Aralast NP

What Is Aralast NP?

Aralast NP [Alpha1-Proteinase Inhibitor (Human)] is an Alpha1-Proteinase Inhibitor (Human) (Alpha1-PI) indicated for chronic augmentation therapy in adults with clinically evident emphysema due to severe congenital deficiency of Alpha1-PI (alpha-antitrypsin deficiency). Aralast NP increases antigenic and functional (anti-neutrophil elastase capacity, ANEC) serum levels and antigenic lung epithelial lining fluid levels of Alpha1-PI.

What Are Side Effects of Aralast NP?

Common side effects of Aralast NP include:

• headache,
• muscle and joint discomfort,
• injection site bruising,
• nausea,
• fatigue, and
• runny nose.

Dosage for Aralast NP

The recommended dosage of Aralast NP is 60 mg/kg body weight administered once weekly by intravenous infusion.

What Drugs, Substances, or Supplements Interact with Aralast NP?

Aralast NP may interact with other drugs. Tell your doctor all medications and supplements you use.

Aralast NP During Pregnancy or Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Aralast NP; it is unknown if it would affect a fetus. It is unknown if Aralast NP passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Aralast NP [Alpha1-Proteinase Inhibitor (Human)] Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Aralast NP Consumer Information

Get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing, difficulty breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Stop using alpha 1-proteinase inhibitor and call your doctor at once if you have a serious side effect such as:

• fever, chills, body aches, flu symptoms, sores in your mouth and throat;
• pain or burning when you urinate;
• wheezing, chest pain or tightness, trouble breathing; or
• vision changes.

Less serious side effects may include:

• nausea, bloating;
• headache, dizziness, drowsiness;
• feeling tired;
• back pain, joint or muscle pain;
• swelling in your hands or feet;
• flushing (warmth, redness, or tingly feeling);
• cold symptoms such as stuffy nose, sneezing, sore throat, cough; or
• mild itching.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Aralast NP (Alpha1-Proteinase Inhibitor (Human) Liquid for Intravenous Infusion )

 

Aralast NP Professional Information

SIDE EFFECTS

Hypersensitivity reactions have been reported in patients following administration of ARALAST/ARALAST NP [see WARNINGS AND PRECAUTIONS].

No serious adverse reactions related to the use of ARALAST NP were reported in clinical trials.The most common adverse reactions occurring in ≥ 5% of infusions in clinical trials were headache, musculoskeletal discomfort, vessel puncture site bruise, nausea, and rhinorrhea.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of ARALAST NP was evaluated in a total of 38 subjects with severe congenital Alpha1-PI deficiency (pre-augmentation therapy serum levels of Alpha1-PI of less than 11 microM) in two clinical trials. The crossover trial was a multicenter, randomized, double-blind, single-dose pharmacokinetic (PK) comparability trial conducted in 25 subjects with severe congenital Alpha1-PI deficiency to evaluate the pharmacokinetics of ARALAST NP (test drug, 60 mg/kg body weight) as compared to ARALAST (reference drug, 60 mg/kg body weight), each infused at a rate of 0.2 mL/kg body weight/minute. The BAL trial was a multicenter, open-label, non-randomized trial in 13 subjects with severe congenital Alpha1-PI deficiency to determine the safety and effects of weekly augmentation therapy with ARALAST NP (60 mg/kg body weight/week) administered at a rate of 0.2 mL/kg body weight/minute in elevating Alpha1-PI levels in serum and epithelial lining fluid (ELF).

In both trials, there were no deaths and no serious adverse reactions associated with ARALAST NP or ARALAST administration. None of the subjects withdrew from the trial due to an adverse reaction. There was no reduction in infusion rate at 0.2 mL/kg body weight/min or infusion discontinuation/interruption due to an adverse reaction, except for one subject in the crossover trial who experienced pain at infusion site during ARALAST administration.

Table 1 summarizes the number of subjects, the total number of infusions, and the rate of adverse reactions (ARs) associated with ARALAST NP or ARALAST treatment for each clinical trial.

Table 1 : Number of Subjects /Infusions /Adverse Reactions (ARs)^a Occurring during ARALAST NP or ARALAST Treatment

