Vivaglobin

Name: Vivaglobin

Clinical pharmacology

Vivaglobin® (immune globulin subcutaneous (human)) Immune Globulin Subcutaneous (Human), supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents.

Vivaglobin® (immune globulin subcutaneous (human)) is to be administered by injection into the subcutaneous tissue. Subcutaneous administration of immune globulin decreases bioavailability compared to intravenous administration.1 The bioavailability of Vivaglobin® (immune globulin subcutaneous (human)) is approximately 73% compared to immune globulin intravenous (IGIV). Various factors, such as the site of administration and IgG catabolism, can affect absorption.1,2 With Vivaglobin® (immune globulin subcutaneous (human)) administration, peak serum IgG levels are lower than those achieved with IGIV. Subcutaneous administration results in relatively stable steady-state serum IgG levels when administered on a weekly basis.2,3 This serum IgG profile is representative of that seen in a normal population.

The pharmacokinetics (PK) of Vivaglobin® (immune globulin subcutaneous (human)) was evaluated in the PK phase of a pivotal 12-month clinical study conducted in the United States and Canada in subjects with primary immune deficiency (PID) (see Clinical Studies). Subjects who were previously treated with IGIV were switched over to weekly Vivaglobin® (immune globulin subcutaneous (human)) subcutaneous treatment and, after a 3-month wash-in/wash-out period, doses were individually adjusted to provide an IgG systemic exposure (area under the curve; AUC) that was not inferior to the AUC of the previous weekly-equivalent IGIV dose. For the 19 per-protocol subjects completing the wash-in/wash-out period, the average Vivaglobin® (immune globulin subcutaneous (human)) dose adjustment was 137% (range: 103 to 192%) of the previous weekly-equivalent IGIV dose. Following 10 to 12 weeks of treatment with Vivaglobin® (immune globulin subcutaneous (human)) at this adjusted dose, the final steady-state AUC determinations were made. The geometric mean ratio of the steady-state AUCs, standardized to a weekly treatment period, for Vivaglobin® (immune globulin subcutaneous (human)) versus IGIV treatment was 94.5% (range: 71.4 to 110.1%) with a lower 95% confidence limit of 89.8% for the per-protocol population (n = 17). Table 2 summarizes additional pharmacokinetic parameters for this study including dosing and serum IgG peak and trough levels following treatment with IGIV and Vivaglobin® (immune globulin subcutaneous (human)) .

Table 2: Summary of Additional Pharmacokinetic Parameters – US and Canada PK Sub-study – Per-protocol Subjects

  IGIV Vivaglobin®
Number of Subjects 17 17
Dose*
  Mean 120 mg/kg 165 mg/kg
  Range 55 – 243 mg/kg 63 – 319 mg/kg
IgG peak levels
  Mean 1735 mg/dL 1163 mg/dL
  Range 1110 – 3230 mg/dL 743 – 2240 mg/dL
IgG trough levels
  Mean 883 mg/dL 1064 mg/dL
  Range 430 – 1600 mg/dL 547 – 2140 mg/dL
*For IGIV: weekly-equivalent dose, § Standardized to a 7-day period

A non-IND 6-month clinical study was conducted in Europe and Brazil in 60 subjects with PID. After the subjects had reached steady state with weekly Vivaglobin® (immune globulin subcutaneous (human)) administration, peak serum IgG levels were observed after a mean of 2.5 days (range 0 to 7 days) in 41 subjects.

In contrast to serum IgG levels observed with monthly IGIV treatment (rapid peaks followed by a slow decline), the serum IgG levels in subjects receiving weekly subcutaneous Vivaglobin® (immune globulin subcutaneous (human)) therapy were relatively stable in both studies.

