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

Actualizado 12/09/2024 - 12:00 Reviewed Jue, 12/09/2024 - 12:00

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 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 antiretroviral (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.

Oral doses of RPV at 75 mg and 300 mg once daily (equivalent to 3 and 12 times the recommended dose) were associated with prolonged QTc (or QT corrected for heart rate) 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.

Nevirapine (NVP) is no longer commonly used in clinical practice in the United States and is not included in this table. Please refer to the U.S. Food and Drug Administration product labels for information regarding drug interactions between NVP and concomitant medications. Information may also be found in archived versions of this guideline.

Concomitant Drug	NNRTI	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Acid Reducers
Antacids	DOR, EFV	↔ 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	↔ DOR 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 and C_min	No dose adjustment needed
	EFV	↔ EFV 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% to 65% and C_min↓ 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
Alfuzosin, Doxazosin, Silodosin, Terazosin	EFV, ETR	↓ 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
Tamsulosin	EFV, ETR	↓ 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
Bedaquiline	EFV, ETR	↓ bedaquiline possible	Do not coadminister.
Rifabutin	DOR	DOR AUC ↓ 50%	Increase DOR dose to 100 mg twice daily. No dose adjustment is needed for rifabutin.
	EFV	Rifabutin ↓ 38%	Increase rifabutin dose to 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.
	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 C_min	Increase RPV dose to 50 mg PO once daily during coadministration. 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.
	RPV IM	↓ RPV possible	Contraindicated
	RPV PO	RPV AUC ↓ 80%	Contraindicated
Rifapentine	DOR	Once-Weekly Rifapentine Plus Isoniazid and DOR 100 mg Twice Daily Compared to DOR 100 mg Twice Daily Alone DOR AUC ↓ 29%, C_min ↓ 31%	Contraindicated. After stopping rifapentine, wait 4 weeks before initiating DOR.
	EFV	Daily Rifapentine (Max 600 mg) With EFV ↔ EFV Weekly Rifapentine (Max 900 mg) With EFV ↔ EFV	No dose adjustment needed
	ETR	↓ ETR possible	Do not coadminister.
	RPV IM, RPV PO	↓ RPV possible	Contraindicated
Antibacterials—Macrolides
Azithromycin	DOR, EFV, ETR, RPV IM, RPV PO	↔ 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.
	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	↑ EFV and ETR 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	No dose adjustment needed
Apixaban	EFV, ETR	↓ apixaban possible	Consider alternative ARV or anticoagulant therapy.
Dabigatran, Edoxaban	DOR, EFV, ETR, RPV IM, RPV PO	↔ DOAC expected	No dose adjustment needed
Rivaroxaban	DOR, RPV IM, RPV PO	↔ rivaroxaban expected	No dose adjustment needed
Rivaroxaban	EFV, ETR	↓ rivaroxaban possible	Consider alternative ARV or anticoagulant therapy.
Warfarin	DOR, RPV IM, RPV PO	↔ warfarin expected	No dose adjustment needed
Warfarin	EFV, ETR	↑ or ↓ warfarin possible	Monitor INR and adjust warfarin dose accordingly.
Antiseizure
Carbamazepine, Phenobarbital, Phenytoin, Primidone	DOR	↓ DOR possible	Contraindicated. After stopping antiseizure medication, wait 4 weeks before initiating DOR.
	EFV	Carbamazepine Plus EFV Carbamazepine AUC ↓ 27% EFV AUC ↓ 36% Phenytoin Plus EFV ↓ EFV ↑ or ↓ phenytoin possible Phenobarbital or Primidone Plus EFV ↓ EFV and antiseizure agent possible	Consider alternative ARV or antiseizure medication. If coadministration is necessary, monitor antiseizure drug and EFV concentrations.
	ETR	↓ antiseizure agent and ETR possible	Do not coadminister.
	RPV IM, RPV PO	↓ RPV possible	Contraindicated
Eslicarbazepine	DOR, EFV, ETR, RPV IM, RPV PO	↓ NNRTI possible	Consider alternative ARV or antiseizure medication. If coadministration is necessary, monitor virologic response and consider monitoring plasma concentrations of ARVs.
Oxcarbazepine	DOR, RPV IM, RPV PO	↓ NNRTI possible	Contraindicated
Oxcarbazepine	EFV, ETR	↓ NNRTI possible	Consider alternative ARV or antiseizure medication. If coadministration is necessary, monitor virologic response and consider monitoring plasma concentrations of ARVs.
