Monkeypox Medication

Updated: Jun 29, 2022
  • Author: Mary Beth Graham, MD; Chief Editor: William D James, MD  more...
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Medication Summary

The CDC recommends a smallpox or smallpox/monkeypox vaccination within 2 weeks of exposure, ideally within 4 days, for exposed health care workers and household contacts of confirmed cases. Antiviral agents (ie, tecovirimat, brincidofovir, cidofovir) are possible treatment options in severe, life-threatening cases. [42, 43] These agents may be used under an expanded access investigational new drug (EA-IND) available from the CDC. [38, 39]  Additionally, vaccinia immune globulin (VIG) may be considered, but has not demonstrated efficacy as either treatment or prophylaxis. [38, 39] Smallpox preparedness research has led to the development of new antiviral agents for the treatment of orthopoxvirus infections. 

In September 2019, the FDA approved an attenuated, live, nonreplicating smallpox and monkeypox vaccine (Jynneos) for immunization of adults at high risk for smallpox or monkeypox infection. [12, 13, 39]  

Also see further vaccine information under Medical Care.


Antiviral Agents

Class Summary

These agents may be used under an expanded access investigational new drug (EA-IND) available from the CDC. 

Brincidofovir (Tembexa)

Indicated for treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.

Tecovirimat (TPOXX)

Antiviral agent indicated for treatment of human smallpox disease caused by variola virus in adults and children who weigh at least 13 kg.


Cidofovir is a nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.


Vaccine, Live Virus

Class Summary

Vaccinia vaccine promotes active immunity against the smallpox virus by inducing specific antibodies. Currently available stocks of vaccinia vaccine were derived from the vaccinia strain maintained at the New York Board of Health. Wyeth Laboratories manufactured the last batches of the vaccine (Dryvax) in the early 1980s. These batches were made by using the calf lymph method, and they were lyophilized but are no longer available.

Several attenuated vaccinia vaccine candidates are undergoing investigation, with ACAM2000 receiving FDA approval as a replacement for Dryvax. Another vaccine (smallpox [vaccinia] and monkeypox vaccine, live, nonreplicating [Jynneos]) has also been approved by the FDA for immunization of adults at high risk for smallpox or monkeypox infection.

New, cell-derived lots of vaccinia appear to have adverse effect profiles similar to the older, calf lymph–derived lots.

Primary immunization as soon as possible after exposure or at the first sign of infection is indicated for the prevention and management of smallpox. Currently, US military personnel, US Department of Defense civilian employees, and health care professionals are recommended candidates to receive the vaccination because they will likely be at highest risk in case of a biologic attack (eg, bioterrorism).

Smallpox vaccine (ACAM2000)

This agent is made from vaccinia, which is related to, but different from, the virus that causes smallpox. It contains live vaccinia virus and works by causing a mild infection that stimulates an immune response that effectively protects against smallpox without actually causing disease.

The vaccine contains live vaccinia virus but does not contain variola virus, the virus that causes smallpox. Vaccinia is a member of the Orthopoxvirus genus, which includes smallpox (variola), cowpox, monkeypox, gerbilpox, camelpox, and others. Following inoculation, the vaccine induces an immune reaction that serves to protect against smallpox.

ACAM2000 is derived from Dryvax, which is the only other smallpox vaccine licensed by the FDA. Dryvax, which was approved in 1931, is now in limited supply because it is no longer being manufactured. The US military resumed vaccination of at-risk personnel in 1999 after concluding that the disease posed a potential bioterrorism threat.

ACAM2000 was studied in 2 populations: (1) persons who had never been vaccinated for smallpox and (2) those who had received smallpox vaccination many years earlier. The percentage of unvaccinated persons who developed a successful immunization reaction was similar to that of Dryvax. ACAM2000 was also found to be acceptable as a booster in persons previously vaccinated for smallpox.

Because ACAM2000 contains live vaccinia virus, care must be taken to prevent the virus from spreading from the inoculation site to other parts of the body and to other individuals. To minimize known risks, vaccine licensing is subject to a Risk Minimization Action Plan (RiskMAP), which requires providers of the vaccine and patients to be educated about vaccination risks.

The medication guide explains proper care of the vaccination site and provides information about serious adverse effects associated with ACAM2000.

In studies, about 1 in 175 healthy adults who received smallpox vaccine for the first time developed myocarditis and/or pericarditis. Of the 10 affected adults, 4 had no symptoms at the end of the study, and symptoms resolved in all but 1 patient.

Smallpox (vaccinia) and monkeypox vaccine, live, nonreplicating (Jynneos)

This vaccine is derived from a vaccinia virus, a virus that is closely related to, but less harmful than, variola and monkeypox viruses and can protect against both of these diseases. It is indicated for prevention of smallpox and monkeypox disease in adults who are at high risk for smallpox or monkeypox infection. It is administered as a 2-dose series administered 4 weeks apart.