Clinical Studies

The pivotal open-label, prospective, multicenter clinical study conducted in the United States and Canada evaluated the pharmacokinetics, efficacy, safety and tolerability of Vivaglobin® Immune Globulin Subcutaneous (Human), in adult and pediatric subjects with primary immune deficiency (PID). In this study, 65 adult and pediatric PID subjects previously treated monthly with IGIV were switched to weekly subcutaneous administrations of Vivaglobin® (immune globulin subcutaneous (human)) for 12 months. The per-protocol efficacy analysis included 51 subjects. Subjects received a weekly mean Vivaglobin® (immune globulin subcutaneous (human)) dose of 158 mg/kg body weight (range: 34 to 352 mg/kg), which was 136% (range: 99 to 188%) of their previous weekly-equivalent IGIV dose.

The annual rate of serious bacterial infections (defined as bacterial pneumonia, meningitis, sepsis, osteomyelitis, and visceral abscesses), the primary endpoint, was 0.04 infections per subject per year (one-sided upper 99% confidence interval: 0.14) for the per-protocol set (n = 51). Pneumonia was reported in two subjects. The annual rate of any infections, a secondary endpoint, was 4.4 infections per subject per year.

The IgG subclass levels observed in this study were consistent with a physiologic distribution pattern (mean values) IgG1: 703 mg/dL, IgG2: 278 mg/dL, IgG3: 36 mg/dL, and IgG4: 30 mg/dL.

Table 3 summarizes the dosing and annual rate of infections for the efficacy phase of this study.

Table 3: Dose and Annual Rate of Infections with Vivaglobin® (immune globulin subcutaneous (human)) – Per-protocol Subjects Efficacy Phase of the US and Canada Study

Number of Subjects (Efficacy) 51
Vivaglobin® Dose  
Mean % Previous IGIV Dose (range): 136% (99 – 188%)
  Mean: 158 mg/kg b.w.
  Range: 34 – 352 mg/kg b.w.
Annual Rate of Serious Bacterial Infections 0.04 infections/subject year
Annual Rate of Any Infections 4.4 infections/subject year
b.w.: body weight

Table 4 provides a summary of missed school or work and hospitalization due to infection, which were secondary endpoints.

Table 4: Summary of Secondary Efficacy Endpoints – Per-protocol Subjects Efficacy Phase of the US and Canada Study

Number of Subjects 51
Total Number of Subject Days 18,949
Total Number of Days Missed School/Work Due to Infection (%) 192 (1.0%)
Annual Rate Missed School/Work Due to Infection (days/subject year) 3.70
Total Number of Days Hospitalized Due to Infection (%) 12 ( < 0.1%)
Annual Rate of Hospitalization (days/subject year) 0.23

In a non-IND clinical study of Vivaglobin® (immune globulin subcutaneous (human)) conducted in Europe and Brazil, 60 adult and pediatric subjects with PID were switched to weekly subcutaneous administration of Vivaglobin® (immune globulin subcutaneous (human)) for six months. Forty-nine (49) subjects had been on IGIV and 11 subjects had been treated long-term with another brand of Immune Globulin Subcutaneous (Human) replacement therapy before entering the study. The forty-seven (47) per-protocol subjects received a weekly mean Vivaglobin® (immune globulin subcutaneous (human)) dose of 89 mg/kg body weight (range: 51 to 147 mg/kg), which was 101% (range: 81 to 146%) of their previous immune globulin treatment. The annualized rates of serious bacterial infections (0.04 infections/subject year, one-sided upper 99% confidence interval: 0.21) and any infections (4.3 infections/subject year) were similar to those reported in the study conducted in the US and Canada.

REFERENCES

1. Smith GN, Griffiths B, Mollison D, Mollison PL. Uptake of IgG after intramuscular and subcutaneous injection. Lancet 1972;1:1208-12.

2. Waniewski I, Gardulf A, Hammarström L. Bioavailability of ã-Globulin after subcutaneous infusions in patients with common variable immunodeficiency. J Clin Immunol 1994;14(2):90-7.

3. Data on file.

What is immune globulin (hizentra, vivaglobin)?

Immune globulin is a sterilized solution made from human plasma. It contains the antibodies to help your body protect itself against infection from various diseases.

Immune globulin subcutaneous (for injection under the skin) is used to treat primary immune deficiency.

Immune globulin may also be used for other purposes not listed in this medication guide.