Ethosuximide, Lacosamide, Tiagabine, Zonisamide	DOR, RPV IM, RPV PO	↔ antiseizure agent expected	No dose adjustment needed
Ethosuximide, Lacosamide, Tiagabine, Zonisamide	EFV, ETR	↓ antiseizure agent possible	Monitor seizure control. Consider anticonvulsant therapeutic drug monitoring.
Lamotrigine	DOR, ETR, RPV IM, RPV PO	↔ lamotrigine expected	No dose adjustment needed
Lamotrigine	EFV	↓ lamotrigine possible	Monitor seizure control and plasma concentrations of lamotrigine.
Antidepressants, Anxiolytics, and Antipsychotics Also see the Sedative/Hypnotics section below.
Antidepressants and Anxiolytics
Bupropion	DOR, ETR, RPV IM, RPV PO	↔ bupropion expected	No dose adjustment needed
Bupropion	EFV	Bupropion AUC ↓ 55%	Titrate bupropion dose based on clinical response.
Citalopram, Escitalopram	DOR, RPV IM, RPV PO	↔ antidepressant expected	No dose adjustment needed
Citalopram, Escitalopram	EFV, ETR	↓ antidepressant possible	Titrate antidepressant dose based on clinical response.
Desvenlafaxine, Venlafaxine	DOR, EFV, ETR, RPV IM, RPV PO	↔ antidepressant expected	No dose adjustment needed
Duloxetine	DOR, EFV, ETR, RPV IM, RPV PO	↔ antidepressant expected	No dose adjustment needed
Fluoxetine, Fluvoxamine	DOR, EFV, ETR, RPV IM, RPV PO	↔ antidepressant expected	No dose adjustment needed
Mirtazapine	DOR, RPV IM, RPV PO	↔ mirtazapine expected	No dose adjustment needed
Mirtazapine	EFV, ETR	↓ mirtazapine possible	Monitor antidepressant effect. Titrate dose as necessary based on clinical response.
Nefazodone	DOR, RPV IM, RPV PO	↑ NNRTI possible	No dose adjustment needed
Nefazodone	EFV, ETR	↓ nefazodone expected ↑ NNRTI possible	Monitor antidepressant effect. Titrate dose as necessary based on clinical response.
Paroxetine	DOR, ETR, RPV IM, RPV PO	↔ paroxetine expected	No dose adjustment needed
Paroxetine	EFV	↔ EFV and paroxetine	No dose adjustment needed
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	↓ sertraline possible
Trazodone	DOR, RPV IM, RPV PO	↔ trazodone expected	No dose adjustment needed
Trazodone	EFV, ETR	↓ trazodone possible	Monitor for therapeutic effectiveness of trazodone and titrate dose as necessary.
Tricyclic Antidepressants (e.g., amitriptyline, doxepin, nortriptyline)	DOR, EFV, ETR, RPV IM, RPV PO	↔ antidepressant expected	No dose adjustment needed
Antipsychotics
Aripiprazole	DOR, RPV IM, RPV PO	↔ aripiprazole expected	No dose adjustment needed
Aripiprazole	EFV, ETR	↓ 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
Brexpiprazole	EFV, ETR	↓ 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
Cariprazine	EFV, ETR	↓ cariprazine and ↑ or ↓ active metabolite possible	Do not coadminister.
Iloperidone	DOR, RPV IM, RPV PO	↔ antipsychotic expected	No dose adjustment needed
Iloperidone	EFV, ETR	↓ antipsychotic possible	Monitor for therapeutic effectiveness of antipsychotic.
Lumateperone	DOR, RPV IM, RPV PO	↔ antipsychotic expected	No dose adjustment needed
Lumateperone	EFV, ETR	↓ antipsychotic possible	Do not coadminister.
Lurasidone	DOR, RPV IM, RPV PO	↔ antipsychotic expected	No dose adjustment needed
Lurasidone	EFV, ETR	↓ antipsychotic possible	Monitor for therapeutic effectiveness of antipsychotic.
Olanzapine, Olanzapine/Samidorphan	DOR, ETR, RPV IM, RPV PO	↔ olanzapine expected	No dose adjustment needed
Olanzapine, Olanzapine/Samidorphan	EFV	↓ olanzapine possible	Monitor for therapeutic effectiveness of olanzapine.
