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SMALLPOX
FACT SHEET - Information
for Clinicians and Public Health Professionals
Medical
Management of Smallpox (Vaccinia) Vaccine Adverse Reactions: Vaccinia
Immune Globulin and Cidofovir |
Smallpox
vaccination (vaccinia) is a generally safe and effective means to prevent
smallpox. However, in a number of individuals, smallpox vaccination can
result in untoward effects and adverse reactions. The majority of adverse
reactions caused by the smallpox vaccine are mild to moderate complications
that resolve on their own. Serious reactions are rare, but can be fatal.
There are
two medications that may help persons who have certain serious reactions
to the smallpox vaccine; vaccinia immune globulin (VIG) and cidofovir.
VIG has been extensively used in the past and felt (but not shown in controlled
studies) to be effective. Cidofovir may be effective based on studies
in animals. Treatment with these medications may require the vaccine recipient
to be in the hospital. They are investigational and may cause a number
of serious side effects themselves.
Vaccinia
Immune Globulin (VIG)
- Vaccinia
immune globulin (VIG) is a product used to treat certain serious adverse
reactions caused by smallpox vaccine. There are about 2,700 treatment
doses of VIG (enough for predicted reactions with more than 27 million
people). Additional doses of VIG are being produced this year.
- VIG
was produced in the 1960s from plasma obtained from recently vaccinated
donors. It contained a high titer of anti-vaccinia neutralizing antibody.
Because it contained a high proportion of aggregated protein it was
administered solely by the intramuscular route and could not be used
intravenously.
- An effort
is underway to produce new lots of VIG that will meet the standards
for intravenous immune globulin. This IV-VIG will require new recommendations
for both dosage and preferred method of administration. The new IV-VIG
has a low level of aggregated protein, allowing it to be used by either
the IM or IV route. Intravenous VIG will be most likely administered
at a lower dose than the intramuscular preparation.
VIG Indications,
Precautions and Contraindications
- Historically,
VIG has been indicated for accidental implantation involving extensive
lesions, eczema vaccinatum, generalized vaccinia, and progressive vaccinia.
- VIG
is NOT recommended for mild instances of accidental implantation, mild
or limited generalized vaccinia, erythema multiforme, or encephalitis
post-vaccination.
- For more
information on the adverse reactions mentioned above, go to www.cdc.gov/smallpox.
Concomitant
Use of VIG with Vaccination
In some instances,
VIG was given concomitantly with vaccination to “prevent”
complications in a susceptible person. Not enough is known about the efficacy
of this practice to recommend its use. Furthermore, there is currently
an insufficient amount of VIG to use prophylactically when the benefits
are uncertain.
Dosage
When it was used in the 1950s-1970s, the dosage of VIG varied. In general
an initial dose of 0.6 ml/kg body weight was injected intramuscularly
and subsequent administration determined by the course of illness.
In severe
cases of eczema vaccinatum and progressive vaccinia as much as 1-10 ml/kg
was used. These large doses were split into smaller units, and injected
at multiple sites spread out over time.
Frequency
of Use
Data from a CDC survey indicates that VIG was administered at a rate of
47 uses per 1 million primary vaccinees and 2 uses per million revaccinees.
Cidofovir
Another drug that may be used to treat certain serious smallpox vaccine
reactions is cidofovir, an antiviral drug marketed as Vistide.
- Cidofovir
is currently licensed for the treatment of CMV retinitis and has demonstrated
antiviral activity against poxviruses in vitro, and against cowpox and
vaccinia viruses in mice.
- However,
its use for the treatment of vaccinia adverse reactions is restricted
under an Investigational New Drug (IND) protocol. Under the IND, cidofovir
would only be used when VIG was not efficacious.
- Renal
toxicity is a known adverse reaction of cidofovir.
Obtaining
VIG and Cidofovir
Indications for VIG/cidofovir release
- Vaccinia
Immune Globulin (VIG) and cidofovir are indicated for the treatment
of certain serious smallpox vaccine adverse events, including progressive
vaccinia, eczema vaccinatum, generalized vaccinia (severe form or if
underlying illness), and inadvertent inoculation (if judged to be severe
due to the number of lesions, toxicity of affected individual, or significant
pain). VIG is recommended as the first line of therapy. Cidofovir may
be considered as a secondary treatment, and will only be released by
CDC after all inventories of VIG have been exhausted, after a patient
fails to improve with VIG treatment, or as a last effort for a patient
who is otherwise near death.
- VIG
and cidofovir are available for civilians through the CDC under Investigational
New Drug (IND) protocols for treatment of specific smallpox vaccine
reactions. Based on the anticipated number of adverse events resulting
from the planned vaccination program for healthcare workers, CDC’s
supply of VIG should be adequate.
- Physicians
at military facilities may request VIG by calling the U.S. Army Medical
Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257
or 888-USA-RIID and asking for the physician on call.
Process
for obtaining VIG/cidofovir under Investigational New Drug Protocol (IND)
- Physicians
should first contact their State Health Department when seeking consultation
for civilian patients experiencing a severe or unexpected adverse event
following smallpox vaccination or when requesting VIG or cidofovir.
If further consultation is required, or VIG or cidofovir is recommended,
the physician will be referred to the CDC Clinical Information
Line (CIL) at 1-877-554-4625. The nurses staffing
the CIL will take basic information and then expedite the call to the
CDC Smallpox Vaccine Adverse Events Clinical Consultation Team. The
CDC Clinical Consultation Team will provide in-depth consultation and
will facilitate VIG or cidofovir release as appropriate.
- According
to FDA regulations, VIG or cidofovir released from the CDC must be administered
according to their investigational new drug protocols (IND). The IND
mandates that the treating physician must become a co-investigator.
The responsibilities of the co-investigator are primarily to complete
follow-up forms describing the clinical status of the patient being
treated with VIG and/or cidofovir, including the prompt report of any
significant adverse reaction in the recipient. Detailed information
on the requirements of the IND will be shipped with the products.
- Details
on the process for requesting VIG from USAMRIID for vaccinated military
personnel with adverse reactions may be obtained at http://www.smallpox.army.mil/resource/vig.asp?ste=milvax.
Shipment
of VIG/cidofovir
- VIG/cidofovir
will be shipped by the National Pharmaceutical Stockpile (NPS). The
CDC Smallpox Vaccine Adverse Events Clinical Consultation Team will
coordinate the shipment of VIG/cidofovir with NPS. The cost of VIG and
cidofovir and the cost of shipping will be covered by the U.S. Government.
Arrival of shipments should be expected within 12 hours of the approval
for release.
CDC public response hotline: |
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English:
(888) 246-2675 |
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Español:
(888) 246-2857 |
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TTY:
(866) 874-2646 |
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Page last reviewed August 5, 2004
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