Brincidofovir
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From MedlinePlus, U.S. National Library of Medicine
Boxed 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 disease [see Warnings and Precautions ( 5.1 )] .
Dosing in kidney impairment
Renal Impairment No dosage adjustment of TEMBEXA is required for patients with mild, moderate, or severe renal impairment or patients with end stage renal disease (ESRD) receiving dialysis [see Clinical Pharmacology] .
Dosing in liver impairment
Testing Before Initiating and During Treatment with TEMBEXA Perform hepatic laboratory testing in all patients before starting TEMBEXA and while receiving TEMBEXA, as clinically appropriate [see Warnings and Precautions and Use in Specific Populations] . Perform pregnancy testing before initiation of TEMBEXA in individuals of childbearing potential to inform risk [see Warnings and Precautions and Use in Specific Populations] .
Preparation and administration
Important Administration Instructions Avoid direct contact with broken or crushed tablets or oral suspension. If contact with skin or mucous membranes occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with water [see Warnings and Precautions] . TEMBEXA Tablets TEMBEXA tablets can be taken on an empty stomach or with a low-fat meal (approximately 400 calories, with approximately 25% of calories from fat) [see Clinical Pharmacology] .
Swallow TEMBEXA tablets whole. Do not crush or divide TEMBEXA tablets. TEMBEXA Oral Suspension Take TEMBEXA oral suspension on an empty stomach [see Clinical Pharmacology] . Shake oral suspension before use. Use an appropriate oral dosing syringe to correctly measure the total prescribed dose [see Patient Counseling Information] .
Discard unused portion after completion of 2 prescribed doses. For patients who cannot swallow, TEMBEXA oral suspension can be administered by enteral tube (naso-gastric or gastrostomy tubes) as follows:
Draw up prescribed dose with a calibrated catheter-tip syringe, and utilize this syringe to administer the dose via the enteral tube.
Refill the catheter-tip syringe with 3 mL of water, shake, and administer the contents via the enteral tube.
Flush with water before and after enteral administration.
Drug interactions
Check brincidofovir against a medication listLabel text (4 paragraphs)
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 )
7.1 Effect of Other Drugs on TEMBEXA Inhibitors for Organic Anion Transporting Polypeptide (OATP) 1B1 and 1B3 Concomitant use of TEMBEXA with OATP1B1 and 1B3 inhibitors (clarithromycin, cyclosporine, erythromycin, gemfibrozil, human immunodeficiency virus [HIV] and hepatitis C virus [HCV] protease inhibitors, rifampin [single dose]) increase brincidofovir AUC and C max which may increase TEMBEXA-associated adverse reactions [see Clinical Pharmacology ( 12.3 )] . Where possible, consider alternative medications that are not OATP1B1 or 1B3 inhibitors.
If concomitant use with TEMBEXA is necessary, increase monitoring for adverse reactions associated with TEMBEXA (elevations in transaminases and bilirubin, diarrhea, or other GI adverse events) [see Warnings and Precautions ( 5.2 , 5.3 )] and postpone the dosing of OATP1B1 or 1B3 inhibitors for at least 3 hours after TEMBEXA administration.
7.2 Vaccine Interactions No vaccine-drug interaction studies have been performed in human subjects. Animal studies have indicated that coadministration of TEMBEXA at the same time as live smallpox vaccine (vaccinia virus) may reduce the immune response to the vaccine. It is also possible that TEMBEXA may reduce the immune response to replication-defective smallpox vaccine (modified vaccinia virus Ankara). The clinical impacts of these potential interactions on vaccine efficacy are unknown.
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
DLikelihood score D: Possible cause of clinically apparent liver injury.
Brincidofovir is an orally available antiviral agent with activity against smallpox and several other DNA viruses that is currently approved for use against smallpox virus (variola) infection in humans and has been given emergency use authorization for treatment of monkeypox (now renamed “mpox”) infection. Brincidofovir therapy has been linked to a low rate of serum aminotransferase elevations during therapy, but has not been implicated in instances of clinically apparent liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, TEMBEXA may cause fetal harm when administered to pregnant individuals. Use an alternative therapy to treat smallpox during pregnancy, if feasible. There are no available data on the use of brincidofovir in pregnant individuals to evaluate for a drug-associated risk of major birth defects, miscarriage, and other adverse maternal and fetal outcomes. In animal reproduction studies, oral administration of brincidofovir to pregnant rats and rabbits during the period of organogenesis resulted in embryotoxicity and structural malformations.
These effects occurred in animals at systemic exposures less than the expected human exposure based on the recommended dose of TEMBEXA ( see Data ). The estimated background risk of major birth defects for the indicated population is unknown, and the estimated background risk of miscarriage for the indicated population is higher than the general population. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals were administered oral doses of brincidofovir up to 4.5 mg/kg/day from gestation days 7 to 20. Maternal toxicity in rats, characterized by decreases in food consumption and decreased body weight gain, was observed at doses of 1.5 and 4.5 mg/kg/day. These effects correlated with decreased fetal weights in rats given 4.5 mg/kg/day. Brincidofovir administration in rats was not associated with effects on intrauterine growth or survival at any dose, and there were no external malformations or developmental variations.
In rabbits, 4.5 mg/kg/day brincidofovir was associated with decreased maternal body weight and food consumption, decreased fetal body weight, increased late resorptions and morphological changes which included external, visceral and skeletal malformations and variations. In the pre-/post-natal development study, administration of brincidofovir at doses of 0, 0.25, 1, and 4 mg/kg/day and 15 mg/kg twice weekly to pregnant rats from gestation day 7 to lactation day 20 resulted in pup toxicity at maternally toxic doses (4 mg/kg/day and 15 mg/kg twice weekly).
Pup body weight and viability were decreased, and reproductive function of the pups was impaired as evidenced by a delay in sexual maturation, decreased testes and epididymal…
Breastfeeding (LactMed)
No information is available on the use of during breastfeeding. Until more safety data become available, an alternate drug is preferred. Individuals with smallpox are recommended to not breastfeed their infant because of the risk of passing variola virus to the infant through direct contact. Providing pumped milk to the infant may be possible if no lesions are near the breast and adequate precautions are taken with respect to cleaning hands, breasts, breast pumps and any other apparatuses used to provide milk to the infant. Individuals with Mpox should feed their infants with pasteurized donor milk or infant formula until all of their lesions are healed. Numerous other safety precautions are advised for mothers with Mpox.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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