Rifampicin Can Be Given as Flat-Dosing Instead of Weight-Band Dosing

Abstract

Background The weight-band dosing in tuberculosis treatment regimen has been implemented in clinical practice for decades. Patients will receive different number of fixed dose combination tablets according to their weight-band. However, some analysis has shown that weight was not the best covariate to explain variability of rifampicin exposure. Furthermore, the rationale for using weight-band dosing instead of flat-dosing becomes questionable. Therefore, this study aimed to compare the average and the variability of rifampicin exposure after weight-band dosing and flat-dosing. Methods Rifampicin exposure were simulated using previously published population pharmacokinetics model at dose 10–40 mg/kg for weight-band dosing and dose 600–2400 mg for flat-dosing. The median area under the curve (AUC0–24 h) after day 7 and 14 were compared as well as the variability of each dose group between weight-band and flat-dosing. Results The difference of median AUC0–24 h of all dose groups between flat-dosing and weight-band dosing were considered low (< 20%) except for the lowest dose. At the dose of 10 mg/kg (600 mg for flat-dosing), flat-dosing resulted in higher median AUC0–24h compared to the weight-band dosing. A marginal decrease in between-patient variability was predicted for weight-band dosing compared to flat-dosing. Conclusions Weight-band dosing yields a small and non-clinically relevant decrease in variability of AUC0–24h.

A narrative review of tuberculosis in the United States among persons aged 65 years and older

“…In patients who are greater than 10% below ideal body weight, clinicians may need to prolong treatment if there is delayed mycobacterial eradication or clinical evidence of poor treatment response. However, some studies have suggested that dosing adjustments for low body weight leads to low plasma drug levels and treatment inefficacy, particularly for rifamycin drugs [60] , [61] . Clinicians must balance the risk of adverse effects with the danger of treatment failure.…”

Population pharmacokinetics analyses of rifampicin in adult and children populations: A systematic review

“…A total of 19 studies, of which 16 involved adults, 19,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] two involved children 50,51 and one involved both adults and children, were included in the review. 47 Six studies were conducted in South Africa, 31,32,52,53,54,55 two in China, 36,43 Mexico, 37,56 South Korea 30,39 and Uganda, 19,49 and one each in Japan, 35 Ghana, 46 Malawi, 47 Singapore 40 and Tanzania. 38 Overall, the number of subjects who participated in the included studies ranged from 25 to 261, while the total number of blood samples ranged between 95 and 2913.…”

Individualized Dosing With High Inter-Occasion Variability Is Correctly Handled With Model-Informed Precision Dosing—Using Rifampicin as an Example

“…In addition, there is a moderate IIV (IIV in AUC 0-24h of 25.4%) (Al-Sallami et al, 2014), and high IOV (IOV in AUC 0-24h of 25.8%) in the PK, which creates difficulties in performing individual dosing. Rifampicin IIV leads to variation in exposure between patients given the same dose, even if weight-based dosing is used (Susanto et al, 2019). While some of the variability between patients can be explained with patient characteristics such as HIV co-infection or sex (McIlleron et al, 2006), differences in drug formulations (McIlleron et al, 2006), pharmacogenetic factors (Weiner et al, 2010;Chigutsa et al, 2011), and variability in drug absorption, depending on concomitant food intake (Polasa and Krishnaswamy, 1983;Zent and Smith, 1995;Peloquin et al, 1999), some remain unexplained and are expressed as IIV.…”