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Congenital Alpha1-Antitrypsin Deficiency
Alpha1-Proteinase Inhibitor (Human), Prolastin (alpha) is indicated for chronic replacement therapy of individuals having congenital deficiency of alpha1-PI (alpha1-antitrypsin deficiency) with clinically demonstrable panacinar emphysema. Clinical and biochemical studies have demonstrated that with such therapy, it is possible to increase plasma levels of alpha1-PI, and that levels of functionally active alpha1-PI in the lung epithelial lining fluid are increased proportionately.18-20 As some individuals with alpha1-antitrypsin deficiency will not go on to develop panacinar emphysema, only those with evidence of such disease should be considered for chronic replacement therapy with Prolastin (alpha) .22 Subjects with the PiMZ or PiMS phenotypes of alpha1-antitrypsin deficiency should not be considered for such treatment as they appear to be at small risk for panacinar emphysema.22 Clinical data are not available as to the long-term effects derived from chronic replacement therapy of individuals with alpha1-antitrypsin deficiency with Prolastin (alpha) . Only adult subjects have received Prolastin (alpha) to date.
Prolastin (alpha) is not indicated for use in patients other than those with PiZZ, PiZ(null) or Pi(null)(null) phenotypes.
DOSAGE AND ADMINISTRATION
FOR INTRAVENOUS USE ONLY
Each bottle of Alpha1-Proteinase Inhibitor (Human), Prolastin (alpha) has the functional activity, as determined by inhibition of porcine pancreatic elastase,1 stated on the label of the bottle.
The “threshold” level of alpha1-PI in the serum believed to provide adequate anti-elastase activity in the lung of individuals with alpha1-antitrypsin deficiency is 80 mg/dL (based on commercial standards for alpha1-PI immunologic assay).12,15,17 However, assays of alpha1-PI based on commercial standards measure antigenic activity of alpha1-PI, whereas the labeled potency value of alpha1-PI is expressed as actual functional activity, i.e., actual capacity to neutralize porcine pancreatic elastase. As functional activity may be less than antigenic activity, serum levels of alpha1-PI determined using commercial immunologic assays may not accurately reflect actual functional alpha1-PI levels. Therefore, although it may be helpful to monitor serum levels of alpha1-PI in individuals receiving Prolastin (alpha) , using currently available commercial assays of antigenic activity, results of these assays should not be used to determine the required therapeutic dosage.
The recommended dosage of Prolastin (alpha) is 60 mg/kg body weight administered once weekly. This dose is intended to increase and maintain a level of functional alpha1-PI in the epithelial lining of the lower respiratory tract, providing adequate anti-elastase activity in the lung of individuals with alpha1-antitrypsin deficiency.
Alpha1-Proteinase Inhibitor (Human), Prolastin (alpha) may be given at a rate of 0.08 mL/kg/min or greater and must be administered intravenously. The recommended dosage of 60 mg/kg takes approximately 30 minutes to infuse.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Safety and effectiveness in pediatric patients has not been established.
Note: Aseptic technique should be carefully followed. All needles and vial tops that will come into contact with the product to be administered via the intravenous route should not come in contact with any nonsterile surface. Any contaminated needles should be discarded by placing in a puncture-proof container and new equipment should be used.
- After removing all items from the box, warm the sterile water (diluent) to room temperature (25°C, 77°F).
- Remove the plastic flip tops from each vial (Fig. A). Cleanse vial tops (grey stoppers) with alcohol swab and allow surface to dry. After cleaning, do not allow anything to touch the latex (rubber) stopper.
- Carefully remove the plastic sheath from the short end of the transfer needle. Insert the exposed needle into the diluent vial to the hub (Fig.B).
- Carefully grip the sheath of the other end of the transfer needle and twist to remove it.
- Invert the diluent vial and insert the attached needle into the vial of concentrate at a 45°angle (Fig. C). This will direct the stream of diluent against the wall of the concentrate vial and minimize foaming. The vacuum will draw the diluent into the concentrate vial.
- Remove the diluent bottle and transfer needle (Fig. D).
- Gently swirl the concentrate bottle until the powder is completely dissolved (Fig. E). The vial should then be visually inspected for particulate matter and discoloration prior to administration.
- Clean the top of the vial of reconstituted Alpha1-Proteinase Inhibitor (Human), Prolastin (alpha) again with alcohol swab and let surface dry.
- Attach the filter needle (from the package) to sterile syringe. Withdraw the Prolastin (alpha) solution into the syringe through the filter needle (Fig. F).
- Remove the filter needle from the syringe and replace with an appropriate injection needle for administration. Discard filter needle into a puncture-proof container.
- The contents of more than one bottle of Prolastin (alpha) may be drawn into the same syringe before administration. If more than one bottle of Prolastin (alpha) is used, withdraw contents from bottles using aseptic technique. Place contents into an administration container (plastic minibag or glass bottle) using a syringe. * Avoid pushing an I.V. administration set spike into the product container stopper as this has been known to force the stopper into the vial, with a resulting loss of sterility.
A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly, that the directions be followed carefully during use, and that the risk of transmitting viruses be carefully weighed before the product is prescribed.
*For a patient of average weight (about 70 kg) the volume needed will exceed the limit of one syringe.
Alpha1-Proteinase Inhibitor (Human), Prolastin (alpha) is supplied in the following single use vials with the total alpha1-PI functional activity, in milligrams, stated on the label of each vial. A suitable volume of Sterile Water for Injection, USP, is provided.
|NDC Number||Approximate alpha1-PI
|13533-601-30||500 mg||20 mL|
|13533-601-35||1000 mg||40 mL|
Prolastin (alpha) should be stored at temperatures not to exceed 25°C (77°F). Freezing should be avoided as breakage of the diluent bottle might occur.
1.Coan MH, Brockway WJ, Eguizabal H, et al: Preparation and properties of alpha1-proteinase inhibitor concentrate from human plasma. Vox Sang 48(6):333-42, 1985.
12. Gadek JE, Fells GA, Zimmerman RL, et al: Antielastases of the human alveolar structures: implications for the protease-antiprotease theory of emphysema. J Clin Invest 68(4):889-98, 1981.
15. Gadek JE, Crystal RG: alpha1-antitrypsin deficiency. In: Stanbury JB, Wyngaarden JB, Frederickson DS, et al, eds.: The Metabolic Basis of Inherited Disease. 5th ed. New York, McGraw-Hill, 1983, p.1450-67.
17. Gadek JE, Klein HG, Holland PV, et al: Replacement therapy of alpha1-antitrypsin deficiency: reversal of pro- tease-antiprotease imbalance within the alveolar structures of PiZ subjects. J Clin Invest 68(5): 1158-65, 1981.
18. Data on file.
19. Wewers MD, Casolaro MA, Sellers SE, et al: Replacement therapy for alpha1-antitrypsin deficiency associated with emphysema. N Engl J Med 316(17): 1055-62,1987.
20. Wewers MD, Casolaro MA, Crystal RG: Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy. Am Rev Respir Dis 135(3):539-43, 1987.
22. Cohen AB: Unraveling the mysteries of alpha1-antitrypsin deficiency. N Engl J Med 314(12):778-9, 1986.
Talecris Biotherapeutics, Inc., Research Triangle Park, NC 27709, USA. FDA revision date: n/aThis monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/6/2008
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