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    Tecovirimat

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    Dec.05.2024

    Tecovirimat

    Indications/Dosage

    Labeled

    • variola virus (smallpox) infection

    Off-Label

    • monkeypox virus (mpox) infection
    • monkeypox virus (mpox) prophylaxis
    † Off-label indication

    For the treatment of variola virus (smallpox) infection

    Oral dosage

    Adults weighing 120 kg or more

    600 mg PO every 8 hours for 14 days. Administer within 30 minutes after a moderate to high fat meal.[63353]

    Adults weighing 40 to 119 kg

    600 mg PO every 12 hours for 14 days. Administer within 30 minutes after a moderate to high fat meal.[63353]

    Adolescents weighing 120 kg or more

    600 mg PO every 8 hours for 14 days. Administer within 30 minutes after a moderate to high fat meal.[63353]

    Children and Adolescents weighing 40 to 119 kg

    600 mg PO every 12 hours for 14 days. Administer within 30 minutes after a moderate to high fat meal.[63353] 

    Children and Adolescents weighing 25 to 39 kg

    400 mg PO every 12 hours for 14 days. Administer within 30 minutes after a moderate to high fat meal.[63353]

    Children weighing 13 to 24 kg

    200 mg PO every 12 hours for 14 days. Administer within 30 minutes after a moderate to high fat meal.[63353] 

    Intravenous dosage

    Adults weighing 120 kg or more

    300 mg IV every 12 hours via intravenous infusion over 6 hours for up to 14 days. Switch patients to the capsules to complete the 14-day treatment course as soon as oral therapy can be tolerated. Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353]

    Adults weighing 35 to 119 kg

    200 mg IV every 12 hours via intravenous infusion over 6 hours for up to 14 days. Switch patients to the capsules to complete the 14-day treatment course as soon as oral therapy can be tolerated. Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353]

    Adolescents weighing 120 kg or more

    300 mg IV every 12 hours via intravenous infusion over 6 hours for up to 14 days. Switch patients to the capsules to complete the 14-day treatment course as soon as oral therapy can be tolerated. Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353]

    Children and Adolescents weighing 35 to 119 kg

    200 mg IV every 12 hours via intravenous infusion over 6 hours for up to 14 days. Switch patients to the capsules to complete the 14-day treatment course as soon as oral therapy can be tolerated. Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353]

    Children and Adolescents weighing 13 to 34 kg

    6 mg/kg/dose IV every 12 hours via intravenous infusion over 6 hours for up to 14 days. Switch patients to the capsules to complete the 14-day treatment course as soon as oral therapy can be tolerated. Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353]

    Infants and Children weighing 3 to 12 kg

    6 mg/kg/dose IV every 12 hours via intravenous infusion over 6 hours for 14 days.[63353]

    Neonates weighing 3 kg or more

    6 mg/kg/dose IV every 12 hours via intravenous infusion over 6 hours for 14 days.[63353]

    For the treatment of monkeypox virus (mpox) infection†

    NOTE: There is no FDA-approved treatment for monkeypox virus (mpox) infections; however, the CDC holds an Expanded Access Investigational New Drug Protocol (EA-IND) that allows for tecovirimat to be used to treat non-variola orthopoxviruses (including monkeypox virus) during an outbreak. State and territorial health authorities can contact the CDC Emergency Operations Center at 770-488-7100 for information regarding the protocol.[67654] [68061]

    NOTE: Many cases of monkeypox virus (mpox) infections are mild and self-limiting in the absence of specific therapy; however, the prognosis depends on multiple factors such as previous vaccination status, initial health status, concurrent illnesses, and comorbidities. Persons for whom treatment may be considered (after consultation with the CDC) include: [67654] [67802] [68061]

    • Persons with severe disease or other complications
    • Involvement of anatomic areas which might result in serious sequelae that include scarring or strictures
    • Persons who may be at high risk for disease:
      • Persons with severe immunocompromise
      • Persons with a condition affecting skin integrity
      • Pediatric patients younger than 1 year of age
      • Pregnant or breast-feeding persons

    Oral dosage

    Adults weighing 120 kg or more

    600 mg PO every 8 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [68061] For people with HIV or severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Adults weighing 40 to 119 kg

    600 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [68061] For people with HIV or severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Adolescents weighing 120 kg or more

    600 mg PO every 8 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with HIV or severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Children and Adolescents weighing 40 to 119 kg

    600 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with HIV or severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Children and Adolescents weighing 25 to 39 kg

    400 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with HIV or severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Children weighing 13 to 24 kg

    200 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment.[70312]

    Infants and Children weighing 6 to 12 kg

    100 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment.[70312]

    Infants and Children weighing 3 to 5 kg

    50 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment.[70312]

    Infants weighing less than 3 kg

    33.3 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment.[70312]

    Neonates weighing 3 to 5 kg

    50 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment.[70312]

    Neonates weighing less than 3 kg

    33.3 mg PO every 12 hours for 14 days; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] For people with severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment.[70312]

    Intravenous dosage

    Adults weighing 120 kg or more

    300 mg IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with HIV or severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Adults weighing 35 to 119 kg

    200 mg IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with HIV or severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Adolescents weighing 120 kg or more

    300 mg IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with HIV or severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Children and Adolescents weighing 35 to 119 kg

    200 mg IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with HIV or severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Children and Adolescents weighing 13 to 34 kg

