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.
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:
|
↑ or ↓ EVG, COBI, and EFV possible | With RAL 400 mg Twice Daily:
|
Dose | Do not coadminister. | In Patients Without INSTI Resistance:
|
Do not coadminister. | No dose adjustment needed. | |
ETR | PK Data | ↓ BIC expected | ETR 200 mg Twice Daily plus DTG 50 mg Once Daily:
|
↑ or ↓ EVG, COBI, and ETR possible | ETR 200 mg Twice Daily plus RAL 400 mg Twice Daily:
|
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:
|
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:
|
↑ 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:
|
↑ 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:
|
(ATV 400 mg plus DTG 30 mg) Once Daily:
|
↑ 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:
|
Not applicable | With Unboosted ATV:
|
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:
|
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:
|
Not applicable | With (DRV 600 mg plus RTV 100 mg) Twice Daily:
|
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:
|
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:
|
Not applicable | With (TPV 500 mg plus RTV 200 mg) Twice Daily and RAL 400 mg Twice Daily:
|
Dose | Do not coadminister. | In Patients Without INSTI Resistance:
|
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.
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:
|
↑ or ↓ EVG, COBI, and EFV possible | With RAL 400 mg Twice Daily:
|
Dose | Do not coadminister. | In Patients Without INSTI Resistance:
|
Do not coadminister. | No dose adjustment needed. | |
ETR | PK Data | ↓ BIC expected | ETR 200 mg Twice Daily plus DTG 50 mg Once Daily:
|
↑ or ↓ EVG, COBI, and ETR possible | ETR 200 mg Twice Daily plus RAL 400 mg Twice Daily:
|
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:
|
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:
|
↑ 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:
|
↑ 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:
|
(ATV 400 mg plus DTG 30 mg) Once Daily:
|
↑ 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:
|
Not applicable | With Unboosted ATV:
|
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:
|
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:
|
Not applicable | With (DRV 600 mg plus RTV 100 mg) Twice Daily:
|
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:
|
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:
|
Not applicable | With (TPV 500 mg plus RTV 200 mg) Twice Daily and RAL 400 mg Twice Daily:
|
Dose | Do not coadminister. | In Patients Without INSTI Resistance:
|
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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