Drug-resistant tuberculosis treatment

Section 3.5
 
and in a table note for 
Table 3.1
. 
With regard to adverse events, among the 750 patients receiving bedaquiline without concomitant 
delamanid in the endTB observational study (total exposure of 6316 person-months), 26 patients 
experienced a drug-related adverse event (rate: 0.44 per 100 person-months of exposure), with 16 
patients having this event classified as a serious adverse event (rate: 0.25 per 100 person-months of 
exposure). In the first 203 days of exposure to bedaquiline (total exposure of 4304 person-months), 
20 of the 26 drug-related adverse events and 15 of the 16 serious adverse events occurred; the 
remaining six of the 26 drug-related adverse events and one of the 16 serious adverse events occurred 
subsequently. All patients who received bedaquiline for more than 203 days did not experience a 
drug-related adverse event (of any grade) in the first 203 days of treatment. Also, rates of treatment 
drug-related adverse events appeared to be lower after the first 203 days – at 0.51 in the first 203 days 
versus 0.30 in the subsequent days per 100 person-months. Similarly, rates of drug-related serious 
adverse events appeared to be lower after the first 203 days – at 0.35 in the first 203 days versus 
0.05 in the subsequent days per 100 person-months.
QTcF measures among people receiving bedaquiline increased by an average of 22 ms (from 397 ms 
to 419 ms) from measures taken before or at the time of first receipt of bedaquiline to the end of the 
first month. In subsequent months of exposure, the mean QTcF measures were all lower than at the end 
of the first month (range: 404–419 ms). Increases in QTcF of more than 60 ms from baseline occurred 
in about 12% of patients. QTcF prolongation of more than 500 ms was rare, occurring in 0.4–1.5% of 
patients during each of the first 9 months, but not thereafter. The greatest number of occurrences of 

---

WHO consolidated 
guidelines 
on
tuberculosis: 
drug-resistant tuberculosis treatment
33
QTcF of more than 500 ms happened among people receiving bedaquiline and clofazimine; however, 
this was also the most common combination of medicines
received.
Drug-related cardiac adverse events occurred in 22 people; of these, 15 were among people receiving 
bedaquiline with clofazimine, but no moxifloxacin or delamanid (rate: 0.3 per 100 person-months), 
five were among people receiving bedaquiline with clofazimine and moxifloxacin, but no delamanid 
(rate: 0.3 per 100 person-months), and two were among people receiving bedaquiline and delamanid, 
regardless of clofazimine and moxifloxacin use (rate: 0.2 per 100 person-months). No events occurred 
among people receiving bedaquiline without clofazimine, moxifloxacin and delamanid.