    6 mg/kg/dose IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with HIV or severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [70312]

    Infants and Children weighing less than 12 kg

    6 mg/kg/dose IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[70312]

    Neonates weighing less than 6 kg

    6 mg/kg/dose IV every 12 hours for 14 days. Switch patients to the oral formulation to complete the treatment course as soon as oral therapy can be tolerated. Based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events.[67654] [67802] [68061] Give the first oral dose at the time of and in place of the next scheduled intravenous dose. In patients receiving oral treatment who subsequently require intravenous therapy, give the first intravenous infusion at the time of and in place of the next scheduled oral dose.[63353] [67654] For people with severe immunocompromise and severe disease, guidelines recommend early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[70312]

    For post-exposure monkeypox virus (mpox) prophylaxis† after high-risk exposure

    Oral dosage

    Adults weighing 120 kg or more

    600 mg PO every 8 hours for 14 days can be considered on a case-by-case basis in consultation with an infectious disease expert in persons with clinical conditions that necessitate an alternative or complementary option to PEP vaccination. There are no clinical data regarding the effectiveness of mpox post-exposure prophylaxis.[34362] [68061]

    Adults weighing 40 to 119 kg

    600 mg PO every 12 hours for 14 days can be considered on a case-by-case basis in consultation with an infectious disease expert in persons with clinical conditions that necessitate an alternative or complementary option to PEP vaccination. There are no clinical data regarding the effectiveness of mpox post-exposure prophylaxis.[34362] [68061]

    Adolescents weighing 120 kg or more

    600 mg PO every 8 hours for 14 days can be considered on a case-by-case basis in consultation with an infectious disease expert in persons with clinical conditions that necessitate an alternative or complementary option to PEP vaccination. There are no clinical data regarding the effectiveness of mpox post-exposure prophylaxis.[34362] [68061]

    Adolescents weighing 40 to 119 kg

    600 mg PO every 12 hours for 14 days can be considered on a case-by-case basis in consultation with an infectious disease expert in persons with clinical conditions that necessitate an alternative or complementary option to PEP vaccination. There are no clinical data regarding the effectiveness of mpox post-exposure prophylaxis.[34362] [68061]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      weight 120 kg or more: 1,800 mg/day PO; 600 mg/day IV.

      weight 40 to 119 kg: 1,200 mg/day PO; 400 mg/day IV.

      weight 35 to 39 kg: 800 mg/day PO; 400 mg/day IV.

    • Geriatric

      weight 120 kg or more: 1,800 mg/day PO; 600 mg/day IV.

      weight 40 to 119 kg: 1,200 mg/day PO; 400 mg/day IV.

      weight 35 to 39 kg: 800 mg/day PO; 400 mg/day IV.

    • Adolescents

      weight 120 kg or more: 1,800 mg/day PO; 600 mg/day IV.

      weight 40 to 119 kg: 1,200 mg/day PO; 400 mg/day IV.

      weight 35 to 39 kg: 800 mg/day PO; 400 mg/day IV.

    • Children

      weight 40 kg or more: 1,200 mg/day PO; 400 mg/day IV.

      weight 35 to 39 kg: 800 mg/day PO; 400 mg/day IV.

      weight 25 to 34 kg: 800 mg/day PO; 12 mg/kg/day IV.

      weight 13 to 24 kg: 400 mg/day PO; 12 mg/kg/day IV.

      weight 6 to 12 kg: 12 mg/kg/day IV; 200 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

      weight 3 to 5 kg: 12 mg/kg/day IV; 100 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

    • Infants

      weight 6 to 12 kg: 12 mg/kg/day IV; 200 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

      weight 3 to 5 kg: 12 mg/kg/day IV; 100 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

      weight less than 3 kg: 12 mg/kg/day IV is authorized for treatment of monkeypox virus (mpox) infection; 66.6 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

    • Neonates

      weight 6 to 12 kg: 12 mg/kg/day IV; 200 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

      weight 3 to 5 kg: 12 mg/kg/day IV; 100 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

      weight less than 3 kg: 12 mg/kg/day IV is authorized for treatment of monkeypox virus (mpox) infection; 66.6 mg PO/day is authorized for treatment of monkeypox virus (mpox) infection.[68061]

    Patients with Hepatic Impairment Dosing

    No dosage adjustments are needed for patients with mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C).

    Patients with Renal Impairment Dosing

    No dosage adjustments are required for any degree of renal impairment when using oral tecovirimat.

    CrCl 30 mL/minute or more: No dosage adjustment needed for IV tecovirimat.

    CrCl less than 30 mL/minute: Use of IV tecovirimat is contraindicated due to potential accumulation of the excipient hydroxypropyl-beta-cyclodextrin.

     

    Dosage Adjustments for Monkeypox Virus (mpox) Infections per EA-IND Protocol:

    CrCl 30 mL/minutes or more: No dosage adjustment needed for IV tecovirimat.

