Print

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

(Last updated:3/9/2015; last reviewed:30/7/2015)

Table 20a. Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors*

#1547 Pharmacokinetic enhancers - COBI
October 2017 - Feedback

Cobicistat (COBI) is only available within Australia as the co-formulated Stribild (EVG/cobi/ TDF/FTC), Genvoya (EVG/cobi/ TAF/FTC), Prezcobix (DRV/cobi) and Evotaz (ATV/cobi) It does not have TGA approval for use as a pharmacological booster with other antiretroviral agents and is not available as a single agent

*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.

 PIs

NNRTIs

EFV

ETR

NVP

RPVa

ATV
  Unboosted
PK data


ATV: AUC ↓ 74%
EFV: no significant change


ETR: AUC ↑ 50%, Cmax ↑ 47%, and Cmin ↑ 58%
ATV: AUC ↓ 17% and
Cmin ↓ 47%

↓ ATV possible
↑ RPV possible
Dose

Do not co-administer 

Do not co-administer  Do not co-administer  Standard doses
ATV/c PK Data ↓ ATV ↓ COBI ↓ ATV ↓ COBI ↓ COBI

↑ RPV possible

<-> ATV expected

Dose

EFV standard dose In ART-Naive Patients:

• ATV 400 mg plus COBI 150 mg Once Daily

Do not coadminister in ART-experienced patients.

Do not co-administer. Do not co-administer. Standard doses
ATV/r PK Data

(ATV 300 mg plus RTV 100 mg) Once Daily:

• ATV concentrations are similar to those with unboosted ATV without EFV.

(ATV 300 mg plus RTV 100 mg) Once Daily:

• ETR AUC and Cmin both ↑ ~30%

• ATV AUC <-> and Cmin ↓ 18%

(ATV 300 mg plus RTV 100 mg) Once Daily:

• ATV AUC ↓ 42% and Cmin ↓ 72%

• NVP AUC ↑ 25%

↑ RPV possible
Dose

EFV standard dose

In ART-Naive Patients:

• (ATV 400 mg plus RTV 100 mg) Once Daily

Do not coadminister in ART-experienced patients.

ETR standard dose

(ATV 300 mg plus RTV 100 mg) Once Daily

Do not co-administer. Standard doses
DRV/c PK Data

↓ DRV possible

↓ COBI possible

Effect on DRV unknown

↓ COBI possible

Effect on DRV unknown

↓ COBI possible

<-> DRV expected

↑ RPV possible

Dose Do not co-administer. Do not co-administer. Do not co-administer. Standard doses
DRV/r 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 doses

Safety and efficacy of this combination, despite decreased ETR concentration, have been established in a clinical trial.

Standard doses Standard doses
FPV +/- RTV 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
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, ATV/c = atazanavir/cobicistat, AUC = area under the curve, BID = twice daily, Cmax = maximum plasma concentration, Cmin = minimum plasma concentration, CYP = cytochrome P, DLV = delavirdine, 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, 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

 

ASHM - Supporting the HIV, Viral Hepatitis and Sexual Health Workforce