Treatment Guidance

Supportive care for mpox includes pain management, skin and wound care, maintenance of fluid balance, and treatment of co-occurring sexually transmitted infections or bacterial superinfections. 

Important aspects of pain control include the following:

• Use of over-the-counter medications for general pain management 
• Prescription pain medications for short-term management of severe pain 
• Topical steroids and anesthetics for local pain relief (use with caution on open skin or draining wounds) 

Skin and wound care is critical for individuals with mpox. This should include prevention and treatment of secondary bacterial infections (and other complications), ensuring hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals.  

• Skin lesions should be kept clean and dry when not showering or bathing to prevent bacterial superinfection. Warm oatmeal baths can also reduce itching and pain. 
• For oral lesions, patients can rinse their mouths with salt water at least four times per day. Alcohol-free oral antiseptics can be used to keep lesions clean. For pain, patients can suck on ice chips or ice pops, use compounds such as “magic” or “miracle” mouthwashes (prescription solutions used to treat mucositis), or apply patches and benzocaine or lidocaine gels. 
• For painful genital and anorectal lesions, warm sitz baths lasting at least 10 minutes several times per day may be helpful. Topical benzocaine or lidocaine gels or creams may provide temporary relief.  
• Proctitis can progress to become severe and debilitating. Stool softeners should be initiated early. Sitz baths are useful for proctitis and may calm inflammation. 
• For itching, oral antihistamines and topical agents such as calamine lotion, petroleum jelly, or colloidal oatmeal may improve symptoms. Patients who use topical steroids for pre-existing skin conditions should avoid applying steroids to active lesions of mpox, unless directed to do so by their treating clinician. 

Please refer to CDC's Clinical Considerations for Pain Management of Mpox for specific treatment steps and tools, including detailed information on pain management for lesions in various locations. 

Provider Resources 

• Mpox: Caring for the Skin (American Academy of Dermatology) 
• Mpox: Treating Severe Lesions (American Academy of Dermatology) 
• CDC Clinical Considerations for Pain Management of Mpox 
• CDC Opioid Prescribing Guideline Resources 

Moderate and severe immunocompromising conditions and treatments may increase the risk of severe, prolonged mpox. These include HIV infection (particularly if there is a low CD4 count (<200 cells/mm³)), primary immunodeficiency, active treatment for a solid tumor or hematologic malignancy, immunosuppressive or immunomodulating therapy, and receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic cell transplant (within 2 years of transplantation or taking immunosuppressive therapy).  

Early optimization of immune function (e.g., initiation of HIV antiretroviral therapy) is critical for patient outcome.

Tecovirimat 

• Should be considered as first line treatment of mpox in people who have advanced or poorly controlled HIV or are otherwise immunocompromised, as they may be at high risk for severe disease. It is important to begin tecovirimat as early as possible in such patients. 
• Should be given IV if there is concern for inadequate or altered oral drug absorption or if the patient is unable to take oral therapy. 
• Consider extending tecovirimat beyond the standard 14-day course on a day-by-day basis. 
• Consider the addition of other therapies (e.g., cidofovir, brincidofovir, and VIGIV). 

For further information on TPOXX, cidofovir (commercially available), brincidofovir, and VIGIV for the treatment of individuals with moderate or severe immunocompromise, please see CDC’s Clinical Considerations for Treatment and Prophylaxis of Mpox Infection in People Who are Immunocompromised. 

Provider Resources 

• Clinical Considerations for Treatment and Prophylaxis of Mpox Infection in People Who are Immunocompromised 
• Interim Clinical Treatment Considerations for Severe Manifestations of Mpox — United States, February 2023 | MMWR (cdc.gov) 
• CDC Health Alert: Severe Manifestations of Monkeypox among People who are Immunocompromised Due to HIV or Other Conditions 
• FDA Mpox Response - Therapeutics 
• TEMBEXA (brincidofovir) fact sheet 
• VDH’s TPOXX Ordering Information for Virginia Providers and LHDs provides guidance for referring patients, ordering, dispensing, and reporting TPOXX and required CDC documentation. 