    CrCl less than 30 mL/minute: IV tecovirimat should not be administered. However, exceptions may be considered ONLY if drug absorption via enteral administration is not anticipated to be dependable or feasible. The treating clinician should evaluate the clinical need for IV tecovirimat based on an individual patient risk-benefit assessment and in consultation with the CDC. In these situations, use with caution and close continuous monitoring of renal function.[68061]

    † Off-label indication
    Revision Date: 12/05/2024, 02:07:00 AM

    References

    34362 - Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the National Institutes of Health, the HIV Medicine Association, and the Infectious Diseases Society of America. Accessed October 31, 2024. Available at https://clinicalinfo.hiv.gov/en/guidelines/63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.67654 - Centers for Disease Control and Prevention (CDC). Interim clinical guidance for the treatment of Mpox. July 10, 2023. Retrieved February 7, 2024. Available on the World Wide Web at https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html#anchor_1655488353796.67802 - Centers for Disease Control and Prevention (CDC). Clinical considerations for monkeypox in children and adolescents. September 1, 2023 Retrieved February 7, 2023. Available on the World Wide Web at https://www.cdc.gov/poxvirus/monkeypox/clinicians/pediatric.html?ACSTrackingID=USCDC_1052-DM86528&ACSTrackingLabel=COCA%20Now%3A%20Clinical%20Considerations%20for%20Monkeypox%20in%20Children%20and%20Adolescents&deliveryName=USCDC_1052-DM86528#anchor_1658856112226.68061 - Centers for Disease Control and Prevention (CDC). Expanded Access IND Protocol: Use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children version 6.3. Updated December 19, 2023. Retrieved February 7, 2024. Available at on the World Wide Web at: https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.70312 - Rao AK, Schrodt CA, Minhaj FS, et al. Interim clinical treatment considerations for severe manifestations of Mpox - United States, February 2023. MMWR 2023;72:232-43.

    How Supplied

    Tecovirimat Oral capsule

    TPOXX 200mg Capsule (50072-0200) (SIGA Technologies, Inc.) null

    Tecovirimat Solution for injection

    TPOXX 200mg/20mL Solution for Injection (50072-0010) (SIGA Technologies, Inc.) null

    Description/Classification

    Description

    Tecovirimat is an antiviral drug approved for treatment of human smallpox disease caused by the variola virus in patients weighing at least 3 kg. Tecovirimat targets a virus specific protein (i.e., p37 envelope wrapping protein), and thus, possesses selective antiviral activity against orthopoxviruses, including variola virus. By blocking the actions of viral p37 protein, tecovirimat inhibits production of extracellular virions, thereby preventing the spread of infection until the body's immune system can clear the virus. Efficacy data has been extrapolated from animal studies, as adequate and well-controlled studies in humans was not feasible.[63353] Tecovirimat is also recommended by the CDC for off-labeled treatment of monkeypox virus (mpox) infections in all eligible patient populations (e.g., children and all adults including pregnant and nursing individuals). For the treatment of monkeypox virus (mpox) infections, tecovirimat has been made available through an Expanded Access Investigational New Drug (EA-IND) protocol and a randomized controlled clinical trial called STOMP (Study of Tecovirimat for Human Monkeypox Virus). To maximize access to tecovirimat, health care providers are encouraged to inform patients about STOMP; use of tecovirimat under the EA-IND protocol should be for patients whose voluntary participation in STOMP is not feasible (e.g., a clinical trial site is not geographically accessible).[67654][68061]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Variola Virus (Smallpox) Antivirals
    Revision Date: 12/05/2024, 02:07:00 AM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.67654 - Centers for Disease Control and Prevention (CDC). Interim clinical guidance for the treatment of Mpox. July 10, 2023. Retrieved February 7, 2024. Available on the World Wide Web at https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html#anchor_1655488353796.68061 - Centers for Disease Control and Prevention (CDC). Expanded Access IND Protocol: Use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children version 6.3. Updated December 19, 2023. Retrieved February 7, 2024. Available at on the World Wide Web at: https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

     

    Monkeypox Virus (mpox) Infections per the Expanded Access Investigational New Drug (EA-IND) Protocol:[68061]

    NOTE: Tecovirimat is not FDA-approved to treat monkeypox virus (mpox) infections; however, the drug is available for the treatment of mpox through an EA-IND. Per the EA-IND, treating clinicians or their designees are responsible for patient assessment, monitoring, and reporting to the CDC. The following are required to be completed, retained, and/or returned to the CDC:

    • Informed consent must be obtained prior to starting treatment.
    • Register online (required for new providers only).
      • All providers must register as a participating provider by completing the Tecovirimat (TPOXX) IND Online Registry for Providers/Facilities (the registry includes an online Form FDA 1572).
      • Providers should register prior to providing tecovirimat treatment to the extent feasible and NO LATER than within 7 calendar days of first prescribing or administering tecovirimat.
      • NOTE: Any provider who has submitted Form FDA 1572, a Patient Intake form, or Clinical Outcomes form to the CDC prior to the online registry being available is considered a participating provider and does not need to register.
    • Complete an electronic Patient Intake form and submit to CDC for each patient treated with tecovirimat.
      • Submit as soon as feasible and no later than within 7 calendar days of tecovirimat initiation.
      • For patients who are being re-initiated on tecovirimat after completing a prior tecovirimat treatment (e.g., re-infection), a new Patient Intake form should be completed and returned to the CDC.
    • Adverse event reporting.
      • Report serious or life-threatening adverse events and medication errors associated with tecovirimat to the CDC within 72 hours of awareness, or sooner if possible.
    • Clinical Outcome form (optional)
      • When feasible, conduct patient follow-up within 3 to 14 calendar days after completion of tecovirimat, and return the completed Clinical Outcomes form electronically to the CDC within 7 calendar days of last patient follow-up.

