June 28, 2016
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Zemaira

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Zemaira




Zemaira Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 3/15/2016

Zemaira [Alpha1-Proteinase Inhibitor (Human)] is a protein (alpha 1-antitrypsin) that occurs naturally in the body. In people who lack the alpha 1-antitrypsin protein, breakdown of lung tissues can lead to emphysema (damage to the air sacs in the lungs). Zemaira is used to treat alpha 1-antitrypsin deficiency in people who have symptoms of emphysema. Alpha 1-antitrypsin deficiency is a genetic (inherited) disorder and Zemaira will not cure this condition. Zemaira may be available in generic form. Common side effects of Zemaira include drowsiness, tiredness, dizziness, weakness, cold symptoms (cough, sore throat, stuffy nose, sneezing), pain or bleeding where the medication was injected, flushing (warmth, redness, or tingly feeling under your skin), nausea, bloating diarrhea, stomach pain, headache, back pain, joint or muscle pain, swelling in your hands or feet, or mild itching.

The recommended dose of Zemaira is 60 mg/kg body weight administered once weekly. Zemaira may interact with other drugs. Tell your doctor all medications and supplements you use. Zemaira may be harmful to a fetus. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is unknown if this drug passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.

Our Zemaira [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.

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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Zemaira in Detail - Patient Information: Side Effects

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 Zemaira (Alpha-Proteinase Inhibitor (Human))

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Zemaira FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The most common adverse reactions (ARs) occurring in at least 5% of subjects receiving Zemaira in all pre-licensure clinical trials were headache, sinusitis, upper respiratory infection, bronchitis, asthenia, cough increased, fever, injection site hemorrhage, rhinitis, sore throat, and vasodilation. Serious adverse reactions reported following administration of Zemaira in pre-licensure clinical trials included one event each in separate subjects of bronchitis and dyspnea, and one event each in a single subject of chest pain, cerebral ischemia and convulsion.

In post-licensure trials, the exposure adjusted incidence rate (EAIR) of serious exacerbations of chronic obstructive pulmonary disease (COPD) among subjects was higher during the RAPID Extension trial as compared to the rate observed during the preceding RAPID trial [see Clinical Trials Experience below].

Serious adverse reactions identified during postmarketing use were hypersensitivity reactions [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

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

The following clinical trials were conducted with Zemaira:

  • Controlled, double-blind trial in 44 subjects, who received a weekly 60 mg/kg body weight dose of either Zemaira (30 subjects) or Prolastin® (a commercially available Alpha1-Proteinase Inhibitor [Human] product) (14 subjects) for 10 weeks, followed by an open-label phase in which 43 subjects received Zemaira weekly for 14 weeks;
  • Open-label trial in 9 subjects who received a weekly 60 mg/kg body weight dose of Zemaira for 26 weeks, followed by a 7-week to 22-week extension;
  • Crossover, double-blind trial in 18 subjects who received a single 60 mg/kg dose of Zemaira and a single 60 mg/kg dose of Prolastin;
  • Open-label trial of 19 subjects who received a single 15 mg/kg (2 subjects), 30 mg/kg (5 subjects), 60 mg/kg (6 subjects), or 120 mg/kg (6 subjects) dose of Zemaira; and
  • Post-Licensure Randomized, Placebo-Controlled Trial of Augmentation Therapy in Alpha-1 Protease Inhibitor Deficiency (RAPID), in 180 subjects who received a weekly 60 mg/kg body weight dose of either Zemaira (93 subjects) or placebo (87 subjects) for 24 months (referred to as years 1 and 2 in Table 3).
  • Post-Licensure Open-label extension of the RAPID trial involving 140 subjects who had completed blinded treatment with Zemaira or placebo for 24 months in the RAPID trial and who entered the extension trial and received open-label Zemaira for up to an additional 24 months (referred to as years 3 and 4 in Table 3).

Table 1 summarizes the ARs, expressed as events per subject-year, and the corresponding number of ARs per infusion, expressed as % of all infusions, for each treatment in prelicensure clinical trials of Zemaira.

