Updated
Reviewed
Dec. 18, 2019

Drug-Drug Interactions

Interactions between Integrase Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Table 22b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Recommendations for managing a particular drug interaction may differ depending on whether a new ARV drug is being initiated in a patient on a stable concomitant medication or a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly.

Table 22b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug Class INSTIs
BIC DTG EVG/c RAL
NNRTIs
DOR PK Data ↔ DOR and BIC expected ↔ DOR

DTG AUC ↑ 36% and Cmin ↑ 27%		 ↑ DOR expected

↔ EVG		 ↔ DOR and RAL expected
Dose No dose adjustment needed. No dose adjustment needed. No dose adjustment needed. No dose adjustment needed.
EFV PK Data ↓ BIC expected With DTG 50 mg Once Daily:
  • DTG AUC ↓ 57% and Cmin ↓ 75%
 ↑ or ↓ EVG, COBI, and EFV possible With RAL 400 mg Twice Daily:
  • RAL AUC ↓ 36% and Cmin ↓ 21%
With RAL 1,200 mg Once Daily:
  • ↔ RAL AUC and Cmin
Dose Do not coadminister. In Patients Without INSTI Resistance:
  • DTG 50 mg twice daily
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
 Do not coadminister. No dose adjustment needed.
ETR PK Data ↓ BIC expected ETR 200 mg Twice Daily plus DTG 50 mg Once Daily:
  • DTG AUC ↓ 71% and Cmin ↓ 88%
ETR 200 mg Twice Daily with (DRV 600 mg plus RTV 100 mg) Twice Daily and DTG 50 mg Once Daily:
  • DTG AUC ↓ 25% and Cmin ↓ 37%
ETR 200 mg Twice Daily with (LPV 400 mg plus RTV 100 mg) Twice Daily and DTG 50 mg Once Daily:
  • DTG AUC ↑ 11% and Cmin ↑ 28%
 ↑ or ↓ EVG, COBI, and ETR possible ETR 200 mg Twice Daily plus RAL 400 mg Twice Daily:
  • ETR Cmin ↑ 17%
  • RAL Cmin ↓ 34%
Dose Do not coadminister. Do not coadminister ETR and DTG without concurrently administering ATV/r, DRV/r, or LPV/r.

In Patients Without INSTI Resistance:
  • DTG 50 mg once daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • DTG 50 mg twice daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
 Do not coadminister. RAL 400 mg twice daily

Coadministration with RAL 1,200 mg once daily is not recommended.
NVP PK Data ↓ BIC expected With DTG 50 mg Once Daily:
  • DTG AUC ↓ 19% and Cmin ↓ 34%
 ↑ or ↓ EVG, COBI, and NVP possible No data
Dose Do not coadminister. No dose adjustment needed. Do not coadminister. No dose adjustment needed.
RPV PK Data No data With DTG 50 mg Once Daily:
  • ↔ DTG AUC and Cmin ↑ 22%
  • ↔ RPV AUC and Cmin ↑ 21%
 ↑ or ↓ EVG, COBI, and RPV possible ↔ RPV

RAL Cmin ↑ 27%
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister. No dose adjustment needed.
PIs
ATV PK Data ATV 400 mg Once Daily plus BIC 75 mg Single Dose:
  • BIC AUC ↑ 315%
 (ATV 400 mg plus DTG 30 mg) Once Daily:
  • DTG AUC ↑ 91% and Cmin ↑ 180%
 ↑ or ↓ EVG, COBI, and ATV possible No data
Dose Do not coadminister. No dose adjustment needed. Do not coadminister. No dose adjustment needed.
ATV/c PK Data BIC AUC ↑ 306% No data Not applicable No data
Dose Do not coadminister. No dose adjustment needed. Do not coadminister two COBI-containing products. No dose adjustment needed.
ATV/r PK Data ↑ BIC expected (ATV 300 mg plus RTV 100 mg) Once Daily plus DTG 30 mg Once Daily:
  • DTG AUC ↑ 62% and Cmin ↑ 121%
 Not applicable With Unboosted ATV:
  • RAL AUC ↑ 72%
With Unboosted ATV and RAL 1,200 mg:
  • RAL AUC ↑ 67%
With (ATV 300 mg plus RTV 100 mg) Once Daily:
  • RAL AUC ↑ 41%
Dose Do not coadminister. No dose adjustment needed. Do not coadminister RTV and COBI. No dose adjustment needed.
DRV PK Data Not applicable Not applicable ↔ DRV or EVG expected Not applicable
Dose Do not administer DRV without RTV or COBI. Do not administer DRV without RTV or COBI. No dose adjustment needed. Do not administer DRV without RTV or COBI.
DRV/c PK Data BIC AUC ↑ 74% DRV/c plus DTG Once Daily:
  • ↔ DTG, DRV, and COBI
DTG 50 mg Once Daily and DRV/r Once Daily Switched to DRV/c:
  • DTG Cmin ↑ 100%
 Not applicable No data
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister two COBI-containing products. No dose adjustment needed.
DRV/r PK Data No data (DRV 600 mg plus RTV 100 mg) Twice Daily with DTG 30 mg Once Daily:
  • DTG AUC ↓ 22% and Cmin ↓ 38%
 Not applicable With (DRV 600 mg plus RTV 100 mg) Twice Daily:
  • RAL AUC ↓ 29% and Cmin ↑ 38%
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister RTV and COBI. No dose adjustment needed.
LPV/r PK Data No data With (LPV 400 mg plus RTV 100 mg) Twice Daily and DTG 30 mg Once Daily:
  • ↔ DTG
 Not applicable ↓ RAL

