Alpha1-Proteinase Inhibitor

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous [preservative free]:

Glassia: 1000 mg/50 mL (1 ea) [latex free]

Prolastin-C: 1000 mg/20 mL (1 ea) [latex free, pyrogen free]

Solution Reconstituted, Intravenous [preservative free]:

Aralast NP: 500 mg (1 ea); 800 mg (1 ea [DSC]); 1000 mg (1 ea) [contains polyethylene glycol, polysorbate 80]

Prolastin-C: 1000 mg (1 ea)

Zemaira: 1000 mg (1 ea)

Pharmacology

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.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~3.5 L

Time to Peak

Serum: ~1 hour; threshold levels achieved after 3 weeks

Half-Life Elimination

Metabolic: ~5-6 days

Use: Labeled Indications

Alpha₁-proteinase inhibitor deficiency: Long-term augmentation and maintenance therapy in adults with severe hereditary deficiency of alpha₁-antitrypsin (AAT) with clinically evident emphysema.

Limitations of use:

Not indicated as therapy for patients with lung disease in whom hereditary AAT deficiency has not been established; long-term effects of chronic augmentation or maintenance therapy of individuals with alpha₁-proteinase inhibitor are not available.

The effect of augmentation therapy with any alpha₁-proteinase inhibitor on pulmonary exacerbations has not been demonstrated in randomized, controlled clinical trials. However, one randomized controlled trial showed a reduction in emphysema progression with alpha₁-proteinase inhibitor augmentation therapy when CT lung density was measured at total lung capacity (Chapman 2015).

Contraindications

History of anaphylaxis or other severe systemic reaction to A₁-proteinase inhibitor or any component of the formulation; IgA deficient patients with antibodies against IgA.

Dosage and Administration

Dosing: Adult

Note: The vial strength (mg) of some products (ie, Prolastin-C, Zemaira) varies by manufacturer lot; consult individual vial labels for exact amount prior to preparation for administration.

Alpha₁-antitrypsin deficiency: IV: 60 mg/kg once weekly

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Reconstitute lyophilized powder with provided diluent (SWFI). Allow product and diluent to reach room temperature (if refrigerated) prior to reconstitution. Filtering requirements during preparation vary by product; consult manufacturer recommendations. May pool vial contents by transferring into a sterile container for IV infusion. To mix, swirl; do not shake. Administer within 3 hours of preparation or within 3 hours of entering the vial (Glassia); products do not contain a preservative.

Note: The vial strength (mg) of some products (ie, Prolastin-C, Zemaira) varies by manufacturer lot; consult individual vial labels for exact amount prior to preparation for administration.

Aralast NP: Each 500 mg and 1,000 mg vial should be diluted with 25 mL and 50 mL of diluent, respectively.

Prolastin-C: Each 1,000 mg vial should be diluted with 20 mL of diluent.

Zemaira: Each 1,000 mg, 4,000 mg, and 5,000 mg vial should be diluted with 20 mL, 76 mL, and 95 mL of diluent, respectively. Total reconstitution time for 1,000 mg vial should be obtained within 5 minutes and total reconstitution time for 4,000 or 5,000 mg vials should be obtained within 10 minutes.

Administration

IV: For IV infusion only. Do not mix with other agents or solutions. If adverse reactions occur during administration, rate may be decreased or temporarily interrupted. Some products require an in-line filter for administration; consult specific product labeling.

Aralast NP, Glassia: Infuse at rate of ≤0.2 mL/kg/minute. Glassia may be self-administered by the patient/caregiver at home after appropriate training

Prolastin-C, Zemaira: Infuse at ~0.08 mL/kg/minute (rate may be increased or decreased based on patient comfort).

Prolastin-C Liquid: Infuse at 0.08 mL/kg/minute (takes ~15 minutes to infuse) as determined by patient response and comfort. Allow vial to warm to room temperature before administration; solution may contain a few protein particles.

Dietary Considerations

Some products may contain sodium.

