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Prolastin (Alpha 1-proteinase Inhibitor (Human))
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Pharmacology
Alpha 1-antitrypsin deficiency is a chronic, hereditary, usually fatal, autosomal recessive disorder in which a low concentration of alpha 1-Pl (alpha 1-antitrypsin) is associated with slowly progressive, severe panacinar emphysema that most often manifests itself in the third to fourth decades of life. (Although the terms alpha 1-proteinase inhibitor and alpha 1-antitrypsin are used interchangeably in the scientific literature, the hereditary disorder associated with a reduction in the serum level of alpha 1-Pl is conventionally referred to as alpha 1-antitrypsin deficiency while the deficient protein is referred to as alpha 1-proteinase inhibitor). The emphysema is typically worse in the lower lung zones. The pathogenesis of development of emphysema in alpha 1-antitrypsin deficiency is not well understood at this time. It is believed, however, to be due to a chronic biochemical imbalance between elastase (an enzyme capable of degrading elastin tissues, released by inflammatory cells, primarily neutrophils, in the lower respiratory tract) and alpha 1-Pl (the principal inhibitor of neutrophil elastase), which is deficient in alpha 1-antitrypsin disease. As a result, it is believed that alveolar structures are unprotected from chronic exposure to elastase released from a chronic, low-level burden of neutrophils in the lower respiratory tract, resulting in progressive degradation of elastin tissues. The eventual outcome is the development of emphysema. Neonatal hepatitis with cholestatic jaundice appears in approximately 10% of newborns with alpha 1-antitrypsin deficiency. In some adults, alpha 1-antitrypsin deficiency is complicated by cirrhosis.
A large number of phenotypic variants of alpha 1-antitrypsin deficiency exists. The most severely affected individuals are those with the PiZZ variant, typically characterized by alpha 1-Pl serum levels <35% normal. Epidemiologic studies of individuals with various phenotypes of alpha 1-antitrypsin deficiency have demonstrated that individuals with endogenous serum levels of alpha 1-Pl £50mg/dL (based on commercial standards) have a risk of >80% of developing emphysema over a lifetime. However, individuals with endogenous alpha 1-Pl levels >80mg/dL, in general, do not manifest an increased risk for development of emphysema above the general population background risk. From these observations, it is believed that the threshold level of alpha 1-Pl in the serum required to provide adequate anti-elastase activity in the lung of individuals with alpha 1-antitrypsin deficiency is about 80mg/dL (based on commercial standards for immunologic assay of alpha 1-Pl).
In clinical studies of alpha 1-proteinase inhibitor (human), 23subjects with the PiZZ variant of congenital deficiency of alpha 1-antitrypsin deficiency and documented destructive lung disease participated in a study of acute and/or chronic replacement therapy with alpha 1-proteinase inhibitor (human). The mean in vivo recovery of alpha 1-Pl was 4.2mg (immunologic)/dL/mg (functional)/kg body weight administered. The half-life of alpha 1-Pl in vivo was approximately 4.5days. Based on these observations, a program of chronic replacement therapy was developed. Nineteen of the subjects in these studies received alpha 1-proteinase inhibitor (human) replacement therapy, 60mg/kg body weight, once weekly for up to 26weeks (average 24weeks of therapy). With this schedule of replacement therapy, blood levels of alpha 1-Pl were maintained above 80mg/dL (based on the commercial standards for alpha 1-Pl immunologic assay). Within a few weeks of commencing this program, bronchoalveolar lavage studies demonstrated significantly increased levels of alpha 1-Pl and functional antineutrophil elastase capacity in the epithelial lining fluid of the lower respiratory tract of the lung, as compared to levels prior to commencing the program of chronic replacement therapy with alpha 1-proteinase inhibitor (human).
All 23 individuals who participated in the investigations were immunized with hepatitis B vaccine and received a single dose of hepatitis B immune globulin (human) on entry into the investigation. Although no other steps were taken to prevent hepatitis, neither hepatitis B nor non-A, non-B hepatitis occurred in any of the subjects. All subjects remained seronegative for HIV antibody. None of the subjects developed any detectable antibody to alpha 1-Pl or other serum protein.
Long-term controlled clinical trials to evaluate the effect of chronic replacement therapy with alpha 1-proteinase inhibitor (human) on the development of or progression of emphysema in patients with congenital alpha 1-antitrypsin deficiency have not been performed. Estimates of the sample size required of this rare disorder and the slow, progressive nature of the clinical course have been considered impediments in the ability to conduct such a trial. Studies to monitor the long-term effects will continue as part of the postapproval process.