    Route-Specific Administration

    Oral Administration

    Oral Solid Formulations

    • Preferred route of administration for patients weighing 13 kg or more.
    • Administer within 30 minutes after a moderate or high fat full meal.
    • For patients weighing 13 kg or more who are unable to swallow capsules:
      • Carefully open the required number of capsules for the dose to be administered.
      • Mix the contents of the capsule(s) in 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., apple sauce, yogurt). NOTE: The EA-IND protocol for the treatment of monkeypox virus (mpox) infections also allows for 30 mL of water to be used for preparing the oral mixture.
      • Administer the entire mixture within 30 minutes of its preparation.[63353][68061]
    • Under the EA-IND protocol for treatment of monkeypox virus (mpox) infections, patients weighing less than 13 kg may receive oral tecovirimat as follows:
      • Carefully open one 200 mg capsule and empty the entire contents into a dosing cup of suitable size.
      • Add 20 mL of water to the dosing cup and thoroughly mix by swirling the cup for at least 30 seconds to ensure the mixture is uniform.
      • Immediately after mixing, use an oral syringe to draw up and administer the following:
        • For patients weighing 6 to 12 kg receiving 100 mg dose: Administer 10 mL of the water and drug mixture, either directly or mixed in a small amount of soft food (e.g., apple sauce, yogurt). Discard the remaining mixture.
        • For patients weighing 3 to 5 kg receiving 50 mg dose: Administer 5 mL of the water and drug mixture. Discard the remaining mixture.
        • For patients weighing less than 3 kg receiving 33.3 mg dose: Administer 3.3 mL of the water and drug mixture. Discard the remaining mixture.
      • Dosing should be followed by a feeding.
      • Oral doses less than 200 mg require careful preparation by a caregiver (e.g., opening a capsule, equally mixing the contents in water, administering a portion of the drug-water preparation) and has the inherent potential for inaccurate dosing. The potential for inaccurate dosing may be higher in the outpatient setting.[68061]
    • Under the EA-IND protocol for treatment of monkeypox virus (mpox) infections, tecovirimat may be administered to inpatients via a nasogastric tube (NGT) per hospital protocol based on clinical judgement on an individual basis if IV tecovirimat is unavailable or IV infusion is not feasible. Although NGT administration is allowed to provide an alternative option, compatibility studies on enteral administration of tecovirimat have not been conducted.[68061]

    Injectable Administration

    • Intravenous administration may be used for patients who are unable to take the oral capsules or drug-water/drug-food preparation. If intravenous therapy is necessary, conversion to the capsules is recommended as soon as oral treatment can be tolerated.
    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Tecovirimat is a clear, colorless to pale yellow solution.[63353]

    Intravenous Administration

    Preparation

    • Use aseptic technique when preparing the infusion. Tecovirimat is available in single-dose vials; do not re-use the vial once it has been punctured.
    • Based on the patients weight, withdraw the following volume of tecovirimat injection from the vial(s) and dilute with 2 equal parts of either 0.9% Sodium Chloride Injection or 5% Dextrose injection as follows:
      • less than 3 kg [for monkeypox virus (mpox) infection only per EA-IND]: 0.6 mL/kg of tecovirimat diluted with 1.2 mL/kg of diluent [68061]
      • 3 to 34 kg: 0.6 mL/kg of tecovirimat diluted with 1.2 mL/kg of diluent
      • 35 to 119 kg: 20 mL of tecovirimat diluted with 40 mL of diluent
      • 120 kg or more: 30 mL tecovirimat diluted with 60 mL of diluent
    • Use a syringe of suitable size to accommodate the required volume. Depending on the size of syringe available and the syringe pump system, 2 separate syringes may be needed for each administration. DO NOT use empty or prefilled infusion bags for product preparation or administration. Due to the high content of the inactive ingredient hydroxypropyl-beta-cyclodextrin in IV tecovirimat, there is an elevated risk for potential leaching of impurities into the solution when equipment other than syringes/syringe pumps are used.[68061]
    • Storage: The diluted injection may be stored at room temperature 15 to 25 degrees C (59 to 77 degrees F) for up to 4 hours or under refrigeration 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours.

     

    Intermittent IV Infusion

    • Gently swirl the syringe of in-use solution prior to inserting into the syringe pump.
    • Administer intravenously over 6 hours using the infusion syringe pump. DO NOT administer via intravenous bolus injection.[63353]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Tecovirimat

    pH Range
    2 to 6.5 (less than 0.1 mg/mL)
    ReferencesTPOXX (tecovirimat) injection package insert. Corvallis, OR. SIGA Technologies, Inc. 2024; Jun
      Revision Date: 12/05/2024, 02:07:00 AMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.68061 - Centers for Disease Control and Prevention (CDC). Expanded Access IND Protocol: Use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children version 6.3. Updated December 19, 2023. Retrieved February 7, 2024. Available at on the World Wide Web at: https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.

