Medical Management of Adverse Reactions

Clinicians who need assistance with the diagnosis and management of patients with suspected complications of vaccinia vaccination should consult with their state/local public health department. CDC will also provide consultation if requested. Reach CDC medical staff by contacting the CDC Emergency Operations Center at 770-488-7100.

Vaccinia Immune Globulin Intravenous (Human) (VIGIV)

VIGIVCdc-pdfExternal has been used safely and effectively to treat vaccinia virus vaccine adverse reactions. Clinical experience suggests VIGIV is effective in the treatment of smallpox vaccine adverse reactions that are secondary to continued vaccinia virus replication after vaccination. VIGIV is licensed by FDA and is indicated for the treatment of:

  • Eczema vaccinatum
  • Progressive vaccinia
  • Severe cases of generalized vaccinia
  • Vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or in individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions
  • Aberrant infections induced by vaccinia virus that include its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard

VIGIV is not indicated for the treatment of isolated vaccinia keratitis or postvaccinial encephalitis. It is not indicated for the treatment of smallpox disease. VIGIV will be made available through the Strategic National Stockpile (SNS) for the treatment of smallpox vaccine complications in patients with serious clinical manifestations.


If treatment with VIGIV alone is inadequate or if VIGIV is not readily available, the following three antivirals may be considered, based on clinical determination for antiviral treatment. None of these antivirals are FDA-approved for treatment of smallpox infection and/or complications from vaccinia vaccination. Currently, tecovirimat and cidofovir are stockpiled by the SNS and would be made available under the appropriate regulatory mechanism. However, brincidofovir is not available through the SNS.

These antivirals may also be used during a smallpox emergency:

  • Tecovirimat: This investigational antiviral was developed for the treatment of smallpox (variola) virus infection. Tecovirimat (also referred to as ST-246 or by its proposed brand name Tpoxx) has shown effectiveness in animal and in vitro studies using related orthopoxviruses and variola as the infecting virus. The drug has been used in the treatment of severe adverse events to vaccinia vaccination; however, there are limited efficacy data in humans. Tecovirimat is known to have fewer side effects than cidofovir.
  • Cidofovir and brincidofovir: Both antivirals have shown effectiveness in animal and in vitro studies; however, there are limited data on the effectiveness in the treatment of vaccinia-related complications in humans. There are also limited data on the effectiveness in treatment of smallpox disease. Brincidofovir (investigational) may have fewer adverse events than cidofovir (FDA-approved for the use in the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS)). Patients being treated with cidofovir have experienced serious renal toxicity and other adverse events that have not been observed in patients being treated with brincidofovir.

VIGIV is recommended as the first line of therapy for treatment of vaccinia virus adverse reactions. Antivirals may be considered as a secondary treatment after consultation with CDC.

Obtaining VIGIV and Antivirals

Clinicians who need clinical consultation for patients experiencing a severe or unexpected adverse event following smallpox vaccination, or to request release of VIGIV or antivirals, should contact their state/local health department or the CDC Emergency Operations Center at 770-488-7100. If during consultation with CDC it is determined that treatment of vaccinia virus adverse reactions requires VIGIV or antivirals, the CDC Smallpox Vaccine Adverse Events Clinical Consultation Team will coordinate shipment with the Strategic National Stockpile.

Health care providers at military medical facilities (or civilian providers treating a U.S. Department of Defense healthcare beneficiary) should call the Defense Health Agency’s 24/7 Immunization Healthcare Support Center at 877-GETVACC (877-438-8222), and select option #1.