Version May 2024
Dosage guidance:
Dosage form information: Initiate with oral therapy when possible. Patients unable to take capsules or drug-food preparation may receive IV therapy; switch to oral therapy as soon as possible. When a change in dosage form is necessary, the first dose of the new dosage form should be given at the same time and in place of the next scheduled dose of the previously prescribed dosage form.
Nonvariola orthopoxvirus infection (eg, mpox [monkeypox]) (off-label use): Note: Reserve use for patients with or at risk for severe disease and those with infection in anatomic sites that may be associated with severe pain or result in sequelae (eg, scarring, strictures) (CDC 2023c). May also be considered for post-exposure prophylaxis on a case-by-case basis in consultation with the CDC (CDC 2023b).
IV:
35 to <120 kg: 200 mg every 12 hours (CDC 2023b).
≥120 kg: 300 mg every 12 hours (CDC 2023b).
Oral:
40 to <120 kg: 600 mg every 12 hours (CDC 2023b).
≥120 kg: 600 mg every 8 hours (CDC 2023b).
Duration of therapy: Typical treatment duration is 14 days but should be individualized based on clinical response and tolerability (CDC 2023b).
Smallpox:
IV:
35 to <120 kg: 200 mg every 12 hours for 14 days.
≥120 kg: 300 mg every 12 hours for 14 days.
Oral:
40 to <120 kg: 600 mg twice daily for 14 days.
≥120 kg: 600 mg 3 times daily for 14 days.
Missed doses: Administer missed oral dose as soon as possible if up to 8 hours prior to next scheduled dose. If <8 hours until the next scheduled oral dose, skip the missed dose and resume dosing at regular scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
IV:
CrCl ≥90 mL/minute: No dosage adjustment necessary.
CrCl 30 to 89 mL/minute: No dosage adjustment necessary; use with caution; accumulation of hydroxypropyl-B-cyclodextrin may occur.
CrCl <30 mL/minute: Use is contraindicated.
Oral: No dosage adjustment necessary.
No dosage adjustment necessary.
Refer to adult dosing.
(For additional information see "Tecovirimat (United States: Availability limited to health department/CDC expanded access protocol): Pediatric drug information")
Note: Has not been formally studied in pediatric patients; dosing is based on pharmacokinetic simulations to achieve comparable exposure to adults.
Nonvariola orthopoxvirus infection (eg, mpox [monkeypox]): Very limited data available: Note: Dosing from the CDC's expanded access investigational new drug (EA-IND) protocol. Data in pediatric patients are extremely limited, particularly in very young infants and children; for additional clinical guidance, contact the CDC. Typical treatment duration is 14 days but should be individualized based on clinical response and tolerability (CDC 2022a).
Oral: Note: The smallest capsule size is 200 mg; doses lower than 200 mg require manipulation of capsule, increasing risk for dose inaccuracy. Use caution; before use, ensure caregivers are able to prepare as directed (CDC 2022a).
Infants, Children, and Adolescents (CDC 2022a):
<3 kg: Oral: 33.3 mg every 12 hours.
3 to <6 kg: Oral: 50 mg every 12 hours.
6 to <13 kg: Oral: 100 mg every 12 hours.
13 to <25 kg: Oral: 200 mg every 12 hours.
25 to <40 kg: Oral: 400 mg every 12 hours.
40 to <120 kg: Oral: 600 mg every 12 hours.
≥120 kg: Oral: 600 mg every 8 hours.
IV: Note: Use IV formulation with caution in patients <2 years of age due to limited experience with hydroxypropyl-B-cyclodextrin excipient.
Infants, Children, and Adolescents (CDC 2022a):
<35 kg: IV: 6 mg/kg/dose every 12 hours.
35 to <120 kg: IV: 200 mg every 12 hours.
≥120 kg: IV: 300 mg every 12 hours.
Smallpox infection: Note: When a change in dosage form is necessary, the first dose of the new dosage form should be given at the time of the next scheduled dose. Treat for 14 days total.
Oral: Children and Adolescents:
13 to <25 kg: Oral: 200 mg every 12 hours.
25 to <40 kg: Oral: 400 mg every 12 hours.
40 to <120 kg: Oral: 600 mg every 12 hours.
≥120 kg: Oral: 600 mg every 8 hours.