↔ LPV/r
Dose Consider alternative combination. No dose adjustment needed. Do not coadminister RTV and COBI. No dose adjustment needed.
TPV/r PK Data ↓ BIC possible With (TPV 500 mg plus RTV 200 mg) Twice Daily and DTG 50 mg Once Daily:
  • DTG AUC ↓ 59% and Cmin ↓ 76%
 Not applicable With (TPV 500 mg plus RTV 200 mg) Twice Daily and RAL 400 mg Twice Daily:
  • RAL AUC ↓ 24% and Cmin ↓ 55%
Dose Do not coadminister. In Patients Without INSTI Resistance:
  • DTG 50 mg twice daily
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
 Do not coadminister RTV and COBI. RAL 400 mg twice daily

Coadministration with RAL 1,200 mg once daily is not recommended.
a Refer to DTG product label for details.

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

Key: ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmin = minimum plasma concentration; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

Drug-Drug Interactions

Interactions between Integrase Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Table 22b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Recommendations for managing a particular drug interaction may differ depending on whether a new ARV drug is being initiated in a patient on a stable concomitant medication or a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly.

Table 22b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug Class INSTIs
BIC DTG EVG/c RAL
NNRTIs
DOR PK Data ↔ DOR and BIC expected ↔ DOR

DTG AUC ↑ 36% and Cmin ↑ 27%		 ↑ DOR expected

↔ EVG		 ↔ DOR and RAL expected
Dose No dose adjustment needed. No dose adjustment needed. No dose adjustment needed. No dose adjustment needed.
EFV PK Data ↓ BIC expected With DTG 50 mg Once Daily:
  • DTG AUC ↓ 57% and Cmin ↓ 75%
 ↑ or ↓ EVG, COBI, and EFV possible With RAL 400 mg Twice Daily:
  • RAL AUC ↓ 36% and Cmin ↓ 21%
With RAL 1,200 mg Once Daily:
  • ↔ RAL AUC and Cmin
Dose Do not coadminister. In Patients Without INSTI Resistance:
  • DTG 50 mg twice daily
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
 Do not coadminister. No dose adjustment needed.
ETR PK Data ↓ BIC expected ETR 200 mg Twice Daily plus DTG 50 mg Once Daily:
  • DTG AUC ↓ 71% and Cmin ↓ 88%
ETR 200 mg Twice Daily with (DRV 600 mg plus RTV 100 mg) Twice Daily and DTG 50 mg Once Daily:
  • DTG AUC ↓ 25% and Cmin ↓ 37%
ETR 200 mg Twice Daily with (LPV 400 mg plus RTV 100 mg) Twice Daily and DTG 50 mg Once Daily:
  • DTG AUC ↑ 11% and Cmin ↑ 28%
 ↑ or ↓ EVG, COBI, and ETR possible ETR 200 mg Twice Daily plus RAL 400 mg Twice Daily:
  • ETR Cmin ↑ 17%
  • RAL Cmin ↓ 34%
Dose Do not coadminister. Do not coadminister ETR and DTG without concurrently administering ATV/r, DRV/r, or LPV/r.