      Adverse Reactions

      Mild

      • abdominal pain
      • arthralgia
      • back pain
      • chills
      • diarrhea
      • dysgeusia
      • dyspepsia
      • eructation
      • fever
      • headache
      • irritability
      • malaise
      • myalgia
      • nausea
      • paresthesias
      • pruritus
      • purpura
      • rash
      • vomiting
      • xerostomia

      Moderate

      • depression
      • dysphoria
      • edema
      • EEG changes
      • erythema
      • infusion-related reactions
      • migraine
      • photophobia
      • sinus tachycardia

      The most frequently reported adverse effect in health subjects receiving at least 1 dose of oral tecovirimat during clinical trials was headache (12%). Headache was also reported by 15% of patients receiving the tecovirimat intravenous infusion. Other clinically significant adverse reactions reported in less than 2% of subjects treated with oral tecovirimat included fever, chills, malaise, paresthesias, increased thirst, dysgeusia, severe headaches or migraine, decreased concentration and disturbance in attention, dysphoria, irritability, panic attack, and depression.[63353]

      Nausea (5%), vomiting (2%), and abdominal pain (2%) were noted by health subjects receiving at least 1 dose of oral tecovirimat during clinical trials. Other gastrointestinal adverse reactions associated with use of the oral drug and reported by less than 2% of subjects included moderate diarrhea, dyspepsia, xerostomia and chapped lips, oral paresthesia, eructation, and oropharyngeal pain. Diarrhea was also reported by less than 4% of patients receiving injectable tecovirimat.[63353]

      Dermatologic adverse events experienced by less than 2% of health subjects receiving at least 1 dose of oral tecovirimat during clinical trials included palpable purpura, facial edema and erythema, pruritus, and rash (including pruritic rash). Generalized pruritus was also reported by less than 4% of patients receiving tecovirimat intravenous infusion.[63353]

      Musculoskeletal adverse events experienced by less than 2% of health subjects receiving at least 1 dose of oral tecovirimat during clinical trials included arthralgia, osteoarthritis, and generalized pain. During the injectable tecovirimat clinical trial, less than 4% of drug recipients reported arthritis, back pain, muscle tightness, and myalgia.[63353]

      Laboratory abnormalities noted in less than 2% of health subjects receiving at least 1 dose of oral tecovirimat during clinical trials included decreased hematocrit and hemoglobin, abnormal electroencephalogram (EEG changes), and increased heart rate (sinus tachycardia).[63353]

      Infusion-related reactions were among the most frequently reported adverse events following treatment with injectable tecovirimat during the clinical trial. Specifically, patients reported infusion site pain (73%), swelling (39%), erythema (23%), extravasation (19%), edema (less than 4%), and discomfort (less than 4%). In 3 patients (12%), treatment was discontinued due to extravasation (mild and moderate), swelling (mild), and pain (mild).[63353]

      Photophobia was reported by less than 4% of patients receiving injectable tecovirimat during the clinical trial.[63353]

      Revision Date: 12/05/2024, 02:07:00 AM

      References

      63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • renal failure
      • breast-feeding
      • chemotherapy
      • children
      • corticosteroid therapy
      • immunosuppression
      • infants
      • infertility
      • neonates
      • pregnancy
      • radiation therapy
      • renal impairment

      Based on data from animal models, the effectiveness of tecovirimat may be reduced in persons with immunosuppression. Potentially immunocompromised persons include those receiving chemotherapy (antimetabolites, alkylating agents, or cytotoxic drugs), radiation therapy, and those on immunosuppressive therapy such as high-dose systemic corticosteroid therapy.[63353]

      Guidelines recommend tecovirimat as first-line treatment of mpox in people who are pregnant or recently pregnant.[34362] When considering the use of tecovirimat in a pregnant patient, take into account the serious, and potentially deadly, risks associated with the untreated infection. The potential benefits of treatment may outweigh the unknown pregnancy risks associated with tecovirimat.[68061] There are no available data on the use of tecovirimat during human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriages, or other maternal or fetal adverse outcomes. In animal studies, no embryofetal toxicities were observed following administration of doses up to 23-times and 0.4-times human exposures at the recommended human dose (RHD) in pregnant mice and rabbits, respectively. In addition, no toxicities were observed in a pre-/post-natal development study involving pregnant mice receiving doses approximately 24-times higher than human exposures at the RHD.[63353]

      Due to the potential for virus transmission through direct contact with the breast-fed infant, breast-feeding is not recommended in patients with variola virus (smallpox) or monkeypox virus (mpox) infection. A lactating individual may consider pumping and discarding breast milk during treatment. There are no data on the presence of tecovirimat in human milk, the effects on the breast-fed infant, or the effects on milk production.[63353] [68061]

      Injectable tecovirimat is formulated with hydroxypropyl-beta-cyclodextrin, which is eliminated in the urine. In patients with renal impairment, the clearance of this excipient is reduced, resulting in higher exposures to hydroxypropyl-beta-cyclodextrin and potential nephrotoxicity. Use of intravenous tecovirimat is contraindicated for treatment of variola virus (smallpox) infections in patients with renal failure or severe renal impairment (i.e., CrCl less than 30 mL/minute). In patients with mild to moderate renal impairment (i.e., CrCl 30 to 89 mL/minute), the intravenous infusion should be administered with caution and close renal function monitoring. If renal toxicity is suspected, consideration should be given to administering tecovirimat orally or using an alternative medication.[63353] For treatment of monkeypox virus (mpox) infections in patients who are renally impaired, the oral tecovirimat option should be exhausted (including enteral administration via NG tube) before considering IV tecovirimat. Similar to smallpox, the IV formulation of tecovirimat should not be administered to patient with CrCl less than 30 mL/minute; however, exceptions may be considered ONLY if drug absorption via enteral administration is not anticipated to be dependable or feasible. The treating clinician should evaluate the clinical need for IV tecovirimat based on an individual patient risk-benefit assessment and in consultation with the CDC. In these situations, use with caution and close continuous monitoring of renal function.[68061] Neonates, infants, and children younger than 2 years may be at increased risk given that renal tubular function matures over the first few years of life. Renal immaturity in young pediatric patients may result in higher exposures to hydroxypropyl-beta-cyclodextrin. Monitor renal function closely in this population.[63353]

