SIDE EFFECTS

Overview

No serious adverse drug reactions have been reported following the administration of Vaccinia Immune Globulin Intravenous (Human) (VIGIV (vaccinia immune globulin intravenous) ). However, drug exposure to date has been in healthy volunteers. The majority of adverse events reported in a clinical trial evaluating the pharmacokinetics of VIGIV (vaccinia immune globulin intravenous) in healthy volunteers were mild and were similar to those regarded as causally related to infusion of other protein products, such as headache, nausea, dizziness, feeling hot, feeling cold and rigors (see ADVERSE REACTIONS - General).

General Adverse Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

In a clinical study, 60 healthy male and female volunteers received a single intravenous dose of either 6000 U/kg or 9000 U/kg VIGIV (vaccinia immune globulin intravenous) in a pharmacokinetics trial. ⁴ The population consisted of vaccinia vaccination-naïve subjects, ages 18 to 32, with both males and females enrolled in an approximate 50:50 ratio.

In another clinical study, 32 healthy male and female volunteers were randomized to receive vaccinia vaccination (n=10), VIGIV (vaccinia immune globulin intravenous) (9000 u/kg) four days prior to vaccinia vaccination (n=10), or VIGIV (vaccinia immune globulin intravenous) (9000 U/kg) concurrent with vaccinia vaccination (n=12). ²⁸ The population consisted of vaccinia vaccination-naïve subjects, ages 18 to 32, with both male and female enrolled in a 75:25 ratio. The ethnic background of patients included those of Caucasian, African American, Asian and Hispanic descent, with the majority of them being Caucasian.

The most frequently reported adverse events related to VIGIV (vaccinia immune globulin intravenous) administration in both studies were headache, rigors, nausea, dizziness, feeling cold, sweating increased and feeling hot. Table 3 describes all adverse events that were temporally related (overall and related) to VIGIV (vaccinia immune globulin intravenous) or placebo administration (within 3 days).

Table 3: Adverse events that occurred temporally^† following VIGIV (vaccinia immune globulin intravenous) administration ( ≥ 5%)

These adverse events were mostly mild and expected, and are related to intravenous infusion of immune globulins. VIGIV (vaccinia immune globulin intravenous) had no effect on blood pressure or heart rate during a clinical trial of 90 days duration. Other less frequently reported adverse events related to VIGIV (vaccinia immune globulin intravenous) included back pain, nonspecific pain, pyrexia, vomiting, muscle cramps, muscle tightness and muscle spasms. One subject in the 9000 U/kg dosage group experienced syncope. These less frequently reported adverse events are also expected with intravenous infusion of immune globulins. There was a lower incidence of adverse events when VIGIV (vaccinia immune globulin intravenous) (9000 U/kg) was infused at 2 mL/min (60%) than 4 mL/min (86%). It is important to note that all subjects were fasted overnight prior to infusion of VIGIV (vaccinia immune globulin intravenous) or placebo.

There were no serious adverse events or adverse events of severe intensity in this clinical trial. There were no instances where VIGIV (vaccinia immune globulin intravenous) was either discontinued due to an adverse event, or where a reduction in either the dose administered or the infusion rate was required.

Increases in serum creatinine and blood urea nitrogen have been observed as soon as 1 to 2 days after treatment with other IGIVs. Other severe renal adverse events seen after IGIV therapy include acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and osmotic nephrosis.^{10, 11, 12, 29}

Post-marketing Experience with Other IGIV Products

The following is a list of adverse reactions that have been identified and reported during the post-approval use of IGIV: ^{17, 18, 19, 20, 21, 22, 23, 24, 30}

• Respiratory: Cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
• Cardiovascular: Thromboembolism, hypotension
• Neurological: Seizures, tremor
• Hematologic: Hemolysis, positive direct antiglobulin (Coombs) test
• General/Body as a Whole: Pyrexia, rigors
• Musculoskeletal: Back pain
• Gastrointestinal: Hepatic dysfunction, abdominal pain
• Rare and Uncommon Adverse Events:
  • Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion Associated Lung Injury (TRALI)
  • Integumentary: Bullous dermatitis, epidermolysis, erythema multiforme, Stevens-Johnson syndrome
  • Cardiovascular: Cardiac arrest, vascular collapse
  • Neurological: Coma, loss of consciousness
  • Hematologic: Pancytopenia, leukopenia

Because post-marketing reporting of these reactions is voluntary and the at-risk populations are uncertain size, it is not always possible to reliably estimate the frequency of a reaction or establish a causal relationship to exposure to the product. This is also the case with literature reports authored independently.

Read the entire FDA prescribing information for VIGIV (Vaccinia Immune Globulin Intravenous) »