Alpha 1-antitrypsin deficiency is a chronic, hereditary, usually fatal, autosomal recessive disorder in which a low concentration of alpha 1-Pl (alpha 1-antitrypsin) is associated with slowly progressive, severe panacinar emphysema that most often manifests itself in the third to fourth decades of life. (Although the terms alpha 1-proteinase inhibitor and alpha 1-antitrypsin are used interchangeably in the scientific literature, the hereditary disorder associated with a reduction in the serum level of alpha 1-Pl is conventionally referred to as alpha 1-antitrypsin deficiency while the deficient protein is referred to as alpha 1-proteinase inhibitor). The emphysema is typically worse in the lower lung zones. The pathogenesis of development of emphysema in alpha 1-antitrypsin deficiency is not well understood at this time. It is believed, however, to be due to a chronic biochemical imbalance between elastase (an enzyme capable of degrading elastin tissues, released by inflammatory cells, primarily neutrophils, in the lower respiratory tract) and alpha 1-Pl (the principal inhibitor of neutrophil elastase), which is deficient in alpha 1-antitrypsin disease. As a result, it is believed that alveolar structures are unprotected from chronic exposure to elastase released from a chronic, low-level burden of neutrophils in the lower respiratory tract, resulting in progressive degradation of elastin tissues. The eventual outcome is the development of emphysema. Neonatal hepatitis with cholestatic jaundice appears in approximately 10% of newborns with alpha 1-antitrypsin deficiency. In some adults, alpha 1-antitrypsin deficiency is complicated by cirrhosis.
A large number of phenotypic variants of alpha 1-antitrypsin deficiency exists. The most severely affected individuals are those with the PiZZ variant, typically characterized by alpha 1-Pl serum levels <35% normal. Epidemiologic studies of individuals with various phenotypes of alpha 1-antitrypsin deficiency have demonstrated that individuals with endogenous serum levels of alpha 1-Pl £50mg/dL (based on commercial standards) have a risk of >80% of developing emphysema over a lifetime. However, individuals with endogenous alpha 1-Pl levels >80mg/dL, in general, do not manifest an increased risk for development of emphysema above the general population background risk. From these observations, it is believed that the threshold level of alpha 1-Pl in the serum required to provide adequate anti-elastase activity in the lung of individuals with alpha 1-antitrypsin deficiency is about 80mg/dL (based on commercial standards for immunologic assay of alpha 1-Pl).
In clinical studies of alpha 1-proteinase inhibitor (human), 23subjects with the PiZZ variant of congenital deficiency of alpha 1-antitrypsin deficiency and documented destructive lung disease participated in a study of acute and/or chronic replacement therapy with alpha 1-proteinase inhibitor (human). The mean in vivo recovery of alpha 1-Pl was 4.2mg (immunologic)/dL/mg (functional)/kg body weight administered. The half-life of alpha 1-Pl in vivo was approximately 4.5days. Based on these observations, a program of chronic replacement therapy was developed. Nineteen of the subjects in these studies received alpha 1-proteinase inhibitor (human) replacement therapy, 60mg/kg body weight, once weekly for up to 26weeks (average 24weeks of therapy). With this schedule of replacement therapy, blood levels of alpha 1-Pl were maintained above 80mg/dL (based on the commercial standards for alpha 1-Pl immunologic assay). Within a few weeks of commencing this program, bronchoalveolar lavage studies demonstrated significantly increased levels of alpha 1-Pl and functional antineutrophil elastase capacity in the epithelial lining fluid of the lower respiratory tract of the lung, as compared to levels prior to commencing the program of chronic replacement therapy with alpha 1-proteinase inhibitor (human).
All 23 individuals who participated in the investigations were immunized with hepatitis B vaccine and received a single dose of hepatitis B immune globulin (human) on entry into the investigation. Although no other steps were taken to prevent hepatitis, neither hepatitis B nor non-A, non-B hepatitis occurred in any of the subjects. All subjects remained seronegative for HIV antibody. None of the subjects developed any detectable antibody to alpha 1-Pl or other serum protein.
Long-term controlled clinical trials to evaluate the effect of chronic replacement therapy with alpha 1-proteinase inhibitor (human) on the development of or progression of emphysema in patients with congenital alpha 1-antitrypsin deficiency have not been performed. Estimates of the sample size required of this rare disorder and the slow, progressive nature of the clinical course have been considered impediments in the ability to conduct such a trial. Studies to monitor the long-term effects will continue as part of the postapproval process.
