Treatment of smallpox patients generally involves supportive care. Vaccination with replication-competent smallpox vaccines (i.e., ACAM2000 and APSV) can prevent or lessen the severity of disease if given within 2 to 3 days of the initial exposure. They may decrease symptoms if given within the first week of exposure.

Treating smallpox patients in a healthcare setting requires isolation and adherence to proper infection and environmental controls.


There are three primary antiviral therapies that have shown effectiveness against poxviruses including variola (the virus that causes smallpox) in animals and in vitro studies. However, there is no treatment for smallpox disease that has been tested in people who are sick with the disease and been proven effective in this population.


In July 2018, the U.S. Food and Drug Administration (FDA) approved tecovirimat (also referred to as ST-246 or its brand name Tpoxx), the first drug with an indication for treatment of smallpox. Tecovirimat has been used in the treatment of severe adverse events to vaccinia vaccination; however, there are limited efficacy data in humans. Tecovirimat’s effectiveness against smallpox was established with in vitro studies using related orthopoxviruses as well as variola. Efficacy of tecovirimat treatment has also been demonstrated within multiple animal model studies measuring survival in animals infected with either variola virus or other closely related orthopoxviruses. Furthermore, treatment with tecovirimat minimized signs of morbidity as well as protected from mortality within prairie dogs challenged with monkeypox virus. The safety of tecovirimat was evaluated in 359 healthy human volunteers.

Tecovirimat was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans. The FDA Antimicrobial Drugs Advisory Committee voted unanimously (17 to 0) that the benefits of tecovirimat outweigh its risks.

Cidofovir and Brincidofovir

In laboratory tests, cidofovir and brincidofovir have been shown to be effective against the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Cidofovir and brincidofovir have not been tested in people who are sick with smallpox, but they have been tested in healthy people and in those with other viral illnesses. These drugs continue to be evaluated for effectiveness and toxicity. Neither are FDA-approved for the treatment of variola virus infections (smallpox), but they could be used for isolated cases or during an outbreak under an appropriate regulatory mechanism (such as an investigational new drug [IND] protocol or Emergency Ise Authorization) for the treatment of complications from vaccinia vaccination.

Antiviral Drugs for the Treatment of Smallpox Disease
Drug FDA approved for smallpox treatment? Available through IND protocol for smallpox treatment? Available in Strategic National Stockpile?
Tecovirimat Yes Not applicable Yes
Cidofovir No Yes Yes
Brincidofovir No No No

Emergency Use of Smallpox Medical Countermeasures

During a declared public health emergency involving smallpox, CDC and the Assistant Secretary for Preparedness and Response (ASPRexternal icon) will provide more detailed guidance regarding the availability and use of smallpox medical countermeasures from the Strategic National Stockpileexternal icon under their appropriate regulatory mechanism(s) (e.g., IND, EUA, or Emergency Use Instructions [EUI]).