Conestat alfa

Summary

Conestat alfa (Ruconest) is a recombinant human C1 esterase inhibitor derived from the milk of transgenic rabbits. It is approved for the treatment of acute attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency in adults and adolescents. By restoring C1-INH activity, it controls complement and contact pathway activation, reducing bradykinin-mediated swelling episodes.

Mechanism of Action

Recombinant human C1 esterase inhibitor (rhC1-INH) that replaces deficient or dysfunctional C1-INH in hereditary angioedema (HAE). It inhibits activated complement proteases C1r and C1s, as well as plasma kallikrein and factor XIIa, thereby reducing bradykinin generation and preventing vascular permeability and edema formation.

Routes of Administration

Goals & Uses

• Treatment of acute HAE attacksTherapeuticHigh
• Reduction of bradykinin-mediated edemaTherapeuticHigh
• Complement pathway regulationMechanisticHigh
• Prophylaxis of HAE attacksTherapeuticLow

Contraindications

• Rabbit allergyHypersensitivityHigh
• Hypersensitivity to conestat alfa or excipientsHypersensitivityHigh

Adverse Effects

• Thrombotic eventsCardiovascularRare
• Hypersensitivity / anaphylaxisImmunologicalRare
• HeadacheNeurologicCommonPain in the head or upper neck
• Injection/infusion site reactionsLocalUncommon
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• DizzinessNeurologicUncommonFeeling faint, lightheaded, or unsteady

Drug Interactions

• tPA (tissue plasminogen activator)Moderate

Population Constraints

• PregnancyReproductive SafetyRelative
• BreastfeedingReproductiveRelative
• Pediatric patients under 13 yearsAgeRelative
• Renal or hepatic impairmentOrgan DysfunctionRelative

Regulatory Status

• European UnionApprovedApproved: Treatment of acute attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency in adults and adolescents (≥13 years)Approved by EMA in 2010 under the brand name Ruconest; centralized procedure.
• United StatesApprovedApproved: Treatment of acute attacks of hereditary angioedema in adults and adolescentsFDA approved in July 2014 under brand name Ruconest; orphan drug designation.
• United KingdomApprovedApproved: Treatment of acute attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency in adults and adolescents (≥13 years)Retains approval in UK post-Brexit under MHRA; same indications as EU approval.

Approved by the EMA (2010) and the FDA (2014) for acute HAE attacks. Not indicated for prophylaxis of HAE attacks. Contraindicated in patients with known or suspected allergy to rabbits due to production in transgenic rabbit milk.

Evidence & Sources

No sources recorded yet.