alpha 1 proteinase inhibitor

Action and Spectrum

Actions and Spectrum: 

Alpha 1 proteinase inhibitor (also known as alpha 1-antitrypsin or A1AT) is a serine protease inhibitor that plays key role in regulating the activity of proteases in the body. Here’s an overview of its action and spectrum: 

• Action: Alpha 1 proteinase inhibitor acts primarily as an inhibitor of neutrophil elastase, a potent protease enzyme that can damage tissues in the body. It binds to and forms a complex with neutrophil elastase, inhibiting its activity and preventing excessive tissue degradation. 
• Spectrum: Alpha 1 proteinase inhibitor is primarily active against neutrophil elastase but can also inhibit other proteases, including proteinase 3 and cathepsin G. These enzymes are released by neutrophils during inflammation and can cause tissue damage if not adequately regulated. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Enhanced AST, ALT 

1-10% 

Increased cough (0.6%) 

Headache (0.7%) 

Pharyngitis (1.6%) 

<1% 

Chest pain (0.1%) 

Rash (0.1%) 

Pruritus (0.1%) 

Dizziness (0.1%) 

Headache (0.3%) 

Chills and fever (0.1%) 

Increased cough (0.1%) 

Vasodilation (0.1%) 

Somnolence (0.3%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

Using alpha 1 proteinase inhibitor (A1PI) may be contraindicated or require special consideration in certain situations. Here are some contraindications and precautions associated with A1PI therapy: 

• Hypersensitivity: A1PI is derived from human plasma, and individuals with known hypersensitivity/allergic reaction to A1PI or any of its components generally should not receive this therapy. 
• IgA deficiency: A1PI products may contain small amounts of immunoglobulin A (IgA). Patients with known IgA deficiency may have an increased risk of developing antibodies against IgA, which could potentially cause severe allergic reactions. A1PI should be used with caution in these individuals. 
• Acute pulmonary edema: A1PI is not indicated for treating acute pulmonary edema. Other appropriate therapies should be considered if a patient presents with acute respiratory distress and requires emergency treatment for acute pulmonary edema. 
• Thrombosis risk: There have been rare reports of thromboembolic events associated with A1PI therapy, particularly in patients receiving high doses or those with risk factors for thrombosis. A1PI should be used with caution in individuals with a history of thrombosis or known risk factors for thrombosis. 
• Pregnancy and breastfeeding: The use of A1PI during pregnancy or breastfeeding should be considered based on the potential benefits and risks. There is lesser data available regarding the safety of A1PI in these situations, and healthcare providers should carefully assess the need for therapy. 

It is important to note that contraindications and precautions may vary depending on the specific product and country-specific labeling. Therefore, it is crucial to consult the prescribing information and guidelines specific to the product and country of use. Additionally, healthcare professionals should evaluate individual patient factors and medical history when considering A1PI therapy. 

Caution 

There are some critical cautions and considerations to remember when using A1PI. These include: 

• Allergic reactions: Although rare, they can occur with A1PI therapy. Patients should be generally monitored for signs of allergic reactions during and after infusion, especially in individuals with a history of allergies to A1PI or any other product components. 
• Administration-related risks: A1PI is administered intravenously, and as with any intravenous therapy, there are risks associated with the administration process. These include infection at the infusion site, venous access-related complications, and potential infusion reactions. Proper sterile techniques should be followed during administration, and patients should be typically monitored for adverse reactions during the infusion. 
• Immunogenicity: In rare cases, patients may develop antibodies against A1PI, which can reduce its effectiveness. Regular monitoring of A1PI levels and clinical response is vital to assess the need for dose adjustments or alternative treatments. 
• Interactions with other therapies: A1PI therapy may interact with other medications, especially those that affect coagulation or platelet function. It is essential to consider potential drug interactions when prescribing A1PI and to monitor patients closely if they take other medications that may increase the risk of bleeding or thrombosis. 
• Disease transmission: A1PI is derived from human plasma, and although stringent screening and purification processes are implemented, there is still a small risk of transmitting infectious agents. This risk is shallow due to extensive manufacturing processes, including viral inactivation and removal steps. However, it is important to follow established guidelines and regulations for using plasma-derived products to minimize the risk of disease transmission. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: B2
US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

A1PI is a serine protease inhibitor that primarily inhibits neutrophil elastase, a protease enzyme involved in tissue degradation. A1PI forms a complex with neutrophil elastase, leading to its inactivation and preventing excessive tissue damage. It also has inhibitory activity against other proteases, including proteinase 3 and cathepsin G. 

Pharmacodynamics: 

Mechanism of action: The action of alpha 1 proteinase inhibitor (A1PI), also known as alpha 1-antitrypsin, involves its role as a serine protease inhibitor. Here’s an overview of its mechanism of action: 