Indications
Alpha 1-antitrypsin Deficiency Is A Chronic, Hereditary, Usually Fatal, Autosomal Recessive Disorder In Which A Low Concentration Of Alpha 1-Pl (alpha 1-antitrypsin) Is Associated With Slowly Progressive, Severe Panacinar Emphysema That Most Often Manifests Itself In The Third To Fourth Decades Of Life. (Although The Terms Alpha 1-proteinase Inhibitor And Alpha 1-antitrypsin Are Used Interchangeably In The Scientific Literature, The Hereditary Disorder Associated With A Reduction In The Serum Level Of Alpha 1-Pl Is Conventionally Referred To As Alpha 1-antitrypsin Deficiency While The Deficient Protein Is Referred To As Alpha 1-proteinase Inhibitor). The Emphysema Is Typically Worse In The Lower Lung Zones. The Pathogenesis Of Development Of Emphysema In Alpha 1-antitrypsin Deficiency Is Not Well Understood At This Time. It Is Believed, However, To Be Due To A Chronic Biochemical Imbalance Between Elastase (an Enzyme Capable Of Degrading Elastin Tissues, Released By Inflammatory Cells, Primarily Neutrophils, In The Lower Respiratory Tract) And Alpha 1-Pl (the Principal Inhibitor Of Neutrophil Elastase), Which Is Deficient In Alpha 1-antitrypsin Disease. As A Result, It Is Believed That Alveolar Structures Are Unprotected From Chronic Exposure To Elastase Released From A Chronic, Low-level Burden Of Neutrophils In The Lower Respiratory Tract, Resulting In Progressive Degradation Of Elastin Tissues. The Eventual Outcome Is The Development Of Emphysema. Neonatal Hepatitis With Cholestatic Jaundice Appears In Approximately 10% Of Newborns With Alpha 1-antitrypsin Deficiency. In Some Adults, Alpha 1-antitrypsin Deficiency Is Complicated By Cirrhosis.
A Large Number Of Phenotypic Variants Of Alpha 1-antitrypsin Deficiency Exists. The Most Severely Affected Individuals Are Those With The PiZZ Variant, Typically Characterized By Alpha 1-Pl Serum Levels <35% Normal. Epidemiologic Studies Of Individuals With Various Phenotypes Of Alpha 1-antitrypsin Deficiency Have Demonstrated That Individuals With Endogenous Serum Levels Of Alpha 1-Pl £50mg/dL (based On Commercial Standards) Have A Risk Of >80% Of Developing Emphysema Over A Lifetime. However, Individuals With Endogenous Alpha 1-Pl Levels >80mg/dL, In General, Do Not Manifest An Increased Risk For Development Of Emphysema Above The General Population Background Risk. From These Observations, It Is Believed That The Threshold Level Of Alpha 1-Pl In The Serum Required To Provide Adequate Anti-elastase Activity In The Lung Of Individuals With Alpha 1-antitrypsin Deficiency Is About 80mg/dL (based On Commercial Standards For Immunologic Assay Of Alpha 1-Pl).
In Clinical Studies Of Alpha 1-proteinase Inhibitor (human), 23subjects With The PiZZ Variant Of Congenital Deficiency Of Alpha 1-antitrypsin Deficiency And Documented Destructive Lung Disease Participated In A Study Of Acute And/or Chronic Replacement Therapy With Alpha 1-proteinase Inhibitor (human). The Mean In Vivo Recovery Of Alpha 1-Pl Was 4.2mg (immunologic)/dL/mg (functional)/kg Body Weight Administered. The Half-life Of Alpha 1-Pl In Vivo Was Approximately 4.5days. Based On These Observations, A Program Of Chronic Replacement Therapy Was Developed. Nineteen Of The Subjects In These Studies Received Alpha 1-proteinase Inhibitor (human) Replacement Therapy, 60mg/kg Body Weight, Once Weekly For Up To 26weeks (average 24weeks Of Therapy). With This Schedule Of Replacement Therapy, Blood Levels Of Alpha 1-Pl Were Maintained Above 80mg/dL (based On The Commercial Standards For Alpha 1-Pl Immunologic Assay). Within A Few Weeks Of Commencing This Program, Bronchoalveolar Lavage Studies Demonstrated Significantly Increased Levels Of Alpha 1-Pl And Functional Antineutrophil Elastase Capacity In The Epithelial Lining Fluid Of The Lower Respiratory Tract Of The Lung, As Compared To Levels Prior To Commencing The Program Of Chronic Replacement Therapy With Alpha 1-proteinase Inhibitor (human).
