Health and Human Services Agency
California Department of Public Health

December 30, 2024

TO:

Health Care Providers

SUBJECT:

Mpox Treatment with Tecovirimat (TPOXX): Updated Guidance for Health Care Providers

On this page: Mpox Treatment Information for Providers | Antiviral Treatment with Tecovirimat (TPOXX) | How to Obtain Tecovirimat (TPOXX) | Additional Considerations on Advanced Therapeutics for Mpox | Considerations for TPOXX Resistance and Testing

Key Messages:

Oral tecovirimat is no longer available via the Study of Tecovirimat for Mpox (STOMP) clinical trial as enrollment has closed due to preliminary findings.
Oral and IV tecovirimat remain available under the CDC EA-IND protocol (PDF) for compassionate use in patients who meet certain eligibility criteria (those with or at risk for protracted or life-threatening mpox, including people with HIV who have a CD4 count <200). Tecovirimat for this use is supplied from the Strategic National Stockpile.
See CDC Interim Clinical Considerations for Severe Manifestations of Mpox for guidance on managing patients who have or are at risk for protracted or life-threatening mpox due to severe immunocompromise. Providers can consider initiating tecovirimat in combination with other therapeutics (e.g., oral brincidofovir, IV cidofovir, or Vaccinia Immune Globulin IV) in these patients. 
Recommendations for medical countermeasures apply to both clade II and clade I mpox.
Reminder: JYNNEOS vaccine is recommended for prevention of mpox. Please refer to Mpox Vaccination and CDC’s Interim Clinical Considerations for Use of JYNNEOS Vaccine for Mpox Prevention in the United States.

Mpox Treatment Information for Providers

Many patients with mpox have a mild, self-limited disease and recover without medical intervention. However, the prognosis for mpox depends on multiple factors, including immune status, previous vaccination, co-morbid conditions, and initial health status.

Supportive Care should be initiated for all patients who have mpox symptoms. This may include topical or systemic medications and/or other clinical interventions to control pain, itching, nausea and vomiting. Patients should be monitored closely to ensure resolution of illness without complications that would require further intervention. Patients with confirmed or suspected mpox should also be screened for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. The CDC has reported that approximately 40% of mpox cases had HIV or another STI in the past year (CDC).

Antiviral Treatment with Tecovirimat (TPOXX)

There is no treatment approved specifically for mpox infections, however tecovirimat (also known as TPOXX) is typically the first therapeutic that is considered if patients with mpox require more than supportive care. Tecovirimat 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. As tecovirimat is not FDA-approved for use in mpox, it is only available through specific channels.

Enrollment in Study of Tecovirimat for Mpox (STOMP) Clinical Trial has closed and oral tecovirimat is no longer available via the STOMP trial. Initial analysis of data from two NIH-sponsored randomized clinical studies designed to assess the efficacy and safety of a 14-day course of tecovirimat in treating human mpox, 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 in participants who received tecovirimat compared to those who received placebo.

PALM007 study participants were adults and children with clade I mpox in the Democratic Republic of the Congo.
STOMP study was conducted in the U.S. and a few other countries with clade IIb mpox outbreaks; participants randomized to tecovirimat or placebo arm were adults with clade IIb mpox who did not have severe immunocompromise or severe mpox and were not pregnant or lactating.

The findings from these clinical trials suggest that most patients with mpox who do not have severe disease or risk factors for severe disease (e.g., severe immunocompromise) will recover with supportive care, including pain management.
The role of tecovirimat in treatment of mpox in patients with severe immunocompromise, including advanced HIV, has not been determined and requires additional clinical trials.

Tecovirimat remains available in oral or IV form through the CDC-held Expanded Access Investigational New Drug (EA-IND) protocol (PDF) for compassionate use for patients who meet eligibility criteria for protracted or life-threatening disease, or risk for protracted or life-threatening disease (see criteria below). The decision to treat is at the clinical discretion of the health care provider as long as the patient meets eligibility criteria. A positive lab result is not necessary to initiate treatment if there is high clinical suspicion. Tecovirimat from the Strategic National Stockpile remains available for treatment of mpox in patients who meet eligibility criteria under the CDC’s EA-IND protocol (PDF):

Persons with severe immunocompromise (i.e., HIV with CD4 <200 or comparable severe immunocompromise).
Persons with protracted or life-threatening manifestations of mpox as defined in the protocol.
Persons with active skin conditions (e.g., atopic dermatitis, eczema, impetigo) that place them at higher risk of disseminated infection.
Pregnant or lactating persons and children, regardless of disease severity or underlying comorbidities.

Providers or facilities providing or prescribing tecovirimat must review and comply by the CDC-held EA-IND protocol (PDF), including eligibility criteria, and should ensure they are using the most up-to-date version of the protocol.