Where can i get more information?

Your doctor or pharmacist can provide more information about immune globulin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Side effects

In clinical studies, administration of Vivaglobin® Immune Globulin Subcutaneous (Human), has been shown to be safe and well tolerated in both adult and pediatric subjects. Reactions similar to those reported with administration of other immune globulin products may also occur with Vivaglobin® (immune globulin subcutaneous (human)) . Rarely, immediate anaphylactoid and hypersensitivity reactions may occur. In exceptional cases, sensitization to IgA may result in an anaphylactic reaction (see CONTRAINDICATIONS).

Should evidence of an acute hypersensitivity reaction be observed, the infusion should be stopped promptly, and appropriate treatment and supportive therapy should be administered.

In the US and Canada clinical study, the safety of Vivaglobin® (immune globulin subcutaneous (human)) was evaluated for 15 months (3-month wash-in/wash-out period followed by 12-month efficacy period) in 65 subjects with PID. The most frequent adverse reaction was local reaction at the injection site. Table 5 summarizes the most frequent adverse events by subject reported in the clinical study, and Table 6 summarizes the most frequent adverse events by infusion.

Table 5: Most Frequent Adverse Events by Subject Irrespective of Causality* in the US and Canada Study

Adverse Events ( ≥ 10% of subjects) No. of Subjects (% of total)
Adverse Events at the Injection Site 60 (92%)
Non-Injection Site Reactions
  Headache 31 (48%)
  Gastrointestinal disorder 24 (37%)
  Fever 16 (25%)
  Nausea 12 (18%)
  Sore throat 11 (17%)
  Rash 11 (17%)
  Allergic reaction 7 (11%)
  Pain 6.7 (10%)†
  Diarrhea 6.7 (10%)†
  Cough increased 6.7 (10%)†
*Excluding infections
† Due to missing subject diary information, values listed are estimates.

Table 6: Most Frequent Adverse Events by Infusion Irrespective of Causality* in the US and Canada Study

Adverse Events ( ≥ 1% of infusions)
(Number of Infusions: 3656)
No. of Adverse Events
(Rate**)
Adverse Events at the Injection Site 1789 (49%)
  Mild 1112 (30%)
  Moderate 601 (16%)
  Severe 65 (2%)
  Unknown Severity 11 ( < 1%)
Non-Injection Site Reactions
  Headache  159 (4%)
  Gastrointestinal disorder 40.3 (1%)†
*Excluding infections
**Rate = number of reactions/infusion
† Due to missing subject diary information, values listed are estimates.

Table 7 summarizes the most frequent related adverse events by subject reported in the clinical study, and Table 8 summarizes the most frequent related adverse events by infusion.

Table 7: Most Frequent Related Adverse Events by Subject* in the US and Canada Study

Related Adverse Event
( ≥ 2 subjects)
No. of Subjects
(% of total)
Adverse Events at the Injection Site 60 (92%)
Non-Injection Site Reactions
  Headache 21 (32%)
  Nausea 7 (11%)
  Rash 4 (6%)
  Asthenia 3 (5%)
  Gastrointestinal disorder 3 (5%)
  Fever 2 (3%)
  Skin disorder 2 (3%)
  Tachycardia 2 (3%)
  Urine abnormality 2 (3%)
*Excluding infections

Table 8: Most Frequent Related Adverse Events by Infusion* in the US and Canada Study

Related Adverse Event
( ≥ 2 AEs)
(Number of Infusions: 3656)
No. of AEs
(Rate**)
Adverse Events at the Injection Site 1787 (49%)
Non-Injection Site Reactions
  Headache 59 (1.6%)
  Rash  9 (0.2%)
  Nausea 9 (0.2%)
  Nervousness 4 (0.1%)
  Asthenia 3 (0.1%)
  Gastrointestinal disorder 3 (0.1%)
  Skin disorder 3 (0.1%)
  Urine abnormality 3 (0.1%)
  Fever 2 (0.1%)
  Dyspnea 2 (0.1%)
  Gastrointestinal pain 2 (0.1%)
  Tachycardia 2 (0.1%)
*Excluding infections
**Rate = number of reactions/infusion

