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 |
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.
TMC207 Drug Interaction
Major: ciprofloxacin, clozapineModerate: aripiprazole, amoxicillin / clavulanate, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, acetaminophenUnknown: albumin human, antihemophilic factor/von willebrand factor, multivitamin, betrixaban, ticagrelor, caplacizumab, multivitamin with minerals, methsuximide, multivitamin with minerals, fenoldopam, aspirin, hyoscyamine / methenamine / methylene blue / phenyl salicylate, linezolid
TMC207 Disease Interaction
Major: arrhythmia, QT prolongationModerate: alcoholism, liver dysfunction, renal impairment
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
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