Updated
Reviewed
Jun. 03, 2021

Drug-Drug Interactions

Drug Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Other Drugs

Table 24b. Drug Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Other Drugs

This table provides information on the known or predicted interactions between non-nucleoside reverse transcriptase inhibitors (NNRTIs) and non-antiretroviral (ARV) drugs. Cabotegravir (CAB) intramuscular (IM) plus rilpivirine (RPV) IM are co-packaged into a single product and are coadministered as a complete regimen; therefore, the dosing recommendations and clinical comments reflect the combination of CAB IM and RPV IM treatments. Drug interaction studies were not conducted with either CAB IM or RPV IM. Drug interaction studies with oral CAB and RPV were leveraged to make the dosing recommendations for CAB IM and RPV IM. For information regarding interactions between NNRTIs and other ARV drugs, including dosing recommendations, refer to Tables 24c, 25a, and 25b.

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 if 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. When an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgment to select the most appropriate alternative medication to use.

RPV 75 mg and 300 mg oral once daily (three and 12 times the recommended dose, respectively) were shown to prolong the QTc interval. Known and expected/theoretical pharmacokinetic interactions, resulting in increased RPV exposures, are included in this table due to the safety concern of QTc prolongation. There is limited information about the potential for pharmacodynamic interactions between RPV (in the absence of increased RPV exposures) and drugs that prolong the QTc interval; therefore, these are not included in this table.

Note: Delavirdine (DLV) is not included in this table. Please refer to the Food and Drug Administration product label for information regarding drug interactions between DLV and other concomitant drugs. The term “All NNRTIs” in this table refers to all NNRTIs except for DLV. 
 

Concomitant Drug NNRTI Effect on NNRTI and/or Concomitant Drug Concentrations Dosing Recommendations and Clinical Comments
Acid Reducers
Antacids DOR, EFV, NVP ↔ NNRTI AUC No dose adjustment needed.
ETR ↔ ETR expected No dose adjustment needed.
RPV IM ↔ RPV IM expected No dose adjustment needed.
RPV PO ↓ RPV expected when given simultaneously Give antacids at least 2 hours before or at least 4 hours after RPV.
H2 Receptor Antagonists DOR, NVP ↔ NNRTI expected No dose adjustment needed.
EFV ↔ EFV AUC No dose adjustment needed.
ETR ↔ ETR AUC No dose adjustment needed.
RPV IM ↔ RPV IM expected No dose adjustment needed.
RPV PO RPV AUC ↓ 76% when famotidine 40 mg is taken 2 hours prior Give H2 receptor antagonists at least 12 hours before or at least 4 hours after RPV.
Proton Pump Inhibitors DOR DOR AUC ↓ 17% and Cmin ↓ 16% No dose adjustment needed.
EFV, NVP ↔ EFV and NVP expected
ETR

With Omeprazole 40 mg Daily: 

  • ETR AUC ↑ 41%
RPV IM ↔ RPV IM expected No dose adjustment needed.
RPV PO

With Omeprazole 20 mg Daily:

  • RPV AUC ↓ 40% and Cmin ↓ 33%
 Contraindicated.
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin, Doxazosin, Silodosin, Terazosin DOR, RPV IM, RPV PO ↔ alpha-adrenergic antagonists expected No dose adjustment needed.
EFV, ETR, NVP ↓ alpha-adrenergic antagonists expected Consider alternative ARV or alpha-antagonist therapy. If coadministration is necessary, monitor for therapeutic effectiveness of alpha antagonist.
Tamsulosin DOR, RPV IM, RPV PO ↔ tamsulosin expected No dose adjustment needed.
EFV, ETR, NVP ↓ tamsulosin expected Monitor for therapeutic effectiveness of tamsulosin after 2–4 weeks. May need to increase dose to tamsulosin 0.8 mg once daily for patients who fail to respond to the 0.4-mg dose.
Antibacterials
Antimycobacterials
Bedaquiline DOR, RPV IM, RPV PO ↔ bedaquiline expected No dose adjustment needed.
EFV, ETR ↓ bedaquiline possible Do not coadminister.
NVP ↔ bedaquiline AUC No dose adjustment needed.
Rifabutin DOR DOR AUC ↓ 50% Increase DOR dose to 100 mg twice daily. No dose adjustment needed for rifabutin.
EFV Rifabutin ↓ 38% The recommended dosing range is rifabutin 450–600 mg per day.
ETR

↔ rifabutin and metabolite AUC ETR AUC ↓ 37%

Do not coadminister ETR plus PI/r with rifabutin.

Use rifabutin 300 mg once daily if ETR is administered without PI/r.
NVP Rifabutin AUC ↑ 17% and metabolite AUC ↑ 24% NVP Cmin ↓ 16% No dose adjustment needed.
RPV IM ↓ RPV IM expected Contraindicated.
RPV PO

Rifabutin plus RPV 50 mg PO Once Daily Compared to RPV 25 mg Once Daily Alone:

  • ↔ RPV AUC and Cmin
 Increase RPV dose to 50 mg PO once daily. No dose adjustment for rifabutin needed.
Rifampin DOR DOR AUC ↓ 88% Contraindicated. After stopping rifampin, wait 4 weeks before initiating DOR.
EFV EFV AUC ↓ 26% Do not use EFV 400 mg with rifampin. Maintain EFV dose at 600 mg once daily and monitor for virologic response.
ETR Significant ↓ ETR possible Do not coadminister.
NVP NVP ↓ 20% to 58% Do not coadminister.
RPV IM ↓ RPV IM expected Contraindicated.
RPV PO RPV PO AUC ↓ 80% Contraindicated.
Rifapentine DOR

DOR 100 Twice Daily plus Once-Weekly Rifapentine and INH Compared to DOR 100 mg Twice Daily Alone:

  • DOR AUC ↓ 29%, Cmin ↓ 31%
 Contraindicated. After stopping rifapentine, wait 4 weeks before initiating DOR.
EFV ↔ EFV concentrations No dose adjustment needed.
ETR ↓ ETR possible Do not coadminister.
NVP NVP Cmin ↓ 27% Do not coadminister.
RPV IM, RPV PO ↓ RPV expected Contraindicated.
Macrolides
Azithromycin All NNRTIs ↔ azithromycin expected No dose adjustment needed.
Clarithromycin DOR ↔ clarithromycin expected ↑ DOR possible Monitor for ARV tolerability if used in combination.
EFV Clarithromycin AUC ↓ 39% Monitor for effectiveness, or consider alternative agent (e.g., azithromycin) for MAC prophylaxis and treatment.
ETR Clarithromycin AUC ↓ 39% ETR AUC ↑ 42% Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
NVP Clarithromycin AUC ↓ 31% NVP AUC ↑ 26% Monitor for effectiveness, or consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
RPV IM, RPV PO ↔ clarithromycin expected ↑ RPV possible Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment. If coadministered, monitor for QTc prolongation.
Erythromycin DOR ↑ DOR possible Monitor for ARV tolerability if used in combination.
EFV, ETR, NVP ↑ EFV, ETR, and NVP possible ↓ erythromycin possible Monitor for ARV tolerability and antibiotic efficacy if used in combination.
RPV IM, RPV PO ↑ RPV PO or IM possible Consider alternative macrolide (e.g., azithromycin). If coadministered, monitor for QTc prolongation.
Anticoagulants
Apixaban DOR, RPV IM, RPV PO ↔ apixaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ apixaban possible Consider alternative ARV or anticoagulant therapy.
Dabigatran All NNRTIs ↔ dabigatran expected No dose adjustment needed.
Edoxaban All NNRTIs ↔ edoxaban expected No dose adjustment needed.
Rivaroxaban DOR, RPV IM, RPV PO ↔ rivaroxaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ rivaroxaban possible Consider alternative ARV or anticoagulant therapy.
Warfarin DOR, RPV IM, RPV PO ↔ warfarin expected No dose adjustment needed.
EFV, ETR, NVP ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose accordingly.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin DOR ↓ DOR possible Contraindicated. After stopping anticonvulsant, wait 4 weeks before initiating DOR.
EFV

Carbamazepine plus EFV:

  • Carbamazepine AUC ↓ 27%
  • EFV AUC ↓ 36%

Phenytoin plus EFV:

