Alpha1-proteinase inhibitor (human)

Alpha 1 -Proteinase Inhibitor (Human), Zemaira™, is a sterile, stable, lyophilized preparation of highly purified human alpha 1 -proteinase inhibitor (A 1 -PI), also known as alpha 1 -antitrypsin, derived from human plasma. Zemaira™ is manufactured from large pools of human plasma by cold ethanol fractionation according to a modified Cohn process followed by additional purification steps.

Zemaira™ is supplied as a sterile, white, lyophilized powder to be administered by the intravenous route. The specific activity of Zemaira™ is >/=0.7 mg of functional A 1 -PI per milligram of total protein. The purity is >/=90% A 1 -PI. Following reconstitution with 20 mL of Sterile Water for Injection, U.S.P., each vial contains approximately 1000 mg of functionally active A 1 -PI, 81 mM sodium, 38 mM chloride, 17 mM phosphate, and 144 mM mannitol. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH. Zemaira™ contains no preservatives.

Each vial of Zemaira™ contains the labeled amount of functionally active A 1 -PI in milligrams as stated on the vial label as determined by its capacity to neutralize human neutrophil elastase.

The plasma used in the manufacture of this product has been tested and found to be nonreactive to HBsAg, nonreactive for antibody to Hepatitis C Virus (Anti-HCV), and negative for antibody to Human Immunodeficiency Virus (Anti-HIV-1/HIV-2).

Two viral reduction steps are employed in the manufacture of Zemaira™: pasteurization at 60°C for 10 hours in an aqueous solution with stabilizers and two sequential ultrafiltration steps. These viral reduction steps have been validated in a series of in vitro experiments for their capacity to inactivate/remove Human Immunodeficiency Virus (HIV), Hepatitis A Virus (HAV), and the following model viruses: Bovine Viral Diarrhea Virus (BVDV) as a model virus for HCV, Canine Parvovirus (CPV) as a model virus for Parvovirus B19, and Pseudorabies Virus (PRV) as a non-specific model virus to cover a wide range of physiochemical properties of the viruses studied. Total mean log 10 reductions range from 6.8 to >12.2 log 10 as shown in Table 1.

Zemaira™ is contraindicated in individuals with a known hypersensitivity to any of its components. Zemaira™ is also contraindicated in individuals with a history of anaphylaxis or severe systemic response to A 1 -PI products.

Individuals with selective IgA deficiencies who have known antibodies against IgA (anti-IgA antibodies) should not receive Zemaira™, since these patients may experience severe reactions, including anaphylaxis, to IgA that may be present in Zemaira™.

Zemaira™ is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. Because Zemaira™ is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses during manufacture. (See DESCRIPTION section for viral reduction measures.) The manufacturing procedure for Zemaira™ includes processing steps designed to reduce further the risk of viral transmission. Stringent procedures utilized at plasma collection centers, plasma testing laboratories, and fractionation facilities are designed to reduce the risk of viral transmission. The primary viral reduction steps of the Zemaira™ manufacturing process are pasteurization (60°C for 10 hours) and two sequential ultrafiltration steps. Additional purification procedures used in the manufacture of Zemaira™ also potentially provide viral reduction. Despite these measures, such products may still potentially contain human pathogenic agents, including those not yet known or identified. Thus, the risk of transmission of infectious agents can not be totally eliminated. Any infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Aventis Behring at 800-504-5434. The physician should discuss the risks and benefits of this product with the patient.

Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections (see Information For Patients ).

During clinical studies, no cases of hepatitis A, B, C, or HIV viral infections were reported with the use of Zemaira™.

General -- Infusion rates and the patient's clinical state should be monitored closely during infusion. The patient should be observed for signs of infusion-related reactions.

As with any colloid solution, there may be an increase in plasma volume following intravenous administration of Zemaira™. Caution should therefore be used in patients at risk for circulatory overload.

Information For Patients -- Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, dyspnea, wheezing, faintness, hypotension, and anaphylaxis. Patients should be advised to discontinue use of the product and contact their physician and/or seek immediate emergency care, depending on the severity of the reaction, if these symptoms occur.

As with all plasma-derived products, some viruses, such as parvovirus B19, are particularly difficult to remove or inactivate at this time. Parvovirus B19 may most seriously affect pregnant women and immune-compromised individuals. Symptoms of parvovirus B19 include fever, drowsiness, chills, and runny nose followed two weeks later by a rash and joint pain. Patients should be encouraged to consult their physician if such symptoms occur.

Pregnancy Category C -- Animal reproduction studies have not been conducted with Zemaira™. It is also not known whether Zemaira™ can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Zemaira™ should be given to a pregnant woman only if clearly needed.

Nursing Mothers -- It is not known whether Zemaira™ is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zemaira™ is administered to a nursing woman.

Pediatric Use -- Safety and effectiveness in the pediatric population have not been established.

Geriatric Use -- Clinical studies of Zemaira™ did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. As for all patients, dosing for geriatric patients should be appropriate to their overall situation.

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Prolastin is a registered trademark of Bayer Corporation.

Manufactured by:

Aventis Behring L.L.C.

Kankakee, IL 60901 U.S.A.

U.S. License No. 1281

19131-02

Revised: December 2003