Бедаквилина фумарат

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

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

Бедаквилина фумарат 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. Бедаквилина фумарат 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.

Бедаквилина фумарат
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	Бедаквилина фумарат
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	Russia
Last Updated:	September 19, 2023 at 7:00 am

Uses

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

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

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

How Бедаквилина фумарат works

Бедаквилина фумарат 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.

Бедаквилина фумарат 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

Бедаквилина фумарат 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

Бедаквилина фумарат 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.