Other Antipsychotics CYP3A4 Substrates (e.g., clozapine, haloperidol, perphenazine, risperidone, thioridazine)	DOR, RPV IM, RPV PO	↔ antipsychotic expected	No dose adjustment needed
	EFV, ETR	↓ antipsychotic possible	Monitor for therapeutic effectiveness of antipsychotic.
Pimavanserin	DOR, RPV IM, RPV PO	↔ pimavanserin expected	No dose adjustment needed
Pimavanserin	EFV, ETR	↓ pimavanserin expected	Do not coadminister.
Pimozide	DOR, RPV IM, RPV PO	↔ pimozide expected	No dose adjustment needed
Pimozide	EFV, ETR	↓ pimozide possible	Monitor for therapeutic effectiveness of pimozide.
Quetiapine	DOR, RPV IM, RPV PO	↔ antipsychotic expected	No dose adjustment needed
Quetiapine	EFV, ETR	↓ antipsychotic possible	Monitor for therapeutic effectiveness of antipsychotic.
Ziprasidone	DOR, RPV IM, RPV PO	↔ antipsychotic expected	No dose adjustment needed
Ziprasidone	EFV, ETR	↓ 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
	RPV IM, RPV PO	↑ RPV possible	No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Ibrexafungerp	DOR, RPV PO	↑ NNRTI possible	No dose adjustment needed
	EFV, ETR	↓ ibrexafungerp expected ↑ NNRTI possible	Do not coadminister.
	RPV IM	↔ ibrexafungerp expected ↔ RPV IM expected	No dose adjustment needed
Isavuconazole	DOR	↑ DOR possible	No dose adjustment needed
	EFV, ETR	↓ 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	EFV With Itraconazole Solution Itraconazole and OH-itraconazole AUC, C_max, and C_min ↓ 37% to 44% EFV With Itraconazole Capsules Itraconazole AUC ↓ 86% and OH-itraconazole AUC 84%	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.
	RPV IM, RPV PO	↑ RPV possible	No dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Posaconazole	DOR, ETR	↑ 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
	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.
Atovaquone/Proguanil	DOR, ETR, RPV IM, RPV PO	No data	Monitor for antimalarial efficacy.
Atovaquone/Proguanil	EFV	Atovaquone AUC ↓ 75% Proguanil AUC ↓ 43%	No dose recommendation. Consider alternative drug for malaria prophylaxis, if possible.
Antimigraine
Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists
Atogepant	DOR, RPV IM, RPV PO	↔ atogepant expected	No dose adjustment needed
Atogepant	EFV, ETR	↓ atogepant possible	Episodic migraine: Increase atogepant dose to 30–60 mg once daily. Chronic migraine: Do not coadminister.
Rimegepant	DOR, RPV IM, RPV PO	↔ rimegepant expected	No dose adjustment needed
Rimegepant	EFV, ETR	↓ rimegepant possible	Consider alternative ARV or migraine medication.
Ubrogepant	DOR, RPV IM, RPV PO	↔ ubrogepant expected	No dose adjustment needed
Ubrogepant	EFV, ETR	↓ ubrogepant expected	Use initial dose of 100 mg, followed by second dose of 100 mg if needed.
Zavegepant	DOR, RPV IM, RPV PO	↔ zavegepant expected	No dose adjustment needed
Zavegepant	EFV, ETR	↓ zavegepant possible	No dose adjustment needed
Serotonin 5-HT1B, 1D Receptor Agonists
Almotriptan, Eletriptan	DOR, RPV IM, RPV PO	↔ almotriptan expected	No dose adjustment needed
Almotriptan, Eletriptan	EFV, ETR	↓ almotriptan possible	No dose adjustment needed
Frovatriptan, Naratripan, Rizatriptan, Sumatriptan, Zolmitriptan	DOR, EFV, ETR, RPV IM, RPV PO	↔ migraine medication expected	No dose adjustment needed
Antiplatelets
Clopidogrel	DOR, RPV IM, RPV PO	↔ clopidogrel expected	No dose adjustment needed
Clopidogrel	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
Ticagrelor	EFV, ETR	↓ ticagrelor expected	Consider alternative ARV or anticoagulant therapy.