All 23 Individuals Who Participated In The Investigations Were Immunized With Hepatitis B Vaccine And Received A Single Dose Of Hepatitis B Immune Globulin (human) On Entry Into The Investigation. Although No Other Steps Were Taken To Prevent Hepatitis, Neither Hepatitis B Nor Non-A, Non-B Hepatitis Occurred In Any Of The Subjects. All Subjects Remained Seronegative For HIV Antibody. None Of The Subjects Developed Any Detectable Antibody To Alpha 1-Pl Or Other Serum Protein.
Long-term Controlled Clinical Trials To Evaluate The Effect Of Chronic Replacement Therapy With Alpha 1-proteinase Inhibitor (human) On The Development Of Or Progression Of Emphysema In Patients With Congenital Alpha 1-antitrypsin Deficiency Have Not Been Performed. Estimates Of The Sample Size Required Of This Rare Disorder And The Slow, Progressive Nature Of The Clinical Course Have Been Considered Impediments In The Ability To Conduct Such A Trial. Studies To Monitor The Long-term Effects Will Continue As Part Of The Postapproval Process.
Alpha 1-antitrypsin Deficiency Is A Chronic, Hereditary, Usually Fatal, Autosomal Recessive Disorder In Which A Low Concentration Of Alpha 1-Pl (alpha 1-antitrypsin) Is Associated With Slowly Progressive, Severe Panacinar Emphysema That Most Often Manifests Itself In The Third To Fourth Decades Of Life. (Although The Terms Alpha 1-proteinase Inhibitor And Alpha 1-antitrypsin Are Used Interchangeably In The Scientific Literature, The Hereditary Disorder Associated With A Reduction In The Serum Level Of Alpha 1-Pl Is Conventionally Referred To As Alpha 1-antitrypsin Deficiency While The Deficient Protein Is Referred To As Alpha 1-proteinase Inhibitor). The Emphysema Is Typically Worse In The Lower Lung Zones. The Pathogenesis Of Development Of Emphysema In Alpha 1-antitrypsin Deficiency Is Not Well Understood At This Time. It Is Believed, However, To Be Due To A Chronic Biochemical Imbalance Between Elastase (an Enzyme Capable Of Degrading Elastin Tissues, Released By Inflammatory Cells, Primarily Neutrophils, In The Lower Respiratory Tract) And Alpha 1-Pl (the Principal Inhibitor Of Neutrophil Elastase), Which Is Deficient In Alpha 1-antitrypsin Disease. As A Result, It Is Believed That Alveolar Structures Are Unprotected From Chronic Exposure To Elastase Released From A Chronic, Low-level Burden Of Neutrophils In The Lower Respiratory Tract, Resulting In Progressive Degradation Of Elastin Tissues. The Eventual Outcome Is The Development Of Emphysema. Neonatal Hepatitis With Cholestatic Jaundice Appears In Approximately 10% Of Newborns With Alpha 1-antitrypsin Deficiency. In Some Adults, Alpha 1-antitrypsin Deficiency Is Complicated By Cirrhosis.
A Large Number Of Phenotypic Variants Of Alpha 1-antitrypsin Deficiency Exists. The Most Severely Affected Individuals Are Those With The PiZZ Variant, Typically Characterized By Alpha 1-Pl Serum Levels <35% Normal. Epidemiologic Studies Of Individuals With Various Phenotypes Of Alpha 1-antitrypsin Deficiency Have Demonstrated That Individuals With Endogenous Serum Levels Of Alpha 1-Pl £50mg/dL (based On Commercial Standards) Have A Risk Of >80% Of Developing Emphysema Over A Lifetime. However, Individuals With Endogenous Alpha 1-Pl Levels >80mg/dL, In General, Do Not Manifest An Increased Risk For Development Of Emphysema Above The General Population Background Risk. From These Observations, It Is Believed That The Threshold Level Of Alpha 1-Pl In The Serum Required To Provide Adequate Anti-elastase Activity In The Lung Of Individuals With Alpha 1-antitrypsin Deficiency Is About 80mg/dL (based On Commercial Standards For Immunologic Assay Of Alpha 1-Pl).
