Skip Navigation LinksMpox-Tecovirimat-Treatment-Information-for-Providers

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EDMUND G. BROWN JR.
Governor

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


December 12, 2023


TO:
Health Care Providers

SUBJECT:
Mpox Treatment with Tecovirimat (TPOXX): Information for Health Care Providers

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Updated as of December 12, 2023: 

  • Includes updates on the methods and eligibility for ordering oral and intravenous (IV) tecovirimat (TPOXX): 
    • ​Oral TPOXX is preferably obtained through the STOMP clinical trial, when patients are eligible and willing to participate. Oral TPOXX can otherwise still be obtained through state supplies. 
    • IV TPOXX can now be obtained for immediate patient use directly from the Center for Disease Control and Prevention (CDC) by contacting the Emergency Operations Center (EOC). ​
  • Includes updates on how to report TPOXX use and inventory, which is now through the new enhanced Health Partner Order Portal (HPOP) system

Mpox Treatment 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 conditions, and initial health status. 

Supportive Care should be initiated for all patients who have mpox symptoms. 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 with confirmed or suspected mpox should also be screened for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The CDC has reported that ~40% of mpox cases had HIV or another STI in the past year (CDC). 

Currently there is no treatment approved specifically for mpox virus infections. However, United States Government (USG)-stockpiled antivirals, developed for use in patients with smallpox, may be beneficial against mpox. Tecovirimat (TPOXX) is an FDA-approved antiviral medication for the treatment of human smallpox disease in adults and children. Safety trials in people have found TPOXX to be safe, with only minor side effects reported. 

Patients who are at high risk for severe disease or progress to severe mpox​ despite supportive care and pain control should be considered for prompt tecovirimat treatment. The decision to treat is at the clinical discretion of the health care provider. A positive lab result is not necessary to initiate treatment if there is high clinic​al suspicion. TPOXX 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. 

People eligible to receive TPOXX through the CDC Expanded Access Investigational New Drug (EA-IND) Protocol​ (PDF) include: Patients with severe disease manifestations — including hemorrhagic disease; a large number of lesions such that they are confluent; sepsis; encephalitis; ocular or periorbital infections; or other conditions requiring hospitalization. 

  • Those with involvement of anatomic areas which might result in serious sequelae that include scarring or strictures — these areas include: 
    • ​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. 

TPOXX should also be considered for use in people who are at high risk for severe disease such as

  • Patients currently experi​​​encing severe immunocompromise due to conditions such as advanced or poorly controlled HIV, leukemia, lymphoma, other malignancies, 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 component 
  • Pediatric populations, particularly patients younger than 1 year of age 
  • Pregnant or breastfeeding people 
  • 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 d​​​iaper dermatitis with extensive areas of denuded skin, psoriasis, or Darier disease (keratosis follicularis) 

TPOXX treatment considerations are also provided in the CDC EA-IND protocol (PDF) on the CDC Guidance for Tecovirimat use​ webpage. 

Note that TPOXX can also be used in mild cases through the Study of Tecovirimat for Human Mpox Virus (STOMP) study. Patients do not have to have severe disease or be at high risk of severe illness to enroll in the study.

How to Obtain Tecovirimat (TPOXX) 

TPOXX is available in oral and intravenous (IV) formulations. As of December 2023, the process for requesting oral TPOXX has not changed. However, given limited state supplies and the fact that the IV formulation is rarely needed, all requests for IV TPOXX for immediate patient use should now be sent directly to the CDC. Note that the US Department of Health and Human Services no longer allows state/local health departments or providers to stockpile/pre-position IV TPOXX. 

I. Ordering Oral TPOXX 

There are two routes to obtain oral TPOXX treatment for immediate patient use: 

Health care providers are first encouraged to enroll their patients in the STOMP trial. If an alternative source of TPOXX is needed, health care providers can contact their Local Health Department (LHD) to obtain oral TPOXX through the state stockpile under the CDC EA-IND Protocol. 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. More detail regarding each of these routes for obtaining oral TPOXX is provided below. 

Option 1 (Preferred)​: The STOMP Clinical Trial: A placebo-controlled NIAID-funded clinical trial to evaluate the effectiveness of the antiviral tecovirimat – is the preferred mechanism for obtaining oral TPOXX. Enrollment in the STOMP trial is critical for possible FDA approval and commercial availability of this medication. 