  • ↓ EFV
  • ↑ or ↓ phenytoin possible
 Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor anticonvulsant and EFV concentrations.
ETR ↓ anticonvulsant and ETR possible Do not coadminister.
NVP ↓ anticonvulsant and NVP possible Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor anticonvulsant and NVP concentrations and virologic response.
RPV IM, RPV PO ↓ RPV possible Contraindicated.
Eslicarbazepine All NNRTIs ↓ NNRTI possible Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor virologic response and consider monitoring plasma concentrations of ARVs.
Oxcarbazepine DOR, RPV IM, RPV PO ↓ NNRTI possible Contraindicated.
EFV, ETR, NVP ↓ NNRTI possible Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor virologic response and consider monitoring plasma concentrations of ARVs.
Ethosuximide, Lacosamide, Tiagabine, Zonisamide DOR, RPV IM, RPV PO ↔ anticonvulsant expected No dose adjustment needed.
EFV, ETR, NVP ↓ anticonvulsant possible Monitor seizure control. Consider anticonvulsant therapeutic drug monitoring.
Lamotrigine DOR, ETR, NVP, RPV IM, RPV PO ↔ lamotrigine expected No dose adjustment needed.
EFV ↓ lamotrigine possible Monitor seizure control and plasma concentrations of lamotrigine.
Antidepressants, Anxiolytics, and Antipsychotics Also see Sedative/Hypnotics section below.
Bupropion DOR, ETR, RPV IM, RPV PO ↔ bupropion expected No dose adjustment needed.
EFV Bupropion AUC ↓ 55% Titrate bupropion dose based on clinical response.
NVP ↓ bupropion possible
Citalopram, Escitalopram DOR, RPV IM, RPV PO ↔ antidepressant expected No dose adjustment needed.
EFV, ETR, NVP ↓ antidepressant possible Titrate antidepressant dose based on clinical response.
Fluoxetine, Fluvoxamine All NNRTIs ↔ antidepressant expected No dose adjustment needed.
Paroxetine DOR, NVP, RPV IM, RPV PO ↔ paroxetine expected No dose adjustment needed.
EFV, ETR ↔ paroxetine No dose adjustment needed.
Nefazodone DOR, RPV IM, RPV PO ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ nefazodone expected ↑ NNRTI possible Monitor antidepressant effect. Titrate dose as necessary based on clinical response.
Sertraline DOR, RPV IM, RPV PO ↔ sertraline expected No dose adjustment needed.
EFV Sertraline AUC ↓ 39% Monitor the antidepressant effect. Titrate dose as necessary based on clinical response.
ETR, NVP ↓ sertraline possible
Trazodone DOR, RPV IM, RPV PO ↔ trazodone expected No dose adjustment needed.
EFV, ETR, NVP ↓ trazodone possible Monitor for therapeutic effectiveness of trazodone and titrate dose as necessary.
Antipsychotics
Aripiprazole DOR, RPV IM, RPV PO ↔ aripiprazole expected No dose adjustment needed.
EFV, ETR, NVP ↓ aripiprazole expected Monitor for therapeutic effectiveness of antipsychotic. Consider doubling usual dose of aripiprazole over 1–2 weeks. Refer to aripiprazole prescribing information for dose recommendations.
Brexpiprazole DOR, RPV IM, RPV PO ↔ brexpiprazole expected No dose adjustment needed.
EFV, ETR, NVP ↓ brexpiprazole expected Monitor for therapeutic effectiveness of antipsychotic. Consider doubling the usual dose of brexpiprazole and making further adjustments based on clinical response. Refer to brexpiprazole prescribing information.
Cariprazine DOR, RPV IM, RPV PO ↔ cariprazine expected No dose adjustment needed.
EFV, ETR, NVP ↓ cariprazine and ↑ or ↓ active metabolite possible Do not coadminister.
Iloperidone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Lumateperone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Do not coadminister.
Lurasidone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Olanzapine DOR, ETR, NVP, RPV IM, RPV PO ↔ olanzapine expected No dose adjustment needed.
EFV ↓ olanzapine possible Monitor for therapeutic effectiveness of olanzapine.
Other Antipsychotics CYP3A4 substrates (e.g., clozapine, perphenazine, risperidone) DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Pimavanserin DOR, RPV IM, RPV PO ↔ pimavanserin expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimavanserin expected Do not coadminister.
Pimozide DOR, RPV IM, RPV PO ↔ pimozide expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimozide possible Monitor for therapeutic effectiveness of pimozide.
Quetiapine DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Ziprasidone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Antifungals
Fluconazole DOR ↑ DOR possible No dose adjustment needed.
EFV ↔ fluconazole ↔ EFV AUC No dose adjustment needed.
ETR ETR AUC ↑ 86% No dose adjustment needed.
NVP NVP AUC ↑ 110% Consider alternative ARV or antifungal agent. Increased risk of hepatotoxicity is possible with this combination.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Isavuconazole DOR ↑ DOR possible No dose adjustment needed.
EFV, ETR, NVP ↓ isavuconazole possible Monitor isavuconazole concentration and antifungal response. Dose adjustments for isavuconazole may be necessary.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Itraconazole DOR ↑ DOR possible No dose adjustment needed.
EFV Itraconazole and OH-itraconazole AUC, Cmax, and Cmin ↓ 37% to 44% Do not coadminister, unless potential benefits outweigh the risks. Failure to achieve therapeutic itraconazole concentrations has been reported. If coadministration is necessary, closely monitor itraconazole concentration and adjust dose accordingly.
ETR ↓ itraconazole possible ↑ ETR possible Dose adjustments for itraconazole may be necessary. Monitor itraconazole concentration and antifungal response.
NVP Itraconazole AUC ↓ 61% ↑ NVP possible Do not coadminister, unless potential benefits outweigh the risks. If coadministration is necessary, monitor itraconazole concentration and adjust dose accordingly.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Posaconazole DOR, ETR, NVP ↑ NNRTI possible No dose adjustment needed.
EFV Posaconazole AUC ↓ 50% ↔ EFV AUC Do not coadminister, unless potential benefits outweigh the risks. If coadministration is necessary, monitor posaconazole concentration and adjust dose accordingly.
RPV PO, RPV IM ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Voriconazole DOR ↑ DOR possible No dose adjustment needed.
EFV Voriconazole AUC ↓ 77% EFV AUC ↑ 44% Contraindicated at standard doses. Adjust dose to voriconazole 400 mg twice daily plus EFV 300 mg daily.
ETR ↔ voriconazole AUC ETR AUC ↑ 36% No dose adjustment needed.
NVP ↓ voriconazole possible ↑ NVP possible Consider alternative ARV or antifungal agent. If coadministration is necessary, monitor ARV tolerability and antifungal response and/or voriconazole concentration.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Antimalarials
Artemether/ Lumefantrine DOR, RPV IM, RPV PO ↔ antimalarial expected No dose adjustment needed.
EFV Artemether AUC ↓ 79% DHA AUC ↓ 75% Lumefantrine AUC ↓ 30% to 56% Consider alternative ARV or antimalarial drug. If used in combination, monitor closely for antimalarial efficacy.
ETR Artemether AUC ↓ 38% ↔ DHA AUC ↔ lumefantrine AUC ↔ ETR AUC Clinical significance of the reduced antimalarial drug concentrations unknown. If used in combination with ETR, monitor for antimalarial efficacy.
NVP

Artemether AUC ↓ 67% to 72%

DHA:

  • Study results are conflicting. DHA AUC ↓ 37% in one study, no difference in another.

Lumefantrine:

