Bedaquiline fumarate

Bedaquiline fumarate is the fumarate salt form of bedaquiline, an important antibiotic used specifically for treating multidrug-resistant tuberculosis (MDR-TB). Bedaquiline inhibits the growth of tuberculosis bacteria in the body and is always used in combination with other tuberculosis medications. It was received accelerated approval from the USFDA on December 28, 2012, for the treatment of pulmonary multidrug- resistant tuberculosis in adults. On June 21,2024, The USFDA granted approval expanding its indication to include pediatric patients by removing previous label restrictions.

BRAND NAME:

Sirturo - It is available as oral tablets containing Bedaquiline as the main active ingredient with strength 100mg.

MECHANISM OF ACTION:

Bedaquiline fumarate exerts its antimycobacterial activity by selectively inhibiting the enzyme ATP synthase, which is essential for the energy production of Mycobacterium tuberculosis. Specifically, it targets the proton pump activity of the c-subunit in the F₀ portion of ATP synthase, preventing the movement of protons across the bacterial cell membrane. This disruption prevents the synthesis of adenosine triphosphate (ATP), which is critical for cellular energy and survival. As a result, bedaquiline depletes the bacterial cell’s energy reserves, leading to cell death. Importantly, this mechanism is distinct from that of other anti-tuberculosis drugs, which makes bedaquiline especially valuable for treating multidrug-resistant tuberculosis (MDR-TB).

Its action is highly specific to the mycobacterial enzyme and does not significantly affect human mitochondrial ATP synthase at therapeutic levels, reducing the potential for off-target toxicity.

PHARMACOKINETICS:

Absorption: After oral administration, its absorption is significantly enhanced when taken with food, leading to approximately double the systemic exposure compared to fasting conditions.

Distribution: It is highly bound to plasma proteins (over 99.9%) and has a large volume of distribution, indicating extensive tissue penetration.

Metabolism: Bedaquiline is metabolized primarily in the liver by the cytochrome P450 enzyme CYP3A4 into its main metabolite, N-monodesmethyl bedaquiline, which has reduced antimicrobial activity.

Excretion: Excretion occurs primarily through the feces, with minimal renal elimination.

PHARMACODYNAMICS:

Bedaquiline fumarate demonstrates concentration-dependent bactericidal activity against Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Its pharmacodynamic profile is primarily driven by its unique inhibition of the ATP synthase enzyme, which is essential for energy production in the bacterial cell.

DOSAGE AND ADMINISTRATION:

Bedaquiline fumarate is administered orally and always in combination with other anti-tuberculosis medications as part of a regimen to treat pulmonary multidrug-resistant tuberculosis (MDR-TB).

Adult dosage: The initial recommended dosage is 400mg once daily upto 1 to 2 weeks. The recommended continuation phase dose is 200mg three times/ week upto 3-24 weeks

Padiatric dosage: The recommended dose in children depends on the weight of the body.

If the child is between 15 to <30kg, 200mg once daily upto 1 – 2 weeks and followed by 100mg three times per week for 3-24 weeks.

For the children above ≥30kg the dosage is as same as adult dosage.

DRUG INTERACTIONS:

Before taking Bedaquiline fumarate it is required to discuss with the doctor if the patient is going through any other treatment. As some medications should be avoid as they get interact with bedaquiline fumarate and can cause serious adverse effects. Below are some drugs that are should be avoid.