Vorapaxar	DOR, RPV IM, RPV PO	↔ vorapaxar expected	No dose adjustment needed
Vorapaxar	EFV, ETR	↓ vorapaxar expected	Insufficient data to make a dose recommendation.
Antipneumocystis and Antitoxoplasmosis
Atovaquone (oral solution)	DOR, ETR, RPV IM, RPV PO	No data	Monitor for therapeutic effectiveness of atovaquone.
Atovaquone (oral solution)	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—Hepatitis C
Elbasvir/Grazoprevir	DOR	↔ elbasvir and grazoprevir DOR AUC ↑ 56% and C_min↑ 41%	No dose adjustment needed
	EFV	Elbasvir AUC ↓ 54% Grazoprevir AUC ↓ 83% ↔ EFV	Contraindicated
	ETR	↓ 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 C_min	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.
	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, C_min, and C_max ↓ 34% ↔ sofosbuvir
	ETR	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%, C_max ↓ 37%, and C_min ↓ 47%	Do not coadminister.
	ETR	↓ 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%, C_max ↓ 37%, and C_min ↓47% ↓ voxilaprevir expected	Do not coadminister.
	ETR	↓ voxilaprevir expected ↓ velpatasvir expected	Do not coadminister.
Antivirals—Miscellaneous (e.g., for CMV, Mpox)
Brincidofovir	All NNRTIs	↔ brincidofovir expected	No dose adjustment needed
Cidofovir	All NNRTIs	↔ cidofovir expected	No dose adjustment needed
Maribavir	DOR RPV IM, RPV PO	↔ maribavir expected	No dose adjustment needed
Maribavir	EFV, ETR	↓ maribavir possible	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	↔ EFV or ETR 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 or within 2 weeks after tecovirimat treatment. (Refer to Table 24d for interaction with CAB.)
Antivirals—SARS-CoV-2
Molnupiravir	All NNRTIs	↔ expected	No dose adjustment needed
Remdesivir	All NNRTIs	↔ expected	No dose adjustment needed
Ritonavir-Boosted Nirmatrelvir	DOR	With Ritonavir 100 mg Twice Daily DOR AUC ↑ 254%	No dose adjustment needed
Ritonavir-Boosted Nirmatrelvir	EFV, ETR, RPV PO, RPV IM	↔ expected	No dose adjustment needed
Cardiac Medications
Beta-Blockers
Atenolol, Metoprolol, Nebivolol	DOR, EFV, ETR, RPV IM, RPV PO	↔ beta-blocker expected	No dose adjustment needed
Bisoprolol, Carvedilol	DOR, RPV IM, RPV PO	↔ beta-blocker expected	No dose adjustment needed
Bisoprolol, Carvedilol	EFV, ETR	↓ beta-blocker possible	No dose adjustment needed. Monitor blood pressure and heart rate and titrate to clinical effect.
Labetalol	DOR, RPV IM, RPV PO	↔ beta-blocker expected	No dose adjustment needed
Labetalol	EFV, ETR	↑ beta-blocker possible	No dose adjustment needed. Monitor blood pressure and heart rate and adjust dose to achieve desired clinical effect.
Calcium Channel Blockers
Dihydropyridine Calcium Channel Blockers (e.g., amlodipine, nifedipine)	DOR, RPV IM, RPV PO	↔ CCBs expected	No dose adjustment needed
	EFV, ETR	↓ CCBs possible	Titrate CCB dose based on clinical response.
Non-Dihydropyridine Calcium Channel Blockers (e.g., 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	↓ diltiazem or verapamil possible
Cardiac—Other
Bosentan	DOR	↓ DOR possible	Consider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor virologic response.
	EFV, ETR	↓ 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.
Eplerenone	DOR, RPV IM, RPV PO	↔ eplerenone expected	No dose adjustment needed
Eplerenone	EFV, ETR	↓ eplerenone possible	Titrate eplerenone dose based on clinical response.
Ivabradine	DOR, RPV IM, RPV PO	↔ ivabradine expected	No dose adjustment needed
Ivabradine	EFV, ETR	↓ ivabradine expected	Contraindicated
Mavacamten	DOR, RPV IM, RPV PO	↔ mavacamten expected ↓ NNRTI possible	Consider alternative ARV or alternative to mavacamten. If coadministration is necessary, monitor virologic response.
