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Drug-Drug Interactions

Table 25b. 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 antiretroviral (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.

Information on drug interactions with oral (PO) cabotegravir (CAB) is not included in this table. The CAB PO tablet is not available in retail pharmacies and will be provided directly to people with HIV for short-term use only (PO lead-in and to bridge if intramuscular [IM] administration is delayed).

CAB IM and rilpivirine (RPV) IM are not included in this table because the combination is a two-drug, co-packaged product. Therefore, it is not anticipated that they will be used with PO non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs).

ARV Drugs by Drug ClassINSTIs
BICDTGEVG/cRAL
NNRTIs
DORPK Data↔ DOR and BIC expected

↔ DOR

DTG AUC ↑ 36% and Cmin ↑ 27%

↑ DOR expected

↔ EVG

↔ DOR and RAL expected
DoseNo dose adjustment needed.No dose adjustment needed.No dose adjustment needed.No dose adjustment needed.
EFVPK 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
DoseDo 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.
ETRPK 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%
↑ or ↓ EVG, COBI, and ETR possible

ETR 200 mg Twice Daily Plus RAL 400 mg Twice Daily

  • ETR Cmin ↑ 17%
  • RAL Cmin ↓ 34%
DoseDo not coadminister.

Do not coadminister ETR and DTG without concurrently administering ATV/r or DRV/r.

In Patients Without INSTI Resistance

  • DTG 50 mg once daily with ETR (concurrently with ATV/r or DRV/r)

In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance

  • DTG 50 mg twice daily with ETR (concurrently with ATV/r or DRV/r)
Do not coadminister.

RAL 400 mg twice daily

Coadministration with RAL 1,200 mg once daily is not recommended.

RPVPK DataNo data

With DTG 50 mg Once Daily

  • ↔ DTG AUC and Cmin ↑ 22%
  • ↔ RPV PO AUC and Cmin ↑ 21%
↑ RPV PO possible

↔ RPV PO

RAL Cmin ↑ 27% 

DoseNo dose adjustment needed.No dose adjustment needed.Do not coadminister.No dose adjustment needed.
PIs
ATV/cPK DataBIC AUC ↑ 306%No dataNot applicableNo data
DoseDo not coadminister.No dose adjustment needed.Do not coadminister two COBI-containing products.No dose adjustment needed.
ATV/rPK 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 (ATV 300 mg Plus RTV 100 mg) Once Daily

  • RAL AUC ↑ 41%
DoseDo not coadminister.No dose adjustment needed.Do not coadminister RTV and COBI.No dose adjustment needed.
DRVPK DataNot applicableNot applicable↔ DRV or EVG expectedNot applicable
DoseDo 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/cPK DataBIC 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 applicableNo data
DoseNo dose adjustment needed.No dose adjustment needed.Do not coadminister two COBI-containing products.No dose adjustment needed.
DRV/rPK DataNo 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%
DoseNo dose adjustment needed.No dose adjustment needed.Do not coadminister RTV and COBI.No dose adjustment needed.
a Refer to DTG product label for details.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = less than 20% change in AUC

Key: ARV = antiretroviral; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmin = minimum plasma concentration; COBI = cobicistat; 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; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PK = pharmacokinetic; PO = oral; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir

Drug-Drug Interactions

Table 25b. Interactions Between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug ClassINSTIs
BICDTGEVG/cRAL
NNRTIs
DORPK Data↔ DOR and BIC expected

↔ DOR

DTG AUC ↑ 36% and Cmin ↑ 27%

↑ DOR expected

↔ EVG

↔ DOR and RAL expected
DoseNo dose adjustment needed.No dose adjustment needed.No dose adjustment needed.No dose adjustment needed.
EFVPK 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
DoseDo 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.
ETRPK 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%
↑ or ↓ EVG, COBI, and ETR possible

ETR 200 mg Twice Daily Plus RAL 400 mg Twice Daily

  • ETR Cmin ↑ 17%
  • RAL Cmin ↓ 34%
DoseDo not coadminister.

Do not coadminister ETR and DTG without concurrently administering ATV/r or DRV/r.

In Patients Without INSTI Resistance

  • DTG 50 mg once daily with ETR (concurrently with ATV/r or DRV/r)

In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance

  • DTG 50 mg twice daily with ETR (concurrently with ATV/r or DRV/r)
Do not coadminister.

RAL 400 mg twice daily

Coadministration with RAL 1,200 mg once daily is not recommended.

RPVPK DataNo data

With DTG 50 mg Once Daily

  • ↔ DTG AUC and Cmin ↑ 22%
  • ↔ RPV PO AUC and Cmin ↑ 21%
↑ RPV PO possible

↔ RPV PO

RAL Cmin ↑ 27% 

DoseNo dose adjustment needed.No dose adjustment needed.Do not coadminister.No dose adjustment needed.
PIs
ATV/cPK DataBIC AUC ↑ 306%No dataNot applicableNo data
DoseDo not coadminister.No dose adjustment needed.Do not coadminister two COBI-containing products.No dose adjustment needed.
ATV/rPK 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 (ATV 300 mg Plus RTV 100 mg) Once Daily

  • RAL AUC ↑ 41%
DoseDo not coadminister.No dose adjustment needed.Do not coadminister RTV and COBI.No dose adjustment needed.
DRVPK DataNot applicableNot applicable↔ DRV or EVG expectedNot applicable
DoseDo 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/cPK DataBIC 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 applicableNo data
DoseNo dose adjustment needed.No dose adjustment needed.Do not coadminister two COBI-containing products.No dose adjustment needed.
DRV/rPK DataNo 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%
DoseNo dose adjustment needed.No dose adjustment needed.Do not coadminister RTV and COBI.No dose adjustment needed.
a Refer to DTG product label for details.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = less than 20% change in AUC

Key: ARV = antiretroviral; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmin = minimum plasma concentration; COBI = cobicistat; 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; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PK = pharmacokinetic; PO = oral; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir

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