      Decreased fertility due to testicular toxicity has been observed in male mice; however, there are no data available associating tecovirimat with human infertility.[63353]

      Revision Date: 12/05/2024, 02:07:00 AM

      References

      34362 - Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the National Institutes of Health, the HIV Medicine Association, and the Infectious Diseases Society of America. Accessed October 31, 2024. Available at https://clinicalinfo.hiv.gov/en/guidelines/63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.68061 - Centers for Disease Control and Prevention (CDC). Expanded Access IND Protocol: Use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children version 6.3. Updated December 19, 2023. Retrieved February 7, 2024. Available at on the World Wide Web at: https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.

      Mechanism of Action

      Tecovirimat is an antiviral medication with selective and specific activity against orthopoxviruses, such as the variola virus (smallpox). Once taken up by an infected cell, the drug targets viral p37 protein (an orthopoxvirus specific protein) and inhibits its interaction with intracellular transport components required for production of enveloped virions (i.e., Rab9 GTPase and TIP47). By blocking this interaction, tecovirimat prevents release of new viruses from the infected cell, thereby halting the spread of infection until the body's immune system can clear the virus. Note, tecovirimat is not active against intracellular mature virus.[63353][63355]

       

      Data from cell culture assays show the effective concentrations of tecovirimat resulting in a 50% reduction in virus-induced cytopathic effect (EC50) to be 0.016 to 0.067 microM for variola virus (smallpox), 0.014 to 0.039 microM for monkeypox virus (mpox), 0.015 microM for rabbitpox, and 0.009 microM for vaccinia viruses. There are no known examples of naturally occurring tecovirimat resistant orthopoxviruses; however, tecovirimat treatment-emergent resistance may develop under drug selection as the drug has a relatively low resistance barrier. Certain amino acid substitutions in the viral p37 protein can confer large reductions in tecovirimat antiviral activity.[63353]

       

      Cross-resistance between tecovirimat and brincidofovir is not expected based on their distinct mechanisms of action. Where tested, orthopoxvirus isolates resistant to cidofovir (the active metabolite of brincidofovir) have not been resistant to tecovirimat. Isolates resistant to tecovirimat retain their sensitivity to cidofovir.[63353]

      Revision Date: 12/05/2024, 02:07:00 AM

      References

      63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.63355 - SIGA Technologies, Inc. Tecovirimat briefing document Antimicrobial Drugs Advisory Committee meeting. Available on the World Wide Web at: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM605890.pdf. Accessed July 13, 2018.

      Pharmacokinetics

      Tecovirimat is administered orally and via intravenous infusion. Once in systemic circulation, the drug is 77% to 82% bound to human plasma proteins with a blood-to-plasma ratio of 0.62 to 0.9 (i.e., 10% to 40% lower in whole blood than in plasma). The volume of distribution is 383 L for the intravenous infusion and 1,030 L for the oral formulation, indicating the drug is extensively distributed throughout the body. In vitro data suggest the parent drug undergoes hydrolysis and glucuronide conjugation by uridine diphospho-glucuronosyltransferase (UGT) 1A1 and 1A4 enzymes, but is not metabolized by any major CYP enzyme. Ten metabolites have been identified, however none are pharmacologically active. The 3 major metabolites are M4, M5, and TFMBA; which constitutes approximately 10.4%, 5.8%, and 70.4% of the total exposure, respectively. The mean terminal half-life is approximately 20 hours, with 73% of the dose being excreted in the urine (predominately as metabolites) and 23% excreted in feces (predominately as tecovirimat).[63353][63355]

       

      Affected cytochrome P450 isoenzymes and transporters: CYP2C8, CYP2C19, CYP3A4, BCRP

      Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19, and a weak inducer of CYP3A4. In vitro data suggest tecovirimat may inhibit the drug transporter breast cancer resistance protein (BCRP). According to the manufacturer, the inhibitory and inducing effects of tecovirimat are not expected to be clinically relevant for most substrates.[63353]

      Route-Specific Pharmacokinetics

      Oral Route

      Following oral administration, tecovirimat is rapidly absorbed with maximum plasma concentrations (Cmax) achieved within 4 to 6 hours (Tmax). When compared to a fasting state, administering the drug with food increases absorption by 39% and the Tmax by approximately 2 hours. Drug exposures (AUC) increase linearly as doses are increased from 100 to 600 mg. Repeated dosing results in drug accumulation (accumulation factor of 1.6), with steady-state exposure being reached by day 6. In adults weighing less than 120 kg, the mean steady state values of AUC, Cmax, and Ctau/trough were 29,816 hour x ng/mL, 2,159 ng/mL, and 845 ng/mL, respectively.[63353][63355]

      Intravenous Route

      Following infusion of the recommended intravenous dose of 200 mg every 12 hours, the mean steady-state values of tecovirimat exposure (AUC), maximum plasma concentration (Cmax), and trough (Cmin) are 39,405 ng x hour/mL, 2,630 ng/mL, and 747 ng/mL, respectively. The median time to Cmax is 6 hours (range: 6 to 6.5 hours).[63353]

