Brincidofovir

TEMBEXA is an orthopoxvirus nucleotide analog DNA polymerase inhibitor and is indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates. Limitations of Use: • TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease. • The effectiveness of TEMBEXA 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. • TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals.

Brincidofovir is an antiviral drug against variola (smallpox) virus.

• Testing: Before initiation and during treatment with TEMBEXA perform hepatic laboratory testing and pregnancy testing. • See full prescribing information for details on important administration instructions. • Adult and pediatric patients weighing 48 kg or above: 200 mg (two 100 mg tablets or 20 mL oral suspension for patients who cannot swallow tablets) once weekly for 2 doses. • Adult and pediatric patients weighing 10 kg to less than 48 kg: 4 mg/kg oral suspension once weekly for 2 doses. • Pediatric patients weighing less than 10 kg: 6 mg/kg oral suspension once weekly for 2 doses.

None. None.

Boxed warning (increased risk for mortality when used for longer duration): An increased incidence of mortality was seen in TEMBEXA-treated subjects compared to placebo-treated subjects in a 24-week clinical trial when TEMBEXA was evaluated in another disease. • Elevations in Hepatic Transaminases and Bilirubin: May cause increases in serum transaminases (ALT or AST) and serum bilirubin. Monitor liver laboratory parameters before and during treatment. • Diarrhea and Other Gastrointestinal Adverse Events: Diarrhea and additional gastrointestinal adverse events including nausea, vomiting, and abdominal pain may occur. Monitor patients, provide supportive care, and if necessary, do not give the second and final dose of TEMBEXA. • Coadministration with Related Products: TEMBEXA should not be coadministered with intravenous cidofovir. • Embryo-fetal Toxicity: May cause fetal harm.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Elevations in hepatic transaminases and bilirubin • Diarrhea and other GI adverse events Common adverse reactions (occurring in at least 2% of TEMBEXA-treated subjects) were diarrhea, nausea, vomiting, and abdominal pain.

Concomitant use with OATP1B1 and 1B3 inhibitors increase TEMBEXA exposure which may increase TEMBEXA-associated adverse reactions. Consider alternative medication that are not OATP1B1 or 1B3 inhibitors. If concomitant use is necessary, increase monitoring for adverse reactions associated with TEMBEXA and postpone the dosing of OATP1B1 or 1B3 inhibitors at least 3 hours after TEMBEXA administration.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted from 15°C to 30°C (59°F to 86°F). Do not freeze.