IV: Infants, Children, and Adolescents: Note: Use with caution in patients <2 years of age due to limited experience with hydroxypropyl-B-cyclodextrin excipient. Initiation with oral therapy is recommended in patients weighing ≥13 kg when possible. Patients unable to take capsules or drug-food preparation may be initiated with IV therapy; in patients weighing ≥13 kg, switch to oral therapy as soon as possible.
3 to <35 kg: IV: 6 mg/kg/dose every 12 hours.
35 to <120 kg: IV: 200 mg every 12 hours.
≥120 kg: IV: 300 mg every 12 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Has not been studied in pediatric patients; dosing is based on pharmacokinetic simulations to achieve comparable exposure to adults.
Oral: Infants, Children, and Adolescents (CDC 2022a; manufacturer's labeling):
Mild, moderate, and severe renal impairment: No dosage adjustment is necessary.
End-stage renal disease requiring hemodialysis: No dosage adjustment is necessary.
IV: Infants, Children, and Adolescents (CDC 2022a; manufacturer's labeling):
Baseline renal impairment:
Mild to moderate renal impairment (CrCl 30 to <90 mL/minute): No dosage adjustment necessary; use with caution; accumulation of hydroxypropyl-B-cyclodextrin may occur.
Severe renal impairment (CrCl <30 mL/minute): Use is contraindicated.
Renal impairment occurring during therapy: Consider switching to oral therapy if possible.
Infants weighing ≥3 kg, Children, and Adolescents: Mild, moderate, or severe hepatic impairment: No dosage adjustment is necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are for the oral product in adults unless otherwise indicated.
>10%:
Local: Pain at injection site (IV)
Nervous system: Headache (oral, IV: 12% to 15%)
1% to 10%:
Cardiovascular: Increased heart rate (<2%)
Dermatologic: Cheilosis (<2%), facial erythema (<2%), pruritic rash (<2%), pruritus (oral, IV: <4%), purpuric rash (palpable: <2%), skin rash (<2%)
Endocrine & metabolic: Increased thirst (<2%)
Gastrointestinal: Abdominal pain (2%), diarrhea (IV: <4%), dysgeusia (<2%), dyspepsia (<2%), eructation (<2%), nausea (5%), oral paresthesia (<2%), vomiting (2%), xerostomia (<2%)
Hematologic & oncologic: Decreased hematocrit (<2%), decreased hemoglobin (<2%)
Hypersensitivity: Facial swelling (<2%)
Local: Discomfort at injection site (IV: <4%), swelling at injection site (IV: <4%)
Nervous system: Abnormal electroencephalogram (<2%), chills (<2%), depression (<2%), disturbance in attention (<2%), dysphoria (<2%), hypertonia (IV: <4%), irritability (<2%), malaise (<2%), migraine (<2%), pain (<2%), panic attack (<2%), paresthesia (<2%)
Neuromuscular & skeletal: Arthralgia (<2%), arthritis (IV: <4%), back pain (IV: <4%), myalgia (IV: <4%), osteoarthritis (<2%)
Ophthalmic: Photophobia (IV: <4%)
Respiratory: Oropharyngeal pain (<2%)
Miscellaneous: Fever (<2%)
IV: Severe renal impairment (CrCl <30 mL/minute).
Oral: There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to tecovirimat or any component of the formulation.
Disease-related concerns:
• Renal impairment: IV: Injection contains hydroxypropyl-B-cyclodextrin, which may accumulate in patients with renal impairment and has the potential to cause renal toxicity. Use injection with caution in patients <2 years of age (due to immature renal function) and patients with mild or moderate renal impairment (CrCl 30 to 89 mL/minute); contraindicated in patients with severe renal impairment (CrCl <30 mL/minute). If renal toxicity is suspected, consider switching to oral tecovirimat if possible or use an alternative agent.
Special populations:
• Patients who are immunocompromised: Efficacy may be reduced (based on studies in immunocompromised animal models).
Injection contains hydroxypropyl-B-cyclodextrin. In pediatric patients <2 years of age, there are limited data with use of hydroxypropyl-B-cyclodextrin and clearance may be reduced due to renal immaturity, resulting in higher exposure. Use with caution in patients <2 years of age and continue monitoring renal function following treatment completion.