In the non-IND Europe and Brazil clinical study, the safety of Immune Globulin Subcutaneous (Human), Vivaglobin® (immune globulin subcutaneous (human)) was evaluated for 10 months in 60 subjects with PID. The adverse events and their rates reported in this study were similar to those reported in the US and Canada study, with two notable exceptions for the related adverse events. These events were 59 episodes of headache (1.6%) and 2 episodes of fever (0.1%) in the US and Canada study and no episodes of headache and 18 episodes of fever (0.8%) in the Europe and Brazil study.

Local (Injection Site) Reactions

Local injection site reactions consisting of mostly mild or moderate swelling, redness and itching, have been observed with the use of Vivaglobin® (immune globulin subcutaneous (human)) . No serious local site reactions were observed. The majority of injection site reactions resolved within four days. Additionally, the number of subjects reporting local injection site reactions decreased substantially after repeated use (see Figure 1). Only three subjects in the US and Canada study and one subject in the Europe and Brazil study discontinued due to local site reactions.

Figure 1: Subjects Reporting Local Site Reactions By Infusion

Read the entire FDA prescribing information for Vivaglobin (Immune Globulin Subcutaneous (Human))

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Uses of Vivaglobin

  • It is used to stop or lower the harshness of other infections in people with a weak immune system.
  • It may be given to you for other reasons. Talk with the doctor.

How is this medicine (Vivaglobin) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as an infusion under the skin over a period of time.
  • Your doctor may teach you how to use.
  • Follow how to use carefully.
  • Do not shake the solution.
  • Wash your hands before and after use.
  • Do not use if the solution is cloudy, leaking, or has particles.
  • Do not use if solution changes color.
  • Do not use if it has been frozen.
  • Do not mix with any other liquid drugs.
  • Do not give into skin that is irritated, bruised, red, infected, or scarred.
  • Move the site where you give Vivaglobin as you were told by the doctor.
  • Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Fever or chills.
  • Change in color of skin to a bluish color like on the lips, nail beds, fingers, or toes.
  • Feeling very tired or weak.
  • Seizures.
  • Bloating.
  • Feeling confused.
  • Swelling.
  • Very bad dizziness or passing out.
  • A heartbeat that does not feel normal.
  • Any unexplained bruising or bleeding.
  • Mood changes.
  • Muscle or joint pain.
  • Change in speech.
  • Change in eyesight.
  • Blurred eyesight.
  • Shakiness.
  • Sweating a lot.
  • Very bad belly pain.
  • Dark urine or yellow skin or eyes.
  • Very bad irritation where the shot was given.
  • Lung problems have happened with this medicine. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.
  • This medicine may raise the chance of a very bad brain problem called aseptic meningitis. Call your doctor right away if you have a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother your eyes, feeling sleepy, or feeling confused.

How do I store and/or throw out Vivaglobin?

  • Most of the time, this medicine will be given in a hospital or doctor's office. If stored at home, follow how to store as you were told by the doctor.
  • Do not freeze.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Contraindications

Vivaglobin is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of Immune Globulin (Human).

Vivaglobin is contraindicated in IgA-deficient patients with antibodies against IgA or a history of hypersensitivity (see Description [11]).

Adverse Reactions

The most common adverse reactions (those AEs considered by the investigator to be at least possibly related to Vivaglobin administration) observed in ≥5% of study subjects receiving Vivaglobin were local injection-site reactions (swelling, redness, and itching), headache, nausea, rash, asthenia, and gastrointestinal disorder.

Clinical Studies Experience

Because clinical studies 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 practice.

US-Canada Study

The safety of Vivaglobin was evaluated in a clinical study in the US and Canada for 12 months in 65 subjects with PI who had been previously treated with IGIV every 3 or 4 weeks (see Clinical Studies [14.1]). After 3 months, subjects were switched from IGIV to weekly subcutaneous administration of Vivaglobin for 12 months. Subjects were treated weekly with Vivaglobin at a mean dose of 158 mg/kg body weight (range: 34 to 352 mg/kg). The 65 subjects received a total of 3,656 infusions of Vivaglobin.