Storage

Aralast NP: Prior to reconstitution, store intact vials up to 25°C (77°F); do not freeze. Keep vial in carton to protect from light.

Glassia: Prior to use, store intact vials between 2°C and 8°C (36°F and 46°F); do not freeze. May also be stored up to 25°C (77°F) for up to 1 month. Keep vial in carton until ready for use.

Prolastin-C, Zemaira: Prior to reconstitution, store intact vials up to 25°C (77°F); avoid freezing.

Prolastin-C Liquid: Store vials between 2°C and 8°C (36°F and 46°F); do not freeze. May also be stored up to 25°C (77°F) for up to 1 month. Keep pooled solution at room temperature and administer within 3 hours.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Actual incidence may vary by product.

>10%:

Central nervous system: Headache (≤18%)

Gastrointestinal: Nausea (≤11%)

Genitourinary: Urinary tract infection (≤13%)

Local: Bruising at injection site (≤16%)

Neuromuscular & skeletal: Myalgia (discomfort: ≤16%)

Respiratory: Respiratory tract infection (≤96%), exacerbation of chronic obstructive pulmonary disease (≤38%), cough (≤24%)

1% to 10%:

Cardiovascular: Chest pain (≤8%), chest discomfort (≤6%), vasodilation (≥5%), peripheral edema (≤4%)

Central nervous system: Dizziness (≤6%), fatigue (≤6%), chills (≤5%)

Dermatologic: Pruritus (≤4%), urticaria (≤4%)

Endocrine & metabolic: Hot flash (≤5%)

Gastrointestinal: Diarrhea (≤6%), sore throat (≥5%), oral candidiasis (≤5%)

Hepatic: Increased liver enzymes (≤11%)

Immunologic: Antibody development (≤8%)

Local: Bleeding at injection site (≥5%)

Neuromuscular & skeletal: Weakness (≥5%), back pain (≤5%)

Respiratory: Rhinorrhea (≤6%), sinusitis (≤6%), bronchitis (≥5%), rhinitis (≥5%), dyspnea (≤5%), pharyngitis (≤1%)

Miscellaneous: Fever (≥5%)

<1%, postmarketing and/or case reports: Abdominal distention, abdominal pain, anaphylactoid reaction, anaphylaxis, arthralgia, asthma, confusion, conjunctivitis, drowsiness, dysmenorrhea, exfoliative dermatitis, facial edema, feeling abnormal, flu-like symptoms, flushing, hyperhidrosis, hypersensitivity reaction, hypertonia, hypoesthesia, hypotension, hypoxia, increased blood pressure, injection site reaction, insomnia, lip edema, lymph node pain, malaise, nervousness, pain, paresthesia, periorbital swelling, pharyngeal edema, pulmonary disease, skin rash, syncope, tachycardia, tinnitus, visual disturbance, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Severe hypersensitivity and anaphylactic/anaphylactoid reactions may occur; stop infusion promptly for acute hypersensitivity; immediate treatment (including epinephrine and/or other supportive therapy) should be available. Monitor vital signs and observe the patient throughout the infusion. May contain trace amounts of IgA; patients with known anti-IgA antibody, which may be present in patients with selective or severe IgA deficiency, have an increased risk of developing potentially severe hypersensitivity and anaphylactic reactions.

Disease-related concerns:

• Fluid overload: Plasma volume may increase following infusion; use with caution in patients at risk for fluid overload.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease (eg, viruses and theoretically the Creutzfeldt-Jakob disease [CJD]). 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.

Monitoring Parameters

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

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

What is this drug used for?

• It is used to treat emphysema caused by alpha₁-antitrypsin deficiency.

Frequently reported side effects of this drug

• Headache
• Signs of common cold
• Sinus pain
• Loss of strength and energy
• Diarrhea
• Muscle pain
• Nausea
• Sore throat
• Runny nose
• Back pain
• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.
• Flushing
• Thrush
• Cough
• Trouble breathing
• Chest pain
• Fast heartbeat
• Severe dizziness
• Passing out
• Confusion
• Shortness of breath
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.