Tembexa

Tembexa Uses, Dosage, Side Effects, Food Interaction and all others data.

Tembexa is an oral antiviral drug used in the treatment of human smallpox infections. It is a lipid conjugate pro-drug of the acyclic nucleotide analogue cidofovir - this lipid conjugate improves drug delivery to the target cells and significantly reduces the nephrotoxicity typically associated with cidofovir therapy. Due to its formulation as a pro-drug brincidofovir also carries a greater bioavailability than cidofovir, allowing for oral administration rather than intravenous. Cidofovir itself has broad antiviral activity against several DNA viruses, resulting in brincidofovir being investigated for the prevention and treatment of cytomegalovirus (CMV), BK Virus (BKV), adenoviruses (AdV), and Epstein-Barr virus (EBV), amongst others.

Tembexa, developed by Chimerix under the brand name Tembexa, was approved by the FDA for the treatment of smallpox infection in June 2021. As smallpox has been eradicated, the efficacy of Tembexa was assessed in animals infected with viruses closely related to variola. The approval was granted under the agency’s Animal Rule, which allows for a drug to be approved based on the results of well-controlled animal studies when human trials would be unethical or infeasible.

The pharmacologically active agent resulting from brincidofovir metabolism, cidofovir diphosphate, has an exceedingly long duration of action that allows for it to be dosed once weekly. The entirety of a brincidofovir smallpox treatment consists of only two doses, on days 1 and 8, which seemingly reduces the risk of adverse reactions. Regimens involving a longer duration of administration (i.e. more than a single dose on days 1 and 8) have been shown to increase mortality compared to placebo and should therefore be avoided. Tembexa is considered a potential human carcinogen and has demonstrated the potential to cause infertility - as such, its use should be restricted to situations in which it is absolutely necessary.

Tembexa
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Tembexa
Generic	Brincidofovir
Brincidofovir Other Names	Brincidofovir, Cidofovir hexadecyloxypropyl ester
Type	Tablets, oral suspension
Formula	C₂₇H₅₂N₃O₇P
Weight	Average: 561.701 Monoisotopic: 561.354288024
Protein binding	Brincidofovir is >99% protein-bound in plasma, although the specific protein(s) to which it binds have not been elucidated.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Tembexa is an oral lipid prodrug of cidofovir used in the treatment of human smallpox disease.

Tembexa is indicated for the treatment of human smallpox disease in adult and pediatric patients.

Tembexa is also used to associated treatment for these conditions: Smallpox

How Tembexa works

Tembexa is a pro-drug comprising cidofovir conjugated to a lipid molecule - the lipid component mimics an endogenous lipid, lysophosphatidylcholine, which allows the molecule to hijack endogenous lipid uptake pathways to enter infected cells. Following uptake, the lipid molecule is cleaved to generate cidofovir, which is then phosphorylated to generate the active antiviral compound, cidofovir disphosphate.

The antiviral effects of cidofovir diphosphate appear to be the result of two distinct mechanisms. Mechanistic studies using recombinant vaccinia DNA polymerase suggest that it inhibits orthopoxvirus DNA polymerase-mediated DNA synthesis. In addition, cidofovir is an acyclic nucleotide analogue of deoxycytidine monophosphate - cidofovir diphosphate can therefore be incorporated into the growing viral DNA chain and consequently slow the rate of viral DNA synthesis.

Toxicity

There is no clinical experience with brincidofovir overdose. Patients experiencing overdosage should be monitored closely and provided supportive therapy as clinically indicated.

Food Interaction

Take on an empty stomach. Tembexa is best absorbed on an empty stomach or alongside a low-fat meal.

Volume of Distribution

The apparent volume of distribution of brincidofovir is 1230 L.

Elimination Route

The oral bioavailability of brincidofovir is 13.4% in its tablet formulation and 16.8% in its suspension formulation. Following oral administration, the C_max and AUC_tau of brincidofovir were 480 ng/mL and 3400 ng·hr/mL, respectively. The C_max and AUC_tau of the active metabolite, cidofovir diphosphate, were 9.7 pg/10⁶

Maximum plasma concentrations (T_max) of brincidofovir are reached at approximately 3 hours post-administration, while maximal plasma concentrations for cidofovir diphosphate are reached at approximately 47 hours post-administration.

Half Life

The mean terminal half-lives of brincidofovir and its pharmacologically active metabolite, cidofovir diphosphate, are 19.3 hours and 113 hours, respectively.