Introduction ⬇
AHFS Class:
Generic Name(s):
- α1-Proteinase Inhibitor (Human)
α1-Proteinase inhibitor is a naturally occurring inhibitor of serine proteases such as neutrophil elastase; this enzyme aids in the proteolytic destruction of the alveolar walls and connective tissue framework of the lung parenchyma.1,2,3,11,15
Uses ⬆ ⬇
Congenital 1-Proteinase Inhibitor Deficiency
α1-Proteinase inhibitor is used for replacement therapy in patients with congenital α1-proteinase inhibitor (also called α1-antitrypsin) deficiency and clinically evident emphysema.1,2,3,7,8,11,15
Congenital α1-proteinase inhibitor deficiency is an autosomal, codominant genetic disorder characterized by deficient serum and lung concentrations of α1-proteinase inhibitor.1,2,3,11 Such a deficiency can create an imbalance between serine proteases (e.g., neutrophil elastase) and α1-proteinase inhibitor in the lungs, resulting in a gradual destruction of pulmonary connective tissue and loss of alveolar units.1,2,3,11 Severe forms of the deficiency are associated with the development of slowly progressive, moderate to severe panacinar emphysema that presents most often in the third or fourth decade of life.1,2,3,11
As some individuals with α1-proteinase inhibitor deficiency will not develop associated panacinar emphysema, 2,3,11 only those with evidence of such disease should be considered for long-term replacement therapy with the drug.1,3,11
α1-Proteinase inhibitor therapy is not indicated as therapy for patients with lung disease in whom congenital α1-proteinase inhibitor deficiency has not been established.1,3,11
The American Thoracic Society and the European Respiratory Society (ATS/ERS) state that α1-proteinase inhibitor therapy does not confer benefit in, and is not recommended for, patients who have α1-proteinase-associated liver disease.
In clinical trials comparing α1-proteinase inhibitor preparations (Aralast®, Zemaira®, Prolastin®) in a limited number of patients with congenital α1-proteinase inhibitor deficiency and emphysema, all preparations produced similar increases in the mean trough serum α1-proteinase inhibitor concentration and antigenic α1-proteinase inhibitor activity in lung epithelial lining fluid.1,5,11 While data from randomized, controlled trials are not available on the long-term clinical effects of α1-proteinase inhibitor therapy, 1,3,11 limited data from cohort studies indicate that such replacement therapy is associated with a lower rate of decline of forced expiratory volume in 1 second (FEV1) among certain patients with congenital α1-proteinase inhibitor deficiency.6,7,8,13
Dosage and Administration ⬆ ⬇
General 
α1-Proteinase inhibitor is administered by IV infusion only.1,3,11
Reconstitution and Administration
The vials of lyophilized α1-proteinase inhibitor and diluent should be at room temperature before reconstitution.1,3,11
Aralast® is reconstituted by adding 25 or 50 mL of sterile water for injection without preservatives from the manufacturer-supplied diluent vial to a vial containing approximately 500 mg (not less than 400 mg) or approximately 1 g (not less than 800 mg) of elastase-inhibitory activity of the drug, respectively, using a transfer needle provided by the manufacturer.1,16
Prolastin® is reconstituted by adding 20 or 40 mL of sterile water for injection without preservatives from the manufacturer-supplied diluent vial to a vial containing approximately 500 mg or 1 m of elastase-inhibitory activity of the drug, respectively, using a transfer needle provided by the manufacturer.3,9,15
Zemaira® is reconstituted by adding 20 mL of sterile water for injection without preservatives from the manufacturer-supplied diluent vial to a vial containing approximately 1 g of elastase-inhibitory activity of the drug, using a transfer device provided by the manufacturer.11,15
Following addition of diluent to the vial of α1-proteinase inhibitor, gently swirl the vial until the contents are completely dissolved.1,3,11 The resultant solution of Aralast®, Prolastin®, or Zemaira® contains not less than 16, not less than 20 mg, or approximately 50 mg of α1-proteinase inhibitor per mL, respectively.1,3,15
If large doses of α1-proteinase inhibitor are to be administered, several reconstituted vials may be pooled into an empty, sterile IV infusion container (e.g., empty IV bag or glass bottle) using aseptic technique.1,3,11,15
Occasionally, a few small particles may remain in the solution of α1-proteinase inhibitor following reconstitution.1,15 The reconstituted solutions of Aralast® and Prolastin® are withdrawn from the vial using a filter needle provided by the manufacturer.1,3,9,16 IV infusions of Zemaira® should be administered through an IV line using an administration set that contains an inline filter (pore size 5 µm); an inline filter is provided by the manufacturer.11,15