For most individuals with intact immune systems, supportive care and pain control will be sufficient for mpox management. However, prognosis can be impacted by initial health status, comorbidities, concurrent illnesses, and vaccination history. Therefore, in some patients, supportive care and pain control may not be adequate and treatment should be considered. Consider tecovirimat (TPOXX) as first-line therapy for eligible patients with mpox. CDC provides Information for Healthcare Providers: TPOXX for Treatment of Mpox, including instructions on accessing the medication for patients.

Resistance 

• Viral resistance to tecovirimat has been rare, and when documented has occurred with prolonged administration and severe clinical outcomes. 
• Consider testing lesion swab specimens for tecovirimat resistance and plasma pharmacokinetic sample collection for any patient who, after completing 14 days of tecovirimat treatment, experiences persistent or newly emergent mpox lesions. CDC provides detailed instructions for collecting and submitting specimens for resistance testing.  
  • Lab-confirmed tecovirimat resistance has been reported in U.S. patients during the current mpox outbreak, though the frequency of resistant viruses has been low (<1%). Most resistance occurred in patients with severe immunocompromise on multiple courses of tecovirimat treatment.
  • There have been rare cases of transmission of tecovirimat resistance-associated mutation in California.
  • Counsel patients about the critical importance of taking oral tecovirimat with fatty meals to ensure adequate gastrointestinal absorption and maximize serum levels of the drug. Inadequate serum levels could promote resistance as described above.

Provider Resources 

• CDC's Clinical Guidance for Mpox 
• CDC's Treatment Information for Healthcare Professionals 
• CDC Health Alert: Update on Managing Mpox in Patients Receiving Therapeutics 
• CDC's Guidance for Tecovirimat Use for Mpox 
• Patient Enrollment: Study of Tecovirmat for Mpox  
• VDH's TPOXX Ordering Information for Virginia Providers and LHDs  provides guidance for referring patients, ordering, dispensing, and reporting TPOXX and required CDC documentation. 
• VDH’s Mpox Trainings for Healthcare Providers recorded in January and February 2024 are available as a resource for clinicians.

STOMP Trial (Preferred)

If you are a provider seeking oral tecovirimat, you are encouraged to seek access first through enrollment in the Study of Tecovirimat for Mpox (STOMP) trial, which is evaluating the efficacy of tecovirimat. In this study, all adults with severe mpox or protracted or life-threatening manifestations of mpox, severe immunocompromise, active skin conditions, or other noted criteria will be enrolled in the open-label arm to receive oral tecovirimat. Patients should be informed about the clinical trial for tecovirimat (STOMP clinical trial) and encouraged to consider enrollment.

Please note that patients do not have to have severe mpox or be at increased risk of severe mpox to enroll in the STOMP trial. Patients with milder disease are being recruited for the randomized, double-blind arm. More information about the trial can be found at https://www.stomptpoxx.org/main.

There are STOMP trial sites that can enroll patients virtually. Please visit https://www.stomptpoxx.org/main or call 1-855-876-9997 (Hours Mon – Fri 9 am to 10 pm, Sat 9 am to 4 pm, Sun 1 to 6 pm Eastern Time). The STOMP team recommends contacting the call center and not directly contacting the participating study sites to be directed to the site that can provide the quickest help. Please note that STOMP enrollment is not available on weekends at this time. TPOXX should be acquired through the expanded access investigational new drug protocol if enrollment is not available (details below).

Expanded Access IND Protocol

Patients or those who require IV tecovirimat can receive tecovirimat under an expanded access investigational new drug (EA-IND) protocol, if they meet protocol eligibility criteria. This protocol was updated on June 5, 2024, as follows:

• To better clarify patients with mpox who are eligible for tecovirimat treatment under the EA-IND protocol – those with severe immunocompromise, with active skin conditions, who are pregnant and/or lactating or children (< 18 years), and those with or are at high risk for protracted or life-threatening manifestations as defined in the protocol.
• Text revision on early intervention in patients with mpox who are at high risk for protracted or life-threatening manifestations of mpox due to severe immunocompromising conditions through initiation of effective HIV antiretrovirals or delaying immunosuppressant treatments to optimize immune function and consideration for tecovirimat treatment in combination with additional therapeutics for mpox (e.g., IV cidofovir or oral brincidofovir (prodrug of cidofovir) and/or vaccinia immune globulin).
• Revisions to Informed Consent Form, Patient Intake Form, and Clinical Outcome Form

If a provider at an LHD is requesting TPOXX through the EA-IND for a patient, they should contact VDH’s Central Pharmacy for assistance with fulfilling this request.