Mavacamten	EFV, ETR	↓ mavacamten expected ↓ NNRTI possible	Contraindicated
Ranolazine	DOR, RPV IM, RPV PO	↔ ranolazine expected	No dose adjustment needed
Ranolazine	EFV, ETR	↓ ranolazine expected	Contraindicated
Corticosteroids
Beclomethasone, Ciclesonide	DOR, EFV, ETR, RPV IM, RPV PO	↔ corticosteroid expected	No dose adjustment needed
Budesonide, Fluticasone, Mometasone	DOR, RPV IM, RPV PO	↔ corticosteroid expected	No dose adjustment needed
Budesonide, Fluticasone, Mometasone	EFV, ETR	↓ corticosteroid possible	Monitor corticosteroid efficacy and titrate as needed. May consider alternative corticosteroid for long-term use.
Dexamethasone	DOR, EFV, ETR	↓ NNRTI possible	Consider alternative corticosteroid for long-term use. If dexamethasone is used with NNRTI, monitor virologic response.
Dexamethasone	RPV IM, RPV PO	Significant ↓ RPV possible	Contraindicated with more than a single dose of dexamethasone.
Prednisone, Prednisolone	DOR, RPV IM, RPV PO	↔ corticosteroid expected	No dose adjustment needed
Prednisone, Prednisolone	EFV, ETR,	↓ corticosteroid possible	Monitor corticosteroid efficacy and titrate as needed. May consider alternative corticosteroid for long-term use.
Glucose-Lowering
Linagliptin, Sitagliptin	DOR, RPV IM, RPV PO	↔ antihyperglycemic expected	No dose adjustment needed
Linagliptin, Sitagliptin	EFV, ETR	↓ antihyperglycemic possible	Monitor glycemic control.
Metformin	DOR	↔ metformin AUC DOR AUC ↓ 26% and C_max ↓ 24%	No dose adjustment needed
	EFV, ETR, RPV IM	↔ metformin expected	No dose adjustment needed
	RPV PO	↔ metformin AUC	No dose adjustment needed
Sodium-Glucose Cotransporter-2 Inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin)	DOR, EFV, ETR, RPV IM, RPV PO	↔ antihyperglycemic expected	No dose adjustment needed
Herbal Products
St. John’s Wort	DOR	↓ DOR expected	Contraindicated. After stopping St. John’s Wort, wait 4 weeks before initiating DOR.
	EFV, ETR	↓ EFV or ETR expected	Do not coadminister.
	RPV IM, RPV PO	↓ RPV expected	Contraindicated
Hormonal Therapies—Contraceptives
Injectable Contraceptives Depot MPA	DOR, ETR, RPV IM, RPV PO	↔ MPA expected	No dose adjustment needed
Injectable Contraceptives Depot MPA	EFV	↔ MPA	No dose adjustment needed. Refer to Women With HIV section for people on EFV and RIF.
Oral Contraceptives (e.g., desogestrel, drospirenone, ethinyl estradiol, levonorgestrel, norgestimate)	DOR	↔ ethinyl estradiol ↔ levonorgestrel ↔ drospirenone expected	No dose adjustment needed
	EFV	↔ ethinyl estradiol Etonogestrel (metabolite of oral desogestrel) C_min ↓ 61% Levonorgestrel (metabolite of oral norgestimate) AUC ↓ 83% Norelgestromin (metabolite of oral norgestimate) AUC ↓ 64% ↓ drospirenone possible	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 ↓ drospirenone possible	No dose adjustment needed for regimens that do not contain drospirenone For drospirenone-containing regimens used for contraception, use alternative ARV or alternative contraceptive method. If using drospirenone for other clinical indications, monitor for clinical effectiveness of hormonal therapy.
	RPV IM	↔ ethinyl estradiol expected ↔ norethindrone expected ↔ drospirenone expected	No dose adjustment needed
	RPV PO	↔ ethinyl estradiol ↔ norethindrone ↔ drospirenone expected	No dose adjustment needed
Subdermal Implant Contraceptives (e.g., etonogestrel, levonorgestrel)	DOR, RPV IM, RPV PO	↔ etonogestrel expected ↔ levonorgestrel expected	No dose adjustment needed
	EFV	Etonogestrel AUC ↓ 63% to 82% Levonorgestrel AUC ↓ 42% to 47% Levonorgestrel 300 mg Implant With 600 mg EFV Compared to Levonorgestrel 150 mg Implant • Levonorgestrel AUC ↓ 34%	Use alternative ARV or contraceptive methods. Unintended pregnancies were observed in women who used EFV and levonorgestrel implant concomitantly.
