Abstract

• Pulmonary tuberculosis due to multidrug-resistant mycobacteria is fatal in about 15% of cases.
   
• Delamanid, an antibiotic that targets bacteria of the genus Mycobacterium in vitro, has been authorised in the European Union for the treatment of multidrug-resistant pulmonary tuberculosis, in combination with other antibiotics, when the choice of antituberculosis drugs is limited, particularly because of bacterial resistance.
   
• Clinical evaluation of delamanid in multidrug-resistant tuberculosis is mainly based on a randomised, double-blind, placebo-controlled trial in 481 patients who also received optimised antituberculosis therapy. The results are undermined by various methodological issues. After 2 months of treatment, 42% of patients in the delamanid 400 mg/day group, 45% of those in the delamanid 200 mg/day group, and 30% of those in the placebo group had negative sputum cultures (statistically significant differences between the delamanid groups and placebo group)
   
• 464 patients in this trial were followed for at least 24 months. They all received "optimised" antituberculosis therapy during this period, and 205 of them also received delamanid for 6 months. About 3% of the patients who received these extra 6 months of delamanid therapy died, versus 12% of the patients who did not. But the evidence is weak due to the lack of randomisation.
   
• Delamanid seems to cause marked QT prolongation in about 10% of patients, with a risk of severe cardiac arrhythmia. Other known adverse effects of delamanid include nausea, vomiting, weight loss, various neurological disorders (including headache, tinnitus and paraesthesia) and psychiatric disorders (including anxiety).
   
• Delamanid is a substrate of cytochrome P450 isoenzyme CYP 3A4, resulting in a risk of interactions with enzyme inducers or inhibitors. Delamanid co-administration with another drug that prolongs the QT interval, such as a fluoroquinolone (often used in multidrug-resistant tuberculosis), increases the risk of this cardiac adverse effect. 

•  POSSIBLY HELPFUL  Despite its rather shaky evaluation, data available in late 2016 suggest that delamanid should be offered to patients with tuberculosis due to multidrug-resistant mycobacteria. The noteworthy impact of delamanid on the QT interval warrants electrocardiographic monitoring and close attention to drug interactions.
  

©Prescrire 1 April 2017

"Delamanid (Deltyba°) and multidrug-resistant pulmonary tuberculosis. For selected patients, with cardiac monitoring" Prescrire Int 2017; 26 (179): 33-37. (Pdf, subscribers only)