Key Messages:
Most patients with mpox have a mild, self-limited infection that can be managed with supportive care and pain management.
Tecovirimat (TPOXX) monotherapy was not effective in treating mild-to-moderate mpox in clinical trials.
The role of tecovirimat in patients with or at risk for severe mpox disease has not been determined. Oral and IV tecovirimat remain available under the CDC EA-IND protocol (PDF) for compassionate use in patients who meet protocol-defined clinical criteria, including people who are:
At high risk for complications due to severe immunocompromise (e.g., HIV with CD4 < 200) or compromised skin integrity (e.g., atopic dermatitis) or
Children, pregnant, or lactating
Providers are advised to consult their infectious disease providers, CDPH, and/or CDC regarding patients with severe or complicated mpox infections.
Patients with severe manifestations of mpox may benefit from the combination of tecovirimat with other antivirals—such as oral brincidofovir, IV cidofovir, and/or VIGIV (Vaccina Immune Globulin IV). Expert consultation is advised.
JYNNEOS vaccine remains recommended for individuals who may be at risk for mpox, particularly if they have HIV or other risk factors for severe mpox.
Recommendations for medical countermeasures apply to both clade II and clade I mpox.
Mpox Clinical Management
Many patients with mpox have a mild, self-limited disease that resolves with appropriate supportive care. However, the prognosis for mpox depends on multiple factors, including immune status, previous vaccination, co-morbid conditions, and baseline health status. Typical clinical management includes:
Supportive care and pain management: Supportive care, including pain management, should be initiated for all patients with mpox. This may include over-the-counter or prescription options to manage symptoms and pain—which may be disproportionate to lesion appearance, especially with mucosal and genital lesions. Patients should be monitored closely to ensure resolution of illness without complications that would require further intervention.
Skin care: Educate patients on skin care and hand hygiene to promote lesion healing and prevent bacterial superinfections. Keeping lesions covered and avoiding scratching is also essential to prevent lesion spread via self-inoculation. After lesion resolution, silicone-based gels or sheeting may be used to prevent scarring and sunscreen is advised to avoid hypo- or hyperpigmentation of scars.
Co-infection testing (and treatment, if applicable): Patients with confirmed or suspected mpox should also be screened for HIV and other sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. The U.S. Centers for Disease Control and Prevention (CDC) has reported that approximately 40% of mpox cases had HIV or another STI in the past year (CDC).
Assessment for severe mpox disease and/or risk of complications: Patients with conditions that put them at risk for severe mpox, or who are severely ill from mpox, may benefit from more aggressive management including mpox-directed treatment options such as antivirals. In particular, persons with severe immunocompromise are known to be at high risk for protracted or life-threatening manifestations of mpox regardless of disease severity at presentation.
When to Consider Additional Treatment Beyond Supportive Care
Providers are advised to consult their infectious disease service regarding any patients with, or at risk for, severe and/or complicated mpox infections. CDC and CDPH are also available for case consultation. Antiviral treatment should be considered for patients who have severe disease or who are at risk for severe disease, such as:
Persons at higher risk of uncontrolled viral spread and disseminated infection due to:
Moderate or severe immunocompromise, including advanced HIV (i.e., CD4 <200)
Active conditions that disrupt skin integrity (e.g., atopic dermatitis, eczema, impetigo)
Persons with protracted or life-threatening manifestations of mpox, such as:
Lesions affecting ≥ 25% of body surface that may be confluent, necrotic, and/or hemorrhagic in appearance or cause sepsis
Ocular infections
Neurologic complications
Myopericarditis
Complications associated with mucosal lesions (e.g., strictures, obstructions, impeding airway, oral intake, or bowel movements)
Pregnant or lactating persons
Children (<18 years of age)
There is no treatment approved specifically for mpox infections. Tecovirimat (also known as TPOXX) is an FDA-approved antiviral medication for the treatment of human smallpox disease in adults and children, based on animal efficacy data and safety data in adults. Tecovirimat may be considered for patients who are severely ill or at risk for severe infection from mpox.
Recent clinical trial data* from two NIH-sponsored, randomized studies has shown that tecovirimat was not effective as a monotherapy for mild-to-moderate mpox infections. However, tecovirimat use in combination with other agents, as well as its role in persons with or at risk for severe disease, has not yet been established. Tecovirimat remains available in oral or IV form through the CDC-held Expanded Access Investigational New Drug (EA-IND) protocol (PDF) for compassionate use in patients who meet eligibility criteria:
Persons with active skin conditions (e.g., atopic dermatitis, eczema, impetigo) affecting skin integrity.
Pregnant or lactating persons and children, regardless of disease severity or underlying comorbidities.
Persons with protracted or life-threatening manifestations of mpox as defined in the protocol.
Combination therapy (i.e., tecovirimat in conjunction with other antivirals) should be considered in patients with severe or refractory disease—see Additional Treatment Considerations. Information on how to request tecovirimat is outlined below.