      Special Populations

      Hepatic Impairment

      No clinically significant differences in the pharmacokinetics of tecovirimat were observed based on hepatic impairment (Child Pugh A, B, or C).[63353]

      Renal Impairment

      No clinically significant differences in the pharmacokinetics of tecovirimat were observed based on renal impairment (based on estimate GFR). Hydroxypropyl-beta-cyclodextrin, an excipient of injectable tecovirimat, is eliminated through glomerular filtration which may be reduced in patients with renal impairment and pediatric patients with renal immaturity.[63353]

      Geriatric

      No clinically significant differences in the pharmacokinetics of tecovirimat were observed based on age.[63353]

      Gender Differences

      No clinically significant differences in the pharmacokinetics of tecovirimat were observed based on sex.[63353]

      Ethnic Differences

      No clinically significant differences in the pharmacokinetics of tecovirimat were observed based on ethnicity.[63353]

      Obesity

      At the 600 mg twice daily dose, tecovirimat exposure was reduced in adult patients weighing more than 120 kg compared to exposures in adult patients weighing less than 120 kg. Specifically, in 34 adult patients weighing more than 120 kg who received 600 mg twice daily, the observed mean steady state values of AUC, Cmax, and Ctrough were 19,500 hour x ng/mL, 1,300 ng/mL, and 585 ng/mL, respectively.[63353]

      Revision Date: 12/05/2024, 02:07:00 AM

      References

      63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.63355 - SIGA Technologies, Inc. Tecovirimat briefing document Antimicrobial Drugs Advisory Committee meeting. Available on the World Wide Web at: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM605890.pdf. Accessed July 13, 2018.

      Pregnancy/Breast-feeding

      pregnancy

      Guidelines recommend tecovirimat as first-line treatment of mpox in people who are pregnant or recently pregnant.[34362] When considering the use of tecovirimat in a pregnant patient, take into account the serious, and potentially deadly, risks associated with the untreated infection. The potential benefits of treatment may outweigh the unknown pregnancy risks associated with tecovirimat.[68061] There are no available data on the use of tecovirimat during human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriages, or other maternal or fetal adverse outcomes. In animal studies, no embryofetal toxicities were observed following administration of doses up to 23-times and 0.4-times human exposures at the recommended human dose (RHD) in pregnant mice and rabbits, respectively. In addition, no toxicities were observed in a pre-/post-natal development study involving pregnant mice receiving doses approximately 24-times higher than human exposures at the RHD.[63353]

      breast-feeding

      Due to the potential for virus transmission through direct contact with the breast-fed infant, breast-feeding is not recommended in patients with variola virus (smallpox) or monkeypox virus (mpox) infection. A lactating individual may consider pumping and discarding breast milk during treatment. There are no data on the presence of tecovirimat in human milk, the effects on the breast-fed infant, or the effects on milk production.[63353] [68061]

      Revision Date: 12/05/2024, 02:07:00 AM

      References

      34362 - Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the National Institutes of Health, the HIV Medicine Association, and the Infectious Diseases Society of America. Accessed October 31, 2024. Available at https://clinicalinfo.hiv.gov/en/guidelines/63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2024 Jun.68061 - Centers for Disease Control and Prevention (CDC). Expanded Access IND Protocol: Use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children version 6.3. Updated December 19, 2023. Retrieved February 7, 2024. Available at on the World Wide Web at: https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.

      Interactions

      Level 2 (Major)

      • Atogepant
      • Cariprazine
      • Lumateperone
      • Mavacamten
      • Nisoldipine
      • Ubrogepant

      Level 3 (Moderate)

      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Oxycodone
      • Aspirin, ASA; Oxycodone
      • Belzutifan
      • Calcium Acetate
      • Celecoxib; Tramadol
      • Fentanyl
      • Ibuprofen; Oxycodone
      • Iron Sucrose, Sucroferric Oxyhydroxide
      • Lanthanum Carbonate
      • Lopinavir; Ritonavir
      • Metformin; Repaglinide
      • Midazolam
      • Nanoparticle Albumin-Bound Paclitaxel
      • Nanoparticle Albumin-Bound Sirolimus
      • Nirmatrelvir; Ritonavir
      • Oxycodone
      • Repaglinide
      • Ritonavir
      • Rosiglitazone
      • Sevelamer
      • Sirolimus
      • Smallpox and Mpox (Vaccinia) Vaccine, Live
      • Sufentanil
      • Tramadol
      • Tramadol; Acetaminophen
      • Warfarin

      Level 4 (Minor)

