Varicella Zoster Immune Globulin (VZIG) Anticipated Short Supply

September 20, 2005

(Information updated 2/8/2006)

(Information updated 11/29/2005)

Summary

The only U.S.-licensed manufacturer of VZIG (Massachusetts Public Health Biologic Laboratories, Boston, MA) has discontinued manufacture of VZIG and will be discontinuing its manufacture of all other plasma products. Consequently, only limited supplies of in date, 625 U vials of VZIG are available from the sole authorized distributor, FFF Enterprises (Temecula, CA). To conserve the VZIG supply pending availability of alternative product sources, we suggest that you place orders for VZIG on an as needed basis (e.g., when you have identified an individual for whom VZIG is indicated). In general, this would be exposed, susceptible children or adults that are at greater risk of complications from varicella than healthy children (see below).

VZIG treatment is expected to be most effective when it is initiated as soon as possible after exposure, but it may be effective if administered as late as 96 hours after exposure. Treatment after 96 hours is of uncertain value. Under normal circumstances, VZIG can be delivered from the authorized distributor to its destination within 24 hours of request.

What are the indications for VZIG?

The following indications are listed in the package insert for VZIG:

Immunocompromised Children¹. VZIG is recommended for passive immunization of susceptible, immunocompromised children after significant exposure to chickenpox or zoster. These children include those with primary cellular immune deficiency disorders or neoplastic diseases and those currently receiving immunosuppressive treatments.
Newborns of Mothers with Varicella Shortly Before or After Delivery¹. VZIG is indicated for newborns of mothers who develop chickenpox within 5 days before or within 48 hours after delivery.
Premature Infants¹. Although the risk of post-natally acquired varicella in the premature infant is unknown, it has been judged prudent to administer Varicella-Zoster Immune Globulin (Human) to exposed premature infants of 28 weeks gestation or more if their mothers have a negative or uncertain history of varicella. Premature infants of less than 28 weeks gestation or birth weight of less than 1000 g should be considered for VZIG regardless of maternal history since they may not yet have acquired transplacental maternal antibody.
Full Term Infants Less Than 1 Year of Age¹. Mortality from varicella in the first year of life is 4 times higher than that in older children, but lower than mortality in immunocompromised children or normal adults. The decision to administer VZIG to infants less than one year of age should be evaluated on an individual basis. After careful evaluation of the type of exposure, susceptibility to varicella including maternal history of varicella and zoster, and presence of underlying disease, VZIG may be administered to selected infants.
Immunocompromised Adults. The complication rate for immunocompromised adults who contract varicella is likely to be substantially greater than for normal adults. Approximately 90% of immunocompromised adults with negative or unknown histories of prior varicella are likely to be immune. After a careful evaluation, which might include the measurement of antibody to Varicella-Zoster virus by a reliable and sensitive assay such as Fluorescent Antibody to Membrane Antigen (FAMA) if available and if time permits, adults who are believed susceptible should receive VZIG.
Healthy Adults. Chickenpox can be severe in normal adults. The decision to administer VZIG to an adult should be evaluated on an individual basis. Approximately 90% of adults with negative or uncertain histories of varicella will be immune. The objective is to modify rather than prevent illness in hopes of inducing lifelong immunity. The clinician should consider the patient's health status, type of exposure, and likelihood of previous unrecognized varicella infection in deciding whether to administer VZIG. Adults who are older siblings of large families and adults whose children have had varicella are more likely to be immune. If reliable and sensitive tests for varicella antibody are available, they might be used to determine susceptibility, if time permits. If, after careful evaluation, a normal adult with significant exposure to varicella is believed susceptible, VZIG may be administered.
Pregnant Women. Pregnant women may be at higher risk of complications of chickenpox than healthy adults. They should be evaluated the same way as other adults. There is no evidence that administration of VZIG to a susceptible, pregnant woman will prevent viremia, fetal infection or congenital varicella syndrome. Therefore the primary indication for VZIG in pregnant women is to prevent complications of varicella in a susceptible adult patient rather than to prevent intrauterine infection. Pregnant women should be evaluated for type of exposure and history of previous infection as described for healthy adults. Timing of VZIG After Varicella or Zoster Exposure.
There is no indication for the prophylactic use of Varicella-Zoster Immune Globulin (Human) in immunodeficient children or adults when there is a past history of varicella, unless the patient has undergone bone marrow transplantation.

The CDC has defined "substantial" varicella exposure, and also recommends evaluation of adults for immunity to varicella to determine the need for VZIG (MMWR July 12, 1996; 45 (RR11): 1-25).

How can I obtain VZIG for a patient in need?

VZIG can be ordered from FFF Enterprises, at 1-800-843-7477.

11/29/2005 update -
FFF Enterprises has an "emergency order policy" whereby products needed for an urgent patient situation are shipped immediately. Be sure to communicate the urgency of the situation to the customer representative when you call to place an order. (1-800-843-7477)

What is FDA doing to prevent a shortage of VZIG?

We have encouraged manufacturers to submit Investigational New Drug (IND) applications for VZIG products, with the goal of licensing a new product. On July 21, 2005 FDA's Blood Products Advisory Committee discussed VZIG supply, clinical needs, and the scientific information that would be needed to license a new VZIG. (http://www.fda.gov/ohrms/dockets/ac/cber05.html#BloodProducts).

How should I report difficulties in obtaining VZIG?

To report a biological product shortage, you may send an email to CBERProductshortages@cber.fda.gov. Also, during business hours, biological product manufacturers and healthcare personnel may report a real or suspected biological product shortage by calling (301) 827-6220.

Appendix 1

VZIG package insert

Reference

¹ Since dosage is weight-based, and the pediatric 125 U vials are no longer available, it would be prudent to calculate and use the appropriate volume from 625 U vials for patients weighing 40 kg or less, to provide the indicated dose.