How do antimycobacterial agents and protease inhibitors (PIs) interact?

Updated: Jan 15, 2019
  • Author: Jason F Okulicz, MD, FACP, FIDSA; Chief Editor: Michelle R Salvaggio, MD, FACP  more...
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Answer

Answer

Coadministration of bedaquiline with RTV-boosted PIs may result in increased AUC of bedaquiline; clinical significance unknown; use with caution if benefit outweighs the risk and monitor QTc prolongation and liver function tests.

ATV +/- RTV increases clarithromycin AUC; reduce the clarithromycin dose by 50% or consider alternative therapy; caution may cause QTc prolongation.

RTV-boosted PIs increase clarithromycin AUC; reduce the clarithromycin dose by 50% in patients with CrCl 30-60 mL/min; reduce by 75% in patients with CrCl < 30 mL/min.

FPV in combination with clarithromycin requires no dose adjustment.

FPV may increase rifabutin levels; when coadministered with FPV, a dose reduction of rifabutin by ≥50% of the recommended dose is required (150 mg/day or 300 mg 3 times/wk); when coadministered with FPV/RTV, a dose reduction of rifabutin by ≥75% of the usual dose is recommended (maximum dose of 150 mg every other day or 3 times/wk).

SQV has been shown to increase rifabutin concentrations; rifabutin dose reduction of ≥75% of usual dose of 300 mg/day is recommended (ie, a maximum dose of 150 mg every other day or 3 times/wk).

Coadministration of TPV with rifabutin may increase concentrations of rifabutin and its metabolite; reduce rifabutin dose 75% (eg, 150 mg every other day).

Concomitant use of rifabutin and DRV in the presence of RTV can increase rifabutin plasma concentrations and decrease DRV plasma concentrations; administer rifabutin 150 mg once every other day when coadministered with DRV/RTV.

ATV increases rifabutin concentrations; rifabutin dose reduction of up to 75% (eg, 150 mg every other day or 3 times/wk) is recommended.

LPV/ RTV may increase serum rifabutin levels; therefore, dosage reduction of rifabutin by ≥75% of the usual dose of 300 mg/day is recommended (ie, a maximum dose of 150 mg every other day or 3 times/wk).

Rifampin and PIs should not be coadministered.


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