  • Study results are conflicting. Lumefantrine AUC ↓ 25% to 58% in two studies, but ↑ 50% to 56% in another.
 Clinical significance unknown. If used in combination, monitor closely for antimalarial efficacy and lumefantrine toxicity.
Atovaquone/ Proguanil DOR, ETR, NVP, RPV IM, RPV PO No data Monitor for antimalarial efficacy.
EFV Atovaquone AUC ↓ 75% Proguanil AUC ↓ 43% No dose recommendation. Consider alternative drug for malaria prophylaxis, if possible.
Antiplatelets
Clopidogrel DOR, NVP, RPV IM, RPV PO ↔ clopidogrel expected No dose adjustment needed.
EFV, ETR ↓ activation of clopidogrel possible Consider alternative ARV or antiplatelet. ETR may prevent metabolism of clopidogrel to its active metabolite.
Prasugrel All NNRTIs ↔ prasugrel expected No dose adjustment needed.
Ticagrelor DOR, RPV IM, RPV PO ↔ ticagrelor expected No dose adjustment needed.
EFV, ETR, NVP ↓ ticagrelor expected Consider alternative ARV or anticoagulant therapy.
Vorapaxar DOR, NVP, RPV IM, RPV PO ↔ vorapaxar expected No dose adjustment needed.
EFV, ETR ↓ vorapaxar expected Insufficient data to make a dose recommendation.
Antipneumocystis and Anti-Toxoplasmosis Drugs
Atovaquone (oral solution) DOR, ETR, NVP, RPV IM, RPV PO No data Monitor for therapeutic effectiveness of atovaquone.
EFV Atovaquone AUC ↓ 44% to 47% Consider alternative ARV or agent for PCP or toxoplasmosis treatment or prophylaxis. If coadministration is necessary, monitor for therapeutic effectiveness of atovaquone.
Cardiac Medications
Bosentan DOR ↓ DOR possible Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor virologic response.
EFV, ETR, NVP ↓ NNRTI possible ↓ bosentan possible Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor bosentan efficacy and virologic response.
RPV IM, RPV PO ↓ RPV possible Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor virologic response.
Dihydropyridine CCBs DOR, RPV IM, RPV PO ↔ CCBs expected No dose adjustment needed.
EFV, ETR, NVP ↓ CCBs possible Titrate CCB dose based on clinical response.
Diltiazem, Verapamil DOR, RPV IM, RPV PO ↔ CCBs expected ↑ NNRTI possible No dose adjustment needed.
EFV Diltiazem AUC ↓ 69% ↓ verapamil possible Titrate diltiazem or verapamil dose based on clinical response.
ETR, NVP ↓ diltiazem or verapamil possible
Corticosteroids
Dexamethasone DOR, EFV, ETR, NVP ↓ NNRTI possible Consider alternative corticosteroid for long-term use. If dexamethasone is used with NNRTI, monitor virologic response.
RPV IM, RPV PO Significant ↓ RPV possible Contraindicated with more than a single dose of dexamethasone.
Glucose-Lowering Agents
Canagliflozin, Dapagliflozin, Empagliflozin, Sitagliptin All NNRTIs ↔ antihyperglycemic expected No dose adjustment needed.
Linagliptin, Saxagliptin DOR, RPV IM, RPV PO ↔ antihyperglycemic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antihyperglycemic possible Monitor glycemic control.
Metformin DOR ↔ metformin AUC DOR AUC ↓ 26% and Cmax ↓ 24% No dose adjustment needed.
EFV, ETR, NVP ↔ metformin expected No dose adjustment needed.
RPV IM ↔ metformin expected No dose adjustment needed.
RPV PO ↔ metformin AUC No dose adjustment needed.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir DOR, RPV IM, RPV PO No data No dose adjustment needed.
EFV, ETR, NVP Daclatasvir 120 mg Once Daily plus EFV 600 mg Daily Compared with Daclatasvir 60 mg Alone: Daclatasvir Cmin ↓ 17% and AUC ↑ 37% The recommended dose is daclatasvir 90 mg once daily.
Dasabuvir plus Paritaprevir/Ombitasvir/RTV DOR ↑ DOR possible No dose adjustment needed.
EFV No data Contraindicated.
ETR, NVP ↓ DAAs possible Do not coadminister.
RPV IM ↑ RPV expected Do not coadminister because of the potential for QTc prolongation with higher concentrations of RPV.
RPV PO RPV AUC ↑ 150% to 225% Do not coadminister because of the potential for QTc prolongation with higher concentrations of RPV.
Elbasvir/Grazoprevir DOR ↔ elbasvir and grazoprevir DOR AUC ↑ 56% and Cmin ↑ 41% No dose adjustment needed.
EFV Elbasvir AUC ↓ 54% Grazoprevir AUC ↓ 83% ↔ EFV Contraindicated.
ETR, NVP ↓ elbasvir and grazoprevir expected Do not coadminister.
RPV IM ↔ elbasvir and grazoprevir expected ↔ RPV expected No dose adjustment needed.
RPV PO ↔ elbasvir and grazoprevir ↔ RPV AUC and Cmin No dose adjustment needed.
Glecaprevir/ Pibrentasvir DOR ↑ DOR expected No dose adjustment needed.
EFV ↓ glecaprevir and pibrentasvir expected Do not coadminister.
ETR ↓ glecaprevir and pibrentasvir possible Do not coadminister.
NVP ↓ glecaprevir and pibrentasvir possible Consider alternative ARV or HCV regimen. If coadministration is necessary, monitor for HCV treatment efficacy.
RPV IM

↔ glecaprevir and pibrentasvir expected

↑ RPV expected

 No dose adjustment needed.
RPV PO

↔ glecaprevir and pibrentasvir

RPV AUC ↑ 84%

 No dose adjustment needed.
Ledipasvir/ Sofosbuvir DOR

↔ ledipasvir and sofosbuvir

↔ DOR

 No dose adjustment needed.
EFV

Ledipasvir AUC, Cmin, and Cmax ↓ 34%

↔ sofosbuvir
ETR, NVP No significant effect expected
RPV IM ↔ ledipasvir, sofosbuvir, and RPV expected
RPV PO

↔ ledipasvir and sofosbuvir

↔ RPV
Sofosbuvir/ Velpatasvir DOR, RPV IM, RPV PO No significant effect expected No dose adjustment needed.
EFV

Velpatasvir AUC ↓ 43%,

Cmax ↓ 37%, and Cmin ↓ 47%

 Do not coadminister.
ETR, NVP ↓ velpatasvir expected Do not coadminister.
Sofosbuvir/ Velpatasvir/ Voxilaprevir DOR, RPV IM, RPV PO No significant effect expected No dose adjustment needed.
EFV

Velpatasvir AUC ↓ 43%, Cmax ↓ 37%, and Cmin ↓47%

↓ voxilaprevir expected

 Do not coadminister.
ETR, NVP

↓ voxilaprevir expected

↓ velpatasvir expected

 Do not coadminister.
Herbal Products
St. John’s Wort DOR ↓ DOR expected Contraindicated. After stopping St. John’s Wort, wait 4 weeks before initiating DOR.
EFV, ETR, NVP ↓ EFV, ETR, and NVP expected Do not coadminister.
RPV IM, RPV PO ↓ RPV expected Contraindicated.
Hormonal Therapies
Contraceptives: Injectable Depot MPA DOR, ETR, RPV IM, RPV PO ↔ MPA expected No dose adjustment needed.
EFV, NVP ↔ MPA No dose adjustment needed.
Contraceptives: Oral DOR

↔ ethinyl estradiol

↔ levonorgestrel

 No dose adjustment needed.
EFV

↔ ethinyl estradiol

Etonogestrel (metabolite of oral desogestrel) Cmin ↓ 61%

Levonorgestrel (metabolite of oral norgestimate) AUC ↓ 83%

Norelgestromin (metabolite of oral norgestimate) AUC ↓ 64%

When Used for Contraception:

  • Use alternative ARV or contraceptive methods.

When Used for Other Clinical Indications (e.g., Acne, Menstrual Cycle Regulation):

  • Monitor for clinical effectiveness of hormonal therapy.
ETR

Ethinyl estradiol AUC ↑ 22%

↔ norethindrone

 No dose adjustment needed.
NVP

Ethinyl estradiol AUC ↓ 29% and Cmin ↓ 58%

Norethindrone AUC ↓ 18%

Etonogestrel (metabolite of oral desogestrel) Cmin ↓ 22%

 No dose adjustment needed based on clinical data that demonstrated no change in effectiveness
RPV IM ↔ ethinyl estradiol expected ↔ norethindrone expected No dose adjustment needed.
RPV PO

↔ ethinyl estradiol

↔ norethindrone

 No dose adjustment needed.
Contraceptives: Subdermal Implant Etonogestrel DOR, RPV IM, RPV PO ↔ etonogestrel expected No dose adjustment needed.
EFV Etonogestrel AUC ↓ 63% to 82% Use alternative ARV or contraceptive methods.
ETR ↓ etonogestrel possible No data available to make dose recommendation.
NVP ↔ etonogestrel No dose adjustment needed.
Contraceptives: Subdermal Implant Levonorgestrel DOR, RPV IM, RPV PO ↔ levonorgestrel expected No dose adjustment needed.
EFV Levonorgestrel AUC ↓ 42% to 47% Use alternative ARV or contraceptive methods. Unintended pregnancies were observed in women who used EFV and levonorgestrel implant concomitantly.
ETR ↓ levonorgestrel possible No data available to make dose recommendation.
NVP Levonorgestrel AUC ↑ 35% No dose adjustment needed.
Contraceptives: Transdermal Ethinyl Estradiol/ Norelgestromin DOR, RPV IM, RPV PO ↔ ethinyl estradiol or norelgestromin expected No dose adjustment needed.
EFV ↓ ethinyl estradiol or norelgestromin expected No data available to make dose recommendation.
ETR, NVP ↓ ethinyl estradiol or norelgestromin possible No data available to make dose recommendation.
Contraceptives: Vaginal Ring Etonogestrel/Ethinyl Estradiol DOR, RPV IM, RPV PO ↔ etonogestrel and ethinyl estradiol expected No dose adjustment needed.
EFV

