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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Drug Interactions

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

(Last updated:3/27/2012; last reviewed:2/12/2013)

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*Delavirdine (DLV), indinavir (IDV), and Nelfinavir (NFV) are not included in this table. Refer to the DLV, IDV, and NFV Food and Drug Administration package inserts for information regarding drug interactions.

 

Table 16b. Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors*
No title EFV ETR NVP RPVa
ATV
 +/-
RTV
PK data With unboosted ATV
ATV: AUC ↓ 74%
EFV: no significant change
With (ATV 300 mg + RTV 100 mg) once daily with food
ATV concentrations similar to those with unboosted ATV without EFV 
With unboosted ATV
ETR: AUC ↑ 50%, Cmax ↑ 47%, and Cmin ↑ 58%
ATV: AUC ↓ 17% and
Cmin ↓ 47%
With (ATV 300 mg + RTV 100 mg) once daily
ETR: AUC, Cmax, and Cmin ↑ approximately 30%
ATV: AUC ↓ 14% and
Cmin ↓ 38%
With (ATV 300 mg + RTV 100 mg) once daily
ATV: AUC ↓ 42%
and
Cmin ↓ 72%
NVP: AUC ↑ 25%
With boosted and unboosted ATV
↑ RPV possible
Dose Do not co-administer with unboosted ATV. In ART-naive patients
(ATV 400 mg + RTV 100 mg) once daily
Do not co-administer in ART experienced patients.
Do not co-administer with
ATV +/− RTV.
Do not co-administer with ATV +/− RTV. Standard
DRV
(always use with RTV)
PK Data With (DRV 300 mg + RTV 100 mg) BID
DRV: AUC ↓ 13%, Cmin ↓ 31%
EFV: AUC ↑ 21%
ETR 100 mg BID with (DRV 600 mg + RTV 100 mg) BID
DRV: no significant change
ETR: AUC ↓ 37%, Cmin ↓ 49%
With (DRV 400 mg + RTV 100 mg) BID
DRV: AUC ↑ 24%b
NVP: AUC ↑ 27% and
Cmin ↑ 47%
RPV 150 mg once daily with (DRV 800 mg + RTV 100 mg) once daily
DRV: no significant change
RPV: AUC ↑ 130% and Cmin ↑ 178%
Dose Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. Standard (ETR 200 mg BID). Safety and efficacy of this combination, despite decreased ETR concentration, have been established in a clinical trial. Standard Standard
EFV PK Data ↓ ETR possible NVP: no significant change
EFV: AUC ↓ 22%
↓ RPV possible
Dose Do not co-administer. Do not co-administer. Do not co-administer. 
ETR PK Data ↓ ETR possible ↓ ETR possible ↓ RPV possible
Dose Do not co-administer. Do not co-administer. Do not co-administer.
FPV PK Data With (FPV 1400 mg + RTV 200 mg) once daily
APV: Cmin ↓ 36%
With (FPV 700 mg + RTV 100 mg) BID
APV: AUC ↑ 69%, Cmin ↑ 77%
With unboosted FPV 1400 mg BID
APV: AUC ↓ 33%
NVP: AUC ↑ 29%
With (FPV 700 mg + RTV 100 mg) BID
NVP: Cmin ↑ 22% 
With boosted and unboosted FPV
↑ RPV possible
Dose (FPV 1400 mg + RTV 300 mg) once daily or (FPV 700 mg + RTV 100 mg) BID
EFV standard
Do not co-administer with
FPV +/− RTV.
(FPV 700 mg + RTV 100 mg) BID
NVP standard
Standard
LPV/r PK Data With LPV/r tablets 500/125 mg BIDc + EFV 600 mg
LPV levels similar to
LPV/r 400/100 mg BID without EFV
With LPV/r tablets
ETR: AUC ↓ 35% (comparable to the decrease with DRV/r)
LPV: AUC↓ 13%
With LPV/r capsules
LPV: AUC ↓ 27% and Cmin ↓51%
RPV 150 mg once daily with LPV/r capsules
LPV: no significant change
RPV: AUC ↑ 52% and
Cmin ↑ 74%
Dose LPV/r tablets 500/125 mgc BID; LPV/r oral solution 533/133 mg BID EFV standard Standard LPV/r tablets 500/125 mgc BID; LPV/r oral solution 533/133 mg BID NVP standard Standard
NVP PK Data NVP: no significant change
EFV: AUC ↓ 22%
↓ ETR possible ↓ RPV possible
Dose Do not co-administer. Do not co-administer.  Do not co-administer. 
RPV PK Data ↓ RPV possible ↓ RPV possible ↓ RPV possible
Dose Do not co-administer.  Do not co-administer.  Do not co-administer. 
RTV PK Data Refer to information for boosted PI. Refer to information for boosted PI. Refer to information for boosted PI. Refer to information for boosted PI.
Dose
SQV
(always use with RTV)
PK Data With SQV 1200 mg TID
SQV: AUC ↓ 62%
EFV: AUC ↓ 12%
With (SQV 1000 mg + RTV 100 mg) BID
SQV: AUC unchanged
ETR: AUC ↓ 33%, Cmin ↓ 29%
Reduced ETR levels similar to reduction with DRV/r
With 600 mg TID
SQV: AUC ↓ 24%
NVP: no significant change
↑ RPV possible
Dose (SQV 1000 mg + RTV 100 mg) BID (SQV 1000 mg +
RTV 100 mg) BID
Dose with SQV/r not established Standard
TPV
(always use with RTV)
PK Data With (TPV 500 mg +
RTV 100 mg) BID

TPV: AUC ↓ 31%, Cmin ↓ 42%
EFV: no significant change
With (TPV 750 mg +
RTV 200 mg) BID
TPV: no significant change
EFV: no significant change
With (TPV 500 mg +
RTV 200 mg) BID
ETR: AUC ↓ 76%, Cmin ↓ 82%
TPV: AUC ↑ 18%, Cmin ↑ 24%
With (TPV 250 mg +
RTV 200 mg) BID and with (TPV 750 mg +
RTV 100 mg) BID
NVP: no significant change
TPV: no data
↑ RPV possible
Dose Standard Do not co-administer.  Standard Standard
a Approved dose for RPV is 25 mg once daily. Most PK interaction studies were performed using 75 mg to 150 mg per dose.

b Based on between-study comparison.

c Use a combination of two LPV/r 200 mg/50 mg tablets + one LPV/r 100 mg/25 mg tablet to make a total dose of LPV/r 500 mg/125 mg. Key to Abbreviations: APV = amprenavir, ART = antiretroviral therapy, ATV = atazanavir, AUC = area under the curve, BID = twice daily, Cmax = maximum plasma concentration, Cmin = minimum plasma concentration, CYP = cytochrome P, DLV = delavirdine, DRV = darunavir, DRV/r = darunavir/ritonavir, EFV = efavirenz, ETR = etravirine, FDA = Food and Drug Administration, FPV = fosamprenavir, IDV = indinavir, LPV = lopinavir, LPV/r = lopinavir/ritonavir, MVC = maraviroc, NFV = nelfinavir, NVP = nevirapine, PI = protease inhibitor, PK = pharmacokinetic, RAL = raltegravir, RPV = rilpivirine, RTV = ritonavir, SQV = saquinavir, SQV/r = saquinavir/ritonavir, TID = three times a day, TPV = tipranavir