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Jul.28.2022

Tecovirimat

Indications/Dosage

Labeled

  • variola virus (smallpox) infection

Off-Label

  • monkeypox virus infection
† 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 infection†

NOTE: There is no FDA-approved treatment for monkeypox virus 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) 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]

NOTE: Many cases of monkeypox virus 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:

  • Persons with severe disease (e.g., hemorrhagic disease, confluent lesions, sepsis, encephalitis, other conditions requiring hospitalization) or other complications (e.g., pneumonia, ocular lesions, cellulitis, or abscess)
  • Persons who may be at high risk for disease:
    • Immunocompromised persons (e.g., HIV/AIDS infection, leukemia, lymphoma, generalized malignancy, solid organ transplantation, autoimmune disease with immunodeficiency as a clinical component, hematopoietic stem cell transplant recipient within 24 months post-transplant or more than 24 months but with graft-versus-host disease or disease relapse, or treatment with alkylating agent, antimetabolites, radiation, tumor necrosis factor inhibitors, or high-dose corticosteroids)
    • Patients with history or presence of atopic dermatitis, or other active exfoliative skin conditions (e.g., eczema, burns, impetigo, varicella zoster virus infection, herpes simplex virus infection, severe acne, severe diaper dermatitis with extensive areas of denuded skin, psoriasis, or Darier disease [keratosis follicularis])
    • Patients with aberrant infections, such as those involving the eyes, face, or genitals
    • Pediatric patients younger than 8 years of age
    • Pregnant or breast-feeding patients [67654] [67802]

Oral dosage

Adults weighing 120 kg or more

600 mg PO every 8 hours for 14 days is the FDA-approved dose. An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. Administer within 30 minutes after a moderate to high fat meal.[63353] [67654]

Adults weighing 40 to 119 kg

600 mg PO every 12 hours for 14 days is the FDA-approved dose. An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. Administer within 30 minutes after a moderate to high fat meal.[63353] [67654]

Adolescents weighing 120 kg or more

600 mg PO every 8 hours for 14 days is the FDA-approved dose. An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. Administer within 30 minutes after a moderate to high fat meal.[63353] [67654]

Children and Adolescents weighing 40 to 119 kg

600 mg PO every 12 hours for 14 days is the FDA-approved dose. An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. Administer within 30 minutes after a moderate to high fat meal.[63353] [67654]

Children and Adolescents weighing 25 to 39 kg

400 mg PO every 12 hours for 14 days is the FDA-approved dose. An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. Administer within 30 minutes after a moderate to high fat meal.[63353] [67654]

Children weighing 13 to 24 kg

200 mg PO every 12 hours for 14 days is the FDA-approved dose. An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. Administer within 30 minutes after a moderate to high fat meal.[63353] [67654]

Infants and Children weighing 3 to 12 kg

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. This protocol includes allowance for opening an oral capsule of tecovirimat and mixing its content with semi-solid food for patients weighing less than 13 kg. Contact the CDC at 770-488-7100 for information regarding dosing in this population.[67654]

Neonates weighing 3 kg or more

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. This protocol includes allowance for opening an oral capsule of tecovirimat and mixing its content with semi-solid food for patients weighing less than 13 kg. Contact the CDC at 770-488-7100 for information regarding dosing in this population.[67654]

Intravenous dosage

Adults weighing 120 kg or more

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose is 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] [67654]

Adults weighing 35 to 119 kg

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose is 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] [67654]

Adolescents weighing 120 kg or more

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose is 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] [67654]

Children and Adolescents weighing 35 to 119 kg

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose for another indication is 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] [67654]

Children and Adolescents weighing 13 to 34 kg

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose is 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] [67654]

Infants and Children weighing 3 to 12 kg

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose is 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] [67654]

Neonates weighing 3 kg or more

An EA-IND held by the CDC allows for tecovirimat to be used to treat monkeypox during an outbreak. The FDA-approved dose is 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] [67654]

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 3 to 12 kg: 12 mg/kg/day IV; safety and efficacy not established for oral capsules.

