871
- Uniprot Name
- Complement C1s subcomponent
- Molecular Weight
- 76683.905 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen an...
- Gene Name
- KLKB1
- Uniprot ID
- P03952
- Uniprot Name
- Plasma kallikrein
- Molecular Weight
- 71369.205 Da
References
- van der Graaf F, Koedam JA, Bouma BN: Inactivation of kallikrein in human plasma. J Clin Invest. 1983 Jan;71(1):149-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII t...
- Gene Name
- F12
- Uniprot ID
- P00748
- Uniprot Name
- Coagulation factor XII
- Molecular Weight
- 67791.53 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thrombospondin receptor activity
- Specific Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
- Gene Name
- F11
- Uniprot ID
- P03951
- Uniprot Name
- Coagulation factor XI
- Molecular Weight
- 70108.56 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in t...
- Gene Name
- PLAT
- Uniprot ID
- P00750
- Uniprot Name
- Tissue-type plasminogen activator
- Molecular Weight
- 62916.495 Da
References
- 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. [Article]
Drug created at October 22, 2015 21:00 / Updated at April 01, 2022 19:23