In Clinical Studies Of Alpha 1-proteinase Inhibitor (human), 23subjects With The PiZZ Variant Of Congenital Deficiency Of Alpha 1-antitrypsin Deficiency And Documented Destructive Lung Disease Participated In A Study Of Acute And/or Chronic Replacement Therapy With Alpha 1-proteinase Inhibitor (human). The Mean In Vivo Recovery Of Alpha 1-Pl Was 4.2mg (immunologic)/dL/mg (functional)/kg Body Weight Administered. The Half-life Of Alpha 1-Pl In Vivo Was Approximately 4.5days. Based On These Observations, A Program Of Chronic Replacement Therapy Was Developed. Nineteen Of The Subjects In These Studies Received Alpha 1-proteinase Inhibitor (human) Replacement Therapy, 60mg/kg Body Weight, Once Weekly For Up To 26weeks (average 24weeks Of Therapy). With This Schedule Of Replacement Therapy, Blood Levels Of Alpha 1-Pl Were Maintained Above 80mg/dL (based On The Commercial Standards For Alpha 1-Pl Immunologic Assay). Within A Few Weeks Of Commencing This Program, Bronchoalveolar Lavage Studies Demonstrated Significantly Increased Levels Of Alpha 1-Pl And Functional Antineutrophil Elastase Capacity In The Epithelial Lining Fluid Of The Lower Respiratory Tract Of The Lung, As Compared To Levels Prior To Commencing The Program Of Chronic Replacement Therapy With Alpha 1-proteinase Inhibitor (human).
All 23 Individuals Who Participated In The Investigations Were Immunized With Hepatitis B Vaccine And Received A Single Dose Of Hepatitis B Immune Globulin (human) On Entry Into The Investigation. Although No Other Steps Were Taken To Prevent Hepatitis, Neither Hepatitis B Nor Non-A, Non-B Hepatitis Occurred In Any Of The Subjects. All Subjects Remained Seronegative For HIV Antibody. None Of The Subjects Developed Any Detectable Antibody To Alpha 1-Pl Or Other Serum Protein.
Long-term Controlled Clinical Trials To Evaluate The Effect Of Chronic Replacement Therapy With Alpha 1-proteinase Inhibitor (human) On The Development Of Or Progression Of Emphysema In Patients With Congenital Alpha 1-antitrypsin Deficiency Have Not Been Performed. Estimates Of The Sample Size Required Of This Rare Disorder And The Slow, Progressive Nature Of The Clinical Course Have Been Considered Impediments In The Ability To Conduct Such A Trial. Studies To Monitor The Long-term Effects Will Continue As Part Of The Postapproval Process.
Contraindications
Individuals with selective IgA deficiencies who have known antibody against IgA (anti-IgA antibody) should not receive alpha 1-proteinase inhibitor (human), since these patients may experience severe reactions, including anaphylaxis, to IgA which may be present.
Individuals with selective IgA deficiencies who have known antibody against IgA (anti-IgA antibody) should not receive alpha 1-proteinase inhibitor (human), since these patients may experience severe reactions, including anaphylaxis, to IgA which may be present.
Safety Information / Warning
Prolastin is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. 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. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Bayer Inc. at 1-800-622-2937 ext. 5425.
The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering to the patient. Prolastin has been heat-treated in solution at 60°C for 10hours in order to reduce the potential for transmission of infectious agents. No cases of hepatitis, either hepatitisB or hepatitisC have been recorded to date in individuals receiving alpha 1-proteinase inhibitor (human). However, as all individuals received prophylaxis against hepatitisB, no conclusions can be drawn at this time regarding potential transmission of hepatitisB virus.
Prolastin is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. 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. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Bayer Inc. at 1-800-622-2937 ext. 5425.
The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering to the patient. Prolastin has been heat-treated in solution at 60°C for 10hours in order to reduce the potential for transmission of infectious agents. No cases of hepatitis, either hepatitisB or hepatitisC have been recorded to date in individuals receiving alpha 1-proteinase inhibitor (human). However, as all individuals received prophylaxis against hepatitisB, no conclusions can be drawn at this time regarding potential transmission of hepatitisB virus.
Precautions
General: 1. Administer within 3hours after reconstitution. Do not refrigerate after reconstitution.
2.Administer only by the i.v. route.
3.As with any colloid solution, there will be an increase in plasma volume following i.v. administration of alpha 1-proteinase inhibitor (human). Caution should therefore be used in patients at risk for circulatory overload.
4.It is recommended that in preparation for receiving alpha 1-proteinase inhibitor (human), recipients be immunized against hepatitis B using a licensed Hepatitis B Vaccine, according to the manufacturer's recommendations. Should it become necessary to treat an individual with alpha 1-proteinase inhibitor (human), and time is insufficient for adequate antibody response to vaccination, individuals should receive a single dose of hepatitis B immune globulin (human), 0.06mL/kg body weight, i.m., at the time of administration of the initial dose of Hepatitis B Vaccine.
