Bedaquiline

Registered South African indications:

• Multidrug resistant tuberculosis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Moderate to severe hepatic impairment
• Elderly
• Treatment longer than 24 weeks
• Extra-pulmonary tuberculosis 
• Infections due to mycobacterial species other than M. tuberculosis
• Latent infection with M. tuberculosis
• Drug-sensitive tuberculosis
• Congenital or acquired QT interval prolongation or risk factors thereof
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Multidrug resistant tuberculosis (MDR TB)

• Oral (tab): 400mg (4 tablets of 100mg), DAILY; Treatment duration: 2 weeks;

then

• Oral (tab): 200mg (2 tablets of 100mg), THREE TIMES PER WEEK with at least 48 hours between doses; Treatment duration: 22 weeks  

Space doses at least 48 hours apart in maintenance phase 

A missed dose in the first 2 weeks of treatment does not require a change to the dosing schedule

If a dose is missed from week 3 onwards, patients should take the missed dose as soon as possible and the resume the 3 times per week regime

Not established for use in children below 18 years

Decisions related to dose adjustment/discontinuing TB regimen must be discussed in advance with Pulmonologists/Infectious Disease specialists, and cases must be dealt with individually

Pregnancy

• Caution; no evidence of risk in studies
• There are limited data on the use of bedaquiline in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity
• As a precautionary measure, avoid the use of bedaquiline during pregnancy unless the benefit of therapy is considered to outweigh the risks

Breastfeeding

• Caution; not recommended
• It is not known whether bedaquiline or its metabolites are excreted in human milk
• In rats, concentrations of bedaquiline in milk were 6- to 12-fold higher than the maximum concentration observed in maternal plasma. Body weight decreases in pups were noted in high dose groups during the lactation period
• Because of the potential for adverse reactions in breastfed infants, a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from bedaquiline therapy taking into account the benefit of breastfeeding for the infant and the benefit of therapy for the mother

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

Hepatic Impairment

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; no dose adjustment recommended
  Severe: Use is not recommended

Elderly 

• Caution; no dose adjustment recommended

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness

Cardiovascular Disorders

• Prolonged QT interval

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea

Hepatobiliary Disorders

• Increased transaminases

Musculoskeletal Disorders

• Arthralgia
• Myalgia

• CYP3A4 inducers
• CYP3A4 inhibitors
• Antiretrovirals
• QT prolonging agents
• Clofazimine

• Serum electrolytes
• Hepatic function

Specific cases may require

• ECG

• Resistance to bedaquiline: Bedaquiline must only be used in an appropriate combination regimen for MDR-TB treatment as recommended by official guidelines to prevent bedaquiline resistance

Bedaquiline is a diarylquinoline. Bedaquiline specifically inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, an essential enzyme for the generation of energy in Mycobacterium tuberculosis. The inhibition of ATP synthase leads to bactericidal effects for both replicating and non-replicating tubercle bacilli.

Tablet 100mg

• Sirturo (Janssen)