Because reconstituted solutions of α1-proteinase inhibitor contain no preservatives, such solutions should be used within 3 hours after reconstitution.1,3,11 No other drug should be added to or administered with an α1-proteinase inhibitor.1 3,15,16 Any unused reconstituted solution should be discarded,1 3,11 and administration equipment should be discarded in accordance with biohazard waste procedures.3,11,16
Dosage
Dosage of α1-proteinase inhibitor in mg is expressed in terms of functionally active α1-proteinase inhibitor, as determined by human neutrophil (Zemaira®) or porcine pancreatic (Aralast®, Prolastin®) elastase inhibitory activity.1,3,5,10,11,15,16 The specific functional activity of α1-proteinase inhibitor in currently available preparations (Aralast®, Prolastin®, Zemaira®) varies from lot to lot. 1,3,11,15,16 The number of mg of functionally active α1-proteinase inhibitor is indicated on the label of each vial.1,3,11,15,16 The specific activity of functional α1-proteinase inhibitor in Aralast®, Prolastin®, or Zemaira® is not less than (NLT) 0.55, NLT 0.35, or NLT 0.7 mg, respectively, per mg of protein.1,3,11
Adults
Congenital 1-Proteinase Inhibitor Deficiency
IV: The recommended dosage of α1-proteinase inhibitor in adults is 60 mg/kg by IV infusion once weekly.1,3,11 An infusion rate not exceeding 0.08 mL/kg per minute generally is recommended.1,11 Infusion rate and clinical status (e.g., vital signs, infusion-related reactions) of the patient should be monitored continuously throughout the infusion.1,11 If adverse effects occur, the rate of infusion should be reduced or the infusion temporarily interrupted until manifestations subside.1,15 The infusion may then be resumed at a rate tolerated by the patient.1,15 (See Sensitivity Reactions under Cautions: Warnings/Precautions.)
Special Populations
No special population dosage recommendations at this time.1,3,11
Cautions ⬆ ⬇
Contraindications
α1-Proteinase inhibitor is contraindicated in individuals with selective IgA deficiencies1,311 (IgA concentrations less than 15 mg/dL)1 who have antibodies to IgA; severe adverse reactions, including anaphylaxis, could result following administration of α-1-proteinase inhibitor preparations, which may contain IgA.1,3,11
Warnings/Precautions
Warnings
Risk of Transmissible Agents in Plasma-derived Preparations
Plasma-derived products such as α1-proteinase inhibitor are potentially capable of transmitting viruses (i.e., hepatitis A [HAV], B [HBV] or C virus [HCV]; human immunodeficiency virus [HIV-1 or HIV-2]; parvovirus B19)1 3,5 11 or agents for other diseases, such as Creutzfeldt-Jakob disease (CJD).1,3,5 11 While currently available α1-proteinase inhibitor preparations are subjected to stringent procedures (e.g., screening of plasma donors, application of a number of viral elimination/reduction steps) to prevent transmission of infectious agents, the risk of infectious agents cannot be totally eliminated.1,3,11,12 (See Risk of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease under Precautions and Contraindications: Risk of Transmissible Agents in Plasma-derived Preparations, in Cautions in Antihemophilic Factor [Human] 20:28.16.) If a patient contracts any infection thought to be transmitted by an α1-proteinase inhibitor, the manufacturer of the product should be notified.1,3,11 To report such infections, the manufacturer of Aralast® may be contacted at 805-372-3281;16 the manufacturer of Prolastin®, at 800-288-8371;3 and the manufacturer of Zemaira®, at 800-504-5434.11
The risk of viral infection associated with use of a plasma-derived preparation such as α1-proteinase inhibitor should be weighed against the benefits of such use.1 3,11 In patients with α1-proteinase inhibitor deficiency who have extrahepatic (e.g., lung) disease alone, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) do not consider immunization for hepatitis B to be essential prior to initiation of α1-proteinase inhibitor therapy.17
Product administration and handling of needles must be done with caution, as percutaneous puncture with a needle contaminated with blood may transmit infectious viruses, including HIV and hepatitis.3,15
Sensitivity Reactions
Epinephrine and other appropriate supportive therapy should be available to treat potential acute anaphylactic or anaphylactoid reactions to α1-proteinase inhibitor.1,11 If acute hypersensitivity reactions (e.g., hives, generalized urticaria, tightness of the chest, dyspnea, wheezing, faintness, hypotension, anaphylaxis) occur, the drug infusion should be discontinued immediately.1,11
General Precautions
Since a transient expansion of plasma volume may occur during infusion of colloidal solutions such as α1-proteinase inhibitor, the drug should be administered cautiously to patients at risk for circulatory overload.3,11
Specific Populations
Pregnancy
Category C. (See Users Guide.)