Table 1: Overall Adverse Reactions (ARs) and Serious ARs

  Number of Subjects* (Events per Sub-ject-Year†) Number of Infusions‡ (% of all Infusions)
Zemaira
(n=66, SY§=28.72)
Prolastin
(n=32), SY§=3.83)
Zemaira
(n=1296)
Prolastin
(n=160)
ARs (AEs assessed by investigator as at least possibly related or occurring during or within 72 hours after the end of the infusion or for which causality assessment was missing or indeterminate). 54 (5.6) 16 (3.8) 160 (12.3) 31 (19.4)
Serious ARs (Serious AEs assessed by investigator as at least possibly related or occurring during or within 72 hours after the end of the infusion or for which causality assessment was missing or indeterminate). 4 (0.2) 1 (1.0) 6 (0.5) 1 (0.6)
* Based on unique subjects. If a subject experienced more than one AR, the subject was only counted once.
† The exposure adjusted event rate was based on total exposure time presented in subject-years and the total number of adverse reactions in the database.
‡ If there were multiple occurrences of ARs following a single infusion, only one occurrence was counted.
§ SY=subject-year.

Table 2 summarizes the ARs occurring in 5% or more ( > 3) subjects, expressed as events per subject-year, and the corresponding number of ARs per infusion, expressed as % of all infusions, for each treatment in clinical trials of Zemaira.

Table 2: Adverse Reactions Occurring in ≥ 5% of Subjects

ARs (AEs assessed by investigator as at least possibly related or occurring during or within 72 hours after the end of the infusion or for which causality assessment was missing or indeterminate). Number of Subjects* (Events per Sub-ject-Year†) Number of Infusions‡ (% of all Infusions)
Zemaira
(n=66, SY§=28.72)
Prolastin
(n=32, SY§=3.83)
Zemaira
(n=1296)
Prolastin
(n=160)
Headache 13 (0.7) 5 (1.3) 19 (1.5) 5 (3.1)
Sinusitis 10 (0.5) 1 (0.3) 13 (1.0) 1 (0.6)
Upper Respiratory Infection 10 (0.4) 1 (0.3) 10 (0.8) 1 (0.6)
Bronchitis 5 (0.2) 0 (0.0) 6 (0.5) 0 (0.0)
Asthenia 5 (0.2) 2 (0.5) 5 (0.4) 2 (1.3)
Cough Increased 5 (0.2) 1 (0.5) 5 (0.4) 2 (1.3)
Fever 4 (0.1) 0 (0.0) 4 (0.3) 0 (0.0)
Injection Site Hemorrhage 4 (0.1) 0 (0.0) 4 (0.3) 0 (0.0)
Rhinitis 4 (0.1) 0 (0.0) 4 (0.3) 0 (0.0)
Sore Throat 4 (0.1) 0 (0.0) 4 (0.3) 0 (0.0)
Vasodilation 4 (0.1) 1 (0.3) 4 (0.3) 1 (0.6)
* Based on unique subjects. If a subject experienced more than one AR of the same type, the subject was only counted once.
†The exposure adjusted event rate was based on total exposure time presented in subject-years and the total number of adverse reactions in the database.
‡ If more than one of the same type of an event occurred after an infusion, only one event was counted.
§ SY=subject-year.

Diffuse interstitial lung disease was noted on a routine chest x-ray of one subject at Week 24. Causality could not be determined.

Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

In a retrospective analysis, during the 10-week blinded portion of the 24-week clinical trial, 6 subjects (20%) of the 30 treated with Zemaira had a total of 7 exacerbations of their chronic obstructive pulmonary disease (COPD). Nine subjects (64%) of the 14 treated with Prolastin had a total of 11 exacerbations of their COPD. The observed difference between groups was 44% (95% confidence interval [CI] from 8% to 70%). Over the entire 24-week treatment period, of the 30 subjects in the Zemaira treatment group, 7 subjects (23%) had a total of 11 exacerbations of their COPD.

In the 24-week double-blind trial, Zemaira-treated subjects were tested for HAV, HBV, HCV, HIV, and parvovirus B19 (B19V), and no evidence of virus transmission was observed. In the RAPID study 25 serious exacerbations of COPD were reported in 15 Zemaira subjects vs. 17 such events in 9 placebo subjects, corresponding to rates of 0.146 exacerbations per subject-year with Zemaira and 0.115 exacerbations per subject-year with placebo, (ratio Zemaira:Placebo [95% confidence interval]: 1.256 [0.457 - 3.454]).

