VariZIG

CLINICAL PHARMACOLOGY

Mechanism of Action

VARIZIG provides passive immunization for non-immune individuals exposed to VZV, reducing the severity of varicella infections (5).

Pharmacokinetics

In a comparative pharmacokinetic clinical trial, 35 volunteers were administered an intramuscular dose of 12.5 IU/kg of VARIZIG (n=18) or the comparator product VZIG™ (n=17). The dose of 12.5 IU/kg of VZIG or VARIZIG given to the subjects was based on the assumption that the potency was similar for both products. For the bioequivalence analysis, a potency correction factor was applied (concentrations of VARIZIG were multiplied by 2.3) to account for higher measured potency of the comparator product. The mean peak concentration (Cmax) of varicella antibodies occurred within five days of administration for both products (Table 4). In the trial, baseline levels of anti-VZV antibodies ranged from 0 to 720 mIU/mL, therefore baseline levels were taken into account for pharmacokinetic calculations, to better represent the indicated population. After potency correction, baseline correction, and exclusion of subjects with baseline values of anti-VZV antibody levels of > 200 mIU/mL, the two products were pharmacokinetically comparable.

Table 4: Pharmacokinetic Comparison of VARIZIG and VZIG

PK Parameters* VARIZIG VZIG Ratio 90% Confidence Interval
AU C0-28 (mIUxDay/mL) 2472 ± 970 2347±535 84.1-124.6
AUC0-84 (mIUxDay/mL) 4087 ± 1620 3916±964 82.0-125.6
C (mIU/mL) 136 ± 66 138 ± 22 76.5-112.8
Tmax (Days) 4.5 ± 2.8 3.3 ± 1.5 Not applicable
t½** (Days) 26.2 ± 4.6 23.1 ± 8.6 Not applicable
CL/F (mL/Day) 0.204 ± 0.045 0.199 ± 0.087 Not applicable
* Potency and subgroup analysis were implemented for pharmacokinetic calculations. Study subjects with elevated baseline anti-VZV levels ( > 200 mIU/mL) from both treatment groups were excluded from pharmacokinetic calculations.
** The half-life is expected to vary from patient to patient.

Clinical Studies

Pregnant Women Exposed to Varicella Zoster Virus

A randomized, open-label, multicenter, active controlled clinical trial was conducted in 60 pregnant women without immunity to VZV as confirmed by a latex agglutination test. Patients were stratified on the basis of time from first exposure to varicella as follows:

  • one to four days post-exposure and
  • five to 14 days post-exposure.

The women were randomized into one of three study arms as follows:

  • a single intravenous dose of 125 IU/10 kg body weight to a maximum dose of 625 IU of VARIZIG
  • a single intramuscular dose of 125 IU/10 kg body weight to a maximum dose of 625 IU of VARIZIG, or
  • a single intramuscular dose of 125 IU/10 kg body weight to a maximum dose of 625 IU of VZIG (licensed comparator product).

Patients were followed for 42 days.

Incidence of clinical varicella was similar across all treatment groups with an overall incidence of 33%; however, in the subset of 28 subjects with more than 24 hours exposure to varicella, the incidence of clinical varicella in the combined treatment groups was 64%.

Mean weighted constitutional illness scores (CIS) (6) were similar across all groups and none of the subjects had serious complications of varicella. The small number of subjects in each treatment stratum and the lack of agreed upon pre-specified hypothesis testing precluded formal statistical comparisons between groups.

REFERENCES

1. Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology. 1994; 44:223-6.

2. Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet. 1986; 2:217-8.

3. Wolberg AS, Kon RH, Monroe DM Hoffman M. Coagulation factor XI is a contaminant in intravenous immunoglobulin preparations. Am J Hematol. 2000; 65:30-4.

4. Josephson C, Nuss R, Jacobson L, Hacker MR, Murphy J, Weinberg A et al. The Varicella-Autoantibody Syndrome. Pediatr Res. 2001; 50:345-52.

5. CDC. Prevention of varicella. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2007; 56(No. RR-4):1-30.

6. Koren G, Money D, Boucher M, Aoki F, Petric M, Innocencion G et al. Serum concentrations, efficacy, and safety of a new, intravenously administered varicella zoster immune globulin in pregnant women. J Clin Pharmacol. 2002; 42(3):267-74.

Last reviewed on RxList: 2/19/2013
This monograph has been modified to include the generic and brand name in many instances.

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