Table 2 shows the number of subjects who withdrew from the US-Canada study due to adverse events (AEs) and the AEs leading to discontinuation.

Table 2: Subjects with Adverse Events (AEs) Leading to Discontinuation, US-Canada Study
AEs Subjects with AEs At Least Possibly Related Subjects with AEs Irrespective of Causality Total Number (%) of Subjects
* One subject experienced hyperventilation and tachycardia.
Subjects with at least 1 AE leading to discontinuation 4 1 5 (8%)
Injection-site reaction 3 3 (5%)
Intestinal obstruction 1 1 (2%)
Hyperventilation 1* 1 (2%)
Tachycardia 1* 1 (2%)

Table 3 summarizes the most frequent AEs (experienced by more than 5% of subjects), irrespective of causality. It includes all AEs and those considered temporally associated with the Vivaglobin infusion, i.e., occurring during the infusion or within 72 hours after the end of the infusion.

Table 3: Incidence of Subjects With Adverse Events (AEs)* (Experienced by >5% of Subjects) and Rate† per Infusion, Irrespective of Causality, in the US-Canada Study
All AEs AEs Occurring During or Within 72 Hours of Infusion
AEs*
(>5% of Subjects)
Number (%) of Subjects
(n=65)
Number (Rate†) of AEs per Infusion
(n=3656)
Number (%) of Subjects
(n=65)
Number (Rate†) of AEs per Infusion
(n=3656)
* Excluding infections. † Rate, number of AEs per infusion. ‡ Includes injection-site inflammation.
AEs at the injection site‡ 60 (92%) 1789 (0.49) 60 (92%) 1767 (0.4848)
Other AEs
  Headache 31 (48%) 159 (0.04) 30 (46%) 104 (0.033)
  Gastrointestinal disorder 24 (37%) 35 (0.01) 18 (28%) 24 (0.007)
  Fever 16 (25%) 28 (0.008) 12 (8%) 20 (0.005)
  Nausea 12 (18%) 18 (0.005) 11 (17%) 15 (0.004)
  Rash 11 (17%) 22 (0.006) 10 (15%) 16 (0.004)
  Sore throat 10 (15%) 17 (0.005) 8 (12%) 11 (0.003)
  Allergic reaction 7 (11%) 8 (0.002) 5 (8%) 5 (0.001)
  Pain 6 (9%) 8 (0.002) 4 (6%) 4 (0.001)
  Diarrhea 6 (9%) 6 (0.002) 5 (8%) 5 (0.001)
  Cough increased 6 (9%) 6 (0.002) 5 (8%) 5 (0.001)
  Gastrointestinal pain 5 (8%) 6 (0.002) 4 (6%) 5 (0.001)
  Migraine 5 (8%) 5 (0.001) 2 (3%) 2 (0.001)
  Skin disorder 5 (8%) 7 (0.002) 3 (5%) 5 (0.001)
  Asthma 5 (8%) 8 (0.002) 3 (5%) 4 (0.001)
  Arthralgia 4 (6%) 4 (0.001) 3 (5%) 3 (0.001)
  Asthenia 4 (6%) 4 (0.001) 2 (3%) 2 (0.001)
  Malaise 4 (6%) 5 (0.001) 2 (3%) 2 (0.001)

The total number of AEs, irrespective of causality, including injection-site reactions, that began during or within 72 hours after the end of an infusion was 2262 (a rate of 0.62 AEs per infusion); excluding injection-site reactions, the rate of AEs per infusion was 0.14.

Table 4 summarizes the severity of local AEs by infusion, irrespective of causality.