Subjects who were randomized to Zemaira in the 2-year RAPID trial who then entered and received open-label Zemaira in the 2 year RAPID extension trial were in the “Early Start” group. Subjects who were randomized to Placebo in the 2-year RAPID trial who then entered and received open-label Zemaira in the 2 year RAPID extension trial were in the “Delayed Start” group. During the RAPID Extension trial 37 serious exacerbations of COPD were reported in 19 subjects (25%) in the Early Start group, corresponding to rates of 0.25 exacerbations per subject-year. In comparison, 20 serious exacerbations were reported in 11 subjects (17%) in the Delayed Start group corresponding to rates of 0.16 exacerbations per subject-year (ratio Early: Delayed [95% confidence interval]: 1.58 [0.68 - 3.66], Table 3). Among the Early Start subjects who entered the RAPID extension trial (N = 76), the exposure adjusted incidence rate of serious exacerbations during the RAPID extension trial (years 3-4) was 0.25 compared to 0.12 for those subjects during the earlier RAPID trial(years 1-2), (ratio RAPID Extension:RAPID: 2.10 [95% confidence interval: 1.21 - 3.67]). Among the Delayed Start subjects who entered the RAPID extension trial (N = 64), the exposure adjusted incidence rate of serious exacerbations during the RAPID extension trial (years 3-4) was 0.16 compared to 0.10 for those subjects during the earlier RAPID trial (years 1-2), (ratio RAPID Extension:RAPID: 1.56 [95% confidence interval: 0.80 - 3.03]).

Table 3: Comparison of Exposure-Adjusted Incidence Rates for Serious COPD Exacerbations Occurring in the RAPID study between Zemaira and Placebo subjects and in the RAPID Extension Studies between Early Start and Delayed Start subjects

Serious COPD Exacer- bations* Episode n % EAIR (95% CI) Episode n % EAIR 95% CI Treatment Ratio for EIAR (95% CI)*
RAPID Study (Years 1 - 2) Zemaira (N = 93) Placebo (N = 87) Zemaira: Placebo
25 15 16.1 0.15 (0.10 -0.22) 17 9 10.3 0.12 (0.07 -0.18) 1.26 (0.46 -3.45)
Extension Study (Years 3 - 4) Early Start† (N = 76) Delayed Start‡ (N = 64) Early: Delayed
37 19 25.0 0.25 (0.18 -0.35) 20 11 17.2 0.16 (0.10 -0.25) 1.58 (0.68 -3.66)
N = total number of safety subjects, n = number of subjects within a category, % = (n/N)*100, CI = Confidence Interval. Subject time at risk: Zemaira = 171.14 years, Placebo = 147.75 years, Early Start Group = 146.46 years, Delay Start Group = 124.71 years.
EAIR = Exposure-Adjusted Incidence Rate (events/subject time at risk). The point estimates and confidence intervals for
EAIR values were calculated using negative binomial models.
*Episode = Serious exacerbations of COPD identified by investigators as meeting the Anthonisen criteria1 plus Serious Adverse Event (SAE) terms COPD, Condition Aggravated, Bronchitis, Lower Respiratory Tract Infection, Pneumonia. Serious exacerbation events that overlap or occur within 1 day of one another were counted as single exacerbation episodes.
†Early Start Group subjects were randomized to Zemaira during the double-blind RAPID trial (years 1-2) and received open-label Zemaira during the RAPID extension trial (years 3-4).
‡Delayed Start Group subjects were randomized to Placebo during the double-blind RAPID trial (years 1-2) and received open-label Zemaira during the RAPID extension trial (years 3-4).

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. No anti-A1PI antibodies have been detected in clinical trials of Zemaira. 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 Zemaira with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

Table 4 lists the ARs that have been identified during postmarketing use of Zemaira. This list does not include reactions already reported in clinical trials with Zemaira [see Clinical Trials Experience above].

Table 4: ARs Reported During the Postmarketing Use of Zemaira

System Organ Class Preferred Term/Symptoms
Blood and lymphatic system disorders Lymph node pain
Gastrointestinal disorders Nausea
General disorders and administration site conditions Chills, infusion site reactions, facial, periorbital, lip and extremity swelling, chest pain
Immune system disorders Hypersensitivity, anaphylactic reactions, tachycardia, hypotension, confusion, syncope, oxygen consumption decreased, pharyngeal edema
Nervous system disorders Hypoesthesia, paresthesia, dizziness
Skin disorders Hyperhidrosis, pruritus, rash including exfoliative and generalized, urticaria
Vascular disorders Flushing

Read the entire FDA prescribing information for Zemaira (Alpha-Proteinase Inhibitor (Human))

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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