• 12/10/2024: The STOMP Trial finds that Tecovirimat (TPOXX) was safe but did not improve mpox resolution or pain: https://www.nih.gov/news-events/news-releases/nih-study-finds-tecovirimat-was-safe-did-not-improve-mpox-resolution-or-pain.
  • NIH announced that STOMP enrollment has been closed as of November 27, 2024, and oral TPOXX is no longer available via the STOMP trial.
  • Oral TPOXX is only available via the CDC EA-IND for those eligible persons with severe mpox or those at high risk for progression to severe disease.
• 06/18/2024: Updated CDC EA-IND Eligibility Criteria for Tecovirimat (TPOXX) – CDC’s EA-IND protocol has recently updated its eligibility criteria for TPOXX. 
• California Reports First Known U.S Case of Emerging Mpox Strain-Clade I (11-16-2024) Website: https://www.cdph.ca.gov/Programs/OPA/Pages/NR24-036.aspx: The laboratory confirmed mpox clade I case within the USA was in an individual who recently traveled from Africa and received health care in San Mateo County, California. Currently, this individual is isolating, not receiving mpox-specific treatment, and recovering at home with symptom improvement. Close contacts to the individual are being contacted by public health workers, and currently there is no evidence or concern for spreading within California or the USA. The specimens were sent to CDC for additional viral characterization. If you have a patient with recent travel to Democratic Republic of Congo (DRC) in the 21 days prior to illness onset or in contact with people from the Republic of Congo (ROC), Central African Republic (CAR), Rwanda, Burundi, Uganda, Zambia, Angola, Tanzania, South Sudan with symptoms, then please contact Los Angeles County DPH, Division of HIV and STD Programs for provider consultation and to coordinate clade-specific testing through the LA County Public Health Laboratory.
  • Weekdays: 8:00am-4:30pm: 213-368-7441.
  • Weekends and holidays: 8:00am-4:30pm or evenings (urgent situations only): 213-974-1234 and ask for physician on call.
• 12/11/2023: Clade I Mpox Virus (MPXV) with Geographic Spread in the Democratic Republic of the Congo: Recommendations for California Health Care Providers – This advisory provides information on Clade I MPXV and specimen submission for clade-specific mpox testing if Clade I Mpox is suspected due to travel history to endemic areas.
• 10/30/2023: Increase in Mpox Cases in California: Updates on Identification, Laboratory Testing, Management and Treatment, and Vaccination for Mpox  - This advisory provides an update on rising mpox cases and encourages providers to consider mpox in their differential diagnoses, test persons with suspected mpox, treat mpox, and offer vaccine to populations at increased risk to prevent severe mpox disease and reduce the number of new infections. 
• Healthcare providers should call the LAC DPH consultation line if a hospitalized patient is worsening clinically, such as being admitted to the ICU. LAC DPH will provide clinical consultation and access to additional therapeutic options.

• Many people infected with mpox have a mild, self-limiting disease course and recover without the need for antiviral medication.
  • The prognosis for mpox depends on multiple factors, such as disease severity, risk factors for severe disease, location of lesions, previous vaccination status among others.

Supportive care and pain control should be initiated early for all patients with suspect or confirmed mpox infection. This may include different topical, systemic medications, or other clinical interventions to ameliorate symptoms such as pain, itching, and nausea. Proctitis can occur and progress to become severe and debilitating, that may require prescription medication. Bacterial superinfection may be present and require antibiotics and drainage for abscesses.

All patients should be provided with instructions on lesion management and return precautions for worsening disease.

Some common supportive care measures are noted below:

Symptoms	Supportive Care Measures
Pain		Multimodal individualized approach: Mild-moderate pain: Over-the-counter (OTC) ibuprofen and/or acetaminophen Targeted pain relief associated with skin lesions: Topical steroids or anesthetics (ex: lidocaine) Caregivers should wear disposable gloves when applying topical agents to prevent autoinoculation Severe pain not improved with #1 and #2: Short course of gabapentin or opiates Opiate initiation should be done cautiously with immediate-release formulation and lowest effective dose. Co-prescribe with bowel regimen to prevent constipation.
Skin Rash		Skin rash with pruritis: Calamine lotion, petroleum jelly, colloidal oatmeal, or cooling lotions (camphor or menthol lotion) Caregivers should wear disposable gloves when applying topical agents to prevent autoinoculation Pruritis NOT controlled with topical agents Oral antihistamines (ex: loratadine)
Oral Lesions		Saltwater rinses 4 times daily Oral antiseptic (ex: chlorhexidine mouth) to keep lesions clean If significant: Prescription analgesic mouthwashes (ex: magic mouthwash)
Genital Lesions, Anorectal lesions, and proctitis		Warm sitz baths lasting 10 minutes several times a day Topical anesthetics (ex: lidocaine gels or creams) Proctitis: Stool softeners, OTC medications (acetaminophen and ibuprofen). If not improving with OTC medications, then consider prescription medications (ex: gabapentin or opioid) If prescribing opioid, then educate and discuss measures for managing side effects such as constipation
Nausea, Vomiting, Dyspepsia		Adequate hydration Antiemetics: Ondansetron, Promethazine Temporary antacid therapy for dyspepsia (ex: proton-pump inhibitors)
Diarrhea		Adequate hydration Electrolyte replacement Anti-motility agents NOT recommended due to potential ileus
Ocular Involvement		Trifluridine (topical antiviral medication) Lesions near the eye or eyelid lesions: Prophylactic trifluridine drops and TPOXX Corneal disease: Topical lubricants/antibiotics to prevent bacterial superinfection
Nutrition and Hydration		Adequate hydration Vitamin A supplementation may aid in wound healing
Mental Health Considerations		Connect patient with mental health counselor Telehealth mental health services

