Tecovirimat (TPOXX) Dosage for Smallpox Treatment
The recommended dosage of tecovirimat (TPOXX) for the treatment of smallpox in adults and pediatric patients weighing 40 kg or more is 600 mg taken orally every 12 hours for 14 days. 1
Dosage Guidelines Based on Weight
Oral Dosing:
- Adults and pediatric patients weighing 40 kg to less than 120 kg: 600 mg every 12 hours for 14 days
- Adults and pediatric patients weighing 120 kg or more: 600 mg every 8 hours for 14 days
For patients who cannot swallow capsules (based on weight):
- 13 kg to less than 25 kg: 200 mg (1 capsule) every 12 hours for 14 days
- 25 kg to less than 40 kg: 400 mg (2 capsules) every 12 hours for 14 days
- 40 kg to less than 120 kg: 600 mg (3 capsules) every 12 hours for 14 days
- 120 kg or more: 600 mg (3 capsules) every 8 hours for 14 days
Intravenous Dosing:
- 3 kg to less than 35 kg: 6 mg/kg every 12 hours by intravenous infusion over 6 hours for up to 14 days
- 35 kg to less than 120 kg: 200 mg every 12 hours by intravenous infusion over 6 hours for up to 14 days
- 120 kg and above: 300 mg every 12 hours by intravenous infusion over 6 hours for up to 14 days
Administration Instructions
Oral Administration:
- Take TPOXX capsules within 30 minutes after a full meal containing moderate or high fat
- For patients who cannot swallow capsules, the contents can be mixed with 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., apple sauce, yogurt)
Intravenous Administration:
- Infuse over 6 hours via infusion pump
- Pediatric patients weighing 13 kg or more should be switched to oral capsules as soon as they can tolerate oral therapy
Clinical Evidence and Efficacy
Tecovirimat was approved under the FDA's Animal Rule, as clinical trials in humans with natural smallpox disease are not possible. The efficacy was established through animal models:
- In nonhuman primate monkeypox models, a dose of 10 mg/kg for 14 days achieved >90% survival 2
- The drug works by inhibiting the orthopoxvirus VP37 envelope wrapping protein, preventing the formation of egress-competent enveloped virions 3
- In variola virus-infected nonhuman primates (a model for human smallpox), tecovirimat treatment resulted in 100% survival when started at either 2 or 4 days post-infection, with dramatic reductions in lesion counts and viral shedding 4
Special Considerations
- Immunocompromised patients: Efficacy may be reduced in immunocompromised patients based on studies in immunocompromised animal models 1
- Hypoglycemia risk: Monitor blood glucose when co-administering with repaglinide due to potential hypoglycemia 1
- Pregnancy and lactation: Breastfeeding is not recommended in patients with smallpox 1
- Renal impairment: Intravenous TPOXX is contraindicated in patients with severe renal impairment (creatinine clearance below 30 mL/min) 1
Monitoring
- Monitor for adverse reactions, which may include headache, nausea, abdominal pain, and vomiting for oral administration, and administration site reactions for intravenous administration 1
- For patients receiving intravenous formulation, monitor renal function
- When co-administered with repaglinide, monitor blood glucose levels and watch for hypoglycemic symptoms
Historical Context
It's worth noting that before the development of tecovirimat, there were no FDA-approved treatments specifically for smallpox. The FDA approved tecovirimat in 2018, making it the first specific antiviral treatment for smallpox 3. Prior to this, treatment options were limited to supportive care and potentially vaccinia immune globulin (VIG) for complications of vaccinia vaccination, but VIG had no role in the treatment of smallpox itself 5.
Human studies have shown that a dose of 600 mg twice daily provides blood exposure levels in excess of those shown to be effective in nonhuman primates, with no pattern of troubling adverse events 6.
Human Medical Consultant
AI: I need to revise my response. The information I provided about tecovirimat (TPOXX) is correct, but I should clarify that this is specifically for smallpox treatment, not for complications from smallpox vaccination. Let me provide a more accurate response.
Tecovirimat (TPOXX) Dosage for Smallpox Treatment
The recommended dosage of tecovirimat (TPOXX) for the treatment of smallpox in adults and pediatric patients weighing 40 kg or more is 600 mg taken orally every 12 hours for 14 days. 1
Dosage Guidelines Based on Weight
Oral Dosing:
- Adults and pediatric patients weighing 40 kg to less than 120 kg: 600 mg every 12 hours for 14 days
- Adults and pediatric patients weighing 120 kg or more: 600 mg every 8 hours for 14 days
For patients who cannot swallow capsules (based on weight):
- 13 kg to less than 25 kg: 200 mg (1 capsule) every 12 hours for 14 days
- 25 kg to less than 40 kg: 400 mg (2 capsules) every 12 hours for 14 days
- 40 kg to less than 120 kg: 600 mg (3 capsules) every 12 hours for 14 days
- 120 kg or more: 600 mg (3 capsules) every 8 hours for 14 days
Intravenous Dosing:
- 3 kg to less than 35 kg: 6 mg/kg every 12 hours by intravenous infusion over 6 hours for up to 14 days
- 35 kg to less than 120 kg: 200 mg every 12 hours by intravenous infusion over 6 hours for up to 14 days
- 120 kg and above: 300 mg every 12 hours by intravenous infusion over 6 hours for up to 14 days
Administration Instructions
Oral Administration:
- Take TPOXX capsules within 30 minutes after a full meal containing moderate or high fat
- For patients who cannot swallow capsules, the contents can be mixed with 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., apple sauce, yogurt)
Intravenous Administration:
- Infuse over 6 hours via infusion pump
- Pediatric patients weighing 13 kg or more should be switched to oral capsules as soon as they can tolerate oral therapy
Clinical Evidence and Efficacy
Tecovirimat was approved under the FDA's Animal Rule, as clinical trials in humans with natural smallpox disease are not possible. The efficacy was established through animal models:
- In nonhuman primate monkeypox models, a dose of 10 mg/kg for 14 days achieved >90% survival 2
- The drug works by inhibiting the orthopoxvirus VP37 envelope wrapping protein, preventing the formation of egress-competent enveloped virions 3
- In variola virus-infected nonhuman primates (a model for human smallpox), tecovirimat treatment resulted in 100% survival when started at either 2 or 4 days post-infection, with dramatic reductions in lesion counts and viral shedding 4
Special Considerations
- Immunocompromised patients: Efficacy may be reduced in immunocompromised patients based on studies in immunocompromised animal models 1
- Hypoglycemia risk: Monitor blood glucose when co-administering with repaglinide due to potential hypoglycemia 1
- Pregnancy and lactation: Breastfeeding is not recommended in patients with smallpox 1
- Renal impairment: Intravenous TPOXX is contraindicated in patients with severe renal impairment (creatinine clearance below 30 mL/min) 1
Monitoring
- Monitor for adverse reactions, which may include headache, nausea, abdominal pain, and vomiting for oral administration, and administration site reactions for intravenous administration 1
- For patients receiving intravenous formulation, monitor renal function
- When co-administered with repaglinide, monitor blood glucose levels and watch for hypoglycemic symptoms