Table 4: Severity of Local Adverse Events (AEs) by Infusion, Irrespective of Causality, in the US-Canada Study
AEs
Number (Rate*) of AEs Number (Rate*) of AEs Occurring During or Within 72 Hours of Infusion
(Number of infusions: 3656)

* Rate, number of AEs per infusion. † Defined as those reactions that did not interfere with routine activities. ‡ Defined as those reactions that interfered with routine activities. § Defined as those reactions that made it impossible to perform routine activities.
AEs at the injection site 1789 (0.49) 1767 (0.48)
  Mild† 1112 (0.30) 1100 (0.30)
  Moderate‡ 601 (0.16) 593 (0.16)
  Severe§ 65 (0.02) 64 (0.02)
  Unknown severity 11 (<0.01) 10 (<0.01)
Discontinuations due to AEs at the injection site 3 subjects

Of the three subjects who discontinued the study due to injection-site reactions, one withdrew on Day 1 (Infusion 1) of the wash-in/wash-out period after a moderate injection-site reaction and a mild headache; one withdrew on Day 22 (Infusion 4) of the wash-in/wash-out period following severe injection-site reactions for two weeks; and one withdrew on Day 78 following a mild injection-site reaction.

Local reactions decreased substantially after repeated use.

Table 5 summarizes the most frequent adverse reactions (experienced by at least 3% of subjects) and considered by the investigator to be at least possibly related to Vivaglobin administration.

Table 5: Incidence of Subjects With Adverse Reactions (Experienced in ≥3% of Subjects) and Rate* per Infusion in the US-Canada Study
Related Adverse Reactions
(≥3% Subjects)
Number (%) of Subjects
(n=65)
Number (Rate*) of Adverse Reactions per Infusion
(n=3656)
* Rate, number of adverse reactions per infusion. † Includes injection-site inflammation.
Adverse reactions at the injection site† 60 (92%) 1787 (0.49)
Other Adverse reactions
  Headache 21 (32%) 59 (0.016)
  Nausea 7 (11%) 9 (0.002)
  Rash 4 (6%) 9 (0.002)
  Asthenia 3 (5%) 3 (0.001)
  Gastrointestinal disorder 3 (5%) 3 (0.001)
  Fever 2 (3%) 2 (0.001)
  Skin disorder 2 (3%) 3 (0.001)
  Tachycardia 2 (3%) 2 (0.001)
  Urine abnormality 2 (3%) 3 (0.001)

Europe-Brazil Study

In a clinical study conducted in Europe and Brazil, the efficacy and safety of Vivaglobin were evaluated for 10 months in 60 subjects with PI. Subjects were treated weekly with Vivaglobin at a mean dose of 89 mg/kg body weight (range: 51 to 147 mg/kg), which was 101% of their previous weekly IGIV or IGSC dose (see Clinical Studies [14.2]). Study subjects received a total of 2,297 infusions of Vivaglobin.

The AEs and their rates reported in this study were similar to those reported in the US-Canada study, with two exceptions: no episodes of headache were reported; and 18 (a rate of 0.008 per infusion) episodes of fever were judged to be related to the administration of Vivaglobin. One subject discontinued due to repeated local reactions of moderate severity.

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.

Vivaglobin

Adverse reactions identified during worldwide postmarketing use of Vivaglobin for treatment of PI are allergic-anaphylactic reactions (including dyspnea, pruritus, urticaria, rash, edema and other cutaneous reactions, wheezing, syncope, hypotension, and throat swelling), generalized reactions (including flu-like symptoms, myalgia, chills, fever, tachycardia, arthralgia, nausea and vomiting, diarrhea, gastrointestinal cramping, stomach pain, back pain, headache, headache possibly caused by increased blood pressure, and chest tightness), migraine, and injection-site reactions.

General

The following adverse reactions have been identified and reported during the postmarketing use of IGIV products11:

  • Renal: Acute renal dysfunction/failure, osmotic nephropathy
  • Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
  • Cardiovascular: Cardiac arrest, thromboembolism, vascular collapse, hypotension
  • Neurological: Coma, loss of consciousness, seizures, tremor, aseptic meningitis syndrome
  • Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis
  • Hematologic: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs') test
  • General/Body as a Whole: Pyrexia, rigors
  • Musculoskeletal: Back pain
  • Gastrointestinal: Hepatic dysfunction, abdominal pain
(web3)