5.Alpha 1-proteinase inhibitor (human) should be given alone, without mixing with other agents or diluting solutions.
6.Product administration and handling of the needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious virus including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs.
Place needles in sharps container after single use. Discard all equipment including any reconstituted Prolastin product in accordance with biohazard procedures.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals to evaluate carcinogenesis, mutagenesis or impairment of fertility have not been conducted.
Pregnancy: Animal reproduction studies have not been conducted with alpha 1-proteinase inhibitor (human). It is also not known whether it can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It should be given to a pregnant woman only if clearly needed.
Lactation: It is not known whether alpha 1-proteinase inhibitor (human) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when alpha 1-proteinase inhibitor (human) is administered to a nursing woman.
Children: Safety and effectiveness in the pediatric poplulation have not been established.
General: 1. Administer within 3hours after reconstitution. Do not refrigerate after reconstitution.
2.Administer only by the i.v. route.
3.As with any colloid solution, there will be an increase in plasma volume following i.v. administration of alpha 1-proteinase inhibitor (human). Caution should therefore be used in patients at risk for circulatory overload.
4.It is recommended that in preparation for receiving alpha 1-proteinase inhibitor (human), recipients be immunized against hepatitis B using a licensed Hepatitis B Vaccine, according to the manufacturer's recommendations. Should it become necessary to treat an individual with alpha 1-proteinase inhibitor (human), and time is insufficient for adequate antibody response to vaccination, individuals should receive a single dose of hepatitis B immune globulin (human), 0.06mL/kg body weight, i.m., at the time of administration of the initial dose of Hepatitis B Vaccine.
5.Alpha 1-proteinase inhibitor (human) should be given alone, without mixing with other agents or diluting solutions.
6.Product administration and handling of the needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious virus including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs.
Place needles in sharps container after single use. Discard all equipment including any reconstituted Prolastin product in accordance with biohazard procedures.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals to evaluate carcinogenesis, mutagenesis or impairment of fertility have not been conducted.
Pregnancy: Animal reproduction studies have not been conducted with alpha 1-proteinase inhibitor (human). It is also not known whether it can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It should be given to a pregnant woman only if clearly needed.
Lactation: It is not known whether alpha 1-proteinase inhibitor (human) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when alpha 1-proteinase inhibitor (human) is administered to a nursing woman.
Children: Safety and effectiveness in the pediatric poplulation have not been established.
Side Effects / Adverse Effects
Therapeutic administration of alpha 1-proteinase inhibitor (human), 60mg/kg weekly, has been demonstrated to be well tolerated. In clinical studies, 6 reactions were observed with 517 infusions of alpha 1-proteinase inhibitor (human), or 1.16%. None of the reactions was severe. The adverse reactions reported included delayed fever (maximum temperature rise was 38.9°C, resolving spontaneously over 24hours) occurring up to 12hours following treatment (0.77%), lightheadedness (0.19%), and dizziness (0.19%). Mild transient leukocytosis and dilutional anemia severalhours after infusion have also been noted. Since market entry, occasional reports of other flu-like symptoms, allergic-like reactions, dyspnea, rash, tachycardia, and, rarely, hypotension have also been received.
Therapeutic administration of alpha 1-proteinase inhibitor (human), 60mg/kg weekly, has been demonstrated to be well tolerated. In clinical studies, 6 reactions were observed with 517 infusions of alpha 1-proteinase inhibitor (human), or 1.16%. None of the reactions was severe. The adverse reactions reported included delayed fever (maximum temperature rise was 38.9°C, resolving spontaneously over 24hours) occurring up to 12hours following treatment (0.77%), lightheadedness (0.19%), and dizziness (0.19%). Mild transient leukocytosis and dilutional anemia severalhours after infusion have also been noted. Since market entry, occasional reports of other flu-like symptoms, allergic-like reactions, dyspnea, rash, tachycardia, and, rarely, hypotension have also been received.
Overdose
Information not available
Information not available
Recommended Dosage
Each bottle of alpha 1-proteinase inhibitor (human) has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label of the bottle.
The threshold level of alpha 1-Pl in the serum believed to provide adequate anti-elastase activity in the lung of individuals with alpha 1-antitrypsin deficiency is 80mg/dL (based on commercial standards for alpha 1-Pl immunologic assay). However, assays of alpha 1-Pl based on commercial standards measure antigenic activity of alpha 1-Pl, whereas the labeled potency value of alpha 1-Pl 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 alpha 1-Pl determined using commercial immunologic assays may not accurately reflect actual functional alpha 1-Pl levels.
