Smallpox:
40 to <120 kg: Oral: 600 mg twice daily for 14 days.
≥120 kg: Oral: 600 mg 3 times daily for 14 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
No dosage adjustment necessary.
(For additional information see "Tecovirimat (United States: Availability limited to strategic national stockpile distribution): Pediatric drug information")
Smallpox: Children and Adolescents:
13 to <25 kg: Oral: 200 mg twice daily for 14 days.
25 to <40 kg: Oral: 400 mg twice daily for 14 days.
40 to <120 kg: Oral: 600 mg twice daily for 14 days.
≥120 kg: Oral: 600 mg 3 times daily for 14 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children weighing ≥13 kg and Adolescents:
Mild, moderate, and severe renal impairment: No dosage adjustment is necessary
End-stage renal disease: No dosage adjustment is necessary
Children weighing ≥13 kg and Adolescents: Mild, moderate, or severe hepatic impairment: No dosage adjustment is necessary
Refer to adult dosing.
Tpoxx: FDA approved July 2018; Tpoxx will be available initially only through the US government's Strategic National Stockpile.
Oral: Administer within 30 minutes after a full meal containing moderate or high fat (about 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 soft food (eg, applesauce, yogurt); powder may not dissolve completely. Administer entire mixture within 30 minutes after preparation.
Oral: Administer within 30 minutes following a full meal of moderate to high fat (~25 grams). For patients unable to swallow capsules, the capsule(s) may be carefully opened and the entire contents added to 30 mL of liquid (eg, milk, chocolate milk, infant formula) or soft food (eg, applesauce, yogurt); powder may not completely dissolve. The entire mixture should be administered within 30 minutes of preparation.
Smallpox: Treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing ≥13 kg.
Limitations of use: 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Central nervous system: Headache (12%)
1% to 10%:
Cardiovascular: Increased heart rate (<2%)
Central nervous system: Abnormal electroencephalogram (<2%), chills (<2%), depression (<2%), disturbance in attention (<2%), dysphoria (<2%), irritability (<2%), malaise (<2%), migraine (<2%), pain (<2%), panic attack (<2%), paresthesia (<2%)
Dermatologic: Cheilosis (<2%), facial erythema (<2%), facial swelling (<2%), pruritic rash (<2%), pruritus (<2%), skin rash (<2%)
Endocrine & metabolic: Increased thirst (<2%)
Gastrointestinal: Nausea (5%), abdominal pain (2%), vomiting (2%), dysgeusia (<2%), dyspepsia (<2%), eructation (<2%), oral paresthesia (<2%), xerostomia (<2%)
Hematologic & oncologic: Decreased hematocrit (<2%), decreased hemoglobin (<2%), purpuric rash (palpable: <2%)
Neuromuscular & skeletal: Arthralgia (<2%), osteoarthritis (<2%)
Respiratory: Oropharyngeal pain (<2%)
Miscellaneous: Fever (<2%)
Frequency not defined: Gastrointestinal: Diarrhea, mild gastric distress
There are no contraindications listed in the manufacturer's labeling.
Special populations:
• Immunocompromised patients: Efficacy may be reduced (based on studies in immunocompromised animal models).
• Obesity: Patients weighing >120 kg may have lower drug exposure.
Substrate of UGT1A1, UGT1A4; Inhibits CYP2C19 (weak), CYP2C8 (weak); Induces CYP3A4 (weak)
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
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
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
Adverse events have not been observed in animal reproduction studies. Pregnant patients were not included in pharmacokinetic studies (Grosenbach 2018).
Smallpox infection is more severe in pregnant patients; transmission to the fetus may occur (Fenner 1988).
It is not known if tecovirimat is present in breast milk.
Breastfeeding patients were not included in pharmacokinetic studies (Grosenbach 2018). According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
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)
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).
Distribution: Vd (Vz/F): 1,030 L
Protein binding: 77% to 82%
Metabolism: Hydrolysis of the amide bond and glucuronidation (UGT1A1, UGT1A4)
Half-life elimination: 20 hours
Time to peak: 4 to 6 hours
Excretion: 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.