Ethinyl estradiol (intravaginal ring) AUC ↓ 56%

Etonogestrel (intravaginal ring) AUC ↓ 81%

 Consider alternative ARV or contraceptive method.
ETR, NVP ↓ etonogestrel and ethinyl estradiol possible No data available to make dose recommendation.
Contraceptives: Vaginal Ring Segesterone/Ethinyl Estradiol DOR, RPV IM, RPV PO ↔ segesterone and ethinyl estradiol expected No dose adjustment needed.
EFV, ETR, NVP ↓ segesterone and ethinyl estradiol possible No data available to make dose recommendation.
Emergency Contraceptives Levonorgestrel (oral) DOR, RPV IM, RPV PO ↔ levonorgestrel expected No dose adjustment needed.
EFV Levonorgestrel AUC ↓ 58% Effectiveness of emergency postcoital contraception may be diminished.
NVP, ETR ↓ levonorgestrel possible No data available to make dose recommendation.
Gender-Affirming Therapy DOR, RPV IM, RPV PO ↔ hormonal concentrations expected No dose adjustment needed.
EFV, ETR, NVP

↓ estradiol possible

↓ cyproterone and progestogens possible

↔ goserelin, leuprolide acetate, and spironolactone expected

↓ dutasteride and finasteride possible

 Monitor feminizing effects of estrogen and antiandrogen therapy. Titrate dose as necessary to achieve therapeutic goals.
EFV, ETR, NVP ↓ testosterone possible Monitor masculinizing effects of testosterone. Titrate testosterone dose as necessary to achieve therapeutic goals.
Menopausal Replacement Therapy DOR, RPV IM, RPV PO ↔ hormonal concentrations expected No dose adjustment needed.
EFV, ETR, NVP

↓estrogen possible with estradiol or conjugated estrogen (equine and synthetic)

↓medroxyprogesterone possible

↓micronized progesterone possible

↓drospirenone possible

See Contraceptives – Oral above for other progestin-NNRTI interactions

 Monitor menopausal symptoms. Titrate to the dose of hormonal therapy that achieves menopausal symptom relief.
Immunosuppressants
Cyclosporine DOR, RPV IM, RPV PO ↔ cyclosporine expected ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ cyclosporine possible Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.
Everolimus, Sirolimus, Tacrolimus DOR, RPV IM, RPV PO ↔immunosuppressant expected No dose adjustment needed.
EFV, ETR, NVP ↓immunosuppressant possible Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.
Lipid-Modifying Agents
Atorvastatin DOR ↔ atorvastatin AUC No dose adjustment needed.
EFV, ETR Atorvastatin AUC ↓ 32% to 43% Adjust atorvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
NVP ↓ atorvastatin possible Adjust atorvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
RPV IM ↔ atorvastatin expected No dose adjustment needed.
RPV PO ↔ atorvastatin AUC No dose adjustment needed.
Fluvastatin DOR, NVP, RPV IM, RPV PO ↔ fluvastatin expected No dose adjustment needed.
EFV, ETR ↑ fluvastatin possible Dose adjustments for fluvastatin may be necessary. Monitor for fluvastatin toxicity.
Lovastatin, Simvastatin DOR, RPV IM, RPV PO ↔ lovastatin and simvastatin expected No dose adjustment needed.
EFV

Simvastatin AUC ↓ 60% to 68%

Simvastatin active metabolite AUC ↓ 60%

 Adjust simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
ETR, NVP

↓ lovastatin possible

↓ simvastatin possible

 Adjust lovastatin or simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Pitavastatin DOR, ETR, NVP, RPV IM, RPV PO ↔ pitavastatin expected No dose adjustment needed.
EFV ↔ pitavastatin AUC No dose adjustment needed.
Pravastatin DOR, NVP, RPV IM, RPV PO ↔ pravastatin expected No dose adjustment needed.
EFV Pravastatin AUC ↓ 44% Adjust statin dose according to lipid responses, but do not exceed the maximum recommended dose.
ETR ↓ pravastatin possible
Rosuvastatin DOR, EFV, ETR, NVP, RPV IM, RPV PO ↔ rosuvastatin expected No dose adjustment needed.
Narcotics and Treatment for Opioid Dependence
Buprenorphine Sublingual or buccal DOR, RPV IM, RPV PO ↔ buprenorphine expected No dose adjustment needed.
EFV

Buprenorphine AUC ↓ 50%

Norbuprenorphine (active metabolite) AUC ↓ 71%

 No dose adjustment needed; monitor for withdrawal symptoms.
ETR Buprenorphine AUC ↓ 25% No dose adjustment needed.
NVP No significant effect No dose adjustment needed.
Buprenorphine Implant DOR, RPV IM, RPV PO ↔ buprenorphine expected No dose adjustment needed.
EFV, ETR, NVP No data Clinical monitoring is recommended when NNRTI is initiated after insertion of buprenorphine implant.
Lofexidine DOR, EFV, ETR, NVP, RPV IM, RPV PO ↔ lofexidine expected No dose adjustment needed.
Methadone DOR

↔ methadone AUC

DOR AUC ↓ 26%

 No dose adjustment needed.
EFV Methadone AUC ↓ 52% Opioid withdrawal common; monitor and increase methadone dose as necessary.
ETR ↔ methadone AUC No dose adjustment needed.
NVP

Methadone AUC ↓ 37% to 51%

↔ NVP

 Opioid withdrawal common; monitor and increase methadone dose as necessary.
RPV IM ↓ methadone AUC expected No dose adjustment needed, but monitor for withdrawal symptoms.
RPV PO R-methadonea AUC ↓ 16% No dose adjustment needed, but monitor for withdrawal symptoms.
PDE5 Inhibitors
Sildenafil DOR ↔ sildenafil expected No dose adjustment needed.
EFV, NVP ↓ sildenafil possible May need to titrate sildenafil dose based on clinical effect.
ETR Sildenafil AUC ↓ 57% May need to titrate sildenafil dose based on clinical effect.
RPV IM ↔ sildenafil expected No dose adjustment needed.
RPV PO ↔ sildenafil AUC and Cmax No dose adjustment needed.
Tadalafil DOR, RPV IM, RPV PO ↔ tadalafil expected No dose adjustment needed.
EFV, ETR, NVP ↓ tadalafil possible May need to titrate tadalafil dose based on clinical effect.
Avanafil, Vardenafil DOR, RPV IM, RPV PO ↔ avanafil or vardenafil expected No dose adjustment needed.
EFV, ETR, NVP ↓ avanafil or vardenafil possible May need to increase PDE5 inhibitor dose based on clinical effect.
Sedative/Hypnotics
Alprazolam, Triazolam DOR, RPV IM, RPV PO ↔ benzodiazepine expected No dose adjustment needed.
EFV, ETR, NVP ↓ benzodiazepine possible Monitor for therapeutic effectiveness of benzodiazepine.
Diazepam DOR, RPV IM, RPV PO ↔ diazepam expected No dose adjustment needed.
EFV, NVP ↓ diazepam possible Monitor for therapeutic effectiveness of diazepam.
ETR ↑ diazepam possible Decreased dose of diazepam may be necessary. Monitor for diazepam toxicity.
Lorazepam DOR, ETR, NVP, RPV IM, RPV PO ↔ lorazepam expected No dose adjustment needed.
EFV ↔ lorazepam AUC No dose adjustment needed.
Midazolam DOR ↔ midazolam AUC No dose adjustment needed.
EFV ↑ or ↓ midazolam possible Monitor for therapeutic effectiveness and toxicity of midazolam.
ETR

Midazolam AUC ↓ 31%

Midazolam active metabolite Cmax ↑ 57%

 Monitor for therapeutic effectiveness of midazolam.
NVP ↓ midazolam possible Monitor for therapeutic effectiveness of midazolam.
RPV IM, RPV PO ↔ midazolam expected No dose adjustment needed.
a R-methadone is the active form of methadone.

