TMC207

TMC207 Uses, Dosage, Side Effects, Food Interaction and all others data.

TMC207 is a bactericidal antimycobacterial drug. Chemically it is a diarylquinoline. FDA approved on December 28, 2012.

TMC207 is primarily subjected to oxidative metabolism leading to the formation of N-monodesmethyl metabolite (M2). M2 is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (4 to 6-fold lower) compared to the parent compound. M2 concentrations appeared to correlate with QT prolongation. TMC207 inhibits mycobacterial TB at a minimal inhibitory concentration (MIC) from 0.002-0.06 μg/ml and with a MIC50 of 0.03 μg/ml. Furthermore, bacteria that have smaller ATP stores (usually in dormant, nonreplicating bacilli) are more susceptible to bedaquiline.

Trade Name TMC207
Availability Prescription only
Generic Bedaquiline
Bedaquiline Other Names Bedaquilina, Bedaquiline, Bédaquiline, Bedaquilinum
Related Drugs pretomanid, aminosalicylic acid, Paser, Sirturo
Type
Formula C32H31BrN2O2
Weight Average: 555.505
Monoisotopic: 554.156890893
Protein binding

>99.9 bound to plasma proteins.

Groups Approved
Therapeutic Class
Manufacturer
Available Country France
Last Updated: September 19, 2023 at 7:00 am
TMC207
TMC207

Uses

TMC207 is a diarylquinoline antimycobacterial used in combination with other antibacterials to treat pulmonary multidrug resistant tuberculosis (MDR-TB).

TMC207 is indicated as part of combination therapy in adults (≥ 18 years) with pulmonary multi-drug resistant tuberculosis (MDR-TB).

TMC207 is also used to associated treatment for these conditions: Tuberculosis, Multidrug Resistant

How TMC207 works

TMC207 is a diarylquinoline antimycobacterial drug that inhibits the proton pump of mycobacterial ATP (adenosine 5'-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis. Bacterial death occurs as a result of bedaquiline.

Toxicity

The most common adverse reactions reported in ≥10% of patients treated with bedaquiline are nausea, arthralgia, and headache.

Food Interaction

  • Take with food. Food significantly increases the oral bioavailability.

[Moderate] ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bedaquiline.

When administered with a standard meal containing approximately 22 grams of fat (558 total Kcal), the relative bioavailability of bedaquiline increased by approximately 2-fold compared to administration under fasted conditions.



GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of bedaquiline.

In clinical trials, hepatic adverse drug reactions developed in more bedaquiline-treated patients than in those who received other drugs used to treat tuberculosis.

In patients receiving bedaquiline or placebo in combination with other drugs used to treat multidrug-resistant tuberculosis, reversible aminotransferase elevations of at least 3 times the upper limit of normal developed more frequently in the bedaquiline treatment group

[10.8%] than in the placebo group

[5.7%].

MANAGEMENT: To ensure maximal oral absorption, bedaquiline should be taken with food.

Patients should avoid alcohol use during treatment.

Volume of Distribution

Vd, central compartment = 164 L

Elimination Route

Tmax, oral dose = 5 hours; Food increases the oral bioavailability. AUC increases proportionally up to the highest dose studied in healthy volunteers. When 400 mg of bedaquiline is administered once daily for a week, the peak plasma concentration (Cmax) is 5.5 μg/ml and an AUC of 64.75 μgh/ml.

Half Life

Terminal elimination half-life, bedaquiline and M2 = 5.5 months. This long half-life suggests slow release of bedaquiline and M2 from peripheral tissues.

Elimination Route

TMC207 is primarily elimination in the feces. The urinary excretion of unchanged bedaquiline was < 0.001% of the dose in clinical studies, indicating that renal clearance of unchanged drug is insignificant.

Innovators Monograph

You find simplified version here TMC207

*** Taking medicines without doctor's advice can cause long-term problems.
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