Because ARALAST NP is derived from pooled human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt–Jakob disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious agent transmission have been employed in the manufacture of this product, from the screening of plasma donors and the collection and testing of plasma through the application of viral elimination/reduction steps such as ethanol fractionation, PEG precipitation, solvent detergent treatment, and nanofiltration. Despite these measures, such products can still potentially transmit disease; therefore, the risk of infectious agents cannot be totally eliminated. ALL infections thought by a physician possibly to have been transmitted by this product should be reported to the manufacturer at 1-800-423-2090 (US). The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient.
ARALAST NP may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. ARALAST NP is contraindicated in patients with antibodies against IgA due to risk of severe hypersensitivity.
The rate of administration specified in DOSAGE AND ADMINISTRATION should be closely followed, at least until the physician has had sufficient experience with a given patient. Vital signs should be monitored continuously and the patient should be carefully observed throughout the infusion. IF ANAPHYLACTIC OR SEVERE ANAPHYLACTOID REACTIONS OCCUR, THE INFUSION SHOULD BE DISCONTINUED IMMEDIATELY. Epinephrine and other appropriate supportive therapy should be available for the treatment of any acute anaphylactic or anaphylactoid reaction.
There is currently no manufacturer warning information available for this drug.
Congenital Alpha1–Proteinase Inhibitor deficiency
ARALAST NP is indicated for chronic augmentation therapy in patients having congenital deficiency of α1–PI with clinically evident emphysema. Clinical and biochemical studies have demonstrated that with such therapy, ARALAST is effective in maintaining target serum α1–PI trough levels and increasing α1–PI levels in epithelial lining fluid (ELF). ARALAST NP pharmacokinetics are comparable with the pharmacokinetics of ARALAST after single-dose administration in 25 subjects with congenital deficiency of α1–PI. Clinical data demonstrating the long–term effects of chronic augmentation or replacement therapy of individuals with ARALAST NP or ARALAST are not available.
The effect of augmentation therapy with ARALAST NP on pulmonary exacerbations and on the progression of emphysema in alpha1-antitrypsin deficiency has not been demonstrated in randomized, controlled clinical trials.
ARALAST NP is not indicated as therapy for lung disease patients in whom congenital α1–PI deficiency has not been established.
ARALAST NP is a sterile, stable, lyophilized preparation of purified human alpha1–proteinase inhibitor (α1–PI), also known as alpha1–antitrypsin.1 ARALAST NP is a similar product to ARALAST, containing the same active components of plasma α1-PI with identical formulations.
ARALAST NP is prepared from large pools of human plasma by using the cold ethanol fractionation process, followed by purification steps including polyethylene glycol and zinc chloride precipitations and ion exchange chromatography. All U.S. licensed α1-PI plasma derived products contain chemical modifications which arise during manufacturing and occur in varying levels from product to product.11 ARALAST NP contains approximately 2% α1-PI with truncated C-terminal lysine (removal of Lys394), whereas ARALAST contains approximately 67% α1-PI with the C-terminal lysine truncation.12 No known data suggest influence of these structural modifications on the functional activity and immunogenicity of α1-PI.13
To reduce the risk of viral transmission, the manufacturing process includes treatment with a solvent detergent (S/D) mixture [tri–n–butyl phosphate and polysorbate 80] to inactivate enveloped viral agents such as human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). In addition, a nanofiltration step is incorporated into the manufacturing process to reduce the risk of transmission of enveloped and non–enveloped viral agents. Based on in vitro studies, the process used to produce ARALAST NP has been shown to inactivate and/or partition various viruses as shown in Table 1 below.2
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| Processing Step | Virus Log Reduction Factors | ||||
| HIV-1 | BVDV | PRV | HAV | MMV | |
| Cold ethanol fractionation | 4.6 | 1.4 | 2.1 | 1.4 | < 1.0* |
| Solvent Detergent-treatment | > 5.8 | > 6.0 | > 5.5 | N/A† | N/A† |
| 15 N nanofiltration | > 5.3 | > 6.0 | > 5.6 | > 5.1 | 4.9 |
| Overall reduction factor | > 15.7 | > 13.4 | > 13.2 | > 6.5 | 4.9 |
| HIV-1: Human immunodeficiency virus-1, BVDV (Bovine Viral Diarrhea Virus, model for Hepatitis C Virus and other lipid enveloped RNA viruses), PRV (Pseudorabies Virus, model for lipid-enveloped DNA viruses, to wich also hepatitis B belongs): HAV: Hepatitus A Virus, MMV (Mice Minute Virus, model for small non-lipid enveloped DNA viruses) | |||||
The unreconstituted, lyophilized cake should be white or off-white to slightly yellow-green or yellow in color. When reconstituted as directed, the concentration of functionally active α1–PI is ≥16 mg/mL and the specific activity is ≥0.55 mg active α1–PI/mg total protein. The composition of the reconstituted product is as follows:
| Component | Quality/mL |
| Elastase Inhibitory Activity | ≥400 mg Active α1–PI/0.5 g vial* |
| ≥800 mg Active α1–PI/1.0 g vial** | |
| Albumin | ≤5 mg/mL |
| Polyethylene Glycol | ≤112 µg/mL |
| Polysorbate 80 | ≤50 µg/mL |
| Sodium | ≤230 mEq/L |
| Tri-n-buyl Phosphate | ≤1.0 µg/mL |
| Zinc | ≤3 ppm |
| * Reconstitution volume: 25mL/0.5 g vial ** Reconstitution volume: 50mL/1.0 g vial |
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Each vial of ARALAST NP is labeled with the amount of functionally active α1–PI expressed in mg/vial. The formulation contains no preservative. The pH of the solution ranges from 7.2 to 7.8. Product must only be administered intravenously.