Tpoxx is available through the US government's Strategic National Stockpile for the treatment of smallpox. For treatment of other Orthopoxvirus infections, including mpox (monkeypox), tecovirimat is available via clinical trial (STOMP) and through an expanded access Investigational New Drug (EA-IND) application.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Tpoxx: 200 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Solution, Intravenous:
Tpoxx: 200 mg/20 mL (20 mL)
No
Capsules (Tpoxx Oral)
200 mg (per each): $0.00
Solution (Tpoxx Intravenous)
200 mg/20 mL (per mL): $0.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Tpoxx: 200 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Tecovirimat is FDA-approved for the treatment of smallpox, but only available through the US government's Strategic National Stockpile.
Tecovirimat is available for treatment of other Orthopoxvirus infections, including mpox (monkeypox), via enrollment in the Study of Tecovirimat for Human Monkeypox virus (STOMP) clinical trial. For patients who decline enrollment in or are ineligible for STOMP, or who require IV tecovirimat, use of tecovirimat is available through an expanded access Investigational New Drug (EA-IND) application. Providers may request tecovirimat for the treatment of mpox (monkeypox) by contacting the CDC Emergency Operations Center at 770-488-7100 or [email protected]. Providers/facilities need to register as participating providers under the CDC-held EA-IND by completing the online registry; providers should register prior to prescribing or administering tecovirimat when possible, and no later than 7 calendar days of first prescribing or administering. (CDC 2023a; CDC 2023b).
IV: Administer via IV infusion pump over 6 hours; not for IV bolus injection.
Oral: Administer within 30 minutes after a full meal containing moderate or high fat (ideally ~600 calories and 25 g of fat). For patients who cannot swallow capsules, capsules may be opened and entire contents mixed with 30 mL of liquid (eg, milk, chocolate milk, or water [CDC 2023b]) or soft food (eg, applesauce, yogurt); powder may not dissolve completely. Administer entire mixture within 30 minutes after preparation. For patients unable to feed by mouth, if IV administration is not available or feasible, may be administered via nasogastric tube as long as patient has no evidence of GI dysfunction; compatibility studies on enteral administration have not been conducted (CDC 2023b).
Parenteral: IV: Must be diluted prior to use; gently swirl syringe(s) prior to inserting in syringe pump. Administer via IV infusion pump over 6 hours; do NOT administer via IV bolus injection.
Oral: For children and adolescents, administer dose within 30 minutes following a full meal of moderate to high fat (~25 grams; ~600 calories total); for infants, dose should be administered just before a feeding. Note: The smallest capsule size is 200 mg; doses lower than 200 mg require manipulation of capsule, increasing risk for dose inaccuracy. Use caution; before use, ensure caregivers are able to prepare as directed (CDC 2022a).
Doses less than 200 mg or patients unable to swallow capsules: Capsules may be opened and mixed with liquid or soft food as per following instructions based on dose needed. The mixture should be administered within 30 minutes of preparation, and any unused portion of the mixture should be discarded; a new mixture should be prepared for each dose (CDC 2022a; manufacturer's labeling).
• 33.3 mg dose (patients weighing <3 kg): Open one 200 mg capsule and pour contents into a small bowl or cup. Add 20 mL of water and mix well by swirling for ≥30 seconds. Immediately after mixing, measure 3.3 mL (33.3 mg) of the tecovirimat-water mixture into an oral syringe and administer (CDC 2022a).
• 50 mg dose (patients weighing 3 to <6 kg): Open one 200 mg capsule and pour contents into a small bowl or cup. Add 20 mL of water and mix well by swirling for ≥30 seconds. Immediately after mixing, measure 5 mL (50 mg) of the tecovirimat-water mixture into an oral syringe and administer (CDC 2022a).
• 100 mg dose (patients weighing 6 to <13 kg): Open one 200 mg capsule and pour contents into a small bowl or cup. Add 20 mL of water and mix well by swirling for ≥30 seconds. Immediately after mixing, measure 10 mL (100 mg) of the tecovirimat-water mixture into an oral syringe and administer either directly or mixed in a small amount of soft food (eg, applesauce, yogurt) (CDC 2022a).
• 200, 400, or 600 mg dose (patients weighing ≥13 kg): The appropriate number of capsules may be carefully opened and the entire contents added to 30 mL of liquid (eg, water, milk, chocolate milk, infant formula) or soft food (eg, applesauce, yogurt, baby food, chocolate syrup); powder may not completely dissolve (CDC 2022a; manufacturer's labeling).
Nasogastric: In patients unable to feed by mouth, may be administered via nasogastric tube as long as patient has no evidence of gastrointestinal dysfunction (CDC 2022a).
Missed dose: Administer missed dose as soon as possible if up to 8 hours prior to next scheduled dose. If <8 hours until the next scheduled dose, skip the missed dose and resume dosing at regular scheduled time.
