On October 27, 2004, the Advisory Committee on Immunization Practices (ACIP) was informed by the only U.S.-licensed manufacturer of varicella zoster immune globulin (VZIG) (Massachusetts Public Health Biologic Laboratories, Boston, Massachusetts) that the company had discontinued production of VZIG. The supply of the licensed VZIG product is now nearly depleted. In February 2006, an investigational (not licensed) VZIG product, VariZIG™ (Cangene Corporation, Winnipeg, Canada) became available under an investigational new drug application (IND) submitted to the Food and Drug Administration (FDA) (available at http://www.fda.gov/cber/infosheets/mphvzig020806.htm). This product can be requested from the sole authorized U.S. distributor, FFF Enterprises (Temecula, California), for patients who have been exposed to varicella and who are at increased risk for severe disease and complications.
The investigational VariZIG, similar to licensed VZIG, is a purified human immune globulin preparation made from plasma containing high levels of anti-varicella antibodies (immunoglobulin class G [IgG]). Unlike the previous product, the investigational product is lyophilized. When properly reconstituted, VariZIG is approximately a 5% solution of IgG that can be administered intramuscularly. As with any product used under IND, patients must be informed of potential risks and benefits and must give informed consent before receiving the product.
Indications for Use of Investigational VariZIG
Patients without evidence of immunity to varicella (i.e., without history of disease or age-appropriate vaccination) who are at high risk for severe disease and complications, who have been exposed to varicella, and from whom informed consent has been obtained, are eligible to receive the Investigational New Drug (IND) application product under an expanded access protocol. The patient groups recommended by Advisory Committee on Immunization Practices (ACIP) to receive VariZIG include the following:
- Immunocompromised patients
- Neonates whose mothers have signs and symptoms of varicella around the time of delivery (i.e., 5 days before to 2 days after)
- Premature infants born at >28 weeks of gestation who are exposed during the neonatal period and whose mothers do not have evidence of immunity
- Premature infants born at <28 weeks of gestation or who weigh <1,000 g at birth and were exposed during the neonatal period, regardless of maternal history of varicella disease or vaccination
- Pregnant women
Varicella vaccine was recommended in 1999 for postexposure prophylaxis of other persons without evidence of varicella immunity and who have no contraindications to vaccination. The vaccine should be administered preferably within 96 hours and possibly up to 120 hours postexposure. If illness occurs, with or without postexposure vaccination, antiviral treatment (e.g., acyclovir) can be considered for adolescents and adults.
Administration
Investigational VariZIG is expected to provide maximum benefit when administered as soon as possible after exposure, although it can be effective if administered as late as 96 hours after exposure; treatment after 96 hours is of uncertain value. VariZIG should be administered intramuscularly as directed by the manufacturer.
When indicated, health-care providers should make every effort to obtain and administer VariZIG. In situations in which administration of VariZIG does not appear possible within 96 hours of exposure, administration of immune globulin intravenous (IGIV) should be considered as an alternative. IGIV should also be administered within 96 hours of exposure. Although licensed IGIV preparations are known to contain anti-varicella antibody titers, the titer of any specific lot of IGIV that might be available is uncertain because IGIV is not routinely tested for anti-varicella antibodies. The recommended IGIV dose for postexposure prophylaxis of varicella is 400 mg/kg, administered once. For pregnant women who cannot receive VariZIG within 96 hours of exposure, clinicians may choose either to administer IGIV or closely monitor the women for signs and symptoms of varicella and institute treatment with acyclovir if illness occurs.
Dosage
Investigational VariZIG is supplied in 125-U vials. The recommended dose is 125 units/10 kg body weight, up to a maximum of 625 units (five vials). The minimum dose is 125 U.
Interval Between Administration of VariZIG and Varicella Vaccine
Any patient who receives investigational VariZIG to prevent varicella subsequently should receive varicella vaccine, provided the vaccine is not contraindicated. Varicella vaccination should be delayed until 5 months after VariZIG administration. Varicella vaccine is not needed if the patient has varicella after administration of VariZIG.
Antiviral Therapy
Any patient who receives investigational VariZIG should be observed closely for signs or symptoms of varicella for 28 days after exposure because VariZIG might prolong the incubation period by >1 week. Antiviral therapy should be instituted immediately if signs or symptoms of varicella disease occur. The route and duration of antiviral therapy should be determined by specific host factors, extent of infection, and initial response to therapy.
See the original guideline document for information on how to obtain investigational VariZIG.
