Drug-Drug Interactions

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Table 22a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Note: Interactions associated with DLV, FPV, IDV, NFV, and SQV are not included in this table. Please refer to the FDA product labels for information regarding interactions between these drugs and other concomitant drugs.

Table 22a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors
PIs NNRTIs
DOR EFV ETR NVP RPV
ATV
Unboosted
PK Data ↑ DOR expected

↔ ATV expected
↔ EFV

ATV AUC ↓ 74%
ETR AUC ↑ 50% and Cmin ↑ 58%

↔ ATV AUC and Cmin ↓ 47%
↑ NVP possible

↓ ATV possible
↑ RPV possible

↔ ATV expected
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/c PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

↓ ATV possible

↓ COBI possible
↑ ETR possible

↓ ATV possible

↓ COBI possible
↑ NVP possible

↓ ATV possible

↓ COBI possible
↑ RPV possible

↔ ATV expected
Dose No dose adjustment needed. ATV/c in ART-Naive Patients:
  • ATV 400 mg plus COBI 150 mg once daily
  • Do not use coformulated ATV 300 mg/COBI 150 mg.
ATV/c in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/r PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

(ATV 400 mg plus RTV 100 mg) Once Daily:
  • ATV concentrations similar to (ATV 300 mg plus RTV 100 mg) without EFV
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ETR AUC and Cmin both ↑ ~30%
  • ↔ ATV AUC and Cmin
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ATV AUC ↓ 42% and Cmin ↓ 72%
  • NVP AUC ↑ 25%
↑ RPV possible

↔ ATV expected
Dose No dose adjustment needed. ATV/r in ART-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) once daily
ATV/r in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
No dose adjustment needed. Do not coadminister. No dose adjustment needed.
DRV/c PK Data ↑ DOR expected

↔ DRV expected
↔ EFV expected

↓ DRV possible

↓ COBI possible
ETR 400 mg Once Daily with (DRV 800 mg plus COBI 150 mg) Once Daily:
  • ↔ ETR AUC and Cmin
  • ↔ DRV AUC and Cmin ↓ 56%
  • COBI AUC ↓ 30% and Cmin ↓ 66%
↑ NVP possible

↓ DRV possible

↓ COBI possible
↔ DRV expected

↑ RPV possible
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
DRV/r PK Data ↑ DOR expected

↔ DRV expected
With (DRV 300 mg plus RTV 100 mg) Twice Daily:
  • EFV AUC ↑ 21%
  • ↔ DRV AUC and Cmin ↓ 31%
ETR 100 mg Twice Daily with (DRV 600 mg plus RTV 100 mg) Twice Daily:
  • ETR AUC ↓ 37% and Cmin ↓ 49%
  • ↔ DRV
With (DRV 400 mg plus RTV 100 mg) Twice Daily:
  • NVP AUC ↑ 27% and Cmin ↑ 47%
  • DRV AUC ↑ 24%a
RPV 150 mg Once Daily with (DRV 800 mg plus RTV 100 mg) Once Daily:
  • RPV AUC ↑ 130% and Cmin ↑ 178%
  • ↔ DRV
Dose No dose adjustment needed. Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. No dose adjustment needed.

Despite reduced ETR concentration, safety and efficacy of this combination have been established in a clinical trial.
No dose adjustment needed. No dose adjustment needed.
LPV/r PK Data ↑ DOR expected

↔ LPV expected
↔ EFV expected

With LPV/r 500 mg/125 mgTwice Daily:
  • LPV concentration similar to that of LPV/r 400 mg/100 mg twice daily without EFV
ETR AUC ↓ 35% (comparable to the decrease seen with DRV/r)

↔ LPV AUC
↑ NVP possible

LPV AUC ↓ 27% and Cmin ↓ 51%
RPV 150 mg Once Daily with LPV/r:
  • RPV AUC ↑ 52% and Cmin ↑ 74%
  • ↔ LPV
Dose No dose adjustment needed. LPV/r 500 mg/125 mgb twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for EFV.
No dose adjustment needed. LPV/r 500 mg/125 mgc twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for NVP.
No dose adjustment needed.
TPV/r

Note: Always use TPV with RTV
PK Data ↑ DOR expected

↔ TPV expected
With (TPV 500 mg plus RTV 100 mg) Twice Daily:
  • ↔ EFV
  • TPV AUC ↓ 31% and Cmin ↓ 42%
With (TPV 750 mg plus RTV 200 mg) Twice Daily:
  • ↔ EFV and TPV
With (TPV 500 mg plus RTV 200 mg) Twice Daily:
  • ETR AUC ↓ 76% and Cmin ↓ 82%
  • ↔ TPV AUC and Cmin ↑ 24%
With (TPV 250 mg plus RTV 200 mg) Twice Daily or with (TPV 750 mg plus RTV 100 mg) Twice Daily:
  • ↔ NVP
  • ↔ TPV expected
↑ RPV possible

↔ TPV expected
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister. No dose adjustment needed. No dose adjustment needed.
a DRV concentration was compared to a historic control.

b Use a combination of two LPV/r 200 mg/50 mg tablets plus one LPV/r 100 mg/25 mg tablet to make a total dose of LPV/r 500 mg/125 mg.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat; DLV = delavirdine; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; FDA = Food and Drug Administration; FPV = fosamprenavir; IDV = indinavir; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

Drug-Drug Interactions

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Table 22a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Note: Interactions associated with DLV, FPV, IDV, NFV, and SQV are not included in this table. Please refer to the FDA product labels for information regarding interactions between these drugs and other concomitant drugs.