Private providers should contact their local health department to request TPOXX through the EA-IND. The LHD may then consult with the CDC directly to facilitate TPOXX access or reach out to Central Pharmacy to request oral TPOXX and/or additional support.

Prescribers must complete the for all new patients started on TPOXX obtained from outside the STOMP trial.

For more information, please see VDH's TPOXX Ordering Information for Virginia Providers and LHDs, which provides guidance for referring patients, ordering, dispensing, and reporting TPOXX and required CDC documentation.

TPOXX is available for the treatment of mpox under an EA-IND protocol through the CDC. A condensed version of the protocol for providers is available on the CDC website. The tecovirimat EA-IND protocol is intended to be used in concert with CDC’s guidance for treatment.

TPOXX IND Online Registry for Providers and Facilities 

New providers and affiliated facilities can register online as participating providers/sites under the CDC-held EA-IND for tecovirimat through the Tecovirimat (TPOXX) IND Online Registry for Providers and Facilities. Detailed information about this registry can be found on CDC’s webpage.  

• New providers and affiliated medical facilities providing tecovirimat under the EA-IND protocol must register with the tecovirimat IND online registry starting October 28, 2022. 
• Through the registry, providers can submit the following forms electronically: 
• Form FDA 1572 
• Patient Intake Form 
• Clinical Outcome Form 
• The tecovirimat IND Online Registry allows for convenient, time-efficient, and secure completion and return of EA-IND forms to CDC. 
• Providers who have returned required IND forms prior to the online registry transition are grandfathered in as participating providers under the EA-IND. Any providers with valid email addresses on record should have received emails providing them access to the electronic Patient Intake and Clinical Outcome forms on October 25, 2022. 
• Any questions about the registry and transition to electronic tecovirimat IND Patient Intake and Clinical Outcome forms can be directed to regaffairs@cdc.gov. 

Required Documentation: 

1. Informed Consent Form: English [238 KB, 6 pages] Obtain prior to treatment.
   1. Other languages: Spanish [263 KB, 7 pages] 
   2. Alternative Consent Forms that can be used to obtain informed consent:  
      • Short Form (English) [155 KB, 3 pages] | Spanish [140 KB, 4 pages] 
      • Written Summary (English) [229 KB, 5 pages] | Spanish [284 KB, 6 pages] 
2. Patient Intake Form: Baseline assessment. Access the electronic form through the Tecovirimat IND Online Registry. 
3. FDA Form 1572: One signed 1572 and treating clinician’s CV per facility suffices for all tecovirimat treatments administered under the EA-IND at the same facility. Access the electronic form through the Tecovirimat IND Online Registry. 
4. Serious Adverse Events: Per FDA requirement, report life-threatening or serious adverse events associated with tecovirimat by completing a PDF MedWatch Form [956 KB, 5 pages] and returning it to CDC via email (regaffairs@cdc.gov) within 72 hours of awareness or sooner, if possible. The PDF MedWatch Form can also be downloaded from the FDA website. Note: The MedWatch Form can only be viewed on the Adobe desktop app. Please save or download the form for viewing. 

Optional Documentation: 

• Clinical Outcome Form: Progress and outcome information post treatment. Access the electronic form through the Tecovirimat IND Online Registry. 
• Lesion samples for resistance testing: Lesion samples may be sent to CDC for tecovirimat-treated patient with persistent lesions and/or any new lesions that develop during and/or after tecovirimat treatment to assess for development of antiviral resistance mutations. See Optional Lesion Samples to CDC for Resistance Testing [147 KB, 2 pages] for instructions on collection, storage, and submission of samples. 
• Pharmacokinetic samples for testing: During tecovirimat treatment, plasma samples may be collected to monitor tecovirimat levels for adequate drug exposure in patients. Optional Pharmacokinetic Samples for Testing [375 KB, 4 pages] has instructions on collection, storage, and submission of samples. 

For more information about the requirements for obtaining TPOXX, please see CDC's Information for Healthcare Providers: Tecovirimat (TPOXX) for Treatment of Mpox. 

