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EDMUND G. BROWN JR.
Governor

State of California—Health and Human Services Agency
California Department of Public Health


December 15, 2022


TO:
Healthcare Providers

SUBJECT:
Mpox Tecovirimat Treatment Information for Healthcare Providers


Updated as of December 15, 2022: 

  • Aligned guidance in relation to the latest CDC HAN regarding management of mpox in patients receiving therapeutics. 
  • Additional information about mpox treatment, which patients should receive treatment, the tecovirimat clinical trial, viral resistance, when to consider testing after 14 days of treatment, and how to obtain tecovirimat. 

Tecovirimat Treatment   

General Information for providers

Many patients with mpox have a mild, self-limited disease and recover without medical intervention. Most patients with mpox who require treatment are being managed as outpatients. However, the prognosis for mpox depends on multiple factors, including immune status, previous vaccination, co-morbid, initial health status. Supportive care and treatment of symptoms (PDF) should be initiated for all patients who have mpox infection. This may include topical or systemic medications 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 should also be tested for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) upon screening. 

Patients who are at high risk for severe disease or progress to severe mpox despite supportive care and treatment should be considered for prompt tecovirimat treatment. Tecovirimat (also known as TPOXX or ST-246) is an FDA-approved antiviral medication for the treatment of human smallpox disease in adults and children. The Centers for Disease Control and Prevention (CDC) holds an expanded access Investigational New Drug (EA-IND) protocol that allows for the use of stockpiled tecovirimat to treat mpox during an outbreak. See CDC Guidelines for Tecovirimat Use for more details.

Per the CDC, clinicians should be aware that at this time there is a paucity of tecovirimat effectiveness data for patients with mpox, including a lack of data on which patients may benefit most from tecovirimat treatment. Studies using a variety of animal species have shown that tecovirimat is effective in treating disease caused by orthopoxviruses. Safety trials in people showed the drug was safe, with minor side effects reported.

The National Institutes of Health (NIH) is currently enrolling patients in a tecovirimat efficacy trial. If you are a healthcare provider prescribing tecovirimat, consider first seeking access through enrollment in the AIDS Clinical Trials Group (ACTG) Study of Tecovirimat for Human Mpox Virus (STOMP) trial, which is evaluating the efficacy of tecovirimat. In this study, all adults with severe mpox, severe immunodeficiency, or other noted criteria will be enrolled in the open-label arm to receive oral tecovirimat. 

Clinicians should also be aware of the concern for development of tecovirimat resistance, especially in patients who are immunocompromised or have severe disease and require prolonged tecovirimat treatment. To date, two cases of tecovirimat resistance have been documented. Transmission of tecovirimat-resistant mpox has not been documented. More information about tecovirimat resistance can be found below, and on the FDA and the CDC websites. 

Tecovirimat is available in oral and intravenous formulations. When prescribed orally, it is critically important to educate patients 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, as described above.

Dosage and administration of tecovirimat guidance for adults and children is provided in the CDC EA-IND protocol (PDF) on the CDC Healthcare Professionals Guidance webpage. 

Which patients should be treated with tecovirimat? 

Treatment considerations are provided in the CDC EA-IND protocol (PDF) on the CDC Guidance for Tecovirimat use webpage. The decision to treat is at the clinical discretion of the healthcare provider. 

A positive lab result is not necessary to initiate treatment. Tecovirimat treatment may be initiated for patients with laboratory confirmed non-variola orthopoxvirus infection or suspected infection based on known exposure(s) and/or clinical manifestations of disease. 

For patients at high risk for progression to severe disease, tecovirimat should be initiated promptly, along with supportive care and pain control. 

Tecovirimat treatment considerations include the following

  • Patients with severe disease — including hemorrhagic disease; large number of lesions such that they are confluent; sepsis; encephalitis; ocular or periorbital infections; or other conditions requiring hospitalization. 
  • Involvement of anatomic areas which might result in serious sequelae that include scarring or strictures — these include lesions directly involving the pharynx causing dysphagia, inability to control secretions, or need for parenteral feeding; penile foreskin, vulva, vagina, urethra, or rectum with the potential for causing strictures or requiring catheterization; anal lesions interfering with bowel movements (for example, severe pain); and severe infections (including secondary bacterial skin infections), especially those that require surgical intervention such as debridement. 

Tecovirimat should be considered for use in people who are at high risk for severe disease: 

  • Patients currently experiencing severe immunocompromise due to conditions such as advanced or poorly controlled HIV, leukemia, lymphoma, generalized malignancy, solid organ transplantation, therapy with alkylating agents, antimetabolites, radiation, tumor necrosis factor inhibitors, or high-dose corticosteroids, being a recipient of a hematopoietic stem cell transplant <24 months post-transplant or ≥24 months but with graft-versus-host disease or disease relapse, or having autoimmune disease with immunodeficiency as a clinical component1
  • Pediatric populations, particularly patients younger than 8 years of age2 
  • Pregnant or breastfeeding people3
  • Patients with a condition affecting skin integrity — conditions such as atopic dermatitis, eczema, burns, impetigo, varicella zoster virus infection, herpes simplex virus infection, severe acne, severe diaper dermatitis with extensive areas of denuded skin, psoriasis, or Darier disease (keratosis follicularis) 

Update on Managing Mpox in Patients Receiving Therapeutics

On November 17, 2022, the CDC issued a Health Alert Network (HAN) update on recommendations for managing mpox in patients requiring therapeutics. 

