Conestat alfa

Identification

Name

Conestat alfa

Accession Number

DB09228

Description

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
• 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.

Associated Conditions

• Acute attack of hereditary angioedema

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

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	inhibitor	Humans
AComplement C1s subcomponent	inhibitor	Humans
APlasma kallikrein	inhibitor	Humans
ACoagulation factor XII	inhibitor	Humans
AProthrombin	inhibitor	Humans
ACoagulation factor XI	inhibitor	Humans
ATissue-type plasminogen activator	inhibitor	Humans

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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Toxicity

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.

Affected organisms

Not Available

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Cyproterone 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.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

Not Available

Products

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
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Ruconest	Injection, powder, for solution	2100 U/1	Intravenous	Pharming Healthcare Inc.	2018-04-01	Not applicable
Ruconest	Injection, powder, for solution	2100 U/1	Intravenous	Bioconnection B.V.	2014-09-22	Not applicable
Ruconest	Injection, powder, for solution	2100 U/1	Intravenous	Santarus, Inc.	2014-09-22	2022-01-18
Ruconest	Injection, powder, for solution	2100 U/1	Intravenous	Tjoapack Netherlands Bv	2016-09-19	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

B06AC04 — Conestat alfa

• B06AC — Drugs used in hereditary angioedema
• B06A — OTHER HEMATOLOGICAL AGENTS
• B06 — OTHER HEMATOLOGICAL AGENTS
• B — BLOOD AND BLOOD FORMING ORGANS

Drug Categories

• Blood and Blood Forming Organs
• C1 inhibitors
• Drugs Used in Hereditary Angioedema
• Protease Inhibitors

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

Chemical Identifiers

UNII

5QS67N4551

CAS number

80295-38-1

References

General References

1. 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. [PubMed:16267649]
2. 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. [PubMed:123251]
3. PENSKY J, LEVY LR, LEPOW IH: Partial purification of a serum inhibitor of C'1-esterase. J Biol Chem. 1961 Jun;236:1674-9. [PubMed:13734157]
4. van der Graaf F, Koedam JA, Bouma BN: Inactivation of kallikrein in human plasma. J Clin Invest. 1983 Jan;71(1):149-58. [PubMed:6184384]
5. 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. [PubMed:6725552]
6. 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. [PubMed:11460008]
7. 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. [PubMed:3756141]

External Links

UniProt

P05155

PubChem Substance

347910420

RxNav

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
3	Completed	Treatment	Angioneurotic Edema / Genetic Disorders / Hereditary Angioedema	1
2	Completed	Prevention	Acute Kidney Injury (AKI)	1
2	Completed	Prevention	Hereditary Angioedema	1
2	Completed	Treatment	Genetic Disorders	1
2	Completed	Treatment	Genetic Disorders / Hereditary Angioedema	1
2	Completed	Treatment	Hereditary Angioedema	1
2	Not Yet Recruiting	Treatment	Confirmed Coronavirus Disease / Novel Coronavirus Infectious Disease (COVID-19)	1
2	Recruiting	Treatment	Infections, Coronavirus / Novel Coronavirus Infectious Disease (COVID-19)	1
2, 3	Completed	Treatment	Angioneurotic Edema / Hereditary Angioedema	1
2, 3	Completed	Treatment	Genetic Disorders	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Parenteral	2000 I.E.
Injection, powder, for solution	Parenteral	3000 I.E.
Injection, powder, for solution	Parenteral	500 I.E.
Injection, powder, for solution	Intravenous	2100 U
Injection, powder, for solution	Intravenous	2100 U/1
Injection, solution	Intravenous	2100 U

Prices

Not Available

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Not Available

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Drug created on October 22, 2015 15:00 / Updated on June 12, 2020 11:42