Last reviewed: 4 Jul 2021
Last updated: 20 Jul 2021
16 Jul 2021

US FDA approves new drug to treat smallpox

The US Food and Drug Administration (FDA) has approved the anti-viral drug brincidofovir for the treatment of smallpox disease in children and adults.

Although naturally occurring smallpox was eradicated in 1980, there have been long standing concerns that the variola virus could be used as a bioweapon.

The effectiveness of brincidofovir was studied in animals infected with viruses that are closely related to the variola virus as human trials are unethical. Effectiveness was determined by measuring animals’ survival at the end of the studies. More animals treated with brincidofovir survived compared to the animals treated with placebo. The approval was based on the FDA’s animal rule which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans.

The safety of brincidofovir was based on clinical trials in humans for a non-smallpox indication, primarily patients who received haematopoietic stem cell transplants. The most common adverse effects were diarrhoea, nausea, vomiting, and abdominal pain.

Brincidofovir is only approved for the treatment of smallpox.

See Management: approach

See Management: treatment algorithm

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History and exam

Key diagnostic factors

  • presence of risk factors
  • fever
  • vesicular rash
  • oropharynx and tongue enanthem
  • lymphadenopathy

Other diagnostic factors

  • headache
  • backache
  • pharyngitis
  • vomiting
  • diarrhoea
  • delirium
  • convulsions

Risk factors

  • contact with laboratory (smallpox)
  • bioterrorism (smallpox)
  • close contact with known case (smallpox)
  • contact with monkeypox in animals or humans

Diagnostic investigations

1st investigations to order

  • vesicle specimen PCR
  • FBC
  • urea and electrolytes
  • LFTs
  • venous lactate
  • clotting screen

Treatment algorithm



Tom Blanchard, DTM&H, PhD, FRCP

Consultant in Infectious Diseases

Department of Infectious Diseases and Tropical Medicine

North Manchester General Hospital




TB is the principal investigator on an MRC/Wellcome/Newton Fund grant to make a Zika vaccine based on recombinant modified vaccinia Ankara.

Peer reviewers

Jimmy Whitworth, MD, FRCP

Professor of International Public Health

London School of Hygiene & Tropical Medicine




JW declares that he has no competing interests.

Ashley Styczynski, MD, MPH

Epidemic Intelligence Service Officer

Poxvirus and Rabies Branch

Centers for Disease Control and Prevention




AS declares that she has no competing interests.

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