Alpha ₁ -Proteinase Inhibitor (Human)

Pronunciation: (AL-fa PROE-tee-nase)
Class: Respiratory enzyme

Trade Names

Aralast NP
- Injection, lyophilized powder for solution 500 mg
- Injection, lyophilized powder for solution 1,000 mg

Glassia
- Injection, solution 1,000 mg

Prolastin-C
- Injection, lyophilized powder for solution 1,000 mg

Zemaira
- Injection, lyophilized powder for solution 1,000 mg

Pharmacology

Inhibits serine proteases (eg, neutrophil elastase), which are capable of degrading protein components of the alveolar walls and are chronically present in the lung.

Pharmacokinetics

Absorption

Aralast NP AUC is 0.0868 days•kg/mL and C _max is 1.6 mg/mL. Glassia AUC is 89 mg•h/mL. Prolastin-C AUC is 155.9 h•mg/mL and C _max is 1.797 mg/mL. Zemaira AUC is 144 mcM and C _max is 44.1 mcM.

Distribution

Aralast NP has a steady-state Vd of approximately 5,632 mL. Glassia has a Vd of approximately 3.2 L.

Elimination

Cl for Aralast NP is about 940 mL/day; half-life is approximately 4.7 days. Glassia has a terminal half-life of 111 h and Cl is 0.68 mL/h/kg. Prolastin-C has a half-life of 146.3 h. Zemaira Cl is 603 mL/day and the terminal half-life is 5.1 days.

Special Populations

Renal Function Impairment

No data available.

Hepatic Function Impairment

No data available.

Indications and Usage

For long-term augmentation and maintenance therapy in patients with congenital deficiency of alpha ₁ –proteinase inhibitor (PI) with clinically evident emphysema.

Contraindications

Immunoglobulin A (IgA)–deficient persons who have known antibodies against IgA; hypersensitivity to any component or a history of anaphylaxis or severe systemic response to alpha ₁ - PI products.

Dosage and Administration

Adults

IV 60 mg/kg infusion once weekly.

General Advice

• For IV use only. Administer at a rate not exceeding 0.08 mL/kg/min (0.04 mL/kg/min for Glassia ).
• Follow manufacturer's instructions for preparing alpha ₁ -PI for administration.
• Alpha ₁ -PI and diluent should be at room temperature before reconstitution.
• After preparing alpha ₁ -PI, keep at room temperature and administer within 3 h after reconstitution (within 3 h of entering the vial for Glassia ).
• Do not shake or agitate vials during reconstitution or dilution.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Glassia solution should be clear and colorless to yellow-green and may contain a few protein particles. Do not use if the product is cloudy. Reconstituted Aralast NP may be a colorless or slightly yellowish-green solution and essentially free of particles.
• Monitor the infusion rate closely during administration and observe the patient for signs of infusion-related reactions. If adverse events occur, the rate should be reduced or the infusion interrupted until the symptoms subside. The infusion may then be resumed at a rate tolerated by the patient.
• Infuse Glassia and Zemaira reconstituted solution through 5 micron in-line filter.
• Do not mix with other agents or diluting solutions.
• If more than 1 vial of alpha ₁ -PI is needed to achieve the required dose, use an aseptic technique to transfer the reconstituted solution from the vials into the administration container (eg, empty IV bag or glass bottle).

Storage/Stability

Aralast NP, Prolastin NP, and Zemaira

Store at temperatures not to exceed 25°C (77°F). Avoid freezing, which may damage container for the diluent. Discard partially used vials. Reconstituted solutions are stable for up to 3 h at room temperature.

Glassia

Refrigerate between 35° and 46°F. Do not freeze. Discard partially used vials. Stability data support short and moderate temperature excursions. Keep vial in carton until required for use. Glassia is stable at room temperature within 3 h of entering the vial.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (2%); hypotension, tachycardia (postmarketing).

CNS

Headache (9%); dizziness (6%); lethargy, malaise (2%); asthenia (1%).

Dermatologic

Urticaria (5%); erythema marginatum, pruritus, rash (2%).

EENT

Sinusitis (6%); nasopharyngitis, pharyngolaryngeal pain, rhinitis, sore throat (1%).

GI

Nausea (7%); hepatic enzyme increased (6%); dysgeusia (2%); cholangitis.

Genitourinary

UTI (7%).

Musculoskeletal

Musculoskeletal discomfort (7%); arthralgia (3%); joint swelling (2%)

Respiratory

COPD exacerbation (28%); cough (15%); upper respiratory tract infection (12%); bronchitis, bronchospasm (1%); dyspnea (postmarketing).

Miscellaneous

Chest discomfort (6%); chills (3%); decreased platelet count, fever, hot flush, influenza-like illness (2%); chest pain, injection-site hemorrhage, pain (1%); hypersensitivity (postmarketing).

Precautions

Monitor Monitor vital signs and infusion rates and carefully observe patient throughout the infusion for the development of an infusion reaction.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Anaphylaxis

Immediately discontinue the infusion if severe anaphylactoid or anaphylactic reactions occur.

Circulatory overload

Use with caution in patients at risk of circulatory overload.

Infection

Because alpha ₁ -PI is derived from pooled human plasma, there is a risk of transmitting infectious agents (eg, viruses) and, theoretically, Creutzfeldt-Jakob disease.

Overdosage

Symptoms

None well documented.

Patient Information

• Inform patients of the signs of hypersensitivity reactions, including hives, generalized urticaria, tightness of the chest, dyspnea, wheezing, faintness, hypotension, and anaphylaxis. Advise patients to discontinue use of the product and contact their health care provider and/or seek immediate emergency care, depending on the severity of the reaction, if these symptoms occur.
• Inform patients that alpha ₁ -PI is made from human plasma and may contain infectious agents that can cause disease (eg, viruses and, theoretically, the CJD agent). Explain that the risk of alpha ₁ -PI transmitting an infectious agent has been reduced by screening the plasma donors, by testing donated plasma for certain virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing.
• 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 2 weeks later by a rash and joint pain. Encourage patients to consult their health care provider if such symptoms occur.
• Inform patients that alpha ₁ -PI administration has been demonstrated to raise the plasma level of alpha ₁ -PI, but the effect of this augmentation on the frequency of pulmonary exacerbations and on the rate of progression of emphysema has not been established in clinical trials.

Copyright © 2009 Wolters Kluwer Health.