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

Key: ARV = antiretroviral; AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CAB = cabotegravir; CCB = calcium channel blocker; DAA = direct-acting antiviral; DHA = dihydroartemisinin; DLV = delavirdine; DOR = doravirine; EFV = efavirenz; ETR = etravirine; HCV = hepatitis C virus; IM = intramuscular; INR = international normalized ratio; MAC = Mycobacterium avium complex; MPA = medroxyprogesterone acetate; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; OH‑itraconazole = active metabolite of itraconazole; PCP = Pneumocystis jirovecii pneumonia; PDE5 = phosphodiesterase type 5; PI/r = protease inhibitor/ritonavir; PO = oral; RPV = rilpivirine; RTV = ritonavir

Drug-Drug Interactions

Drug Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Other Drugs

Table 24b. Drug Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Other Drugs

This table provides information on the known or predicted interactions between non-nucleoside reverse transcriptase inhibitors (NNRTIs) and non-antiretroviral (ARV) drugs. Cabotegravir (CAB) intramuscular (IM) plus rilpivirine (RPV) IM are co-packaged into a single product and are coadministered as a complete regimen; therefore, the dosing recommendations and clinical comments reflect the combination of CAB IM and RPV IM treatments. Drug interaction studies were not conducted with either CAB IM or RPV IM. Drug interaction studies with oral CAB and RPV were leveraged to make the dosing recommendations for CAB IM and RPV IM. For information regarding interactions between NNRTIs and other ARV drugs, including dosing recommendations, refer to Tables 24c, 25a, and 25b.

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 if 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. When an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgment to select the most appropriate alternative medication to use.

RPV 75 mg and 300 mg oral once daily (three and 12 times the recommended dose, respectively) were shown to prolong the QTc interval. Known and expected/theoretical pharmacokinetic interactions, resulting in increased RPV exposures, are included in this table due to the safety concern of QTc prolongation. There is limited information about the potential for pharmacodynamic interactions between RPV (in the absence of increased RPV exposures) and drugs that prolong the QTc interval; therefore, these are not included in this table.

Note: Delavirdine (DLV) is not included in this table. Please refer to the Food and Drug Administration product label for information regarding drug interactions between DLV and other concomitant drugs. The term “All NNRTIs” in this table refers to all NNRTIs except for DLV. 
 

Concomitant Drug NNRTI Effect on NNRTI and/or Concomitant Drug Concentrations Dosing Recommendations and Clinical Comments
Acid Reducers
Antacids DOR, EFV, NVP ↔ NNRTI AUC No dose adjustment needed.
ETR ↔ ETR expected No dose adjustment needed.
RPV IM ↔ RPV IM expected No dose adjustment needed.
RPV PO ↓ RPV expected when given simultaneously Give antacids at least 2 hours before or at least 4 hours after RPV.
H2 Receptor Antagonists DOR, NVP ↔ NNRTI expected No dose adjustment needed.
EFV ↔ EFV AUC No dose adjustment needed.
ETR ↔ ETR AUC No dose adjustment needed.
RPV IM ↔ RPV IM expected No dose adjustment needed.
RPV PO RPV AUC ↓ 76% when famotidine 40 mg is taken 2 hours prior Give H2 receptor antagonists at least 12 hours before or at least 4 hours after RPV.
Proton Pump Inhibitors DOR DOR AUC ↓ 17% and Cmin ↓ 16% No dose adjustment needed.
EFV, NVP ↔ EFV and NVP expected
ETR

With Omeprazole 40 mg Daily: 

  • ETR AUC ↑ 41%
RPV IM ↔ RPV IM expected No dose adjustment needed.
RPV PO

With Omeprazole 20 mg Daily:

  • RPV AUC ↓ 40% and Cmin ↓ 33%
 Contraindicated.
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin, Doxazosin, Silodosin, Terazosin DOR, RPV IM, RPV PO ↔ alpha-adrenergic antagonists expected No dose adjustment needed.
EFV, ETR, NVP ↓ alpha-adrenergic antagonists expected Consider alternative ARV or alpha-antagonist therapy. If coadministration is necessary, monitor for therapeutic effectiveness of alpha antagonist.
Tamsulosin DOR, RPV IM, RPV PO ↔ tamsulosin expected No dose adjustment needed.
EFV, ETR, NVP ↓ tamsulosin expected Monitor for therapeutic effectiveness of tamsulosin after 2–4 weeks. May need to increase dose to tamsulosin 0.8 mg once daily for patients who fail to respond to the 0.4-mg dose.
Antibacterials
Antimycobacterials
Bedaquiline DOR, RPV IM, RPV PO ↔ bedaquiline expected No dose adjustment needed.
EFV, ETR ↓ bedaquiline possible Do not coadminister.
NVP ↔ bedaquiline AUC No dose adjustment needed.
Rifabutin DOR DOR AUC ↓ 50% Increase DOR dose to 100 mg twice daily. No dose adjustment needed for rifabutin.
EFV Rifabutin ↓ 38% The recommended dosing range is rifabutin 450–600 mg per day.
ETR

↔ rifabutin and metabolite AUC ETR AUC ↓ 37%

Do not coadminister ETR plus PI/r with rifabutin.

Use rifabutin 300 mg once daily if ETR is administered without PI/r.
NVP Rifabutin AUC ↑ 17% and metabolite AUC ↑ 24% NVP Cmin ↓ 16% No dose adjustment needed.
RPV IM ↓ RPV IM expected Contraindicated.
RPV PO

Rifabutin plus RPV 50 mg PO Once Daily Compared to RPV 25 mg Once Daily Alone:

  • ↔ RPV AUC and Cmin
 Increase RPV dose to 50 mg PO once daily. No dose adjustment for rifabutin needed.
Rifampin DOR DOR AUC ↓ 88% Contraindicated. After stopping rifampin, wait 4 weeks before initiating DOR.
EFV EFV AUC ↓ 26% Do not use EFV 400 mg with rifampin. Maintain EFV dose at 600 mg once daily and monitor for virologic response.
ETR Significant ↓ ETR possible Do not coadminister.
NVP NVP ↓ 20% to 58% Do not coadminister.
RPV IM ↓ RPV IM expected Contraindicated.
RPV PO RPV PO AUC ↓ 80% Contraindicated.
Rifapentine DOR

DOR 100 Twice Daily plus Once-Weekly Rifapentine and INH Compared to DOR 100 mg Twice Daily Alone:

  • DOR AUC ↓ 29%, Cmin ↓ 31%
 Contraindicated. After stopping rifapentine, wait 4 weeks before initiating DOR.
EFV ↔ EFV concentrations No dose adjustment needed.
ETR ↓ ETR possible Do not coadminister.
NVP NVP Cmin ↓ 27% Do not coadminister.
RPV IM, RPV PO ↓ RPV expected Contraindicated.
Macrolides
Azithromycin All NNRTIs ↔ azithromycin expected No dose adjustment needed.
Clarithromycin DOR ↔ clarithromycin expected ↑ DOR possible Monitor for ARV tolerability if used in combination.
EFV Clarithromycin AUC ↓ 39% Monitor for effectiveness, or consider alternative agent (e.g., azithromycin) for MAC prophylaxis and treatment.
ETR Clarithromycin AUC ↓ 39% ETR AUC ↑ 42% Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
NVP Clarithromycin AUC ↓ 31% NVP AUC ↑ 26% Monitor for effectiveness, or consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
RPV IM, RPV PO ↔ clarithromycin expected ↑ RPV possible Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment. If coadministered, monitor for QTc prolongation.
Erythromycin DOR ↑ DOR possible Monitor for ARV tolerability if used in combination.
EFV, ETR, NVP ↑ EFV, ETR, and NVP possible ↓ erythromycin possible Monitor for ARV tolerability and antibiotic efficacy if used in combination.
RPV IM, RPV PO ↑ RPV PO or IM possible Consider alternative macrolide (e.g., azithromycin). If coadministered, monitor for QTc prolongation.
Anticoagulants
Apixaban DOR, RPV IM, RPV PO ↔ apixaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ apixaban possible Consider alternative ARV or anticoagulant therapy.
Dabigatran All NNRTIs ↔ dabigatran expected No dose adjustment needed.
Edoxaban All NNRTIs ↔ edoxaban expected No dose adjustment needed.
Rivaroxaban DOR, RPV IM, RPV PO ↔ rivaroxaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ rivaroxaban possible Consider alternative ARV or anticoagulant therapy.
Warfarin DOR, RPV IM, RPV PO ↔ warfarin expected No dose adjustment needed.
EFV, ETR, NVP ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose accordingly.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin DOR ↓ DOR possible Contraindicated. After stopping anticonvulsant, wait 4 weeks before initiating DOR.
EFV

Carbamazepine plus EFV:

  • Carbamazepine AUC ↓ 27%
  • EFV AUC ↓ 36%

Phenytoin plus EFV:

  • ↓ EFV
  • ↑ or ↓ phenytoin possible
 Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor anticonvulsant and EFV concentrations.
ETR ↓ anticonvulsant and ETR possible Do not coadminister.
NVP ↓ anticonvulsant and NVP possible Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor anticonvulsant and NVP concentrations and virologic response.
RPV IM, RPV PO ↓ RPV possible Contraindicated.
Eslicarbazepine All NNRTIs ↓ NNRTI possible Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor virologic response and consider monitoring plasma concentrations of ARVs.
Oxcarbazepine DOR, RPV IM, RPV PO ↓ NNRTI possible Contraindicated.
EFV, ETR, NVP ↓ NNRTI possible Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor virologic response and consider monitoring plasma concentrations of ARVs.
Ethosuximide, Lacosamide, Tiagabine, Zonisamide DOR, RPV IM, RPV PO ↔ anticonvulsant expected No dose adjustment needed.
EFV, ETR, NVP ↓ anticonvulsant possible Monitor seizure control. Consider anticonvulsant therapeutic drug monitoring.
Lamotrigine DOR, ETR, NVP, RPV IM, RPV PO ↔ lamotrigine expected No dose adjustment needed.
EFV ↓ lamotrigine possible Monitor seizure control and plasma concentrations of lamotrigine.
Antidepressants, Anxiolytics, and Antipsychotics Also see Sedative/Hypnotics section below.
Bupropion DOR, ETR, RPV IM, RPV PO ↔ bupropion expected No dose adjustment needed.
EFV Bupropion AUC ↓ 55% Titrate bupropion dose based on clinical response.
NVP ↓ bupropion possible
Citalopram, Escitalopram DOR, RPV IM, RPV PO ↔ antidepressant expected No dose adjustment needed.
EFV, ETR, NVP ↓ antidepressant possible Titrate antidepressant dose based on clinical response.
Fluoxetine, Fluvoxamine All NNRTIs ↔ antidepressant expected No dose adjustment needed.
Paroxetine DOR, NVP, RPV IM, RPV PO ↔ paroxetine expected No dose adjustment needed.
EFV, ETR ↔ paroxetine No dose adjustment needed.
Nefazodone DOR, RPV IM, RPV PO ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ nefazodone expected ↑ NNRTI possible Monitor antidepressant effect. Titrate dose as necessary based on clinical response.
Sertraline DOR, RPV IM, RPV PO ↔ sertraline expected No dose adjustment needed.
EFV Sertraline AUC ↓ 39% Monitor the antidepressant effect. Titrate dose as necessary based on clinical response.
ETR, NVP ↓ sertraline possible
Trazodone DOR, RPV IM, RPV PO ↔ trazodone expected No dose adjustment needed.
EFV, ETR, NVP ↓ trazodone possible Monitor for therapeutic effectiveness of trazodone and titrate dose as necessary.
Antipsychotics
Aripiprazole DOR, RPV IM, RPV PO ↔ aripiprazole expected No dose adjustment needed.
EFV, ETR, NVP ↓ aripiprazole expected Monitor for therapeutic effectiveness of antipsychotic. Consider doubling usual dose of aripiprazole over 1–2 weeks. Refer to aripiprazole prescribing information for dose recommendations.
Brexpiprazole DOR, RPV IM, RPV PO ↔ brexpiprazole expected No dose adjustment needed.
EFV, ETR, NVP ↓ brexpiprazole expected Monitor for therapeutic effectiveness of antipsychotic. Consider doubling the usual dose of brexpiprazole and making further adjustments based on clinical response. Refer to brexpiprazole prescribing information.
Cariprazine DOR, RPV IM, RPV PO ↔ cariprazine expected No dose adjustment needed.
EFV, ETR, NVP ↓ cariprazine and ↑ or ↓ active metabolite possible Do not coadminister.
Iloperidone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Lumateperone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Do not coadminister.
Lurasidone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Olanzapine DOR, ETR, NVP, RPV IM, RPV PO ↔ olanzapine expected No dose adjustment needed.
EFV ↓ olanzapine possible Monitor for therapeutic effectiveness of olanzapine.
Other Antipsychotics CYP3A4 substrates (e.g., clozapine, perphenazine, risperidone) DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Pimavanserin DOR, RPV IM, RPV PO ↔ pimavanserin expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimavanserin expected Do not coadminister.
Pimozide DOR, RPV IM, RPV PO ↔ pimozide expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimozide possible Monitor for therapeutic effectiveness of pimozide.
Quetiapine DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Ziprasidone DOR, RPV IM, RPV PO ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Antifungals
Fluconazole DOR ↑ DOR possible No dose adjustment needed.
EFV ↔ fluconazole ↔ EFV AUC No dose adjustment needed.
ETR ETR AUC ↑ 86% No dose adjustment needed.
NVP NVP AUC ↑ 110% Consider alternative ARV or antifungal agent. Increased risk of hepatotoxicity is possible with this combination.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Isavuconazole DOR ↑ DOR possible No dose adjustment needed.
EFV, ETR, NVP ↓ isavuconazole possible Monitor isavuconazole concentration and antifungal response. Dose adjustments for isavuconazole may be necessary.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Itraconazole DOR ↑ DOR possible No dose adjustment needed.
EFV Itraconazole and OH-itraconazole AUC, Cmax, and Cmin ↓ 37% to 44% Do not coadminister, unless potential benefits outweigh the risks. Failure to achieve therapeutic itraconazole concentrations has been reported. If coadministration is necessary, closely monitor itraconazole concentration and adjust dose accordingly.
ETR ↓ itraconazole possible ↑ ETR possible Dose adjustments for itraconazole may be necessary. Monitor itraconazole concentration and antifungal response.
NVP Itraconazole AUC ↓ 61% ↑ NVP possible Do not coadminister, unless potential benefits outweigh the risks. If coadministration is necessary, monitor itraconazole concentration and adjust dose accordingly.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Posaconazole DOR, ETR, NVP ↑ NNRTI possible No dose adjustment needed.
EFV Posaconazole AUC ↓ 50% ↔ EFV AUC Do not coadminister, unless potential benefits outweigh the risks. If coadministration is necessary, monitor posaconazole concentration and adjust dose accordingly.
RPV PO, RPV IM ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Voriconazole DOR ↑ DOR possible No dose adjustment needed.
EFV Voriconazole AUC ↓ 77% EFV AUC ↑ 44% Contraindicated at standard doses. Adjust dose to voriconazole 400 mg twice daily plus EFV 300 mg daily.
ETR ↔ voriconazole AUC ETR AUC ↑ 36% No dose adjustment needed.
NVP ↓ voriconazole possible ↑ NVP possible Consider alternative ARV or antifungal agent. If coadministration is necessary, monitor ARV tolerability and antifungal response and/or voriconazole concentration.
RPV IM, RPV PO ↑ RPV possible No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Antimalarials
Artemether/ Lumefantrine DOR, RPV IM, RPV PO ↔ antimalarial expected No dose adjustment needed.
EFV Artemether AUC ↓ 79% DHA AUC ↓ 75% Lumefantrine AUC ↓ 30% to 56% Consider alternative ARV or antimalarial drug. If used in combination, monitor closely for antimalarial efficacy.
ETR Artemether AUC ↓ 38% ↔ DHA AUC ↔ lumefantrine AUC ↔ ETR AUC Clinical significance of the reduced antimalarial drug concentrations unknown. If used in combination with ETR, monitor for antimalarial efficacy.
NVP

Artemether AUC ↓ 67% to 72%

DHA:

  • Study results are conflicting. DHA AUC ↓ 37% in one study, no difference in another.

Lumefantrine:

