Updated
Reviewed Sep. 01, 2022

Drug-Drug Interactions

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, 24e, 24f, 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 (3 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.

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 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 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 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.

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 is 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 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 is 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 expected

Contraindicated.

RPV PO

RPV AUC ↓ 80%

Contraindicated.

Rifapentine

DOR

DOR 100 mg Twice Daily plus Once-Weekly Rifapentine and Isoniazid 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.

Antibacterials—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 possible

Consider alternative macrolide (e.g., azithromycin). If coadministered, monitor for QTc prolongation.

Anticoagulants

Apixaban

DOR, RPV IM, RPV PO

↔ apixaban expected

 

EFV, ETR, NVP

↓ apixaban possible

.

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 the 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 expected

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 expected

↔ 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 IM, RPV PO

↑ 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 is 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 is 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.

Antivirals—Orthopoxviruses (Smallpox, Monkeypox)

Brincidofovir

All NNRTIs

↔ brincidofovir expected

No dose adjustment needed.

Cidofovir

All NNRTIs

↔ cidofovir expected

No dose adjustment needed.

Tecovirimat

DOR, RPV PO

↓ DOR or RPV expected but not likely to be clinically relevant

No dose adjustment needed.

EFV, ETR, NVP

↔ EFV, ETR, or NVP expected

No dose adjustment needed.

RPV IM

↓ RPV expected but not likely to be clinically relevant

No dose adjustment needed. If there is a concern for suboptimal RPV exposure, seek expert consultation.

Do not initiate CAB/RPV IM during and within 2 weeks after tecovirimat treatment. (Refer to Table 24d for interaction with CAB.)

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 to 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 due to the potential for QTc prolongation with higher concentrations of RPV.

RPV PO

RPV AUC ↑ 150% to 225%

Do not coadminister due to 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

↔ alprazolam or triazolam expected

No dose adjustment needed.

EFV, ETR, NVP

↓ alprazolam or triazolam 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.

aR-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; DOR = doravirine; EFV = efavirenz; ETR = etravirine; HCV = hepatitis C virus; IM = intramuscular; INR = international normalized ratio; isoniazid = isonicotinic acid hydrazide; 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 = orally; QTc = QT corrected for heart rate; RPV = rilpivirine; RTV = ritonavir.

Drug-Drug Interactions

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

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 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 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 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.

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 is 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 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 is 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 expected

Contraindicated.

RPV PO

RPV AUC ↓ 80%

Contraindicated.

Rifapentine

DOR

DOR 100 mg Twice Daily plus Once-Weekly Rifapentine and Isoniazid 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.

Antibacterials—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 possible

Consider alternative macrolide (e.g., azithromycin). If coadministered, monitor for QTc prolongation.

Anticoagulants

Apixaban

DOR, RPV IM, RPV PO

↔ apixaban expected

 

EFV, ETR, NVP

↓ apixaban possible

.

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 the 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 expected

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 expected

↔ 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 IM, RPV PO

↑ 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 is 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 is 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.

Antivirals—Orthopoxviruses (Smallpox, Monkeypox)

Brincidofovir

All NNRTIs

↔ brincidofovir expected

No dose adjustment needed.

Cidofovir

All NNRTIs

↔ cidofovir expected

No dose adjustment needed.

Tecovirimat

DOR, RPV PO

↓ DOR or RPV expected but not likely to be clinically relevant

No dose adjustment needed.

EFV, ETR, NVP

↔ EFV, ETR, or NVP expected

No dose adjustment needed.

RPV IM

↓ RPV expected but not likely to be clinically relevant

No dose adjustment needed. If there is a concern for suboptimal RPV exposure, seek expert consultation.

Do not initiate CAB/RPV IM during and within 2 weeks after tecovirimat treatment. (Refer to Table 24d for interaction with CAB.)

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 to 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 due to the potential for QTc prolongation with higher concentrations of RPV.

RPV PO

RPV AUC ↑ 150% to 225%

Do not coadminister due to 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

↔ alprazolam or triazolam expected

No dose adjustment needed.

EFV, ETR, NVP

↓ alprazolam or triazolam 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.

aR-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; DOR = doravirine; EFV = efavirenz; ETR = etravirine; HCV = hepatitis C virus; IM = intramuscular; INR = international normalized ratio; isoniazid = isonicotinic acid hydrazide; 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 = orally; QTc = QT corrected for heart rate; RPV = rilpivirine; RTV = ritonavir.

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