Quality of Evidence:
Pretomanid is metabolized in the liver via multiple reductive and oxidative pathways with CYP3A4 mediated metabolism representing 20% of its metabolism. Coadministration of lopinavir/ritonavir (400/100g mg twice daily) and pretomanid (200 mg once daily) reduced pretomanid exposure by 17% (n=16). No a priori dosage adjustment is needed for pretomanid. However, caution should be exercised as both drugs have possible risks of QT prolongation and/or TdP on the CredibleMeds.org website.
Coadministration of pretomanid (200 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) was studied in 16 healthy, HIV-uninfected subjects without TB disease. Compared to pretomanid alone, plasma pretomanid (based on geometric mean ratios) for Cmax, AUC and Cmin decreased by 13%, 17%, and 21%, respectively. There was no significant effect on lopinavir Cmax (17% decrease), AUC (14% decrease) or Cmin (3% increase). The effect of lopinavir/ritonavir on pretomanid was considered to be minimal and supports pretomanid use with lopinavir/ritonavir without dose adjustment.
Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin. Dooley KE, Luetkemeyer AF, Park JG, et al. Antimicrob Agents Chemother. 2014; 58(9):5245-52.
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