References:

• CDPH Supportive Care Suggestions for Patients with Mpox
• CDC: Clinical Considerations for Pain Management of Mpox

General Information

• In addition to supportive care, some patients might benefit from the use of antivirals especially those at high risk for severe manifestations or certain vulnerable populations.
• There are no treatments specifically for Mpox.
  • Antiviral drugs that have been developed against smallpox may be used to treat mpox effectively since the viruses that cause smallpox and mpox are similar.
• Antivirals: Tecovirimat (TPOXX).
• Additional treatment options to consider in severe disease:
  • Brincidofovir (Tembexa)
  • Vaccinia Immune Globulin Intravenous (VIGIV)
  • Cidofovir (Vistide)
• Access to treatment options can be arranged through consultation with LACDPH.

General Information

• Tecovirimat (also known as TPOXX or ST-246) is an FDA-approved antiviral medication for the treatment of human smallpox disease.
• Available TPOXX formulations: Oral and Intravenous.
• Tpoxx Access Route
  • Providers can access TPOXX under the CDC Expanded Access Investigational New Drug (EA-IND) for patients with suspected or laboratory-confirmed non-variola orthopoxvirus infection that are at high risk for severe disease or progressing to severe disease despite supportive care and pain control measures.
    • Informed consent is required for all patients treated with TPOXX and providers must follow the CDC EA-IND protocol.
     
  • Reference: CDC Tecovirimat EA-IND: Tecovirimat-IND-Protocol-CDC-IRB.pdf
• For patients at high risk for progression to severe disease based on the criteria listed below in the table TPOXX should be administered early in the course of illness along with supportive care and pain control. Treatment may be initiated empirically if the suspicion for mpox is high while lab confirmation is pending.

TPOXX Recommendations for Patients with Mpox:
Patients with protracted or life-threatening manifestations of mpox at presentation	Lesions affecting 25% or more of body surface that may be confluent, necrotic, and/or hemorrhagic in appearance or cause sepsis Disease resulting in airway compromise or affecting the nervous system Cardiac (e.g., myocarditis) and/or neurologic disease (e.g., encephalitis) which might occur in a small number of patients with mpox Ocular or periorbital infection, regardless of the time since infection onset Because the full scope of protracted or life-threatening mpox infections is not known at this time, TPOXX may also be considered on a case-by-case basis for an unusual situation wherein CDC consult team and/or CDC Principal Investigator in discussion with the treating clinician deem treatment under the EA-IND may potentially be beneficial; such consideration is expected to be rare and intended for unusual situations associated with disease that could result in clear long-term sequelae (e.g., urethral stricture).
Patients with severe immunocompromised conditions	HIV with CD4 < 200 cells/mm3 Leukemia or lymphoma Generalized malignancy Solid organ transplantation Therapy with alkylating agents within 180 days prior to mpox illness onset Taking antimetabolites within 180 days prior to mpox illness onset Having radiation therapy within 180 days prior to mpox illness onset Taking tumor necrosis factor inhibitors within 180 days prior to mpox illness onset Taking high-dose corticosteroids (equivalent of 20 mg or greater of prednisone for at least 14 days) within 90 days prior to mpox illness onset Being a recipient with 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 Other comparable severe immunocompromise Patients with severe immunocompromise are known to be at high risk for protracted or life-threatening manifestations of mpox, regardless of disease severity at presentation.
Active skin conditions placing the person at higher risk for disseminated infection	Atopic dermatitis Active exfoliative skin condition(s) such as eczema, burns, impetigo, active varicella zoster virus infection, psoriasis, or Darier disease (keratosis follicularis) These patients might be at high risk for protracted or life-threatening manifestations of mpox based on prior experience from other orthopoxvirus infections in humans.
Special Populations	Pregnant or lactating individuals, regardless of illness severity or underlying comorbidities at presentation Children (< 18 years), regardless of illness severity or underlying comorbidities at presentation These patients might be at high risk for protracted or life-threatening manifestations of mpox based on prior experience from other orthopoxvirus infections in humans.