Smallpox: Treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing ≥3 kg.
Limitations of use: Effectiveness for treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible and inducing smallpox disease in humans to study the drug's efficacy is not ethical.
Nonvariola orthopoxvirus infection (eg, mpox [monkeypox])
Substrate of UGT1A1, UGT1A4; Inhibits CYP2C19 (weak), CYP2C8 (weak); Induces CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Atogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Daprodustat: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Daprodustat. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
Mavacamten: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor. For those stable on mavacamten who are initiating a weak CYP2C19 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Smallpox Vaccine Live: Tecovirimat may diminish the therapeutic effect of Smallpox Vaccine Live. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
Food (~600 kcal, ~25 g fat) increased mean AUC 39%. Management: Administer within 30 minutes after a full moderate or high fat meal.
Outcome data related to the use of tecovirimat during pregnancy are limited (Oakley 2023; Sampson 2023).
Smallpox infection during pregnancy is associated with adverse events. Contracting smallpox while pregnant increases the risk of severe maternal disease (including hemorrhagic smallpox) and death; the fatality rate in unvaccinated pregnant patients can be up to 70% (CDC [Petersen 2015]).
Infection with the monkeypox virus may also lead to adverse pregnancy outcomes, including spontaneous pregnancy loss, stillbirth, and transmission of the monkeypox virus to the fetus or newborn. When a pregnant patient is diagnosed with mpox (monkeypox), neonatal health care providers should be informed of the diagnosis (CDC 2023d).
In consultation with the CDC, tecovirimat is the preferred antiviral treatment for pregnant and recently pregnant patients who otherwise meet the eligibility criteria for treatment of mpox (monkeypox). Pregnant and recently pregnant patients diagnosed with monkeypox virus infection should be prioritized for treatment. Patients should be closely monitored for severe disease and pregnancy complications (CDC 2023d).
It is not known if tecovirimat is present in breast milk.
Breastfeeding patients were not included in initial pharmacokinetic studies (Grosenbach 2018).
Lactating patients with smallpox infection have the potential to transmit the virus via direct contact to a breastfed infant. Therefore, breastfeeding is not recommended.
Tecovirimat is the preferred antiviral treatment for lactating patients who otherwise meet the eligibility criteria for treatment of mpox (monkeypox). Lactating patients diagnosed with monkeypox virus infection should be prioritized for treatment. Breastfed children diagnosed with mpox (monkeypox) should be treated as indicated (CDC 2023d).
Patients diagnosed with mpox (monkeypox) should not have direct skin to skin contact with their newborn. Patients should observe recommendations for isolation and breastfeeding should be delayed until criteria for discontinuing isolation are met. Patients can pump and discard breast milk until they no longer have symptoms or require isolation. During this time, infants should be fed with formula or pasteurized donor milk by a healthy caregiver (CDC 2023d).
Take ≤30 minutes after a full meal containing moderate or high fat (about 25 g of fat).
Blood glucose, symptoms of hypoglycemia (when coadministered with repaglinide); CrCl in patients receiving IV therapy prior to initiation and as clinically appropriate.
Tecovirimat inhibits the activity of the orthopoxvirus VP37 protein and blocks its interaction with cellular Rab9 GTPase and TIP47, preventing formation of egress-competent enveloped virions (necessary for dissemination of virus).
Absorption: Oral: Administration with food (~600 kcal, ~25 g fat) increased mean AUC 39%.
Distribution: Vd (Vz or Vz/F): IV: 383 L; Oral: 1,030 L.
Protein binding: 77% to 82%.
Metabolism: Hydrolysis of the amide bond and glucuronidation (UGT1A1, UGT1A4).
Half-life elimination: IV: 21 hours; Oral: 19 hours.
Time to peak: IV: 6 hours (range: 6 to 6.5 hours); Oral: 6 hours (range: 2 to 24 hours).
Excretion: Oral: Urine (73%, predominantly metabolites); feces (23%, predominantly as unchanged drug)
Tecovirimat exposure was reduced in patients weighing >120 kg and receiving a dose of 600 mg twice daily compared to patients weighing <120 kg receiving the same dose.
Pediatric: Pharmacokinetics have not been evaluated in pediatric patients; based on pharmacokinetic simulation, recommended pediatric dosing regimens are expected to result in exposures comparable to those in adults receiving recommended doses.
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