*Two trials designed to assess the efficacy and safety of a 14-day course of tecovirimat in treating human mpox were PALM007, for clade I mpox in the Democratic Republic of the Congo, and The Study of Tecovirimat for Mpox (STOMP) for clade II mpox in the US and several other countries. Initial results from PALM007 and STOMP became available in August and December 2024, respectively. These studies showed that tecovirimat was safe, but did not reduce the time to resolution of mpox lesions or improve pain control in adults with mild-to-moderate mpox. More information about the clinical trial data is available on the CDC.
Treatment considerations for those with or at risk for protracted or life-threatening disease include the following:
For immunocompromised patients, make all efforts to minimize immune suppression (e.g., ensure persons with HIV are receiving effective antiretroviral therapy) and limit the use of immunosuppressive therapies (e.g., chemotherapy, TNF inhibitors) if feasible.
When administering tecovirimat through the CDC's EA-IND protocol, the medication should be administered early in the course of illness along with supportive care and pain control as needed.
The standard tecovirimat treatment course is 14 days. If needed, tecovirimat treatment can be extended beyond the standard 14-day course on a short-term basis (e.g., an additional 3-7 day course, with close monitoring for safety and clinical response).
Patients taking oral tecovirimat should be advised to take it with fatty meals to ensure adequate gastrointestinal absorption and to maximize serum levels of the drug. Inadequate serum levels could promote resistance. Dosage and administration of tecovirimat guidance for adults and children is provided in the CDC EA-IND protocol (PDF).
Ocular infections
People with protracted or life-threatening manifestations of mpox (e.g., due to severe immunocompromise such as HIV CD4 cell count <200 cells/mm3 or other comparable severe immunocompromise)
People with clinically significant disease progression while receiving tecovirimat or who have recrudescence (initial improvement followed by worsening) of disease after an initial period of improvement on tecovirimat
People for whom there is concern that the virus affecting the patient is resistant to tecovirimat (e.g., new mpox lesions have developed despite more than 2 weeks of tecovirimat treatment)
See CDC Mpox Clinical Treatment of Mpox for general treatment guidance as well as care considerations for mpox in special populations:
Requesting Tecovirimat and Additional Therapeutics
Tecovirimat: Providers or facilities providing or prescribing tecovirimat must review and comply with the CDC-held EA-IND protocol (PDF). Providers and facilities must ensure their patient(s) meet the EA-IND eligibility criteria, ensure they are using the most up-to-date version of the protocol, and submit required forms. Tecovirimat is only available via the Strategic National Stockpile so must be requested through specific channels:
Oral tecovirimat: Contact and submit a completed request form to your local health department Medical Health Operational Area Coordinator (MHOAC) who will coordinate supply delivery to the healthcare facility.
IV tecovirimat: IV tecovirimat is available from the CDC for use in mpox patients that require an IV formulation (i.e., those who are unable to take oral therapy or for whom there is a concern that oral absorption may be altered). Call the CDC Emergency Operations Center at (770) 488-7100 (including off-hours), or email poxvirus@cdc.gov and mpxtreatment@cdph.ca.gov (during business hours) to reach the CDC and CDPH Clinical Consultation Teams.
Note: It is requested that providers report tecovirimat use to their local health department for tracking purposes. Additionally, the federal government requires tecovirimat inventory reporting. Providers/facilities should report their inventory through the US Department of Health and Human Services enhanced Health Partner Order Portal (HPOP) weekly and at the time of resource requests. For questions on HPOP use, contact hpop.support@hhs.gov or (833) 868-6386 (5AM – 2PM PST).
Other therapeutics: Consultation with CDC and CDPH is encouraged. Some therapeutics (brincidofovir, VIGIV) are supplied by the Strategic National Stockpile. See CDC Clinical Treatment of Mpox for more information on indications for use and how to access alternate therapeutics.
Considerations for Tecovirimat (TPOXX) Resistance and Testing
Clinicians should be aware of the concern for development of TPOXX resistance, especially in patients who are immunocompromised or have severe disease and require prolonged TPOXX treatment.
Please contact your local health department, CDPH, and the CDC to discuss any concerns about tecovirimat resistance, any cases requiring prolonged tecovirimat courses, or any situations in which advanced therapeutics are being considered.
Individual patient results from tecovirimat resistance testing cannot be made available to inform clinical decision making or treatment plans. Considerations for tecovirimat resistance testing in public health surveillance:
In patients with persistent or progressive mpox after completing 14 days of tecovirimat, consider testing lesion swab samples (PDF) for possible resistance to tecovirimat and performing plasma pharmacokinetics (PDF). Ideally, resistance and pharmacokinetic testing should be performed concurrently to determine if any cases of confirmed resistance are associated with drug levels below target concentrations.
Collection of lesion samples for the purpose of whole genome sequencing with testing for resistance-associated mutations will help monitor for the potential emergence of antiviral resistance.
More information about tecovirimat resistance can be found on the FDA and the CDC websites.