Lactation
Not known whether α1-proteinase inhibitor is distributed into milk.1,3 11 Since many drugs are distributed into milk, caution is advised if the drug is administered to nursing women.1,3,11
Pediatric Use
Safety and efficacy not established in children younger than 18 years of age.1 However, symptomatic obstructive lung disease usually occurs in patients with α1-proteinase inhibitor deficiency and a history of smoking in the third or fourth decade of life.17
Hepatic Impairment
The American Thoracic Society and the European Respiratory Society (ATS/ERS) do not recommend α1-proteinase inhibitor replacement therapy in patients who have liver disease associated with α1-proteinase inhibitor deficiency.17
Common Adverse Effects
The most common adverse effects reported in patients receiving Aralast® in clinical trials and deemed to be drug-related were headache1 and somnolence.1 Adverse effects reported with Prolastin® therapy in clinical trials include delayed fever (occurring up to 12 hours following treatment),3 lightheadedness,3 and dizziness.3 The most common treatment-related adverse effects reported with Zemaira® in clinical trials include asthenia,11 injection site pain,11 dizziness,11 headache,11 paresthesia,11 and pruritus.11
Other Information ⬆ ⬇
Description
α1-Proteinase inhibitor is a naturally occurring inhibitor of serine proteases, enzymes that aid in proteolytic destruction of the connective tissue framework of the lung parenchyma.1,2,3,11 In patients with congenital α1-proteinase inhibitor deficiency, exogenous administration of an α1-proteinase inhibitor provides another source of enzyme inhibitor that protects lung tissues from proteolytic destruction.1,3,11
Commercially available α1-proteinase inhibitors are sterile lyophilized concentrates of highly purified α1-proteinase inhibitor derived from pooled human plasma.1,3,11 Currently available α1-proteinase inhibitor preparations use cold alcohol fractionation to isolate the enzyme inhibitor from plasma.1,3,11 In addition, to reduce the risk of viral transmission, the manufacture of Aralast® includes a chemical (solvent/detergent) treatment procedure1,5 and additional purification steps (PEG and zinc chloride preparations, ion exchange chromatography).1 .1,5 Solvent/detergent inactivation processes inactivate lipid-enveloped viruses (e.g., hepatitis B, hepatitis C, human immunodeficiency virus type 1 and type 2 [HIV-1 and HIV-2]) but are less effective against viruses that do not have a lipid envelope (e.g., hepatitis A, parvoviruses).1,12,16 The manufacturer of Zemaira® also includes ion exchange chromatography to remove extraneous protein such as albumin.15 The manufacture of Aralast® or Zemaira® incorporates nanofiltration or ultrafiltration step(s), respectively,1 11 to reduce the risk of transmission of nonenveloped viruses.1 The manufacture of Prolastin® or Zemaira® also incorporates a heat-inactivation procedure to reduce the risk of transmission of viral infections.3,5,11
Advice to Patients
Importance of patients understanding potential risks of therapy of α1-proteinase inhibitor therapy, including hypersensitivity reactions and possible transmission of infectious agents.1,3,11 (See Warnings: Risk of Transmissible Agents in Plasma-derived Preparations, in Cautions.)
