- May 9, 2022
- Newsletter
- 617-430-5616
Menu
Menu
Menu
Menu
Menu
Menu
Brand Name :
Tembexa
Synonyms :
brincidofovir
Class :
Antivirals
Dosage forms & strengths
Tablet
100mg
Oral suspension
10mg/ml
For patients (oral suspension or tablet) ≥48 kg: 2 doses of 200 mg orally every week (on 1st and 8th day)
For patients <48 kg (oral suspension) 2 doses of 4 mg/kg orally every week (on 1st and 8th day)
Dosage forms & strengths
Tablet
100mg
Oral suspension
10mg/ml
4 - 8
mg/kg
Orally
every week
Tablet
For ≥48 kg: 2 doses of 200 mg orally each week (on 1st and 8th day)
For patients 10-48 kg: 2 doses of 4 mg/kg orally every week (on 1st and 8th day)
For patients <10 kg: 2 doses of 6 mg/kg orally every week (on 1st and 8th day)
For ≥48 kg: 2 doses of 200 mg orally each week (on 1st and 8th day)
For patients 10-48 kg: 2 doses of 4 mg/kg orally every week (on 1st and 8th day)
For patients <10 kg: 2 doses of 6 mg/kg orally every week (on 1st and 8th day)
Refer to the adult dosing
may enhance the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) inhibitors
may enhance the serum concentration
may enhance the serum concentration of OATP1/1B3 substrates
may enhance the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors
may enhance the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors
may enhance the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors
the combination with doxorubicin may decrease the therapeutic effects of another drug
may enhance the immunosuppressive effect of immunosuppressants
may enhance the immunosuppressive effect of immunosuppressants
may increase the levels of serum concentration of elagolix
may enhance the serum concentration of elbasvir/grazoprevir
MRP2 inhibitors increase the concentration of cabozantinib in serum
it decreases the effect of brincidofovir
it increases the concentration of OATP1B1/1B3 substrates in serum
Corticosteroids may reduce the therapeutic effect of Brincidofovir
Corticosteroids may reduce the therapeutic effect of Brincidofovir
Corticosteroids may reduce the therapeutic effect of Brincidofovir
Corticosteroids may reduce the therapeutic effect of Brincidofovir
Corticosteroids may reduce the therapeutic effect of Brincidofovir
immunosuppressants decrease the efficacy of brincidofovir
immunosuppressants decrease the efficacy of brincidofovir
immunosuppressants decrease the efficacy of brincidofovir
immunosuppressants decrease the efficacy of brincidofovir
immunosuppressants decrease the efficacy of brincidofovir
OATP1B1/1B3 inhibitors increase the concentration of brincidofovir in the serum
OATP1B1/1B3 inhibitors increase the concentration of brincidofovir in the serum
OATP1B1/1B3 inhibitors increase the concentration of brincidofovir in the serum
OATP1B1/1B3 inhibitors increase the concentration of brincidofovir in the serum
OATP1B1/1B3 inhibitors increase the concentration of brincidofovir in the serum
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
may decrease the therapeutic effect when combined with brincidofovir
brincidofovir: they may decrease the therapeutic effect of immunostimulants
brincidofovir: they may decrease the therapeutic effect of immunostimulants
brincidofovir: they may decrease the therapeutic effect of immunostimulants
brincidofovir: they may decrease the therapeutic effect of immunostimulants
brincidofovir: they may decrease the therapeutic effect of immunostimulants
methotrexate may diminish the therapeutic effect of brincidofovir
may diminish the therapeutic effect of brincidofovir
may diminish the therapeutic effect of brincidofovir
oncologic agents may diminish the therapeutic effects of brincidofovir
may reduce therapeutic effects of brincidofovir
when both drugs are combined, there may be an increase in immunosuppressive activity and the risk of severe infection
chemotherapeutic agents may diminish the therapeutic effects of brincidofovir
immunosuppressants reduce the therapeutic efficacy of brincidofovir
it may reduce the therapeutic effect of brincidofovir
may decrease the therapeutic effect of immunosuppressants
may decrease the therapeutic effect of immunosuppressants
may increase the serum concentration of OAT1/3 substrates
may increase the serum concentration of OAT1/3 substrates
may increase the immunosuppressive effect of immunosuppressive agents
may result in a significant increase in zavegepant exposure
may decrease the therapeutic effect of Immunosuppressants
may decrease the therapeutic effect of Immunosuppressants
Actions and Spectrum:
brincidofovir is an antiviral drug that is structurally similar to cidofovir, another antiviral drug that is used to treat a range of viral infections. brincidofovir has a broader spectrum of activity than cidofovir, and is active against a wide range of DNA viruses, including cytomegalovirus (CMV), adenovirus, smallpox, and human herpesviruses (HHV) 6, 7, and 8.
brincidofovir works by inhibiting viral DNA synthesis through the incorporation of its active metabolite, cidofovir diphosphate, into the growing DNA chain, resulting in chain termination and inhibition of viral replication. In addition, brincidofovir has been shown to have immunomodulatory effects, which may contribute to its antiviral activity.
brincidofovir has been studied for the treatment of a range of viral infections, including CMV infection, adenovirus infection, smallpox, and HHV infections. However, the efficacy of brincidofovir varies depending on the virus and the clinical setting in which it is used. For example, brincidofovir has shown promise as a treatment for adenovirus infection in immunocompromised patients but has not been effective in treating Ebola virus disease.
Frequency defined
1-10%
Diarrhea
Nausea
Vomiting
Serum creatinine elevated
Abdominal pain
ALT elevated
Total bilirubin elevated
AST elevated
<2%
Peripheral edema
Decreased appetite
Muscular weakness
Dysgeusia
Rash
Black Box Warning
brincidofovir is an antiviral drug that has been studied for the treatment of various viral infections, including cytomegalovirus (CMV) infection and adenovirus infection. While brincidofovir has shown promise as a potential treatment option for these viral infections, there have been reports of increased mortality observed in brincidofovir-treated individuals compared with placebo-treated individuals in some clinical trials.
