Bedaquiline, as a novel anti tuberculosis drug, has a unique mechanism of action and complex drug interactions, which requires special attention to its impact on the CYP3A4 enzyme system and the risk of cardiac toxicity. The following provides a detailed explanation from two aspects: pharmacological effects and drug interactions.

1. Effect of action

(1) Mechanism of action: Selective inhibition of ATP synthase in Mycobacterium tuberculosis, leading to bacterial death by blocking energy metabolism, and killing both dormant and active bacteria.

(2) Antibacterial spectrum: Specifically targeting the complex of Mycobacterium tuberculosis, including multidrug-resistant strains (MDR-TB), but ineffective against non tuberculous mycobacteria.

(3) Effective time: The blood drug concentration reaches its peak within 2-4 hours, and clinical efficacy usually appears after 4 weeks of treatment. The sputum culture conversion rate is 30% higher than traditional methods.

2. Drug interactions

(1) Metabolic related interactions

CYP3A4 strong inhibitors (such as ketoconazole): can increase the AUC of bedaquiline by 2.5 times, and combined use requires a 50% reduction and enhanced electrocardiogram monitoring.

CYP3A4 strong inducers (such as rifampicin): Combination therapy is prohibited as it can reduce the blood concentration of bedaquiline by up to 75%, leading to treatment failure.

(2) Cardiotoxic interaction

QT prolongation drugs (such as fluoroquinolones): there is a risk of synergistically prolonging the QT interval. When used in combination, weekly electrocardiogram monitoring is required, and medication should be stopped immediately if QTc>500ms.

Antiarrhythmic drugs (such as amiodarone): Do not use them in combination, as the risk of tip torsion induced ventricular tachycardia is significantly increased.

(3) Other important interactions

Antiretroviral drugs: Dosage adjustment is required when used in combination with efavirenz, and liver function monitoring is necessary when used in combination with lopinavir/ritonavir.

Antifungal medication: Itraconazole can increase the Cmax of bedaquiline by 52%, and it is recommended to take it every 12 hours.