Table 22a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors
PIs NNRTIs
DOR EFV ETR NVP RPV
ATV
Unboosted
PK Data ↑ DOR expected

↔ ATV expected
↔ EFV

ATV AUC ↓ 74%
ETR AUC ↑ 50% and Cmin ↑ 58%

↔ ATV AUC and Cmin ↓ 47%
↑ NVP possible

↓ ATV possible
↑ RPV possible

↔ ATV expected
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/c PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

↓ ATV possible

↓ COBI possible
↑ ETR possible

↓ ATV possible

↓ COBI possible
↑ NVP possible

↓ ATV possible

↓ COBI possible
↑ RPV possible

↔ ATV expected
Dose No dose adjustment needed. ATV/c in ART-Naive Patients:
  • ATV 400 mg plus COBI 150 mg once daily
  • Do not use coformulated ATV 300 mg/COBI 150 mg.
ATV/c in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/r PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

(ATV 400 mg plus RTV 100 mg) Once Daily:
  • ATV concentrations similar to (ATV 300 mg plus RTV 100 mg) without EFV
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ETR AUC and Cmin both ↑ ~30%
  • ↔ ATV AUC and Cmin
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ATV AUC ↓ 42% and Cmin ↓ 72%
  • NVP AUC ↑ 25%
↑ RPV possible

↔ ATV expected
Dose No dose adjustment needed. ATV/r in ART-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) once daily
ATV/r in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
No dose adjustment needed. Do not coadminister. No dose adjustment needed.
DRV/c PK Data ↑ DOR expected

↔ DRV expected
↔ EFV expected

↓ DRV possible

↓ COBI possible
ETR 400 mg Once Daily with (DRV 800 mg plus COBI 150 mg) Once Daily:
  • ↔ ETR AUC and Cmin
  • ↔ DRV AUC and Cmin ↓ 56%
  • COBI AUC ↓ 30% and Cmin ↓ 66%
↑ NVP possible

↓ DRV possible

↓ COBI possible
↔ DRV expected

↑ RPV possible
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
DRV/r PK Data ↑ DOR expected

↔ DRV expected
With (DRV 300 mg plus RTV 100 mg) Twice Daily:
  • EFV AUC ↑ 21%
  • ↔ DRV AUC and Cmin ↓ 31%
ETR 100 mg Twice Daily with (DRV 600 mg plus RTV 100 mg) Twice Daily:
  • ETR AUC ↓ 37% and Cmin ↓ 49%
  • ↔ DRV
With (DRV 400 mg plus RTV 100 mg) Twice Daily:
  • NVP AUC ↑ 27% and Cmin ↑ 47%
  • DRV AUC ↑ 24%a
RPV 150 mg Once Daily with (DRV 800 mg plus RTV 100 mg) Once Daily:
  • RPV AUC ↑ 130% and Cmin ↑ 178%
  • ↔ DRV
Dose No dose adjustment needed. Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. No dose adjustment needed.

Despite reduced ETR concentration, safety and efficacy of this combination have been established in a clinical trial.
No dose adjustment needed. No dose adjustment needed.
LPV/r PK Data ↑ DOR expected

↔ LPV expected
↔ EFV expected

With LPV/r 500 mg/125 mgTwice Daily:
  • LPV concentration similar to that of LPV/r 400 mg/100 mg twice daily without EFV
ETR AUC ↓ 35% (comparable to the decrease seen with DRV/r)

↔ LPV AUC
↑ NVP possible

LPV AUC ↓ 27% and Cmin ↓ 51%
RPV 150 mg Once Daily with LPV/r:
  • RPV AUC ↑ 52% and Cmin ↑ 74%
  • ↔ LPV
Dose No dose adjustment needed. LPV/r 500 mg/125 mgb twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for EFV.
No dose adjustment needed. LPV/r 500 mg/125 mgc twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for NVP.
No dose adjustment needed.
TPV/r

Note: Always use TPV with RTV
PK Data ↑ DOR expected

↔ TPV expected
With (TPV 500 mg plus RTV 100 mg) Twice Daily:
  • ↔ EFV
  • TPV AUC ↓ 31% and Cmin ↓ 42%
With (TPV 750 mg plus RTV 200 mg) Twice Daily:
  • ↔ EFV and TPV
With (TPV 500 mg plus RTV 200 mg) Twice Daily:
  • ETR AUC ↓ 76% and Cmin ↓ 82%
  • ↔ TPV AUC and Cmin ↑ 24%
With (TPV 250 mg plus RTV 200 mg) Twice Daily or with (TPV 750 mg plus RTV 100 mg) Twice Daily:
  • ↔ NVP
  • ↔ TPV expected
↑ RPV possible

↔ TPV expected
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister. No dose adjustment needed. No dose adjustment needed.
a DRV concentration was compared to a historic control.

b Use a combination of two LPV/r 200 mg/50 mg tablets plus one LPV/r 100 mg/25 mg tablet to make a total dose of LPV/r 500 mg/125 mg.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat; DLV = delavirdine; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; FDA = Food and Drug Administration; FPV = fosamprenavir; IDV = indinavir; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir
Updated
Reviewed
Dec. 18, 2019

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