  • Study results are conflicting. Lumefantrine AUC ↓ 25% to 58% in two studies, but ↑ 50% to 56% in another.
 Clinical significance unknown. If used in combination, monitor closely for antimalarial efficacy and lumefantrine toxicity.
Atovaquone/ Proguanil DOR, ETR, NVP, RPV IM, RPV PO No data Monitor for antimalarial efficacy.
EFV Atovaquone AUC ↓ 75% Proguanil AUC ↓ 43% No dose recommendation. Consider alternative drug for malaria prophylaxis, if possible.
Antiplatelets
Clopidogrel DOR, NVP, RPV IM, RPV PO ↔ clopidogrel expected No dose adjustment needed.
EFV, ETR ↓ activation of clopidogrel possible Consider alternative ARV or antiplatelet. ETR may prevent metabolism of clopidogrel to its active metabolite.
Prasugrel All NNRTIs ↔ prasugrel expected No dose adjustment needed.
Ticagrelor DOR, RPV IM, RPV PO ↔ ticagrelor expected No dose adjustment needed.
EFV, ETR, NVP ↓ ticagrelor expected Consider alternative ARV or anticoagulant therapy.
Vorapaxar DOR, NVP, RPV IM, RPV PO ↔ vorapaxar expected No dose adjustment needed.
EFV, ETR ↓ vorapaxar expected Insufficient data to make a dose recommendation.
Antipneumocystis and Anti-Toxoplasmosis Drugs
Atovaquone (oral solution) DOR, ETR, NVP, RPV IM, RPV PO No data Monitor for therapeutic effectiveness of atovaquone.
EFV Atovaquone AUC ↓ 44% to 47% Consider alternative ARV or agent for PCP or toxoplasmosis treatment or prophylaxis. If coadministration is necessary, monitor for therapeutic effectiveness of atovaquone.
Cardiac Medications
Bosentan DOR ↓ DOR possible Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor virologic response.
EFV, ETR, NVP ↓ NNRTI possible ↓ bosentan possible Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor bosentan efficacy and virologic response.
RPV IM, RPV PO ↓ RPV possible Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor virologic response.
Dihydropyridine CCBs DOR, RPV IM, RPV PO ↔ CCBs expected No dose adjustment needed.
EFV, ETR, NVP ↓ CCBs possible Titrate CCB dose based on clinical response.
Diltiazem, Verapamil DOR, RPV IM, RPV PO ↔ CCBs expected ↑ NNRTI possible No dose adjustment needed.
EFV Diltiazem AUC ↓ 69% ↓ verapamil possible Titrate diltiazem or verapamil dose based on clinical response.
ETR, NVP ↓ diltiazem or verapamil possible
Corticosteroids
Dexamethasone DOR, EFV, ETR, NVP ↓ NNRTI possible Consider alternative corticosteroid for long-term use. If dexamethasone is used with NNRTI, monitor virologic response.
RPV IM, RPV PO Significant ↓ RPV possible Contraindicated with more than a single dose of dexamethasone.
Glucose-Lowering Agents
Canagliflozin, Dapagliflozin, Empagliflozin, Sitagliptin All NNRTIs ↔ antihyperglycemic expected No dose adjustment needed.
Linagliptin, Saxagliptin DOR, RPV IM, RPV PO ↔ antihyperglycemic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antihyperglycemic possible Monitor glycemic control.
Metformin DOR ↔ metformin AUC DOR AUC ↓ 26% and Cmax ↓ 24% No dose adjustment needed.
EFV, ETR, NVP ↔ metformin expected No dose adjustment needed.
RPV IM ↔ metformin expected No dose adjustment needed.
RPV PO ↔ metformin AUC No dose adjustment needed.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir DOR, RPV IM, RPV PO No data No dose adjustment needed.
EFV, ETR, NVP Daclatasvir 120 mg Once Daily plus EFV 600 mg Daily Compared with Daclatasvir 60 mg Alone: Daclatasvir Cmin ↓ 17% and AUC ↑ 37% The recommended dose is daclatasvir 90 mg once daily.
Dasabuvir plus Paritaprevir/Ombitasvir/RTV DOR ↑ DOR possible No dose adjustment needed.
EFV No data Contraindicated.
ETR, NVP ↓ DAAs possible Do not coadminister.
RPV IM ↑ RPV expected Do not coadminister because of the potential for QTc prolongation with higher concentrations of RPV.
RPV PO RPV AUC ↑ 150% to 225% Do not coadminister because of the potential for QTc prolongation with higher concentrations of RPV.
Elbasvir/Grazoprevir DOR ↔ elbasvir and grazoprevir DOR AUC ↑ 56% and Cmin ↑ 41% No dose adjustment needed.
EFV Elbasvir AUC ↓ 54% Grazoprevir AUC ↓ 83% ↔ EFV Contraindicated.
ETR, NVP ↓ elbasvir and grazoprevir expected Do not coadminister.
RPV IM ↔ elbasvir and grazoprevir expected ↔ RPV expected No dose adjustment needed.
RPV PO ↔ elbasvir and grazoprevir ↔ RPV AUC and Cmin No dose adjustment needed.
Glecaprevir/ Pibrentasvir DOR ↑ DOR expected No dose adjustment needed.
EFV ↓ glecaprevir and pibrentasvir expected Do not coadminister.
ETR ↓ glecaprevir and pibrentasvir possible Do not coadminister.
NVP ↓ glecaprevir and pibrentasvir possible Consider alternative ARV or HCV regimen. If coadministration is necessary, monitor for HCV treatment efficacy.
RPV IM

↔ glecaprevir and pibrentasvir expected

↑ RPV expected

 No dose adjustment needed.
RPV PO

↔ glecaprevir and pibrentasvir

RPV AUC ↑ 84%

 No dose adjustment needed.
Ledipasvir/ Sofosbuvir DOR

↔ ledipasvir and sofosbuvir

↔ DOR

 No dose adjustment needed.
EFV

Ledipasvir AUC, Cmin, and Cmax ↓ 34%

↔ sofosbuvir
ETR, NVP No significant effect expected
RPV IM ↔ ledipasvir, sofosbuvir, and RPV expected
RPV PO

↔ ledipasvir and sofosbuvir

↔ RPV
Sofosbuvir/ Velpatasvir DOR, RPV IM, RPV PO No significant effect expected No dose adjustment needed.
EFV

Velpatasvir AUC ↓ 43%,

Cmax ↓ 37%, and Cmin ↓ 47%

 Do not coadminister.
ETR, NVP ↓ velpatasvir expected Do not coadminister.
Sofosbuvir/ Velpatasvir/ Voxilaprevir DOR, RPV IM, RPV PO No significant effect expected No dose adjustment needed.
EFV

Velpatasvir AUC ↓ 43%, Cmax ↓ 37%, and Cmin ↓47%

↓ voxilaprevir expected

 Do not coadminister.
ETR, NVP

↓ voxilaprevir expected

↓ velpatasvir expected

 Do not coadminister.
Herbal Products
St. John’s Wort DOR ↓ DOR expected Contraindicated. After stopping St. John’s Wort, wait 4 weeks before initiating DOR.
EFV, ETR, NVP ↓ EFV, ETR, and NVP expected Do not coadminister.
RPV IM, RPV PO ↓ RPV expected Contraindicated.
Hormonal Therapies
Contraceptives: Injectable Depot MPA DOR, ETR, RPV IM, RPV PO ↔ MPA expected No dose adjustment needed.
EFV, NVP ↔ MPA No dose adjustment needed.
Contraceptives: Oral DOR

↔ ethinyl estradiol

↔ levonorgestrel

 No dose adjustment needed.
EFV

↔ ethinyl estradiol

Etonogestrel (metabolite of oral desogestrel) Cmin ↓ 61%

Levonorgestrel (metabolite of oral norgestimate) AUC ↓ 83%

Norelgestromin (metabolite of oral norgestimate) AUC ↓ 64%

When Used for Contraception:

  • Use alternative ARV or contraceptive methods.

When Used for Other Clinical Indications (e.g., Acne, Menstrual Cycle Regulation):

  • Monitor for clinical effectiveness of hormonal therapy.
ETR

Ethinyl estradiol AUC ↑ 22%

↔ norethindrone

 No dose adjustment needed.
NVP

Ethinyl estradiol AUC ↓ 29% and Cmin ↓ 58%

Norethindrone AUC ↓ 18%

Etonogestrel (metabolite of oral desogestrel) Cmin ↓ 22%

 No dose adjustment needed based on clinical data that demonstrated no change in effectiveness
RPV IM ↔ ethinyl estradiol expected ↔ norethindrone expected No dose adjustment needed.
RPV PO

↔ ethinyl estradiol

↔ norethindrone

 No dose adjustment needed.
Contraceptives: Subdermal Implant Etonogestrel DOR, RPV IM, RPV PO ↔ etonogestrel expected No dose adjustment needed.
EFV Etonogestrel AUC ↓ 63% to 82% Use alternative ARV or contraceptive methods.
ETR ↓ etonogestrel possible No data available to make dose recommendation.
NVP ↔ etonogestrel No dose adjustment needed.
Contraceptives: Subdermal Implant Levonorgestrel DOR, RPV IM, RPV PO ↔ levonorgestrel expected No dose adjustment needed.
EFV Levonorgestrel AUC ↓ 42% to 47% Use alternative ARV or contraceptive methods. Unintended pregnancies were observed in women who used EFV and levonorgestrel implant concomitantly.
ETR ↓ levonorgestrel possible No data available to make dose recommendation.
NVP Levonorgestrel AUC ↑ 35% No dose adjustment needed.
Contraceptives: Transdermal Ethinyl Estradiol/ Norelgestromin DOR, RPV IM, RPV PO ↔ ethinyl estradiol or norelgestromin expected No dose adjustment needed.
EFV ↓ ethinyl estradiol or norelgestromin expected No data available to make dose recommendation.
ETR, NVP ↓ ethinyl estradiol or norelgestromin possible No data available to make dose recommendation.
Contraceptives: Vaginal Ring Etonogestrel/Ethinyl Estradiol DOR, RPV IM, RPV PO ↔ etonogestrel and ethinyl estradiol expected No dose adjustment needed.
EFV

