Tpoxx

Uses

Tpoxx is an antiviral medication used to treat smallpox.

Tpoxx is indicated for the treatment of smallpox infection. It can be administered in children and adults with a minimum body weight of 13 kg . Tpoxx is an inhibitor of the Orthopoxvirus VP37 envelope wrapping protein .

Tpoxx is also used to associated treatment for these conditions: Smallpox

How Tpoxx works

Tpoxx inhibits the production of extracellular viral forms, which are responsible for the systemic spread of infection, inhibiting virus-induced cytopathic effects. Tpoxx does not inhibit the formation of intracellular forms of the virus (IMV); however, by inhibiting envelopment, and therefore preventing the exit of viral particles from an infected cell, the smallpox infection is slowed to a point where the immune system can eliminate the virus .

Tpoxx has shown a high level of selectivity and specificity for orthopoxviruses. Tpoxx targets the viral p37 protein, a highly conserved protein with no homologs outside of the Orthopoxvirus genus, inhibiting its function that is necessary for required for the viral envelopment of IMV (intracellular mature virus). Tpoxx interferes with the cellular localization of p37 viral protein and prevents its association with cellular proteins involved in membrane trafficking .

Toxicity

Tpoxx has demonstrated to be well tolerated, with no serious adverse events (AEs). Common adverse reactions in healthy adult subjects (≥ 2%) were headache, nausea, abdominal pain, and vomiting , .

Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia .

Oral administration of tecovirimat is generally well-tolerated at dose levels up to 2,000 mg/kg/day (mice) .

Food Interaction

• Take with food. Take tecovirimat within 30 minutes of eating a fatty meal containing approximately 25 grams of fat.

[Moderate] ADJUST DOSING INTERVAL: Food may increase the extent of tecovirimat absorption following oral administration.

When the recommended oral dose of tecovirimat (600 mg every 12 hours) was administered with a meal (approximately 600 calories and 25 g of fat) in healthy adults weighing less than 120 kg, tecovirimat absorption increased by 39% relative to fasting.

MANAGEMENT: Oral tecovirimat should be taken within 30 minutes after a full meal containing moderate or high fat (approximately 600 calories and 25 g of fat) with 6 to 8 ounces of water.

Tpoxx Disease Interaction

Major: renal dysfunction

Volume of Distribution

Approximately 1,356 L. Following oral administration in mice, [14C]-tecovirimat was distributed to all tissues analyzed with the highest concentrations noted in liver and gallbladder, respiratory tract tissues (i.e., nasal turbinates), and bone marrow. Studies in dogs and NHPs suggest that tecovirimat crosses the blood-brain barrier .

Elimination Route

Readily absorbed following oral administration, with mean times to maximum concentration from 3 to 4 h . A study was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 administered as a single daily oral dose. Steady state was reached by day 6 (within 3 to 5 half-lives).

Half Life

Approximately 20h .

Clearance

Mainly renal .

Elimination Route

Less than 0.02% of the drug is excreted unchanged in the kidney, with a majority of the drug being excreted in glucuronidated form. Approximately 23% of unchanged drug is found in the feces .

Innovators Monograph

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