FDA label 6edc2f5d-5169-440f-a1ec-da702fd2abfd

WARNINGS Because ARALAST NP is derived from pooled human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt–Jakob disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious agent transmission have been employed in the manufacture of this product, from the screening of plasma donors and the collection and testing of plasma through the application of viral elimination/reduction steps such as ethanol fractionation, PEG precipitation, solvent detergent treatment, and nanofiltration. Despite these measures, such products can still potentially transmit disease; therefore, the risk of infectious agents cannot be totally eliminated. ALL infections thought by a physician possibly to have been transmitted by this product should be reported to the manufacturer at 1-800-423-2090 (US). The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient. ARALAST NP may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. ARALAST NP is contraindicated in patients with antibodies against IgA due to risk of severe hypersensitivity. The rate of administration specified in DOSAGE AND ADMINISTRATION should be closely followed, at least until the physician has had sufficient experience with a given patient. Vital signs should be monitored continuously and the patient should be carefully observed throughout the infusion. IF ANAPHYLACTIC OR SEVERE ANAPHYLACTOID REACTIONS OCCUR, THE INFUSION SHOULD BE DISCONTINUED IMMEDIATELY. Epinephrine and other appropriate supportive therapy should be available for the treatment of any acute anaphylactic or anaphylactoid reaction.

ADVERSE REACTIONS The safety of ARALAST NP was evaluated with ARALAST after a single dose IV infusion in a multicenter, randomized, double-blind, crossover clinical PK comparability study (Study 460501). The number of subjects with one or more adverse events, regardless of causality, was 23 of 25 (92%) when receiving ARALAST NP and 19 of 25 (76%) when receiving ARALAST. Treatment-related adverse events were reported in 8 of 25 subjects (32%) for ARALAST NP and 7 of 25 subjects (28%) for ARALAST. Of a total of 61 adverse events reported for ARALAST NP, 43 (70%) were mild, 16 (26%) moderate, and 2 (3%) severe. Seventeen of 61 (28%) adverse events were deemed possibly or probably related to ARALAST NP of which 14 (82%) were mild and 3 (18%) were moderate. Of a total of 60 adverse events reported for ARALAST, 45 (75%) were mild, 12 (20%) moderate, and 3 (5%) severe. Eleven of 60 (18%) adverse events were deemed possibly or probably related to ARALAST of which 8 (73%) were mild and 3 (27%) were moderate. No serious adverse events or deaths were reported in the study. No clinically significant changes in the peri-infusion vital signs (blood pressure, heart rate, or respiratory rate) were reported. The most common adverse events deemed related to ARALAST NP included: headache (4 of 61 [7%] events) and musculoskeletal discomfort (4 of 61 [7%] events). These adverse events, as well as most of the other adverse events, were also reported in subjects treated with ARALAST. In Clinical Study ATC 97-01, ARALAST was evaluated for up to 96 weeks in 27 subjects with a congenital deficiency of α 1 –PI and clinically evident emphysema. The number of subjects with an adverse event, regardless of causality, was 22 of 27 (81.5%). The number of subjects with an adverse event deemed possibly, probably, or definitely related to study drug was 7 of 27 (25.9%). The frequency of infusions associated with an adverse event, regardless of causality, was 108 of 1127 (9.6%) infusions administered per protocol. The most common symptoms were pharyngitis (1.6%), headache (0.7%), and increased cough (0.6%). Symptoms of bronchitis, sinusitis, pain, rash, back pain, viral infection, peripheral edema, bloating, dizziness, somnolence, asthma, and rhinitis were each associated with ≥0.2% but < 0.6% of infusions. All symptoms were mild to moderate in severity. The overall frequency of adverse events deemed to be possibly, probably, or definitely related to study drug was 15 of 1127 (1.3%) infusions. The most common symptoms included headache (0.3%) and somnolence (0.3%). Symptoms of chills and fever, vasodilation, dizziness, pruritus, rash, abnormal vision, chest pain, increased cough, and dyspnea were each associated with one (0.1%) infusion. Five (5) of 27 (18.5%) subjects experienced eight (8) serious adverse reactions during the study. None of these serious adverse events were considered to be causally related to the administration of ARALAST. Twenty-six (26) of 27 (96.3%) subjects experienced a total of 94 upper and lower respiratory-tract infections during the 96-week study (median: 3.0; range: 1 to 8; mean ± SD: 3.6 ± 2.3 infections). Twenty-eight (29.8%) of the respiratory infections occurred in 19 (70.4%) subjects during the first 24 weeks of the 96-week study suggesting that the risk of infection did not change with time on ARALAST. In a post-hoc analysis, subjects experienced a range of 0 to 8 exacerbations of COPD over the 96-week study with a median of less than one exacerbation per year (median: 0.61; mean ± SD: 0.83 ± 0.87 exacerbations per year). Treatment-emergent elevations (> two times the upper limit of normal) in aminotransferases (ALT or AST), up to 3.7 times the upper limit of normal, were noted in 3 of 27 (11.1%) subjects. Elevations were transient lasting three months or less. No subject developed any evidence of viral hepatitis or hepatitis seroconversion while being treated with ARALAST, including 13 evaluable subjects who were not vaccinated against hepatitis B. No clinically relevant alterations in blood pressure, heart rate, respiratory rate, or body temperature occurred during infusion of ARALAST. Mean hematology and laboratory parameters were little changed over the duration of the study, with individual variations not clinically meaningful. During the initial 10 weeks of the study, subjects were randomized to receive either ARALAST or a commercially available preparation of α 1 -PI (Prolastin ® ). The overall frequency, severity and symptomatology of adverse reactions were similar in both the ARALAST and Prolastin ® groups. There were two serious adverse events in the Prolastin ® group, both of which were considered to be possibly related to Prolastin ® . These included chest pain, dyspnea and bilateral pulmonary infiltrates in one individual that withdrew from the study prematurely following an unscheduled bronchoscopy to remove a foreign body and the other, a positive seroconversion to Parvovirus B-19. There were no serious adverse events or seroconversions reported for the ARALAST group during the 96 week study period. No subject developed an antibody to α 1 –PI.