Lopinavir/Ritonavir + Rifampin = Precautionary

Effect on Concentration

Lopinavir/Ritonavir
Decrease
Applies within class?
No
Rifampin
No change
Applies within class?
No

Pharmacologic Effects

Lopinavir/Ritonavir
Effect
N/A
Applies within class?
No
Rifampin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 02-Jul-2018

Summary

Adjusted-dose regimens of lopinavir-ritonavir in combination with therapeutic drug monitoring and monitoring of liver function may allow concomitant use of rifampin.

Sources

Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets. ^

Study Design

Authors evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults virologically suppressed on an LPV/r regimen who were given rifampin, and the dose of the LPV/r tablet formulation was gradually increased. The steady-state pharmacokinetics of LPV/r were evaluated at baseline, a week after commencing rifampin, a week after the LPV/r dose was increased 1.5 times, and a week after the LPV/r dose was doubled. Twenty-one participants were enrolled.

Study Results

The median [interquartile range (IQR)] predose LPV concentrations (C0) were 8.1 (6.2 to 9.8) mg/liter at baseline, 1.7 (0.3 to 3.0) mg/liter after 7 days of rifampin, 5.9 (2.1 to 9.9) mg/liter with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/liter with double-dose LPV/r. There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC0-12), C0, C12, maximum concentration of drug in serum (Cmax), or half-life (t1/2) between the baseline and double-dose LPV/r time points. Treatment was generally well tolerated, with two participants developing asymptomatic grade 3/4 transaminitis.

Study Conclusions

Adjusted-dose regimens of lopinavir-ritonavir in combination with therapeutic drug monitoring and monitoring of liver function may allow concomitant use of rifampin. Doubling the dose of the tablet formulation of LPV/r overcomes induction by rifampin. Less hepatotoxicity occurred in our cohort of HIV-infected participants than was reported in healthy-volunteer studies.

References

Decloedt EH, McIlleron H, Smith P, Merry C, Orrell C, Maartens G. Pharmacokinetics of lopinavir in hiv-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets. Antimicrobial Agents And Chemotherapy . 2011; 7: 3195-3200.