  • Infants

    weight 3 kg or more: 12 mg/kg/day IV; safety and efficacy not established for oral capsules.

    weight less than 3 kg: Safety and efficacy not established.

  • Neonates

    weight 3 kg or more: 12 mg/kg/day IV; safety and efficacy not established for oral capsules.

    weight less than 3 kg: Safety and efficacy not established.

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.

† Off-label indication
Revision Date: 07/28/2022, 01:59:57 PM

References

63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.67654 - Centers for Disease Control and Prevention (CDC). Interim Clinical Guidance for the Treatment of Monkeypox. July 28, 2022. Retrieved July 29, 2022. Available on the World Wide Web at https://www.cdc.gov/poxvirus/monkeypox/treatment.html.67802 - Centers for Disease Control and Prevention (CDC). Clinical Considerations for Monkeypox in Children and Adolescents. Retrieved July 26, 2022. 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.

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, via an investigational use protocol, for the treatment of monkeypox virus infections.[67654]

Classifications

  • General Anti-infectives Systemic
    • Antivirals For Systemic Use
      • Variola Virus (Smallpox) Antivirals
Revision Date: 07/28/2022, 03:19:43 PM

References

63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.67654 - Centers for Disease Control and Prevention (CDC). Interim Clinical Guidance for the Treatment of Monkeypox. July 28, 2022. Retrieved July 29, 2022. Available on the World Wide Web at https://www.cdc.gov/poxvirus/monkeypox/treatment.html.

Administration Information

General Administration Information

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

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 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).
    • Administer the entire mixture within 30 minutes of its preparation.[63353]

Injectable Administration

  • Intravenous administration may be used for patients who are unable to take the oral capsules or 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:
    • 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 prefilled infusion bags for product preparation or administration.
  • 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
    Revision Date: 05/19/2022, 12:51:37 PM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.

    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: 05/23/2022, 12:59:00 PM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.

    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]

    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 variola virus transmission through direct contact with the breast-fed infant, breast-feeding is not recommended in patients with smallpox. 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]

    Use of intravenous tecovirimat is contraindicated 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. 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. 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: 05/23/2022, 01:02:42 PM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.

    Mechanism of Action

    Tecovirimat is an antiviral medication with selective and specific activity against orthopoxviruses, such as the variola (smallpox) virus. 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 (smallpox), 0.014 to 0.039 microM for monkeypox, 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: 12/07/2021, 01:19:40 PM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.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: 05/20/2022, 05:06:35 PM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.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

    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 variola virus transmission through direct contact with the breast-fed infant, breast-feeding is not recommended in patients with smallpox. 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]

    Revision Date: 05/20/2022, 09:26:54 AM

    References

    63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.

    Interactions

    Level 2 (Major)

    • Lumateperone
    • Mavacamten
    • Nisoldipine
    • Ubrogepant

    Level 3 (Moderate)