Importance of informing clinicians if symptoms of parvovirus B19 infection (e.g., fever, drowsiness, chills, and rhinitis followed in 2 weeks by rash and joint pain) occur.11
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 3,11
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1,3,11
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations ⬆ ⬇
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Aralast® and Zemaira® must be obtained from specialty distributors; these preparations are not available through community pharmacies.4,15 For information regarding the Aralast® distribution program, contact the manufacturer at 800-423-2090.4 For information regarding the distribution of Zemaira®, contact the manufacturer at 866-ZEMAIRA (866-936-2472).15
α1-Proteinase Inhibitor (Human)
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Parenteral | For injection, for IV infusion only | number of mg indicated on label | Aralast® (with sterile water for injection diluent, a double-ended transfer needle, and filter) | Baxter |
| | number of mg indicated on label | Prolastin® (with sterile water for injection diluent, double-ended transfer needle, filter needle) | Bayer |
| | number of mg indicated on label | Zemaira® (with sterile water for injection diluent, a double-ended transfer needle, and filter) | ZLB Behring |
Copyright ⬆ ⬇
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions August 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
References ⬆
1. Baxter Healthcare Corporation. Aralast® (alpha1-proteinase inhibitor[human]) prescribing information. Westlake Village, CA; 2003 Jan.
2. Coakley RJ, Taggart C, O'Neill S et al. α1-antitrypsin deficiency: biological answers to clinical questions. Am J Med Sci . 2001; 321:33-41. [PubMed 11202478]
3. Bayer Healthcare Corporation. Prolastin® (alpha1-proteinase inhibitor [human]) prescribing information. Elkhart, IN; 2002 Jan.
4. Baxter Healthcare Corporation. Baxter announces launch of Aralast for patients with hereditary emphysema in need of new therapy. Deerfield,IL; 2003 May 30. Press release.
5. Stoller JK, Rouhani F, Brantly M et al. Biochemical efficacy and safety of a new pooled human plasma alpha(1)-antitrypsin, respitin. Chest . 2002; 122:66-74. [PubMed 12114340]
6. Stoller JK, Fallat R, Schluchter MD et al. Augmentation therapy with alpha1-antitrypsin: patterns of use and adverse events. Chest . 2003; 123:1425-34. [PubMed 12740257]
7. The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in patients with severe deficiency of α1-antitrypsin. Am J Respir Care Med . 1998; 158:49-59.
8. Wencker M, Fuhrmann B, Banik N et al. Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency before and during therapy with IV alpha(1) protease inhibitor. Chest . 2001; 119:676-8. [PubMed 11243938]
9. Bayer Pharmaceutical Division, West Haven, CT: Personal communication.
10. Coan MH, Brockway WJ, Eguizabal H et al. Preparation and properties of alpha1-proteinase inhibitor concentrate from human plasma. Vox Sang . 1985; 48:333-42. [PubMed 3874474]
11. Aventis Behring. Alpha1-proteinase inhibitor (Zemaira®) prescribing information. Kankakee, IL; 2003 Jul.
12. AuBuchon JP, Birkmeyer JD. Safety and cost-effectiveness of solvent-detergent-treated plasma. In search of a zero-risk blood supply. JAMA . 1994; 272:1210-4. [PubMed 7933351]
13. Seersholm N, Wencker M, Banik N et al. Does α1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary α1-antitrypsin deficiency? Eur Respir J . 1997; 10:2260-3.
14. Dirksen A, Dijkman JH, Madsen F et al. A randomized clinical trial of α1-antitrypsin augmentation therapy. Am J Respir Care Med . 1999; 160:1468-72.
15. ZLB Behring, King of Prussia, PA: Personal communication.
16. Baxter Healthcare, Westlake Village, CA: Personal communication.
17. Anon. American Thoracic Society/European Respiratory Society Statement: Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med . 2003; 168:818-900. [PubMed 14522813]