I. Requesting Oral Tecovirimat (TPOXX)

Health care providers prescribing under the EA-IND Protocol (PDF) can obtain oral tecovirimat from the state stockpile, coordinated through your local health department (LHD). To request oral tecovirimat:

Providers can submit a completed request form to their LHD Medical Health Operational Area Coordinator (MHOAC) who may source oral tecovirimat locally or will submit a resource request to the CDPH. Medications will be shipped to the healthcare facility.
Providers or facilities must review and comply by the eligibility criteria and follow the CDC requirements for use under the EA-IND protocol (PDF), including submission of the required forms.
Whenever a patient is initiated on tecovirimat, health care providers are asked to inform the LHD corresponding to the patient’s residence. This is so that: (1) treatment information can be accurately reported in the state surveillance system (CalREDIE) and (2) local medication supplies can be monitored.

Pre-positioning supply: The CDC EA-IND protocol (PDF) allows the use of pre-positioned tecovirimat to treat mpox during an outbreak for patients who meet eligibility criteria. Any remaining tecovirimat from previously deployed supply still within expiry can be used for EA-IND eligible patients (PDF).

II. Requesting IV Tecovirimat (TPOXX)

IV tecovirimat remains available 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).

All supply requests for IV tecovirimat for immediate patient use under the CDC EA-IND Protocol (PDF) should be sent directly to the CDC. To request IV tecovirimat for immediate patient use:

Contact the CDC by calling the CDC Emergency Operations Center at (770) 488-7100 (including off-hours), or emailing poxvirus@cdc.gov and mpxtreatment@cdph.ca.gov (during business hours) to reach the CDC and CDPH Clinical Consultation Teams. If it is determined during the case consultation that CDC is unable to fulfill the request within 24 hours, a temporary stopgap with state supply of IV tecovirimat (limited) via the LHD MHOAC may be coordinated.
Providers or facilities must review and comply by the eligibility criteria and follow the CDC requirements for use under the EA-IND protocol (PDF), including submission of the required forms.
Whenever a patient is initiated on tecovirimat, health care providers are asked to inform the LHD corresponding to the patient’s residence. This is so that: (1) treatment information can be accurately reported in the state surveillance system (CalREDIE) and (2) local medication supplies can be monitored.

Pre-positioning supply: The US Department of Health and Human Services (HHS) no longer allows pre-positioning of IV tecovirimat but facilities may still have inventory available. There was a product shelf-life extension released for IV tecovirimat and lot numbers and expiration dates for remaining tecovirimat is found on HHS SNS Products: Vaccines and Treatment Available for Use in the Mpox Response.

III. Tecovirimat (TPOXX) Reporting

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. HPOP is used to report and track tecovirimat inventory. For questions on HPOP use, contact hpop.support@hhs.gov or (833) 868-6386 (5AM – 2PM PST).

Additional Considerations on Advanced Therapeutics for Mpox

When tecovirimat is prescribed orally via the CDC’s EA-IND protocol, patients should be advised to take tecovirimat 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).

Treatment considerations for those with or at risk for protracted or life-threatening disease include the following:

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).
Certain patients with severe mpox or at high risk for severe mpox (e.g., patients with HIV and CD4 count <200 cell/mm3 or other severely immunocompromising conditions) should be considered for concurrent administration of other therapeutics, including cidofovir, brincidofovir, and vaccinia immune globulin IV (VIGIV). Consultation with CDC, infectious disease specialists, and other experts for any patient who may benefit from receiving multiple therapeutics is encouraged.
For immunocompromised patients, make all efforts to minimize immune suppression to the extent possible (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.

Additional medical countermeasures currently available from the Strategic National Stockpile as options for the treatment of mpox include brincidofovir and vaccinia immune globulin. Cidofovir is also available commercially. These additional antivirals are typically used in conjunction with tecovirimat for severe or refractory cases. For more information, see CDC MMWR on Treatment Considerations for Severe Manifestations of Mpox and CDC Clinical Treatment of Mpox for details on how to access additional 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.

CDC scientists are actively monitoring for changes in the mpox virus that could make the virus less susceptible to tecovirimat. Because of the potential for the virus to become resistant to tecovirimat, it is important the drug be used in a judicious manner. More information about tecovirimat resistance can be found below, and on the FDA and the CDC websites.

Tecovirimat resistance testing considerations:

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), for public health surveillance purposes.
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. However, individual patient results cannot be made available for directly informing individual patient treatment decisions at this time.

Please contact your LHD, CDPH, and the CDC to discuss any concerns about tecovirimat resistance, any cases requiring prolonged tecovirimat courses, or any situations in which advanced therapeutics is being considered.