Treatment considerations:

  • Tecovirimat treatment can be extended on a day-by-day basis beyond the standard 14-day course based on clinical course. 
  • Certain patients with severe mpox or at high risk for severe mpox (patients with HIV and CD4 count <350 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 facilitate competent native immunity (e.g., ensure persons with HIV are receiving effective antiretroviral therapy) and limit the use of immunocompromising therapies (e.g., chemotherapy, TNF inhibitors), if feasible.   

While viral resistance has been rare, two cases of laboratory-confirmed tecovirimat resistance have been documented in immunocompromised patients. Both patients had progressive, severe manifestations of disease requiring prolonged (greater than14 days) tecovirimat courses.

Testing considerations:

  • In patients with persistent or progressive mpox after completing 14 days of tecovirimat, consider testing lesion swab samples for tecovirimat resistance and performing plasma pharmacokinetics (PDF), for public health surveillance purposes.
    • Ideally, both resistance testing and pharmacokinetic testing should be performed to determine if any cases of confirmed resistance are associated with drug levels below target concentrations.
  • Every sexually active person considered for mpox, should also be tested for HIV and other STIs.  

Please contact your local health department (LHD), CDPH, and the CDC regarding concerns about tecovirimat resistance, cases requiring prolonged tecovirimat courses (greater than14 days), and/or cases under consideration for advanced therapeutics. For more information on additional recommendations for therapeutics and testing, visit: CDC HAN Update on Managing Mpox in Patients Receiving Therapeutics

What does CDC require tecovirimat healthcare providers to do?  

Healthcare providers interested in offering tecovirimat to patients not eligible for the STOMP trial or who decline to participate should review the EA-IND protocol (PDF) and CDC requirements with their clinical facility, including the following considerations: 

1. Healthcare providers can either rely on the CDC Institutional Review Board (IRB), which serves as the central IRB for the tecovirimat EA-IND protocol (recommended by CDC), or can submit the protocol to their local IRB for review. This decision is at the discretion of the healthcare provider and their clinical institution. 

  • CDC IRB has determined that the TPOXX EA-IND protocol does not constitute research involving human subjects. 
  • CDC has a written reliance agreement that facilities can sign to document their reliance on CDC IRB. 

2. Healthcare providers should understands CDC's minimum requirements for obtaining and submitting the required forms found in the Information for Healthcare Providers on Obtaining and Using TPOXX (Tecovirimat) for Treatment of Mpox, which includes:

  • Obtaining Informed Consent (forms in multiple languages are located at this link) and maintain in patient's chart;  
  • Submitting  FDA Form 1572 (within 7 days of the first treatment initiation, one time per facility), which can be accessed through the Tecovirimat IND Online Registry
  • Submitting the Patient Intake Form (within 7 days of initiating treatment), which can also be accessed through the Tecovirimat IND Online Registry; and
  • Reporting of life-threatening or serious adverse events using MedWatch Form FDA Form 3500 and returning it to CDC via email (regaffairs@cdc.gov) within 72 hours of awareness or sooner, if possible. 

3. October 28, 2022, an online registry became available for healthcare providers and their affiliated medical facilities providing tecovirimat to submit these forms under the CDC-held expanded access Investigational New Drug (IND) protocol to register as participating healthcare providers and sites. More information can be found at the TPOXX IND Registry site.

  • Healthcare providers who have returned required IND forms prior to the online registry transition are grandfathered in as participating providers under the EA-IND. Any healthcare 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.

4. If a healthcare provider has a patient in urgent need of treatment, they may proceed with prescribing tecovirimat treatment once informed consent has been obtained from the patient. Other steps listed above can be completed after the patient has initiated treatment. 

5. All patient visits may be conducted via telemedicine. 

All healthcare providers are asked to inform the local health department (LHD) of the patient's residence when new treatment starts so that treatment can be recorded in the patient's case record (CalREDIE) and the local medication supply monitored. 

The CDC EA-IND provides liability coverage under the Public Readiness and Emergency Preparedness (PREP) Act for healthcare providers prescribing, administering, or dispensing the drug and for patients to seek compensation if they are seriously injured by the medication via the Countermeasure Injury Compensation Program. 

For questions on the TPOXX IND registry or electronic forms, contact CDC IMS TPOXXIND (eocevent477@cdc.gov). 

How do I obtain tecovirimat for my facility? 

Healthcare providers can contact their LHD. The LHD  Medical Health Operational Area Coordinator (MHOAC) will submit a resource request to California Department of Public Health (CDPH), and medications will be shipped to the healthcare facility. 

For information on other mpox therapies, see CDC's  Mpox Treatment Information for Healthcare Providers webpage


References:

  1. Ogoina D, Iroezindu M, James HI, Oladokun R, Yinka-Ogunleye A, Wakama P, Otike-Odibi B, Usman LM, Obazee E, Aruna O, Ihekweazu C. Clinical Course and Outcome of Human Mpox in Nigeria. Clin Infect Dis. 2020 Nov 5;71(8):e210-e214. doi: 10.1093/cid/ciaa143. PMID: 32052029. 

  2. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human Mpox: clinical features of 282 patients. J Infect Dis. 1987 Aug;156(2):293-8. doi: 10.1093/infdis/156.2.293. PMID: 3036967. 

  3. Mbala PK, Huggins JW, Riu-Rovira T, Ahuka SM, Mulembakani P, Rimoin AW, Martin JW, Muyembe JT. Maternal and Fetal Outcomes Among Pregnant Women With Human Mpox Infection in the Democratic Republic of Congo. J Infect Dis. 2017 Oct 17;216(7):824-828. doi: 10.1093/infdis/jix260. PMID: 29029147. 

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