Alpha-1 Antitrypsin Deficiency (AATD)


Prolastin®-C is an alanine-stabilized formulation available in the form of a liquid (0.25 M). It is an alpha1 proteinase inhibitor (A1-PI) intended for maintenance therapy and chronic augmentation in adults with emphysema due to a severe hereditary deficiency of alpha-1 antitrypsin deficiency (AATD). Patients with AATD, also known as deficiency of A1-PI, have increased risks of chronic obstructive lung disease and emphysema and have low serum AAT. Patients with emphysema have asthma symptoms with reversible components of their airway obstruction. Patients with A1-PI serum levels <11 mM have the Pi*ZZ phenotype/genotype, which leads to misfolding of the protein in the hepatocytes and point mutation in the gene coding for A1-PI. Patients with A1-PI may suffer from symptomatic lung disease, as they experience airway obstruction and dyspnea. Prolastin-C is licensed in the United States as the first member of the class A1-PI products. Prolastin-C licensure depends on the assessment of serum, lung epithelial lining fluid, biomarkers, levels of functioning, and antigenic A1-PI. It also involves the evaluation of the effectiveness of Prolastin-C Liquid. Initially, a conclusion was uncertain based on the results of a randomized controlled clinical trial. It involved a clinical endpoint such as forced expiratory volume in 1 second. Prolastin-C is a lyophilized product for reconstitution that replaced Prolastin®. The proposed trade name of the drug is Prolastin Liquid. It is also known as liquid alpha 1-PI or liquid alpha1 proteinase inhibitor.1

Get detailed prescribing information on the Prolastin-C monograph page at MPR.

Safety Information

Prolastin-C Liquid is a ready-to-use formulation and has been proven to effectively raise AAT protein levels in patients suffering from AATD. It is contraindicated for immunoglobulin A-deficient patients with antibodies against immunoglobulin A. There is a significant risk for severe hypersensitivity and other systemic reactions to A1-PI. It is indicated for maintenance therapy and chronic augmentation in adults with emphysema due to AATD. According to randomized controlled clinical trials, the progression of emphysema in A1-PI deficiency was not conclusively demonstrated. Clinical data lack evidence related to the long-term effects of maintenance therapy or chronic augmentation with Prolastin-C Liquid. Prolastin-C is not indicated for patients with lung disease who do not receive a confirmed diagnosis of A1-PI. During Prolastin-C infusion, the patient’s vital signs need to be monitored.2 

Adverse Effects

The adverse effects of Prolastin-C can range from drowsiness, fever, dizziness, numbness, or tingling sensation on the skin, muscle aches, pain at the injection site, and headaches. If patients suffer from any of these adverse effects after administration of Prolastin-C, they should inform their healthcare provider and pharmacist promptly. Prolastin-C is prescribed by physicians on a case-by-case basis, considering that the prescribed medication has benefits greater than the risk of adverse effects. Many patients who receive Prolastin-C have not experienced significant adverse effects. Prolastin-C is made from human blood, and the chances of viral infections such as hepatitis and parvovirus B19 are reduced. Various tests are performed, including blood donor screening, and Prolastin-C undergoes special manufacturing processes to reduce risk. Patients are advised to inform their healthcare provider right away if they develop an infection or signs of hepatitis including unusual tiredness, drowsiness, joint pain, persistent fever, sore throat, yellowing eyes/skin, dark urine, stomach/abdominal pain, or nausea/vomiting. Serious allergic reactions to Prolastin-C are rare. If any patient suffers from serious allergic reactions and experiences symptoms such as chest tightness, severe dizziness, trouble breathing, hives, rash, or itching/swelling of the tongue, throat, or face, they should stop taking the medication immediately and consult their healthcare provider for further guidance.3

Pharmacokinetic Properties

Prolastin-C is a new concentrated form of A1-PI used as augmentation therapy for individuals with AATD. It is prepared from human plasma and has increased purity and higher A1-PI concentration compared to Prolastin. It can be administered with a shorter infusion time and improved convenience for patients diagnosed with AATD to receive weekly doses of A1-PI. Based on the potency assay, bioequivalence was demonstrated in A1-PI preparations, and a dosage equivalent to 60 mg/kg was administered to patients with AATD in a randomized controlled trial. Augmentation therapy was evaluated based on the A1-PI present in the serum of patients using an antigenic content assay after the A1-PI product was administered. Functionally active and inactive forms of A1-PI were measured using the antigenic content assay. Polymerized, oligomerized, and oxidized A1-PI proteins are considered functionally inactive forms.4

Administration and Adverse Events

Prolastin-C is available in the form of a single-use vial along with a 20-ml vial of sterile water for injection. Administration of Prolastin-C requires a color-coded sterile transfer needle, a 20-mL vial of sterile water for injection (diluent), a single-use vial of Prolastin-C, and a sterile filter needle. The dose should be administered within 3 hours after reconstitution using the aseptic technique. Before reconstitution, the Prolastin-C and the diluent must be kept at room temperature. Plastic flip tops can be removed from each vial, and the exposed stopper surfaces can be swabbed with alcohol. The surface needs to be dried up, and the plastic cover from the short end of the transfer needle can be removed. The exposed end of the needle can be inserted through the center of the stopper in the diluent vial. The plastic cover from the transfer needle can be removed as well, and the diluent vial needs to be inverted into it. The attached needle can be inserted into the Prolastin-C vial at a 45-degree angle. It will minimize foaming and direct the stream of diluent into the wall of the product vial (Prolastin-C). As per clinical studies, administration of Prolastin-C led to extremity and abdominal rash in an individual. The rash resolved with subsequent treatment with steroids and antihistamines in an outpatient clinic. A participant in the trial experienced pruritic abdominal rash with continued steroid and antihistamine treatment, which led to the withdrawal of the participant from the trial. Some of the adverse drug-related reactions are malaise, chills, rash, hot flush, pruritus, and headache.5

References

  1. Summary basis for regulatory action – Prolastin-C. United States Food and Drug Administration. September 8, 2017. Accessed August 12, 2021.
  2. Prolastin-C Liquid for alpha1-antitrypsin deficiency. Grifols. Accessed August 12, 2021.
  3. Prolastin-C intravenous: uses, side effects, interactions. WebMD. Accessed August 12, 2021.
  4. Stocks JM, Brantly ML, Wang-Smith L, et al. Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha₁-antitrypsin deficiency: a randomized study. BMC Clin Pharmacol. 2010;10:13. doi:10.1186/1472-6904-10-13
  5. Prolastin-C by Grifols USA LLC. Drugs Library. Accessed August 12, 2021.

Reviewed by Harshi Dhingra, MD on 8/23/2021.

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