General Information

Zemaira is an alpha1 -proteinase inhibitor (A1 -PI).

Zemaira is specifically indicated for chronic augmentation and maintenance therapy in adults with A1 -PI deficiency and clinical evidence of emphysema.

Zemaira is supplied as lyophilized powder for reconstitution for intravenous use. The recommended weekly dose of Zemaira is 60 mg/kg body weight.

Dose ranging studies using efficacy endpoints have not been performed with Zemairaor any A1 -PI product.

Administer through a suitable 5 micron infusion filter (not supplied) at room temperature within 3 hours after reconstitution.

Do not mix with other medicinal products. Administer through a separate dedicated infusion line.

Administer at a rate of approximately 0.08 mL/kg/min as determined by the response and comfort of the patient.

Monitor closely the infusion rate and the patient’s clinical state, including vital signs, throughout the infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient.

Mechanism of Action

Alpha1-proteinase inhibitor (A1-PI) deficiency is a chronic, hereditary disorder that can cause severe tissue damage and death. Pulmonary diseases, such as emphysema, are one of the main results of A1-PI deficiency. Emphysema is caused by the protease-antiprotease imbalance in the lungs which causes inflammation and tissue damage. A1-PI is the primary antiprotease in the lower respiratory tract, where it inhibits neutrophil elastase (NE), an enzyme that destroys pulmonary tissue. Those individuals without A1PI deficiency produce sufficient A1-PI to control the NE produced by activated neutrophils and are thus able to prevent inappropriate damage to lung tissue by NE. Zemaira acts to increase and maintain serum levels and lung epithelial lining fluid (ELF) levels of A1-PI. Low blood levels of A1-PI are also associated with liver disease and liver cirrhosis.

Side Effects

Adverse events associated with the use of Zemaira may include (but are not limited to) the following:

• Asthenia
• Injection Site Pain
• Dizziness
• Headache
• Pruritus
• Paresthesia

Clinical Trial Results

FDA approval of Zemaira is based on a several pivotal studies conducted on a total of 89 subjects with A1-PI deficiency. Subjects ranged in age from 29 to 68 years with a median age of 49 years. In one double blind, controlled clinical study, 44 subjects were randomized to receive 60 mg/kg of either Zemaira or Prolastin once weekly for 10 weeks. After 10 weeks, all subjects received Zemaira for an additional 14 weeks. All subjects were followed for a total of 24 weeks to complete the safety evaluation. The mean trough serum A1-PI levels at steady state (Weeks 7-11) in the Zemaira-treated subjects were statistically equivalent to those in the Prolastin-treated subjects. The difference between the Zemaira and the Prolastin groups was not considered clinically significant and may be related to the higher specific activity of Zemaira.

In a subgroup of subjects enrolled in the study, bronchoalveolar lavage was performed at baseline and at Week 11. Four A1-PI related analytes in ELF were measured: antigenic A1-PI, A1-PI: NE complexes, free NE, and functional A1-PI (anti-neutrophil elastase capacity, ANEC). A blinded retrospective analysis of the study, which revised the prospectively established acceptance criteria showed that within each treatment group, ELF levels of antigenic A1-PI and A1-PI:NE complexes increased from baseline to Week 11. No clinically significant differences were detected between the two treatment groups.