• N Misra, N Padayatchi, and P Naidoo.
• Discipline of Pharmaceutical Sciences, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. nirupa.misra@kznhealth.gov.za.
• S. Afr. Med. J. 2020 Dec 14; 111 (1): 61-67.

BackgroundOptimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients' prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis (TB). The optimal dose of clofazimine (CFZ), a repurposed medicine for DR-TB, that is safe and effective in the South African (SA) population is unknown.ObjectivesTo report on dose-related final treatment outcomes in patients receiving CFZ plus a background regimen for DR-TB.MethodsIn a retrospective review of patient folders from 2012 to 2014, treatment outcomes documented for patients receiving high- (≥200 mg) and low-dose (100 mg) CFZ in a centralised DR-TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and outcomes.ResultsA total of 600 patients were included, of whom 169 (28.2%) received 100 mg. Of these, 87 (51.5%) weighed <50 kg and 82 (48.5%) ≥50 kg. Four hundred and thirty-one (71.8%) received ≥200 mg, of whom 41 (9.5%) were <50 kg and 390 (90.5%) ≥50 kg. Overall 77.2% were HIV-positive, with 93.95% on antiretroviral medicine. The majority of patients presented with extremely drug-resistant TB (55.3%). Forty-seven and a half percent of patients received a standardised background regimen, and 52.5% received an individualised regimen containing a new or repurposed medicine including CFZ. On multivariate analysis, adjusting for age, gender, HIV status and concomitant antiretrovirals, previous TB history, type of TB and background regimen, patients ≥50 kg prescribed 100 mg CFZ were 60% less likely to have a successful outcome (adjusted odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2 - 0.8; p=0.009) compared with patients <50 kg receiving 100 mg CFZ. Patients <50 kg who received ≥200 mg were 40% less likely to have a successful treatment outcome (adjusted OR 0.6, p=0.3), and were found to have a higher risk of adverse events than patients <50 kg receiving 100 mg CFZ (82.9% v. 65.5%).ConclusionsDose-weight interaction plays a role in the odds of a successful outcome. There is an association between dose-weight interactions, outcomes and adverse events. Weight-based dosing in patients <50 kg and ≥50 kg must be considered to achieve optimal treatment outcomes and reduce adverse events. Active drug safety monitoring must be implemented as a package of care for patients receiving CFZ as part of a DR-TB treatment regimen.

26 keywords...

hide…