Alpha-1 proteinase inhibitor

U.S. BRAND NAMES — Aralast; Aralast NP; Prolastin®; Zemaira®

PHARMACOLOGIC CATEGORY
Antitrypsin Deficiency Agent
Blood Product Derivative

DOSING: ADULTS — Alpha1-antitrypsin deficiency: I.V.: 60 mg/kg once weekly

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:
Aralast, Aralast NP: 500 mg, 1000 mg [contains sodium ≤ 230 mEq/L and polysorbate 80; packaged with diluent]
Prolastin®: 500 mg, 1000 mg [contains sodium 100-210 mEq/L and sucrose; packaged with diluent]
Zemaira®: 1000 mg [contains sodium 81 mEq/1000 mg; packaged with diluent]

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Aralast, Aralast NP, Prolastin®: 500 mg, 1000 mg
Zemaira®: 1000 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — For I.V. infusion only; reduce rate or temporarily discontinue infusion if adverse effects occur. Infuse at ~0.08 mL/kg/minute; actual rate may be increased or decreased based on patient response. Emergency equipment (including epinephrine) should be available during infusion. Do not mix with other agents or solutions.

USE — Replacement therapy in congenital alpha1-antitrypsin deficiency with clinical emphysema

ADVERSE REACTIONS SIGNIFICANT
>10%: Hepatic: ALT increased (11%; ~4 times ULN), AST increased (11%; ~4 times ULN)

1% to 10%:
Central nervous system: Headache (≤ 7%)
Neuromuscular & skeletal: Musculoskeletal discomfort (7%)
Respiratory: Pharyngitis (2%)

<1% (Limited to important or life-threatening): Allergic reactions, asthma, back pain, bilateral pulmonary infiltrates, bloating, bronchitis, chest pain, chills, cough increased, dizziness, dyspnea, fever <102ºF (delayed up to 12 hours after treatment), flu-like syndrome, hypotension, leukocytosis, lightheadedness, pain, peripheral edema, pruritus, rash, rhinitis, sinusitis, somnolence, tachycardia, vasodilation, viral infection, vision abnormal. Severe reactions (anaphylaxis) may occur in patients with anti-IgA antibody.

CONTRAINDICATIONS — Hypersensitivity to any component of the formulation or other A1-PI products; selective IgA deficiency with known anti-IgA antibody

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions can occur; immediate treatment (including epinephrine 1:1000) should be available. Severe anaphylaxis may occur in patients with anti-IgA antibody; use in patients with selective IgA deficiency with known anti-IgA antibody is contraindicated

Disease-related concerns: Fluid overload: Use with caution in patients at risk for fluid overload. Hepatitis B: May consider hepatitis B immunization.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

Dosage form specific issues: Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Reproduction studies have not been conducted.

LACTATION — Excretion in breast milk unknown/use caution

DIETARY CONSIDERATIONS — Sodium content of 1 L after reconstitution:

Aralast, Aralast NP: ≤ 230 mEq/L

Prolastin®: 100-210 mEq/L

Zemaira®: 81 mEq/1000 mg

MONITORING PARAMETERS — Alpha1-PI serum levels; lung function; vital signs during infusion

CANADIAN BRAND NAMES — Prolastin®

INTERNATIONAL BRAND NAMES — Prolastin (CA)

MECHANISM OF ACTION — Alpha1-antitrypsin (AAT) is the principle protease inhibitor in serum. Its major physiologic role is to render proteolytic enzymes (secreted during inflammation) inactive. A decrease in AAT, as seen in congenital AAT deficiency, leads to increased elastic damage in the lung, causing emphysema.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: ~3.5 L

Half-life elimination: Metabolic: 5.9 days (Aralast)

Time to peak, serum: ~1 hour; threshold levels achieved after 3 weeks

PATIENT INFORMATION — This medication is given by injection only.