Alpha-1-proteinase inhibitor

Summary

Alpha-1-proteinase inhibitor (also known as alpha-1-antitrypsin) is a plasma-derived or recombinant glycoprotein used as augmentation therapy in adults with clinically evident emphysema due to severe hereditary alpha-1-antitrypsin deficiency. It protects the lower respiratory tract from proteolytic damage by neutrophil-derived serine proteases.

Mechanism of Action

Alpha-1-proteinase inhibitor (A1PI) is an endogenous serine protease inhibitor that irreversibly binds to and neutralizes neutrophil elastase, proteinase 3, and cathepsin G, preventing proteolytic degradation of lung connective tissue, particularly elastin. In deficiency states, augmentation therapy restores serum and lung A1PI levels above a protective threshold (~11 µM).

Routes of Administration

Goals & Uses

• Reduction of acute exacerbationsPulmonaryLow
• Slowing emphysema progression in alpha-1-antitrypsin deficiencyPulmonary / Disease ModificationModerate
• Raising serum A1PI above protective thresholdBiochemical/Surrogate EndpointHigh

Contraindications

• IgA deficiency with anti-IgA antibodiesImmunologicalHigh
• Hypersensitivity to A1PI or any product excipientImmunologicalHigh
• Alpha-1-antitrypsin deficiency without emphysema (Pi*MZ heterozygotes with normal levels)Indication MismatchModerate

Adverse Effects

• AnaphylaxisImmunologicRareSevere life-threatening allergic reaction
• HeadacheNeurologicCommonPain in the head or upper neck
• Upper respiratory tract infectionInfectiousCommon
• Theoretical risk of transmissible pathogensInfectiousRare
• Infusion-related reactions (fever, chills, flushing)Immunological / InfusionUncommon
• DizzinessNeurologicUncommonFeeling faint, lightheaded, or unsteady

Drug Interactions

• Tobacco smoke / cigarette smokingHigh

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• Patients with cardiac or renal impairmentComorbidityRelative

Regulatory Status

• European UnionApprovedApproved: Augmentation therapy in adults with severe alpha-1-proteinase inhibitor deficiency and established emphysemaRespreeza (CSL Behring) approved by EMA; other formulations may vary by member state.
• United StatesApprovedApproved: Chronic augmentation and maintenance therapy in adults with alpha-1-antitrypsin deficiency and clinically evident emphysemaMultiple brand formulations approved (Prolastin-C, Zemaira, Glassia, Aralast NP). Weekly IV dosing at 60 mg/kg.
• United KingdomApprovedApproved: Augmentation therapy in adults with severe hereditary alpha-1-antitrypsin deficiency and emphysemaMHRA-approved products available; NHS access subject to commissioning criteria.

Multiple plasma-derived formulations (Prolastin-C, Zemaira, Glassia, Aralast NP) are FDA-approved in the US for augmentation therapy in adults with alpha-1-antitrypsin deficiency and emphysema. EMA has approved several formulations in the EU. All products are derived from pooled human plasma and undergo viral inactivation procedures.

Evidence & Sources

No sources recorded yet.