Brincidofovir

Brincidofovir is a prodrug of cidofovir that is approved by the FDA for the treatment of human smallpox disease in adult and pediatric patients, including neonates. Data are not available on the effectiveness of brincidofovir in treating mpox  in people. However, it has shown to be effective against orthopoxviruses in in vitro and animal studies. Brincidofovir should not be used simultaneously with cidofovir.

Brincidofovir is made available from the Strategic National Stockpile (SNS) for treatment of mpox to clinicians who request and obtain an FDA-authorized single-patient emergency use IND (e-IND). On June 14, 2024, FDA updated its criteria for brincidofovir e-IND. Brincidofovir can be considered for use under an e-IND for treatment of mpox in adults and pediatric patients (including neonates) with positive results of mpox viral testing who:

• Have severe disease OR are at high risk for progression to severe disease,
• AND meet any of the following:
  • Experience clinically significant disease progression while receiving tecovirimat or who develop recrudescence (initial improvement followed by worsening) of disease after an initial period of improvement on tecovirimat, OR
  • Are otherwise ineligible or have a contraindication for oral or intravenous tecovirimat, OR

• Are enrolled in the open-label treatment arm (Arm C) of the STOMP trial, OR

• • Are severely immunodeficient (e.g., uncontrolled HIV infection – CD4 < 200). Severely immunodeficient patients without prior tecovirimat use can simultaneously initiate combination therapy with brincidofovir and tecovirimat (Note: For these cases, FDA will encourage STOMP enrollment and provide link to trial information).

Clinicians with mpox patients necessitating brincidofovir treatment may submit an e-IND request to FDA by email (DDI.EIND@fda.hhs.gov) or phone 301-796-3400 or 1-855-543-3784 during normal business hours (8 am-4:30 pm ET M-F) or completing an electronic request to FDA. During after hours, call the FDA Emergency Coordinator at 1-866-300-4374 or 301-796-8240 or email CDER-EIND@fda.hhs.gov and call the CDER Emergency Coordinator at 301-796-9900.

Vaccinia Immune Globulin Intravenous (VIGIV)

VIGIV is licensed by FDA for the treatment of complications due to vaccinia vaccination. However, it is not approved for treatment of mpox. Therefore, CDC holds an expanded access IND protocol that allows the use of stockpiled VIGIV for the treatment of orthopoxviruses (including mpox) in an outbreak.

Data are not available on the effectiveness of VIGIV in treatment of mpox in people. Use of VIGIV has no proven benefit in the treatment of mpox and it is unknown whether a person with severe mpox infection will benefit from treatment with VIGIV. However, healthcare providers may consider its use in severe cases where the development of a robust antibody response may be impaired.

VIGIV is not prepositioned by the USG. It is available upon clinician request to CDC on a case-by-case basis. To request VIGIV, clinicians can contact the CDC Clinical Consultation Team by email (poxvirus@cdc.gov) during business hours, or for urgent clinical situations, contact the CDC Emergency Operations Center (770-488-7100). An informed consent must be obtained prior to administration. The remaining VIGIV IND fillable forms will be provided to clinicians requesting VIGIV.

Cidofovir

Cidofovir is an antiviral medication that is approved by the FDA for the treatment of cytomegalovirus (CMV) retinitis in patients with Acquired Immunodeficiency Syndrome (AIDS), and is commercially available as an injection. Data are not available on the effectiveness of cidofovir in treatment of mpox  in people. However, it has shown to be effective against orthopoxviruses in in vitro and animal studies. It is unknown whether a person with severe mpox infection will benefit from treatment with cidofovir, although its use may be considered in such instances. Brincidofovir (a prodrug of cidofovir) may have an improved safety profile over cidofovir. Serious renal toxicity or other adverse events have not been observed during treatment of cytomegalovirus infections with brincidofovir as compared to treatment using cidofovir. Cidofovir should not be used simultaneously with brincidofovir.

Provider Resources

• CDC's Mpox Clinical Guidance
• CDC's Mpox Treatment Information for Healthcare Professionals
• FDA Mpox Response - Therapeutics
• TEMBEXA (brincidofovir) fact sheet
• VDH Mpox Trainings for Healthcare Providers
• CDC COCA Mpox Update: Clinical Management and Outbreaks webinar recorded June 27, 2024
• CDC/IDSA Clinician Call: Mpox Updates webinar recorded June 5, 2024