    • Acetaminophen; Caffeine; Dihydrocodeine
    • Acetaminophen; Oxycodone
    • Aspirin, ASA; Caffeine; Dihydrocodeine
    • Aspirin, ASA; Oxycodone
    • Belzutifan
    • Chlorpheniramine; Dihydrocodeine; Phenylephrine
    • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Dihydrocodeine; Guaifenesin; Pseudoephedrine
    • Fentanyl
    • Glimepiride; Rosiglitazone
    • Ibuprofen; Oxycodone
    • Lopinavir; Ritonavir
    • Metformin; Repaglinide
    • Metformin; Rosiglitazone
    • Midazolam
    • Nanoparticle Albumin-Bound Paclitaxel
    • Nanoparticle Albumin-Bound Sirolimus
    • Nirmatrelvir; Ritonavir
    • Ombitasvir; Paritaprevir; Ritonavir
    • Oxycodone
    • Repaglinide
    • Ritonavir
    • Rosiglitazone
    • Sirolimus
    • Smallpox Vaccine, Vaccinia Vaccine
    • Sufentanil
    • 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; 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] 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] 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] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (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] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (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] Dasabuvir; Ombitasvir; Paritaprevir; 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] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (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] 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] Glimepiride; 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] 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] 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] Metformin; 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] 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 loss of efficacy of sirolimus during coadministration of tecovirimat; a sirolimus dose adjustment may be necessary. Monitor sirolimus serum concentrations as appropriate. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; tecovirimat is a weak CYP3A inducer. [28610] [63353] [67136] Nirmatrelvir; Ritonavir: (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of tecovirimat is necessary. Concomitant use of nirmatrelvir and tecovirimat may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and tecovirimat is a weak CYP3A inducer. [63353] [67203] (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] Ombitasvir; Paritaprevir; 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] 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] Sirolimus: (Moderate) Monitor for loss of efficacy of sirolimus during coadministration of tecovirimat; a sirolimus dose adjustment may be necessary. Monitor sirolimus serum concentrations as appropriate. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; tecovirimat is a weak CYP3A inducer. [28610] [63353] [67136] Smallpox Vaccine, Vaccinia Vaccine: (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] 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: 05/21/2022, 02:27:00 AM

    References

    28172 - Avandia (rosiglitazone) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Feb.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.28610 - Rapamune (sirolimus) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2021 Jun.29088 - Sular (nisoldipine) package insert. Atlanta, GA: Shionogi Pharma, Inc.; 2017 Jun.29623 - Duragesic (fentanyl transdermal system) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Mar.29763 - Actiq (oral transmucosal fentanyl citrate) package insert. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2021 Mar.30282 - Synalgos-DC (aspirin; caffeine; dihydrocodeine) capsules package insert. Atlanta, GA: Mikart, Inc.; 2019 Oct.30742 - Abraxane (paclitaxel protein-bound particles) injection package insert. Summit, NJ: Celgene Corporation; 2020 Aug.30966 - Sufenta (sufentanil citrate injection) package insert. Lake Forest, IL: Akorn Pharmaceuticals, Inc.; 2019 Oct32731 - Fentora (fentanyl buccal tablet) package insert. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2021 Mar.39926 - OxyContin (oxycodone HCl extended-release) package insert. Stamford, CT: Purdue Pharma L.P.; 2021 Oct.40943 - Onsolis (fentanyl buccal soluble film) package insert. Raleigh, NC: BioDelivery Sciences, International, Inc.; 2021 Mar.63353 - TPOXX (tecovirimat) package insert. Corvallis, OR: SIGA Technologies, Inc; 2022 May.63484 - Pifeltro (doravirine) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2022 Jan.63731 - Dsuvia (sufentanil) sublingual tablets package insert. Redwood City, CA: AcelRx Pharmaceuticals, Inc.; 2019 Oct.64874 - Ubrelvy (ubrogepant) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2019 Dec.64885 - Caplyta (lumateperone) capsules package insert. New York, NY; Intra-Cellular Therapies, Inc.; 2022 Apr.66875 - Welireg (belzutifan) tablets package insert. Whitehouse Station, NJ: Merck Sharp and Dohme Corp.; 2021 Aug.67136 - Fyarro (sirolimus protein-bound particles) injectable suspension package insert. Pacific Palisades, CA: Aadi Bioscience, Inc.; 2021 Nov.67203 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization for Paxlovid (nirmatrelvir; ritonavir). Retrieved July 6, 2022. Available on the World Wide Web at https://www.fda.gov/media/155050/download?utm_medium=email&utm_source=govdelivery67543 - Camzyos (mavacamten) package insert. Brisbane, CA: MyoKardia, Inc.; 2022 May.

    Monitoring Parameters

    • serum creatinine

    US Drug Names

    • TPOXX
    ;