For example, in a 24-week clinical trial evaluating brincidofovir for the prevention of CMV infection in patients undergoing hematopoietic stem cell transplantation, an increased incidence of mortality was observed in brincidofovir-treated individuals compared with placebo-treated individuals. Specifically, the study found that the mortality rate was 9.6% in the brincidofovir group compared with 3.7% in the placebo group.
It is important to note that the increased mortality observed in this study was specific to the population studied (patients undergoing hematopoietic stem cell transplantation), and the results may not necessarily apply to other populations or diseases. In addition, the mechanism behind the increased mortality observed with brincidofovir in this study is not fully understood, and further research is needed to better understand the potential risks and benefits of this drug for the treatment of viral infections.
\
Contraindication/Caution:
Pregnancy consideration:
brincidofovir may cause harm to the fetus when administered to pregnant females.
Breastfeeding warnings:
brincidofovir is found to be present in animal milk.
Excretion in human milk is not known.
Hence breastfeeding is not suggested in patients with smallpox.
Pregnancy category:
Pharmacology:
brincidofovir is a prodrug that is rapidly converted to its active form, cidofovir diphosphate, in cells infected with DNA viruses. Cidofovir diphosphate is a nucleoside analogue that inhibits viral DNA synthesis by incorporating into the growing viral DNA chain, resulting in chain termination and inhibition of viral replication.
brincidofovir is structurally similar to cidofovir, but has an added lipid side chain that enhances its bioavailability and cellular uptake. This modification allows for once-weekly dosing and improved safety and tolerability compared to cidofovir.
In addition to its antiviral activity, brincidofovir has been shown to have immunomodulatory effects. Specifically, it has been shown to reduce pro-inflammatory cytokine production and increase regulatory T cell function, which may contribute to its antiviral activity. brincidofovir is primarily eliminated through the kidneys, and therefore, dose adjustments are necessary in patients with impaired renal function to avoid toxicity.
Pharmacodynamics:
The pharmacodynamics of brincidofovir are like those of cidofovir, the active metabolite of brincidofovir. Cidofovir diphosphate, the active form of the drug, competes with deoxyadenosine triphosphate (dATP) for incorporation into the growing viral DNA chain. Once incorporated, it inhibits viral DNA synthesis by terminating the chain elongation.
Cidofovir diphosphate has a long intracellular half-life, allowing for sustained antiviral activity. It has broad-spectrum antiviral activity against a range of DNA viruses, including cytomegalovirus (CMV), adenovirus, and polyomavirus. However, it is not effective against RNA viruses or retroviruses.
brincidofovir has been shown to have a higher intracellular concentration of cidofovir diphosphate compared to cidofovir, which may contribute to its improved antiviral activity and tolerability. The lipid side chain of brincidofovir enhances its cellular uptake and enables once-weekly dosing, which may improve patient adherence to therapy.
Pharmacokinetics:
Absorption
The bioavailability is 16.8% (for oral suspension); and 13.4% (for tablet)
Peak plasma concentration is achieved in 3 hours (brincidofovir); and 47 hours (cidofovir diphosphate)
Peak plasma concentration is 480 ng/mL (brincidofovir) and 9.7 pg/106 cells (for cidofovir diphosphate)
The area under the curve is 3400 ng⋅hr/mL(for brincidofovir) and 1200 pg⋅hr/106 cells (for cidofovir diphosphate)
Distribution
The bound protein is >99.9%
The volume of distribution is 1230 L
The blood/plasma ratio is 0.48-0.61
Metabolism
The drug is metabolised through the pathways: Hydrolysis, CYP4F2
Elimination and Excretion
The half-life is 19.3 hours (for brincidofovir) and 113 hours (for cidofovir diphosphate)
The rate of clearance is 44.1 L/hr
The drug is excreted 51% in urine; and 40% in feces
Administration:
brincidofovir is administered orally in the form of delayed-release tablets. The recommended dose of brincidofovir for the treatment of cytomegalovirus (CMV) infection in adult patients is 100 mg once weekly for up to 14 weeks. The dose may be adjusted based on renal function. brincidofovir tablets should be taken with food to enhance absorption.
They should be swallowed whole and not crushed, broken, or chewed. Patients with impaired renal function may require dose adjustments to avoid toxicity. The use of brincidofovir is contraindicated in patients with severe renal impairment (estimated glomerular filtration rate less than 30 mL/min/1.73 m2) or end-stage renal disease.
Patient information leaflet
Generic Name: brincidofovir
Pronounced: Brin-cid-o-fovir
Why do we use brincidofovir?
brincidofovir is used to treat certain viral infections, including cytomegalovirus (CMV) infection and adenovirus infection. It works by inhibiting the replication of DNA viruses, including CMV and adenovirus. CMV is a common virus that can cause severe disease in immunocompromised individuals, such as those who have received organ transplants or those who are undergoing chemotherapy for cancer.
CMV infection can cause serious complications, including pneumonia, gastrointestinal disease, and retinitis. Adenovirus infection can cause a range of illnesses, including respiratory illness, conjunctivitis, gastroenteritis, and urinary tract infections. Adenovirus infections can be severe in immunocompromised individuals, including transplant recipients and those with HIV.
brincidofovir is used to treat these viral infections in adults who have compromised immune systems, and for whom there are no other available treatment options. The once-weekly dosing regimen of brincidofovir is designed to improve patient adherence to therapy and reduce the risk of side effects associated with frequent dosing.
ADVERTISEMENT
