Pharmacology
Mechanism of Action
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).
Pharmacokinetics/Pharmacodynamics
Distribution
Vd (Vz/F): 1,030 L
Metabolism
Hydrolysis of the amide bond and glucuronidation (UGT1A1, UGT1A4)
Excretion
Urine (73%, predominantly metabolites); feces (23%, predominantly as unchanged drug)
Time to Peak
4 to 6 hours
Half-Life Elimination
20 hours
Protein Binding
77% to 82%
Use: Labeled Indications
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.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Smallpox: Oral: 600 mg twice daily for 14 days
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Smallpox disease: Children and Adolescents: Oral:
13 to <25 kg: 200 mg twice daily for 14 days
25 to <40 kg: 400 mg twice daily for 14 days
≥40 kg: 600 mg twice daily for 14 days
Administration
Oral: Administer ≤30 minutes after a full meal of 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, infant formula) or soft food (eg, applesauce, yogurt); powder may not dissolve completely. Administer entire mixture within 30 minutes after preparation.
Dietary Considerations
Take ≤30 minutes after a full meal of moderate or high fat (about 25 g of fat).
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted 15°C to 30°C (59°F to 86°F).
Drug Interactions
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy
Midazolam: Tecovirimat may decrease the serum concentration of Midazolam. Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy
Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Monitor therapy
Smallpox Vaccine Live: Tecovirimat may diminish the therapeutic effect of Smallpox Vaccine Live. 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. Consider therapy modification
Adverse Reactions
>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
Warnings/Precautions
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Immunocompromised patients: Efficacy may be reduced (based on studies in immunocompromised animal models).
Monitoring Parameters
Blood glucose, symptoms of hypoglycemia (when coadministered with repaglinide)
Pregnancy
Pregnancy Considerations
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).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, nausea, vomiting, or abdominal pain (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