CDC EA-IND Protocol Requirements

• All providers and affiliated facilities must be registered as participating providers and facilities to utilize the CDC EA-IND for TPOXX.
• Registration and EA-IND form submission can now be done online at the Tecovirimat (TPOXX) IND registry.
• 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 3-7 calendar days of patient completing TPOXX, one form per patient).
  • Submitting the Clinical Outcome Form (within 7 days of last follow up, one per patient).
  • 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.

How to obtain Oral TPOXX:

• Clinic or Hospital Pharmacies: Contact LACDPH DHSP at TPOXX@ph.lacounty.gov to request delivery of oral TPOXX from the warehouse to clinic or hospital pharmacies.
• Providers can also call in TPOXX prescription to pharmacies that have prepositioned TPOXX.
  • Providers without onsite access to the drug can use the LAC DPH TPOXX Treatment Checklist for Providers to prescribe TPOXX through an outpatient community pharmacy. If you need assistance with access to TPOXX, then please call LAC DPH.

How to obtain Intravenous (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).
• 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.
• If CDC is unable to fulfill the request within 24 hours, providers should contact LACDPH DHSP Clinical Consult line to secure IV TPOXX through county 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.

Considerations for TPOXX 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.
• 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.
• LACDPH continues to work with CDC in regards to resistance. Please reach out to LACDPH to discuss resistance.
  • As with any antimicrobial, CDC guidance emphasizes the importance of stewardship principles including using tecovirimat in patients where appropriate.
  • Educating patients on the importance of adherence to the full treatment course, including anticipating the possible side effects of tecovirimat, is also critical to minimizing selection pressure.
  • Individual patient results cannot be made available for directly informing individual patient treatment decisions at this time.

Prolonged TPOXX Medication Duration Considerations

• The standard TPOXX treatment course is 14 days.
  • Under CDC EA-IND, extending TPOXX duration beyond 14 days is permissible based on the provider’s clinical judgement weighing potential benefits and harms and needs to be reported to CDC utilizing the clinical outcome form.
  • CDC must be consulted and approval given prior to changes being made in standard dose and/or dosing internal.
    • For CDC consultations regarding changes in dosing interval or modifying the dose, then please contact the CDC mpox consultatnt 24 hours a day/7 days a week at 770-488-7100.
    • Reference: CDC Tpoxx EA-IND: https://www.cdc.gov/mpox/media/pdfs/2024/08/Tecovirimat-IND-Protocol-CDC-IRB.pdf.

Additional Mpox therapeutic options

• In severe disease (patients with HIV and CD4 count <350 cell/mm³ or other severely immunocompromising conditions), additional treatment options are available and access can be arranged through LACDPH:
  • Brincidofovir is an oral pro-drug of cidofovir without the renal toxicity and other adverse effects observed with cidofovir. It is approved for the treatment of smallpox.
  • Cidofovir is an intravenous antiviral medication approved for the treatment of CMV retinitis with in vitro and animal efficacy against orthopoxviruses. It is commercially available as an injection and should not be used simultaneously with brincidofovir.
  • Vaccinia immune globulin is licensed for complications of vaccinia vaccination.
  • See CDC Mpox Treatment Information for more details.

Treatment failure

If outpatient treatment failure is suspected (ex: new lesions appearing while on treatment), then patient should be reexamined.

1. Collect new swabs for specialized testing through our public health lab.
2. For patients that have worsening, non-healing, recurrent, and new skin lesions while on TPOXX, consider repeat HIV testing as they might be immunocompromised.
3. Contact LACDPH DHSP for public health lab authorization and clinical consultation.
   1. If continuing TPOXX beyond the suggested 14 days, then clinician should contact LACDPH to discuss unless there is clinical improvement (no more than 90 days).  

Hospitalized Patients

• Clinicians must report hospitalizations due to mpox to LAC DPH. In addition, please call the LAC DPH consultation line if a hospitalized patient is worsening clinically, such as being admitted to the ICU.
• LAC DPH will provide clinical consultation, and if needed arrange CDC consultation and facilitate access to additional therapeutic options.
• Intravenous tecovirimat should be used in patients who are unable to take oral therapy, who may have impaired oral drug absorption, or who are failing to improve on oral therapy.

Persons with advanced and uncontrolled HIV are at higher risk for severe (PDF) or prolonged mpox disease.

• Low CD4 counts (<200 per mm³) can lead to prolonged and a severe form of illness.
• Inadequately treated HIV can lead to higher rates of secondary bacterial infection and prolonged illness.

For Mpox patients living with HIV:

• Order HIV viral load and CD4 counts.
• Start and ensure patient is on anti-retroviral treatment (ART) for HIV.
• New HIV diagnoses or out of care patients may be referred to the Los Angeles County Rapid and Ready Program by calling 833-351-2298 during weekdays 8am to 4:30pm or by emailing rapid@ph.lacounty.gov.

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• Division of HIV and STD Programs - offers FREE HIV/STD screening. Please call (323) 629-3411 for the current testing site schedule.