      • Doravirine
      • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
      Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with tecovirimat can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If tecovirimat is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Tecovirimat is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. [30282] [63353] Acetaminophen; oxyCODONE: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of oxycodone as needed. If tecovirimat is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [39926] [63353] Aspirin, ASA; oxyCODONE: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of oxycodone as needed. If tecovirimat is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [39926] [63353] Atogepant: (Major) Avoid use of atogepant and tecovirimat when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with tecovirimat. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration. [63353] [67011] Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of tecovirimat with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and tecovirimat is a CYP2C19 inhibitor. [63353] [66875] Calcium Acetate: (Moderate) Monitor patients for tecovirimat-related adverse events when tecovirimat is administered with phosphate binders, such as calcium acetate. Concomitant use has been observed to increase tecovirimat overall exposure by 1.16-fold. [63353] Cariprazine: (Major) Avoid concomitant use of cariprazine and tecovirimat. Concurrent use may decrease cariprazine exposure which may reduce its efficacy. Cariprazine is a CYP3A substrate and tecovirimat is a CYP3A inducer. [60164] [63353] Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of tramadol as needed. If tecovirimat is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [32475] [40255] [51440] [63353] Doravirine: (Minor) Concurrent administration of doravirine and tecovirimat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; tecovirimat is a weak CYP3A4 inducer. [63353] [63484] Doravirine; lamiVUDine; Tenofovir disoproxil fumarate: (Minor) Concurrent administration of doravirine and tecovirimat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; tecovirimat is a weak CYP3A4 inducer. [63353] [63484] fentaNYL: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of tecovirimat is necessary. If tecovirimat is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like tecovirimat with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression. [29623] [29763] [32731] [40943] [63353] Ibuprofen; oxyCODONE: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of oxycodone as needed. If tecovirimat is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [39926] [63353] Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Monitor patients for tecovirimat-related adverse events when tecovirimat is administered with phosphate binders, such as oral iron sucrose, sucroferric oxyhydroxide. Concomitant use has been observed to increase tecovirimat overall exposure by 1.2-fold. [63353] Lanthanum Carbonate: (Moderate) Monitor patients for tecovirimat-related adverse events when tecovirimat is administered with phosphate binders, such as lanthanum carbonate. Concomitant use has been observed to increase tecovirimat overall exposure by 1.22-fold. [63353] Lopinavir; Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with tecovirimat. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. [63353] [67203] Lumateperone: (Major) Avoid coadministration of lumateperone and tecovirimat as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; tecovirimat is a weak CYP3A4 inducer. [63353] [64885] Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting tecovirimat therapy. Avoid initiation of tecovirimat in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable tecovirimat therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and tecovirimat is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%. [63353] [67543] metFORMIN; Repaglinide: (Moderate) Closely monitor patients receiving repaglinide with tecovirimat for changes blood glucose concentrations. In a drug interaction study, cases of mild to moderate hypoglycemia were observed in repaglinide recipients who were administered tecovirimat. In all subjects, symptoms resolved after ingestion of food or oral glucose. Repaglinide is a sensitive CYP2C8 substrate; tecovirimat is a weak inhibitor of this enzyme. [63353] Midazolam: (Moderate) Monitor for reduced midazolam efficacy during concurrent use of tecovirimat. In a drug interaction study, the maximum plasma concentration (Cmax) and exposure (AUC) of midazolam were reduced in patients receiving concurrent tecovirimat therapy. Midazolam is a sensitive CYP3A4 substrate; tecovirimat is a weak inducer of this enzyme. [63353] Nanoparticle Albumin-Bound PACLitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel or an increase in paclitaxel-related adverse reactions if coadministration with tecovirimat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Tecovirimat is a weak CYP3A4 inducer and a weak CYP2C8 inhibitor. [30742] [63353] Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with tecovirimat. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. [63353] [67136] Nirmatrelvir; Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with tecovirimat. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. [63353] [67203] Nisoldipine: (Major) Avoid coadministration of nisoldipine with tecovirimat due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels. [29088] [63353] oxyCODONE: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of oxycodone as needed. If tecovirimat is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [39926] [63353] Repaglinide: (Moderate) Closely monitor patients receiving repaglinide with tecovirimat for changes blood glucose concentrations. In a drug interaction study, cases of mild to moderate hypoglycemia were observed in repaglinide recipients who were administered tecovirimat. In all subjects, symptoms resolved after ingestion of food or oral glucose. Repaglinide is a sensitive CYP2C8 substrate; tecovirimat is a weak inhibitor of this enzyme. [63353] Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with tecovirimat. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. [63353] [67203] Rosiglitazone: (Moderate) Monitor for an increase in rosiglitazone-related adverse effects during concomitant use with tecovirimat; adjust the dose of rosiglitazone based on clinical response. Coadministration may increase the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and tecovirimat is a weak CYP2C8 inhibitor. [28172] [63353] Sevelamer: (Moderate) Monitor patients for tecovirimat-related adverse events when tecovirimat is administered with phosphate binders, such as sevelamer. Concomitant use has been observed to increase tecovirimat overall exposure by 1.26-fold. [63353] Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of tecovirimat. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. [28610] [63353] Smallpox and Mpox (Vaccinia) Vaccine, Live: (Moderate) Data from animal studies suggest tecovirimat may decrease the immune response to the smallpox vaccine (live). The clinical impact of this interaction on vaccine efficacy is unknown. [63353] SUFentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if tecovirimat must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of sufentanil injection as needed. If tecovirimat is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [30966] [63353] [63731] traMADol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of tramadol as needed. If tecovirimat is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [32475] [40255] [51440] [63353] Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of tramadol as needed. If tecovirimat is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [32475] [40255] [51440] [63353] Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with tecovirimat as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; tecovirimat is a weak CYP3A4 inducer. [63353] [64874] Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with tecovirimat is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Tecovirimat is a weak CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance. [28549] [63353]
      Revision Date: 12/05/2024, 02:07:00 AM

      References

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      Monitoring Parameters

      • serum creatinine

      US Drug Names

      • TPOXX
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