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Drug-Drug Interactions

Table 25a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Note: Interactions associated with unboosted atazanavir (ATV), delavirdine (DLV), fosamprenavir (FPV), indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), nevirapine (NVP), saquinavir (SQV), and tipranavir (TPV) are not included in this table. Please refer to the U.S. Food and Drug Administration product labels for information regarding interactions between these drugs and other concomitant drugs.

Rilpivirine (RPV) intramuscular (IM) is not included in this table, because the combination of cabotegravir (CAB) IM plus RPV IM is a two-drug co-packaged product. Therefore, RPV IM is not expected to be used with a protease inhibitor.

PIsNNRTIs
DOREFVETRRPV
ATV/cPK Data

↑ DOR expected

↔ ATV expected

↔ EFV expected

↓ ATV possible

↓ COBI possible

↑ ETR possible

↓ ATV possible

↓ COBI possible

↑ RPV PO possible

↔ ATV expected

DoseNo 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.No dose adjustment needed
ATV/rPK 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
↑ RPV PO possible

↔ ATV expected
DoseNo 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 neededNo dose adjustment needed
DRV/cPK 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%
↔ DRV expected

↑ RPV PO possible
DoseNo dose adjustment neededDo not coadminister.Do not coadminister.No dose adjustment needed
DRV/rPK 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

RPV 150 mg PO Once Daily With (DRV 800 mg Plus RTV 100 mg) Once Daily

  • RPV PO AUC ↑ 130% and Cmin ↑ 178%
  • ↔ DRV
DoseNo dose adjustment neededClinical 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
Key to Symbols: 
↑ = increase
↓ = decrease
↔ = less than 20% change in AUC

Key: ART = antiretroviral therapy; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PO = oral; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir

Drug-Drug Interactions

Table 25a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

PIsNNRTIs
DOREFVETRRPV
ATV/cPK Data

↑ DOR expected

↔ ATV expected

↔ EFV expected

↓ ATV possible

↓ COBI possible

↑ ETR possible

↓ ATV possible

↓ COBI possible

↑ RPV PO possible

↔ ATV expected

DoseNo 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.No dose adjustment needed
ATV/rPK 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
↑ RPV PO possible

↔ ATV expected
DoseNo 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 neededNo dose adjustment needed
DRV/cPK 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%
↔ DRV expected

↑ RPV PO possible
DoseNo dose adjustment neededDo not coadminister.Do not coadminister.No dose adjustment needed
DRV/rPK 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

RPV 150 mg PO Once Daily With (DRV 800 mg Plus RTV 100 mg) Once Daily

  • RPV PO AUC ↑ 130% and Cmin ↑ 178%
  • ↔ DRV
DoseNo dose adjustment neededClinical 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
Key to Symbols: 
↑ = increase
↓ = decrease
↔ = less than 20% change in AUC

Key: ART = antiretroviral therapy; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PO = oral; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir

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