In Patients Without INSTI Resistance:
  • DTG 50 mg once daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • DTG 50 mg twice daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
 Do not coadminister. RAL 400 mg twice daily

Coadministration with RAL 1,200 mg once daily is not recommended.
NVP PK Data ↓ BIC expected With DTG 50 mg Once Daily:
  • DTG AUC ↓ 19% and Cmin ↓ 34%
 ↑ or ↓ EVG, COBI, and NVP possible No data
Dose Do not coadminister. No dose adjustment needed. Do not coadminister. No dose adjustment needed.
RPV PK Data No data With DTG 50 mg Once Daily:
  • ↔ DTG AUC and Cmin ↑ 22%
  • ↔ RPV AUC and Cmin ↑ 21%
 ↑ or ↓ EVG, COBI, and RPV possible ↔ RPV

RAL Cmin ↑ 27%
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister. No dose adjustment needed.
PIs
ATV PK Data ATV 400 mg Once Daily plus BIC 75 mg Single Dose:
  • BIC AUC ↑ 315%
 (ATV 400 mg plus DTG 30 mg) Once Daily:
  • DTG AUC ↑ 91% and Cmin ↑ 180%
 ↑ or ↓ EVG, COBI, and ATV possible No data
Dose Do not coadminister. No dose adjustment needed. Do not coadminister. No dose adjustment needed.
ATV/c PK Data BIC AUC ↑ 306% No data Not applicable No data
Dose Do not coadminister. No dose adjustment needed. Do not coadminister two COBI-containing products. No dose adjustment needed.
ATV/r PK Data ↑ BIC expected (ATV 300 mg plus RTV 100 mg) Once Daily plus DTG 30 mg Once Daily:
  • DTG AUC ↑ 62% and Cmin ↑ 121%
 Not applicable With Unboosted ATV:
  • RAL AUC ↑ 72%
With Unboosted ATV and RAL 1,200 mg:
  • RAL AUC ↑ 67%
With (ATV 300 mg plus RTV 100 mg) Once Daily:
  • RAL AUC ↑ 41%
Dose Do not coadminister. No dose adjustment needed. Do not coadminister RTV and COBI. No dose adjustment needed.
DRV PK Data Not applicable Not applicable ↔ DRV or EVG expected Not applicable
Dose Do not administer DRV without RTV or COBI. Do not administer DRV without RTV or COBI. No dose adjustment needed. Do not administer DRV without RTV or COBI.
DRV/c PK Data BIC AUC ↑ 74% DRV/c plus DTG Once Daily:
  • ↔ DTG, DRV, and COBI
DTG 50 mg Once Daily and DRV/r Once Daily Switched to DRV/c:
  • DTG Cmin ↑ 100%
 Not applicable No data
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister two COBI-containing products. No dose adjustment needed.
DRV/r PK Data No data (DRV 600 mg plus RTV 100 mg) Twice Daily with DTG 30 mg Once Daily:
  • DTG AUC ↓ 22% and Cmin ↓ 38%
 Not applicable With (DRV 600 mg plus RTV 100 mg) Twice Daily:
  • RAL AUC ↓ 29% and Cmin ↑ 38%
Dose No dose adjustment needed. No dose adjustment needed. Do not coadminister RTV and COBI. No dose adjustment needed.
LPV/r PK Data No data With (LPV 400 mg plus RTV 100 mg) Twice Daily and DTG 30 mg Once Daily:
  • ↔ DTG
 Not applicable ↓ RAL

↔ LPV/r
Dose Consider alternative combination. No dose adjustment needed. Do not coadminister RTV and COBI. No dose adjustment needed.
TPV/r PK Data ↓ BIC possible With (TPV 500 mg plus RTV 200 mg) Twice Daily and DTG 50 mg Once Daily:
  • DTG AUC ↓ 59% and Cmin ↓ 76%
 Not applicable With (TPV 500 mg plus RTV 200 mg) Twice Daily and RAL 400 mg Twice Daily:
  • RAL AUC ↓ 24% and Cmin ↓ 55%
Dose Do not coadminister. In Patients Without INSTI Resistance:
  • DTG 50 mg twice daily
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
 Do not coadminister RTV and COBI. RAL 400 mg twice daily

Coadministration with RAL 1,200 mg once daily is not recommended.
a Refer to DTG product label for details.

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

Key: ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmin = minimum plasma concentration; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

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