Ethinyl estradiol (intravaginal ring) AUC ↓ 56%

Etonogestrel (intravaginal ring) AUC ↓ 81%

 Consider alternative ARV or contraceptive method.
ETR, NVP ↓ etonogestrel and ethinyl estradiol possible No data available to make dose recommendation.
Contraceptives: Vaginal Ring Segesterone/Ethinyl Estradiol DOR, RPV IM, RPV PO ↔ segesterone and ethinyl estradiol expected No dose adjustment needed.
EFV, ETR, NVP ↓ segesterone and ethinyl estradiol possible No data available to make dose recommendation.
Emergency Contraceptives Levonorgestrel (oral) DOR, RPV IM, RPV PO ↔ levonorgestrel expected No dose adjustment needed.
EFV Levonorgestrel AUC ↓ 58% Effectiveness of emergency postcoital contraception may be diminished.
NVP, ETR ↓ levonorgestrel possible No data available to make dose recommendation.
Gender-Affirming Therapy DOR, RPV IM, RPV PO ↔ hormonal concentrations expected No dose adjustment needed.
EFV, ETR, NVP

↓ estradiol possible

↓ cyproterone and progestogens possible

↔ goserelin, leuprolide acetate, and spironolactone expected

↓ dutasteride and finasteride possible

 Monitor feminizing effects of estrogen and antiandrogen therapy. Titrate dose as necessary to achieve therapeutic goals.
EFV, ETR, NVP ↓ testosterone possible Monitor masculinizing effects of testosterone. Titrate testosterone dose as necessary to achieve therapeutic goals.
Menopausal Replacement Therapy DOR, RPV IM, RPV PO ↔ hormonal concentrations expected No dose adjustment needed.
EFV, ETR, NVP

↓estrogen possible with estradiol or conjugated estrogen (equine and synthetic)

↓medroxyprogesterone possible

↓micronized progesterone possible

↓drospirenone possible

See Contraceptives – Oral above for other progestin-NNRTI interactions

 Monitor menopausal symptoms. Titrate to the dose of hormonal therapy that achieves menopausal symptom relief.
Immunosuppressants
Cyclosporine DOR, RPV IM, RPV PO ↔ cyclosporine expected ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ cyclosporine possible Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.
Everolimus, Sirolimus, Tacrolimus DOR, RPV IM, RPV PO ↔immunosuppressant expected No dose adjustment needed.
EFV, ETR, NVP ↓immunosuppressant possible Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.
Lipid-Modifying Agents
Atorvastatin DOR ↔ atorvastatin AUC No dose adjustment needed.
EFV, ETR Atorvastatin AUC ↓ 32% to 43% Adjust atorvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
NVP ↓ atorvastatin possible Adjust atorvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
RPV IM ↔ atorvastatin expected No dose adjustment needed.
RPV PO ↔ atorvastatin AUC No dose adjustment needed.
Fluvastatin DOR, NVP, RPV IM, RPV PO ↔ fluvastatin expected No dose adjustment needed.
EFV, ETR ↑ fluvastatin possible Dose adjustments for fluvastatin may be necessary. Monitor for fluvastatin toxicity.
Lovastatin, Simvastatin DOR, RPV IM, RPV PO ↔ lovastatin and simvastatin expected No dose adjustment needed.
EFV

Simvastatin AUC ↓ 60% to 68%

Simvastatin active metabolite AUC ↓ 60%

 Adjust simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
ETR, NVP

↓ lovastatin possible

↓ simvastatin possible

 Adjust lovastatin or simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Pitavastatin DOR, ETR, NVP, RPV IM, RPV PO ↔ pitavastatin expected No dose adjustment needed.
EFV ↔ pitavastatin AUC No dose adjustment needed.
Pravastatin DOR, NVP, RPV IM, RPV PO ↔ pravastatin expected No dose adjustment needed.
EFV Pravastatin AUC ↓ 44% Adjust statin dose according to lipid responses, but do not exceed the maximum recommended dose.
ETR ↓ pravastatin possible
Rosuvastatin DOR, EFV, ETR, NVP, RPV IM, RPV PO ↔ rosuvastatin expected No dose adjustment needed.
Narcotics and Treatment for Opioid Dependence
Buprenorphine Sublingual or buccal DOR, RPV IM, RPV PO ↔ buprenorphine expected No dose adjustment needed.
EFV

Buprenorphine AUC ↓ 50%

Norbuprenorphine (active metabolite) AUC ↓ 71%

 No dose adjustment needed; monitor for withdrawal symptoms.
ETR Buprenorphine AUC ↓ 25% No dose adjustment needed.
NVP No significant effect No dose adjustment needed.
Buprenorphine Implant DOR, RPV IM, RPV PO ↔ buprenorphine expected No dose adjustment needed.
EFV, ETR, NVP No data Clinical monitoring is recommended when NNRTI is initiated after insertion of buprenorphine implant.
Lofexidine DOR, EFV, ETR, NVP, RPV IM, RPV PO ↔ lofexidine expected No dose adjustment needed.
Methadone DOR

↔ methadone AUC

DOR AUC ↓ 26%

 No dose adjustment needed.
EFV Methadone AUC ↓ 52% Opioid withdrawal common; monitor and increase methadone dose as necessary.
ETR ↔ methadone AUC No dose adjustment needed.
NVP

Methadone AUC ↓ 37% to 51%

↔ NVP

 Opioid withdrawal common; monitor and increase methadone dose as necessary.
RPV IM ↓ methadone AUC expected No dose adjustment needed, but monitor for withdrawal symptoms.
RPV PO R-methadonea AUC ↓ 16% No dose adjustment needed, but monitor for withdrawal symptoms.
PDE5 Inhibitors
Sildenafil DOR ↔ sildenafil expected No dose adjustment needed.
EFV, NVP ↓ sildenafil possible May need to titrate sildenafil dose based on clinical effect.
ETR Sildenafil AUC ↓ 57% May need to titrate sildenafil dose based on clinical effect.
RPV IM ↔ sildenafil expected No dose adjustment needed.
RPV PO ↔ sildenafil AUC and Cmax No dose adjustment needed.
Tadalafil DOR, RPV IM, RPV PO ↔ tadalafil expected No dose adjustment needed.
EFV, ETR, NVP ↓ tadalafil possible May need to titrate tadalafil dose based on clinical effect.
Avanafil, Vardenafil DOR, RPV IM, RPV PO ↔ avanafil or vardenafil expected No dose adjustment needed.
EFV, ETR, NVP ↓ avanafil or vardenafil possible May need to increase PDE5 inhibitor dose based on clinical effect.
Sedative/Hypnotics
Alprazolam, Triazolam DOR, RPV IM, RPV PO ↔ benzodiazepine expected No dose adjustment needed.
EFV, ETR, NVP ↓ benzodiazepine possible Monitor for therapeutic effectiveness of benzodiazepine.
Diazepam DOR, RPV IM, RPV PO ↔ diazepam expected No dose adjustment needed.
EFV, NVP ↓ diazepam possible Monitor for therapeutic effectiveness of diazepam.
ETR ↑ diazepam possible Decreased dose of diazepam may be necessary. Monitor for diazepam toxicity.
Lorazepam DOR, ETR, NVP, RPV IM, RPV PO ↔ lorazepam expected No dose adjustment needed.
EFV ↔ lorazepam AUC No dose adjustment needed.
Midazolam DOR ↔ midazolam AUC No dose adjustment needed.
EFV ↑ or ↓ midazolam possible Monitor for therapeutic effectiveness and toxicity of midazolam.
ETR

Midazolam AUC ↓ 31%

Midazolam active metabolite Cmax ↑ 57%

 Monitor for therapeutic effectiveness of midazolam.
NVP ↓ midazolam possible Monitor for therapeutic effectiveness of midazolam.
RPV IM, RPV PO ↔ midazolam expected No dose adjustment needed.
a R-methadone is the active form of methadone.

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

Key: ARV = antiretroviral; AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CAB = cabotegravir; CCB = calcium channel blocker; DAA = direct-acting antiviral; DHA = dihydroartemisinin; DLV = delavirdine; DOR = doravirine; EFV = efavirenz; ETR = etravirine; HCV = hepatitis C virus; IM = intramuscular; INR = international normalized ratio; MAC = Mycobacterium avium complex; MPA = medroxyprogesterone acetate; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; OH‑itraconazole = active metabolite of itraconazole; PCP = Pneumocystis jirovecii pneumonia; PDE5 = phosphodiesterase type 5; PI/r = protease inhibitor/ritonavir; PO = oral; RPV = rilpivirine; RTV = ritonavir

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