Therefore, although it may be helpful to monitor serum levels of alpha 1-Pl in individuals receiving alpha 1-proteinase inhibitor (human), 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 alpha 1-proteinase inhibitor (human) is 60mg/kg body weight administered once weekly. This dose is intended to increase and maintain a level of functional alpha 1-Pl in the epithelial lining of the lower respiratory tract, providing adequate anti-elastase activity in the lung of individuals with alpha 1-antitrypsin deficiency.
Alpha 1-proteinase inhibitor (human) may be given at a rate of 0.08mL/kg/min or greater and must be administered i.v. The recommended dosage of60mg/kg takes approximately 30minutes to infuse.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Reconstitution (see package insert for illustrations): 1.Warm the unopened diluent and concentrate to room temperature (not more than 37°C).
2.After removing the plastic flip-top caps, aseptically cleanse rubber stoppers of both bottles.
3.Remove the protective cover from the plastic transfer needle cartridge with tamper-proof seal and penetrate the stopper of the diluent bottle.
4.Remove the remaining portion of the plastic cartridge. Invert the diluent bottle and penetrate the rubber seal on the concentrate bottle with the needle at an angle. Alternate method of transferring sterile water: With a sterile needle and syringe, withdraw the appropriate volume of diluent and transfer to the bottle of lyophilized concentrate.
5.The vacuum will draw the diluent into the concentrate bottle. For best results, and to avoid foaming, hold the diluent bottle at an angle to the concentrate bottle in order to direct the jet of diluent against the wall of the concentrate bottle.
6.After removing the diluent bottle and transfer needle, gently swirl the concentrate bottle until the powder is completely dissolved.
7.Swab top of reconstituted bottle of alpha 1-proteinase inhibitor (human), again.
8.Attach the sterile filter needle provided to syringe. With filter needle in place, insert syringe into reconstituted bottle and withdraw solution into syringe.
9.To administer alpha 1-proteinase inhibitor (human), replace filter needle with appropriate injection needle and follow procedure for i.v. administration.
10.The contents of more than 1bottle may be drawn into the the same syringe before administration. If more than 1bottle 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.
*For a patient of average weight (about 70kg), the volume needed will exceed the limit of 1syringe.
Each bottle of alpha 1-proteinase inhibitor (human) has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label of the bottle.
The threshold level of alpha 1-Pl in the serum believed to provide adequate anti-elastase activity in the lung of individuals with alpha 1-antitrypsin deficiency is 80mg/dL (based on commercial standards for alpha 1-Pl immunologic assay). However, assays of alpha 1-Pl based on commercial standards measure antigenic activity of alpha 1-Pl, whereas the labeled potency value of alpha 1-Pl 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 alpha 1-Pl determined using commercial immunologic assays may not accurately reflect actual functional alpha 1-Pl levels.
Therefore, although it may be helpful to monitor serum levels of alpha 1-Pl in individuals receiving alpha 1-proteinase inhibitor (human), 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 alpha 1-proteinase inhibitor (human) is 60mg/kg body weight administered once weekly. This dose is intended to increase and maintain a level of functional alpha 1-Pl in the epithelial lining of the lower respiratory tract, providing adequate anti-elastase activity in the lung of individuals with alpha 1-antitrypsin deficiency.
Alpha 1-proteinase inhibitor (human) may be given at a rate of 0.08mL/kg/min or greater and must be administered i.v. The recommended dosage of60mg/kg takes approximately 30minutes to infuse.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Reconstitution (see package insert for illustrations): 1.Warm the unopened diluent and concentrate to room temperature (not more than 37°C).
2.After removing the plastic flip-top caps, aseptically cleanse rubber stoppers of both bottles.
3.Remove the protective cover from the plastic transfer needle cartridge with tamper-proof seal and penetrate the stopper of the diluent bottle.
4.Remove the remaining portion of the plastic cartridge. Invert the diluent bottle and penetrate the rubber seal on the concentrate bottle with the needle at an angle. Alternate method of transferring sterile water: With a sterile needle and syringe, withdraw the appropriate volume of diluent and transfer to the bottle of lyophilized concentrate.
5.The vacuum will draw the diluent into the concentrate bottle. For best results, and to avoid foaming, hold the diluent bottle at an angle to the concentrate bottle in order to direct the jet of diluent against the wall of the concentrate bottle.
6.After removing the diluent bottle and transfer needle, gently swirl the concentrate bottle until the powder is completely dissolved.