  1. Providers are encouraged to inform patients with mpox about STOMP and to recommend they consider seeking enrollment. The trial has both randomized and open label treatment arms. 
  2. Patients do not have to have severe disease or be at high risk of severe illness to enroll in the study, and remote enrollment is available. 
  3. 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. 
  4. Interested participants can contact one of the clinical research sites through STOMP: Study of Tecovirimat for Mpox​ or by calling the “Mpox Study Hotline” at 1-855-876-9997. 
  5. Clinic friendly promotional summaries of the STOMP study for patient and providers a can be found here: CA Prevention Training Center’s STOMP Study Patient and Provider Handouts​. These have been translated in to three languages. 

Option 2 (Alternative)​: Accessing state supplies of oral TPOXX through the CDC EA-IND: The CDC holds an EA-IND protocol, which allows the use of stockpiled tecovirimat available at the CDPH to treat mpox during an outbreak. 

  1. Patients treated with TPOXX through the state supply must meet eligibility criteria under the CDC EA-IND Protocol (PDF) (indications detailed above) and follow the CDC requirements for use (detailed below). 
  2. ​To obtain oral TPOXX through this route, providers can contact their LHD MHOAC to submit a resource request to CDPH, and medications will be shipped to the healthcare facility. 

CDC EA-IND Protocol Requirements:

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

  1. Health care providers can either rely on the CDC Institutional Review Board (IRB), which serves as the central IRB for the tecovirimat EA-IND protocol, or can submit the protocol to their local IRB for review. This decision is at the discretion of the health care provider and their clinical institution. 
  2. Health care providers should understand CDC's minimum requirements for obtaining and submitting the required forms on the TPOXX IND Registry site. Required steps include: ​
    • ​​​​Obtaining Informed Consent​ (forms in multiple languages are located at this link) and maintaining this in each patient's chart; 
    • Submitting FDA Form 1572 (within 7 days of the first treatment initiation, one time per facility); 
    • Submitting the Patient Intake Form (within 7 days of initiating treatment); and 
    • Reporting any 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. Health care 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 health care provider has a patient in urgent need of treatment, they may proceed with prescribing TPOXX once informed consent has been obtained from the patient. Other steps listed above can be completed after the patient has initiated treatment. 

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​).

II. Ordering IV TPOXX

IV TPOXX can no longer be pre-positioned to state/local jurisdictions. IV TPOXX remains available for immediate use in mpox patients who meet eligibility under the CDC EA-IND protocol (PDF) and 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). 

  1. To request IV TPOXX for immediate patient use, the first line option is through the CDC. Providers should be contact the CDC by calling the CDC Emergency Operations Center at 770-488-7100 (after hours), or emailing poxvirus@cdc.gov and mpxtreatment@cdph.ca.gov​ (during business hours) to reach the CDC and CDPH Clinical Consultation Teams.
  2. ​If CDC is unable to fulfill the request within 24 hours, providers should contact their LHD MHOAC to secure IV TPOXX through state supplies as a temporary stop-gap. Please note, there was a product shelf-life extension released for IV TPOXX and facilities may still have inventory available. The lot numbers and expiration dates for remaining oral and IV TPOXX products is found here.

TPOXX Reporting

Whenever a patient is initiated on TPOXX, 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. 

Additionally, the US Department of Health and Human Services enhanced Health Partner Order Portal (HPOP) is the new reporting system used to track IV and oral TPOXX inventory. The federal government requires tecovirimat inventory reporting and providers/facilities should report their inventory through HPOP weekly and at the time of resou​​​rce requests. 

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 prescribed orally, it is critically important to educate patients to take TPOXX 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) on the CDC Healthcare Professionals Guidance webpage. 

The CDC has published an MMWR on Treatment Considerations for Severe Manifestations of Mpox, in addition to a previously published Health Alert Network (HAN) update​ containing recommendations for managing mpox in patients requiring therapeutics. 

Treatment considerations in severe or prolonged 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 (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 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 (SNS) 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 TPOXX for severe or refractory cases. 

Considerations for Tecovirimat Resistance and Testing 

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, while antiviral resistance has been rare, at least two cases of laboratory-confirmed TPOXX resistance have been documented in immunocompromised patients. Both patients had progressive, severe manifestations of disease requiring prolonged (greater than 14 days) tecovirimat courses. 

To date, 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. 

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. 

NOTE: 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 with any concerns about tecovirimat resistance, or to discuss cases requiring prolonged TPOXX courses (greater than 14 days), and/or being considered for advanced therapeutics.​

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