A New Product (VariZIG™) for Postexposure Prophylaxis of
Varicella Available Under an Investigational New Drug Application Expanded
Access Protocol
On February 24, this report was posted as an
MMWR Early Release on the MMWR website
(http://www.cdc.gov/mmwr).
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).* 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 (1).
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 IND application product under an expanded access protocol. The patient
groups recommended by 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.
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Varicella vaccine was recommended in 1999 for postexposure prophylaxis of other persons without evidence of
varicella immunity and who have no contraindications to vaccination
(2). 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.
How to Obtain Investigational VariZIG
Investigational VariZIG is produced by Cangene Corporation (Winnipeg, Canada) and is distributed by
FFF Enterprises (Temecula, California). An expanded access protocol under the IND application enables use of
investigational VariZIG for patients who meet the protocol's enrollment
criteria† and who choose to participate. The expanded
access protocol has received central institutional review board (IRB) approval. With this central IRB review and approval, FDA
does not require an additional approval by the IRB at the treatment site. However, some institutions might require that
the institution's IRB be notified before the institution or its physicians participate in a study reviewed by a central IRB. In
such cases, notification and any local IRB review may take place before a patient who needs the investigational product is
identified. However, if a patient who needs the investigational product is identified before any required local IRB
review has taken place, the investigational product may be shipped under the
approval of the central IRB while coordination with the
institution's IRB is addressed. In any event, all informed consent and other patient protections must still be in place.
Pharmacists and health-care providers who expect to have patients who will need VariZIG may participate in a program
that allows them to acquire inventory in advance. VariZIG delivered for inventory will be accompanied by all forms
required by the IND expanded access protocol (i.e., release form, protocol, informed consent form, case report forms,
investigator brochure, drug accountability form, and contact information for FFF Enterprises and Cangene Corporation); IRB
approval (i.e., central or local) should be in place. Providers who identify a patient for whom VariZIG is indicated should contact
FFF Enterprises (24-hour telephone, 800-843-7477) and fax the completed release form. FFF Enterprises will review the form
to determine patient eligibility and allot a patient number to
eligible patients at the time of the call.
Alternatively, if VariZIG is not available on site to the pharmacist or health-care provider, a product release form can
be requested directly from FFF Enterprises by calling the 24-hour telephone line. FFF Enterprises will transmit the
product
release form by e-mail or fax for completion and return. If the patient is eligible, FFF Enterprises will allot a patient
number, and investigational VariZIG will be shipped with the required forms. Under normal circumstances, investigational
VariZIG can be delivered from the distributor to its destination within 24 hours of request.
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