a1-Proteinase Inhibitor (Human)

Class: Respiratory Tract Agents, Miscellaneous
VA Class: RE900
Brands: Aralast, Prolastin, Zemaira

Introduction

A naturally occurring serine protease inhibitor.1 2 3 11 15

Uses for a1-Proteinase Inhibitor (Human)

Congenital α1-Proteinase Inhibitor Deficiency

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

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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.a

a1-Proteinase Inhibitor (Human) Dosage and Administration

Administration

IV Administration

Administer by IV infusion.1 3 11

Administer IV infusions of Zemaira through an IV line using an administration set that contains an inline filter (pore size 5 mcm).b

Monitor infusion rate and clinical status (e.g., vital signs, infusion-related reactions) of the patient continuously throughout the infusion.1 11

Administer with caution; percutaneous puncture with a needle contaminated with blood may transmit infectious agents.3 15 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.)

Reconstitution

Vials of lyophilized α1-proteinase inhibitor and diluent should be at room temperature before reconstitution.1 3 11

Reconstitute vials of lyophilized α1-proteinase inhibitor with manufacturer-supplied sterile water for injection without preservatives.b c d Using the supplied transfer needle or device, add the appropriate volume of the supplied diluent to a vial containing α1-proteinase inhibitor. (See Table 1.)b c d Swirl vial gently to ensure dissolution; do not shake.b c d

Approximate amount (mg or g) of functionally active α1-proteinase inhibitor.b c d

Manufacturer-supplied sterile water for injection without preservatives.b c d

Table 1. Reconstitution of α1-Proteinase Inhibitor Preparations

α1-Proteinase Inhibitor Preparation

Dosage Strength Labeled on Vial

Diluent Volume

Aralast

500 mg

25 mL1 16

Aralast

1 g

50 mL1 16

Prolastin

500 mg

20 mL3 9 15

Prolastin

1 g

40 mL3 9 15

Zemaira

1 g

20 mL11 15

Resultant solution of Aralast, Prolastin, or Zemaira contains not less than (NLT) 16 mg, NLT 20 mg, or approximately 50 mg of α1-proteinase inhibitor per mL, respectively.1 3 15

For administration of large doses, 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

Withdraw reconstituted solutions of Aralast and Prolastin from the vial using a filter needle provided by the manufacturer.1 3 9 16

Reconstituted solutions contain no preservatives; administer within 3 hours after reconstitution.1 3 11

Any unused solution should be discarded; discard administration equipment in accordance with biohazard waste procedures.3 11 16 1 3 11

Rate of Administration

Administer Aralast at an infusion rate ≤0.08 mL/kg per minute.1 11

Administer Zemaira at an infusion rate of approximately 0.08 mL/kg per minute.b

Administer Prolastin at an infusion rate of ≥0.08 mL/kg per minute.b

If adverse effects occur, reduce infusion rate or temporarily interrupt infusion until manifestations subside.1 15 Infusion may then be resumed at a rate tolerated by the patient.1 15

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

Number of mg of functionally active α1-proteinase inhibitor is indicated on the label of each vial.1 3 11 15 16

Specific activity of functional α1-proteinase inhibitor in Aralast, Prolastin, or Zemaira is NLT 0.55, NLT 0.35, or NLT 0.7 mg, respectively, per mg of protein.1 3 11

Adults

Congenital α1-Proteinase Inhibitor Deficiency
IV

60 mg/kg by IV infusion once weekly.1 3 11

Cautions for a1-Proteinase Inhibitor (Human)

Contraindications

  • Individuals with selective IgA deficiencies1 3 11 (IgA concentrations <15 mg/dL) who have antibodies to IgA.1

  • History of anaphylaxis or severe systemic reaction to α1-proteinase inhibitors.b

  • Known hypersensitivity to α1-proteinase inhibitor or any ingredient in the formulation.b

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Potential vehicle for transmission of human viruses (i.e., hepatitis A [HAV] or C virus [HCV]; HIV-1 or HIV-2; parvovirus B19)1 3 5 11 or other infectious agents.1 3 5 11

Despite stringent procedures (e.g., screening of plasma donors, application of a number of viral elimination/reduction steps) to prevent transmission of infectious agents, a risk of transmission still remains.1 3 11 12

Risk of viral infection should be weighed against the benefits of α1-proteinase inhibitor therapy.1 3 11

All infections thought possible to have been transmitted by α1-proteinase inhibitor products should be reported to the appropriate manufacturer.1 3 11

Risk of Creutzfeldt-Jakob Disease

May carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD), although transmission via human blood, blood components, or plasma derivatives (including α1-proteinase inhibitor) has not been documented.b c d e CJD is a rare, but invariably fatal, degenerative disease of the CNS associated with a poorly understood transmissable agent.e

There remains a theoretical risk that CJD can be transmitted through blood or blood products, although the risk is considered extremely remote.b c d e

Sensitivity Reactions

Hypersensitivity Reactions

Potential serious hypersensitivity reactions (e.g., anaphylactic or anaphylactoid reactions).1 11

If acute hypersensitivity reactions (e.g., hives, generalized urticaria, tightness of the chest, dyspnea, wheezing, faintness, hypotension, anaphylaxis) occur, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen).1 11

General Precautions

Expansion of Plasma Volume

Transient expansion of plasma volume may occur during infusion; administer cautiously to patients at risk for circulatory overload.3 11

Specific Populations

Pregnancy

Category C.b c d

Lactation

Not known whether α1-proteinase inhibitor is distributed into milk.1 3 11 Caution advised if α1-proteinase inhibitor is used.1 3 11

Pediatric Use

Safety and efficacy not established.1

Hepatic Impairment

Use not recommended in patients with liver disease associated with α1-proteinase inhibitor deficiency.17

Common Adverse Effects

Headache,1 11 somnolence,1 delayed fever,3 lightheadedness,3 dizziness,3 11 asthenia,11 injection site pain,11 paresthesia,11 pruritus.11

Stability

Storage

Parenteral

Powder for Injection

Prolastin and Zemaira: ≤25°C; do not freeze.b d

Aralast: 2–8°C (may be exposed to ≤25°C); do not freeze.c Use within 1 month of removing from refrigeration.c

Actions

  • Inhibits serine proteases, which thereby helps prevent proteolytic destruction of the connective tissue framework of the lung parenchyma.1 3 11

Advice to Patients

  • Importance of patients understanding potential risks of therapy, including hypersensitivity reactions and possible transmission of infectious agents.1 3 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 patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

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

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 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. [IDIS 458419] [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. [IDIS 484066] [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. [IDIS 497645] [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. [IDIS 461320] [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. [IDIS 337029] [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]

a. AHFS drug information 2006. McEvoy GK, ed. α1-Proteinase Inhibitor (Human). Bethesda, MD: American Society of Health-System Pharmacists; 2006:2678-80.

b. ZLB Behring LLC. Alpha1-proteinase inhibitor Zemaira (alpha1-proteinase inhibitor[human]) prescribing information. Kankakee, IL; 2006 Mar.

c. Baxter Healthcare Corporation. Aralast (alpha1-proteinase inhibitor[human]) prescribing information. Westlake Village, CA; 2005 Aug.

d. Talecris Biotherapeutics, Inc. Prolastin (alpha1-proteinase inhibitor [human]) prescribing information. Research Triangle Park, NC; 2005 Jan.

e. AHFS drug information 2006. McEvoy GK, ed. Albumin Human. Bethesda, MD: American Society of Health-System Pharmacists; 2006:1414-6.

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