7.Swab top of reconstituted bottle of alpha 1-proteinase inhibitor (human), again.
8.Attach the sterile filter needle provided to syringe. With filter needle in place, insert syringe into reconstituted bottle and withdraw solution into syringe.
9.To administer alpha 1-proteinase inhibitor (human), replace filter needle with appropriate injection needle and follow procedure for i.v. administration.
10.The contents of more than 1bottle may be drawn into the the same syringe before administration. If more than 1bottle 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.
*For a patient of average weight (about 70kg), the volume needed will exceed the limit of 1syringe.
Supplied / Packaging
Each single use vial of sterile, stable, lyophilized preparation contains: purified human alpha 1-proteinase inhibitor with a functional activity of500or 1000mg. A suitable volume of Sterile Water for Injection USP (20or40mL, respectively), a sterile double-ended transfer needle and a sterile filter needle are provided. Preservative-free. Must be administered by the i.v. route.
Alpha 1-proteinase inhibitor (human) is prepared from pooled human plasma of normal donors by modification and refinements of the cold ethanol method of Cohn. In order to reduce the potential risk of transmission of infectious agents, alpha 1-proteinase inhibitor (human) has been heat-treated in solution at 60±0.5°C for not less than 10hours. However, no procedure has been found to be totally effective in removing viral infectivity from plasma fractionation products.
The specific activity of alpha 1-proteinase inhibitor (human) is ³0.35mg functional alpha 1-Pl/mg protein and when reconstituted as directed, the concentration of alpha 1-Pl is ³20mg/mL. When reconstituted, alpha 1-proteinase inhibitor (human) has a pH of6.6to 7.4, a sodium content of100to 210mEq/L a chloride content of60to 180mEq/L, a sodium phosphate content of 0.015to 0.025M, a polyethylene glycol content of not more than 5ppm, and not more than 0.1% sucrose. Alpha 1-proteinase inhibitor (human) contains small amounts of other plasma proteins including alpha 2-plasmin inhibitor, alpha 1-antichymotrypsin, C 1-esterase inhibitor, haptoglobin, antithrombinIII, alpha 1-lipoprotein, albumin, and IgA.
Each vial contains the labeled amount of functionally active alpha 1-Pl in mg/vial, as determined by capacity to neutralize porcine pancreatic elastase.
Store under refrigeration (2to8°C). Freezing should be avoided as breakage of the diluent bottle might occur.
Each single use vial of sterile, stable, lyophilized preparation contains: purified human alpha 1-proteinase inhibitor with a functional activity of500or 1000mg. A suitable volume of Sterile Water for Injection USP (20or40mL, respectively), a sterile double-ended transfer needle and a sterile filter needle are provided. Preservative-free. Must be administered by the i.v. route.
Alpha 1-proteinase inhibitor (human) is prepared from pooled human plasma of normal donors by modification and refinements of the cold ethanol method of Cohn. In order to reduce the potential risk of transmission of infectious agents, alpha 1-proteinase inhibitor (human) has been heat-treated in solution at 60±0.5°C for not less than 10hours. However, no procedure has been found to be totally effective in removing viral infectivity from plasma fractionation products.
The specific activity of alpha 1-proteinase inhibitor (human) is ³0.35mg functional alpha 1-Pl/mg protein and when reconstituted as directed, the concentration of alpha 1-Pl is ³20mg/mL. When reconstituted, alpha 1-proteinase inhibitor (human) has a pH of6.6to 7.4, a sodium content of100to 210mEq/L a chloride content of60to 180mEq/L, a sodium phosphate content of 0.015to 0.025M, a polyethylene glycol content of not more than 5ppm, and not more than 0.1% sucrose. Alpha 1-proteinase inhibitor (human) contains small amounts of other plasma proteins including alpha 2-plasmin inhibitor, alpha 1-antichymotrypsin, C 1-esterase inhibitor, haptoglobin, antithrombinIII, alpha 1-lipoprotein, albumin, and IgA.
Each vial contains the labeled amount of functionally active alpha 1-Pl in mg/vial, as determined by capacity to neutralize porcine pancreatic elastase.
Store under refrigeration (2to8°C). Freezing should be avoided as breakage of the diluent bottle might occur.
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Brand Name
Prolastin
Prolastin
Generic Name
Alpha 1-proteinase Inhibitor (Human)
Alpha 1-proteinase Inhibitor (Human)
General Indications
Alpha 1-antitrypsin Replenisher
Alpha 1-antitrypsin Replenisher