	Crossover Trial		BAL Trial
	ARALAST NP	ARALAST	ARALAST NP
No. of subjects treated	25	25	13
No. of infusions	25	25	104
No. (%) of subjects with serious ARs	0 (0%)	0 (0%)	0 (0%)
No. of serious ARs	0	0	0
No. (%) of subjects with non-serious	12 (48%)	13 (52%)	4 (31%)
ARs
No. of non-serious ARs	26	21	14
No. (%) of Mildb ARs	21 (81%)	16 (76%)	8 (57%)
No. (%) of Moderatec ARs	5 (19%)	5 (24%)	5 (36%)
No. (%) of Severed ARs	0 (0%)	0 (0%)	1 (7%)
aAn adverse reaction (AR) is any adverse event which met any of the following criteria: (a) an adverse event that began during infusion or within 72 hours following the end of product infusion, or (b) an adverse event considered by the investigator to be at least possibly related to product administration, or (c) an adverse event for which causality assessment was missing or indeterminate. bA mild reaction was defined as a transient discomfort that does not interfere in a significant manner with the subject's normal functioning level, or an event that resolves spontaneously or may require minimal therapeutic intervention cA moderate reaction was defined as an event that is considered related to study product and that produces limited impairment of function and can require therapeutic intervention, or that produces no sequelae dA severe reaction was defined as an event that is considered related to study product and that results in a marked impairment of function and can lead to temporary inability to resume usual life pattern, or that produces sequelae which requires prolonged therapeutic intervention

The most common ARs (defined as adverse reactions occurring in ≥ 5% of infusions) in each clinical trial are shown in Table 2.

Table 2 : Adverse Reactions (ARs)^a Occurring in ≥ 5% of Infusions

Reaction	Cross over Trial (Number of Subjects = 25; Number of infus ions per product = 25)		BAL Trial (Number of Subjects = 13; Number of infus ions = 104)
	ARALAST NP N (%)b	ARALAST N (%)b	ARALAST NP N (%)b
Headache	4 (16%)	3 (12%)	0 (0%)
Musculoskeletal discomfort	4 (16%)	2 (8%)	0 (0%)
Vessel puncture site bruise	2 (8%)	4 (16%)	0 (0%)
Lethargy	0 (0%)	2 (8%)	0 (0%)
Nausea	2 (8%)	2 (8%)	0 (0%)
Rhinorrhea	1 (4%)	0 (0%)	6 (6%)
aAn adverse reaction (AR) is any adverse event which met any of the following criteria: (a) an adverse event that began during infusion or within 72 hours following the end of product infusion, or (b) an adverse event considered by the investigator to be at least possibly related to product administration, or (c) an adverse event for which causality assessment was missing or indeterminate. bExpressed as number of events (N) divided by total number of infusions, then multiplied by 100.

ARALAST versuss PROLASTIN Trial

ARALAST was evaluated for up to 96 weeks in 27 subjects with a congenital deficiency of Alpha1-PI and clinically evident emphysema. During the initial 10 weeks of the trial, subjects were randomized to receive either ARALAST or a commercially available preparation of Alpha1-PI (PROLASTIN).

During the entire period of administration of ARALAST, the most common adverse reactions occurring at a rate of > 0.5% of infusions included pharyngitis (1.2%), headache (0.8%), and cough increased (0.5%). Adverse reactions that occurred at rates < 0.5% included somnolence, rash, tinnitus, back pain, chest pain, peripheral edema, dizziness, insomnia, bronchitis, abdomen enlarged, abdominal pain, allergic reaction, pruritus, chills, fever, vasodilation, nausea, hypertonia, hypesthesia, nervousness, asthma, dyspnea, lung disorder, abnormal vision, conjunctivitis, and dysmenorrhea.

Twenty-six (26) of 27 (96.3%) subjects experienced a total of 94 upper and lower respiratory-tract infections during the 96-week trial (median: 3.0; range: 1 to 8; mean ± SD: 3.6 ± 2.3 infections). Twentyeight (29.8%) of the respiratory infections occurred in 19 (70.4%) subjects during the first 24 weeks of the 96-week trial suggesting that the risk of infection did not change with time on ARALAST. In a posthoc analysis, subjects experienced a range of 0 to 8 exacerbations of COPD over the 96-week trial 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 routine clinical chemistry (other than ALT) laboratory parameters were little changed over the duration of the trial, with individual variations not clinically meaningful.

There were no serious adverse reactions or seroconversions reported for the ARALAST group during the 96 week trial period. No subject developed antibodies to Alpha1-PI.

Immunogenicity

a. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ARALAST NP with the incidence of antibodies to other products may be misleading.

b. Immunogenicity of ARALAST NP was evaluated in the BAL trial. None of the treated subjects developed antibodies against ARALAST NP.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ARALAST NP. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Vascular Disorders: Flushing

Gastrointestinal Disorders: Vomiting, Diarrhea

Skin and Subcutaneous Tissue Disorders: Urticaria

Musculoskeletal and Connective Tissue Disorders: Myalgia

General and Administration Site Conditions: Injection site reaction, Fatigue, Malaise, Asthenia, Feeling abnormal

Read the entire FDA prescribing information for Aralast NP (Alpha1-Proteinase Inhibitor (Human) Liquid for Intravenous Infusion )