• Inhibition of protease enzymes: A1PI acts as a natural inhibitor of various protease enzymes, with its primary target being neutrophil elastase. Neutrophil elastase is an enzyme released by neutrophils, a type of white blood cell, during inflammation. It is involved in the breakdown of connective tissues, particularly elastin, which contributes to the structural integrity of organs such as the lungs. 
• Formation of protease-inhibitor complexes: A1PI forms reversible covalent complexes with neutrophil elastase and other proteases. By binding to these enzymes, A1PI blocks their catalytic activity and prevents them from degrading tissue components. This interaction between A1PI and proteases occurs via a reactive site loop in the A1PI molecule. 
• Protection of tissues from damage: The primary function of A1PI’s inhibition of protease enzymes, particularly neutrophil elastase, is to protect tissues from excessive proteolysis. In conditions like alpha 1-antitrypsin deficiency, where A1PI levels are reduced or dysfunctional, the balance between proteases and their inhibitors is disrupted. This imbalance can lead to tissue damage, particularly in the lungs. 
• Preservation of lung function: By inhibiting neutrophil elastase, A1PI helps preserve lung tissue integrity and function. Neutrophil elastase activity contributes to the development and progression of lung diseases such as chronic obstructive pulmonary disease (COPD) and emphysema. A1PI therapy aims to restore the protease-antiprotease balance, reducing the impact of protease-mediated tissue damage and preserving lung function. 

Pharmacokinetics: 

Absorption 

A1PI is administered intravenously as it is a protein-based therapeutic. 

Distribution 

Once administered intravenously, A1PI is distributed within the extracellular fluid compartment. It can reach various tissues and organs throughout the body, including the lungs, where it exerts its therapeutic effects. 

Metabolism 

A1PI is primarily metabolized in the liver. The exact metabolic pathways and enzymes involved in the breakdown of A1PI have yet to be extensively studied. However, the liver metabolizes proteins and clears them from circulation. 

Elimination and Excretion 

A1PI has a relatively long half-life of approximately 5-6 days. It is primarily eliminated via hepatic clearance, where the liver removes A1PI from the bloodstream and processes it. Some portion of A1PI may also be cleared by other elimination pathways, such as renal excretion, although the exact contribution of renal clearance needs to be well-established. 

Adminstartion

Administration: 

Intravenous administration 

Alpha 1 proteinase inhibitor (A1PI) is administered through intravenous infusion. Here are some general guidelines for the administration of A1PI: 

• Preparation: A1PI is typically supplied as a lyophilized powder in vials. According to the manufacturer’s instructions, the powder must be reconstituted with the provided diluent or a compatible sterile diluent. Care should be taken to follow aseptic techniques during reconstitution. 
• Infusion rate: The recommended infusion rate may vary depending on the specific product and individual patient factors. It is essential to refer to the product’s prescription information for instructions on infusion rates. In general, the infusion rate should be slow initially, and if well-tolerated, it can be increased gradually over time. The infusion rate and duration can vary from patient to patient, but it is typically completed within 15-30 minutes. 
• Administration site: A1PI is typically administered through a peripheral vein or a central line. Proper venous access should be established using aseptic techniques per the healthcare facility’s standard protocols. The infusion site should be generally monitored for signs of infection, infiltration, or other adverse reactions during and after administration. 
• Precautions during administration: Healthcare providers should closely monitor patients during the infusion for any signs of allergic reactions, infusion-related adverse events, or other adverse reactions. Vital signs should be regularly assessed, including heart rate, blood pressure, and oxygen saturation. 
• Follow-up care: Following the administration of A1PI, patients should be monitored for any delayed adverse reactions or complications. Healthcare providers should provide appropriate post-infusion care instructions to the patient, including any signs or symptoms that should be reported and steps to take in case of adverse events. 

The specific administration guidelines may differ depending on the product, dosage, and country-specific recommendations. As with any medical treatment, the administration of A1PI should be performed by qualified healthcare professionals familiar with the specific product and its administrative requirements. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: alpha 1 proteinase inhibitor 

Pronounced: [ AL-fa-1-PRO-tee-nase-in-HIB-i-tor ] 

Why do we use alpha 1 proteinase inhibitor? 

Alpha 1 proteinase inhibitor (A1PI), also known as alpha 1-antitrypsin, has several important therapeutic uses. The primary use of A1PI is in treating individuals with alpha 1-antitrypsin deficiency (AATD). Here are the primary uses of A1PI: 

• Alpha 1-antitrypsin deficiency: A1PI therapy is a cornerstone treatment for individuals with AATD, a genetic disorder characterized by a deficiency or dysfunction of the A1PI protein. AATD primarily affects the lungs and liver, increasing the risk of developing COPD (chronic obstructive pulmonary disease), emphysema, and liver disease. A1PI therapy involves the administration of exogenous A1PI to restore normal levels and protect the lungs from further damage. It can help slow the progression of lung disease and improve lung function in individuals with AATD. 
• Emphysema associated with AATD: AATD-related emphysema is a form of lung disease characterized by the destruction of lung tissue due to a deficiency of A1PI. A1PI therapy can help slow down the progression of emphysema, improve lung function, and reduce symptoms such as shortness of breath. 
• Maintenance therapy for COPD: In addition to its use in AATD-related lung disease, A1PI therapy may also be considered a maintenance treatment for individuals with severe COPD and documented A1PI deficiency. In these cases, A1PI therapy aims to supplement the deficient protein and reduce the risk of further lung damage. 

It is important to note that A1PI therapy is primarily indicated for patients with confirmed A1PI deficiency and associated lung disease. The use of A1PI in other conditions or individuals without deficiency is limited. 

Please remember that the specific therapeutic uses and indications of A1PI may vary based on factors such as regional guidelines, the severity of the condition, and individual patient characteristics.

Consultation with a healthcare professional familiar with A1PI therapy is essential to determine the appropriate use and dosage in specific clinical situations.