Brincidofovir

Brand Names: Tembexa

Drug Class: General Prescription

Overview

11 DESCRIPTION TEMBEXA (brincidofovir) tablets, 100 mg, for oral use are immediate release film-coated tablets containing the following inactive ingredients: Colloidal Silicon Dioxide, Crospovidone, FD&C Blue #1/Brilliant Blue FCF Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake, Magnesium Stearate, Mannitol, Microcrystalline Cellulose, Polyethylene Glycol, Polyvinyl Alcohol, Purified...

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Brincidofovir is an antiviral drug against variola (smallpox) virus [see Microbiology ( 12.4 )] . 12.2 Pharmacodynamics Brincidofovir and its active metabolite cidofovir diphosphate exposure-response relationships and time course of pharmacodynamic responses are unknown. Cardiac Electrophysiology TEMBEXA does not prolong the QT interval at the anticipated therapeutic exposure. 12.3 Pharmacokinetics Brincidofovir is a prodrug that is converted intracellularly to cidofovir, which is subsequently phosphorylated to cidofovir diphosphate, the active antiviral moiety, following oral administration. Brincidofovir plasma exposures do not accumulate after repeat doses.

Indications

  • 1 INDICATIONS AND USAGE 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. ( 1.1 ) Limitations of Use: • TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease. ( 1.2 ) • 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. ( 1.

Common Doses

  • 200 mg
  • 100 mg
  • 20 mL
  • 4 mg

Dosage

2 DOSAGE AND ADMINISTRATION • Testing: Before initiation and during treatment with TEMBEXA perform hepatic laboratory testing and pregnancy testing. ( 2.1 ) • See full prescribing information for details on important administration instructions. ( 2.2 ) • 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. ( 2.3 ) • Adult and pediatric patients weighing 10 kg to less than 48 kg: 4 mg/kg oral suspension once weekly for 2 doses. ( 2.

Black Box Warning

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 [see Warnings and Precautions ( 5.1 )] . WARNING: INCREASED RISK FOR MORTALITY WHEN USED FOR LONGER DURATION See full prescribing information for complete boxed warning. 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...

Contraindications

  • 4 CONTRAINDICATIONS None. None. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Elevations in hepatic transaminases and bilirubin [see Warnings and Precautions ( 5.2 )] • Diarrhea and other GI adverse events [see Warnings and Precautions ( 5.3 )] Common adverse reactions (occurring in at least 2% of TEMBEXA-treated subjects) were diarrhea, nausea, vomiting, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Emergent BioDefense Operations Lansing LLC at 1-877-246-8472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.

Interactions

  • 7 DRUG INTERACTIONS 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. ( 7.1 ) 7.