Tembexa (brincidofovir)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

*Before initiation and during treatment with brincidofovir perform hepatic laboratory testing. Perform pregnancy testing before initiation of the drug in individuals of childbearing potential.

*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.

*Administration instructions for tablets: Take on an empty stomach or with a low-fat meal (approximately 400 calories, with approximately 25% of calories from fat). Swallow the tablets whole; do not crush or divide.

*Administration instructions for oral suspension: Take on an empty stomach. Shake oral suspension before use. Use an appropriate oral dosing syringe to correctly measure the total prescribed dose. Discard unused portion after completion of 2 prescribed doses. For patients who cannot swallow, the oral suspension can be administered by enteral tube (naso-gastric or gastrostomy tubes).

*See full prescribing information for additional details on administration and preparation of the drug.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Brincidofovir/Oatp1b1-3 Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: OATP1B1 and 1B3 inhibitors may increase the absorption and/or decrease the hepatic uptake of brincidofovir.(1)

CLINICAL EFFECTS: Concurrent use of OATP1B1 or 1B3 inhibitors may result in elevated levels of and side effects from brincidofovir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of brincidofovir states that alternative medications that are not OATP1B1 or 1B3 inhibitors should be considered. If concurrent use is necessary, instruct the patient to take the OATP1B1 or 1B3 inhibitor at least 3 hours after brincidofovir and increase monitoring for side effects, including transaminase and bilirubin elevations and GI side effects like diarrhea.(1)

DISCUSSION: In a clinical trial, single-dose oral cyclosporine (600 mg, an OATP1B1 and 1B3 inhibitor) increased the mean brincidofovir area-under-curve (AUC) and maximum concentration (Cmax) by 374% and 269%, respectively.(1) OATP1B1 and 1B3 inhibitors include: atazanavir, belumosudil, boceprevir, clarithromycin, cyclosporine, darunavir, eltrombopag, encorafenib, erythromycin, gemfibrozil, glecaprevir-pibrentasvir, ledipasvir, leflunomide, leniolisib, letermovir, lopinavir, ombitasvir-paritaprevir, paritaprevir, resmetirom, rifampin, ritonavir, roxadustat, saquinavir, simeprevir, sofosbuvir, telaprevir, teriflunomide, tipranavir, vadadustat, velpatasvir, and voclosporin.(1,2)

There are no moderate interactions for this drug.

None.

• Lactation

• Pregnancy

There are no moderate contraindications for this drug.

Common adverse reactions (occurring in at least 2% of brincidofovir-treated subjects) were diarrhea, nausea, vomiting, and abdominal pain.

Less Frequent

• Gastroenteritis
• Hyperbilirubinemia
• Increased alanine transaminase
• Increased aspartate transaminase

More Frequent

• Acute abdominal pain
• Diarrhea
• Nausea
• Vomiting

Less Frequent

• Anorexia
• Dehydration
• Dysgeusia
• Dyspepsia
• Muscle weakness
• Peripheral edema
• Skin rash

No enhanced messaging available.

As in adults, the effectiveness of brincidofovir in smallpox infected pediatric patients, including neonates, is based solely on efficacy studies in animal models of orthopoxvirus disease. The recommended pediatric dosing regimen is expected to produce brincidofovir exposures that are comparable to those in adults based on a population pharmacokinetic modeling and simulation approach. The dosage for pediatric patients is based on weight.

There have been 23 pediatric subjects aged 7 months to 17 years who received brincidofovir in a randomized, placebo-controlled clinical trial. The safety in adult and pediatric subjects treated with brincidofovir were similar. An additional 166 pediatric subjects 3 months to 18 years of age received brincidofovir from uncontrolled studies and expanded access. The dosage of brincidofovir in pediatric patients <3 months of age was based on modeling and simulations.

Based on findings from animal reproduction studies, brincidofovir 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 brincidofovir.

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.

Because of the potential for variola virus transmission through direct contact with the breastfed infant, breastfeeding is not recommended in patients with smallpox. There are no data on the presence of brincidofovir in human milk, the effects of the drug on the breastfed infant, or on milk production. Brincidofovir is present in animal milk.

Of the 392 subjects in the controlled clinical studies, 21% were >=65 years of age and 1% were >=75 years of age. The nature and severity of adverse events was comparable between subjects older and younger than 65 years. No alteration of dosing is recommended for patients >=65 years of age.