	ETR	↓ etonogestrel possible ↓ levonorgestrel possible	Consider using alternative ARV or contraceptive method.
Transdermal Contraceptives (e.g., ethinyl estradiol/norelgestromin, ethinyl estradiol/levonorgestrel)	DOR, RPV IM, RPV PO	↔ ethinyl estradiol or norelgestromin expected	No dose adjustment needed
	EFV	↓ ethinyl estradiol or norelgestromin possible	Consider using alternative ARV or contraceptive method.
	ETR	↓ ethinyl estradiol or norelgestromin possible	Consider using alternative ARV or contraceptive method.
Vaginal Ring Contraceptives (e.g., etonogestrel/ethinyl estradiol, segesterone/ethinyl estradiol)	DOR, RPV IM, RPV PO	↔ etonogestrel and ethinyl estradiol expected ↓ segesterone and ethinyl estradiol expected	No dose adjustment needed
	EFV	Ethinyl estradiol (intravaginal ring) AUC ↓ 56% Etonogestrel (intravaginal ring) AUC ↓ 81%	Use alternative ARV or contraceptive method.
	EFV	↓ segesterone and ethinyl estradiol possible	Consider alternative ARV or contraceptive method.
	ETR	↓ etonogestrel and ethinyl estradiol possible ↓ segesterone and ethinyl estradiol possible	Consider alternative ARV or contraceptive method.
Emergency Contraceptives Levonorgestrel (oral)	DOR, RPV IM, RPV PO	↔ levonorgestrel expected	No dose adjustment needed
	EFV	Levonorgestrel 1.5 mg Plus 600 mg EFV Levonorgestrel AUC ↓ 58% Levonorgestrel 3 mg Plus 600 mg EFV Compared to Levonorgestrel 1.5 mg Alone ↔ levonorgestrel AUC	Increase dose of levonorgestrel to 3mg when used for emergency postcoital contraception.
	ETR	↓ levonorgestrel possible	Consider alternative ARV or contraceptive method.
Hormonal Therapies—Gender Affirming and Menopause
Estradiol	DOR, RPV IM, RPV PO	↔ estradiol expected	No dose adjustment needed
	EFV	Estradiol AUC ↓ 28% ↔ EFV AUC	Monitor feminizing effects of estrogen and therapy. Titrate dose as necessary to achieve therapeutic goals.
	ETR	↓ estradiol possible
5-Alpha Reductase Inhibitors (e.g., dutasteride, finasteride)	DOR, RPV IM, RPV PO	↔ dutasteride and finasteride expected	No dose adjustment needed
	EFV, ETR	↓ dutasteride and finasteride possible	Monitor masculinizing effects of testosterone. Titrate testosterone dose as necessary to achieve therapeutic goals.
Testosterone	DOR, RPV IM, RPV PO	↔ testosterone expected	No dose adjustment needed
Testosterone	EFV, ETR	↓ testosterone possible	Monitor masculinizing effects of testosterone. Titrate testosterone dose as necessary to achieve therapeutic goals.
Other Gender-Affirming Medications	DOR, RPV IM, RPV PO	↔ hormonal concentrations expected	No dose adjustment needed
Other Gender-Affirming Medications	EFV, ETR	↓ cyproterone and progestogens possible ↔ goserelin, leuprolide acetate, and spironolactone expected	Monitor feminizing effects of estrogen and antiandrogen therapy. Titrate dose as necessary to achieve therapeutic goals.
Menopausal Hormone Replacement Therapy (e.g., conjugated estrogens, drospirenone, estradiol, medroxyprogesterone, progesterone)	DOR, RPV IM, RPV PO	↔ hormonal concentrations expected	No dose adjustment needed
	EFV, ETR	↓ 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
Cyclosporine	EFV, ETR	↓ 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
Everolimus, Sirolimus, Tacrolimus	EFV, ETR	↓ immunosuppressant possible	Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.
Lipid-Modifying
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.
	RPV IM	↔ atorvastatin expected	No dose adjustment needed
	RPV PO	↔ atorvastatin AUC	No dose adjustment needed
Fluvastatin	DOR, RPV IM, RPV PO	↔ fluvastatin expected	No dose adjustment needed
Fluvastatin	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	↓ lovastatin possible ↓ simvastatin possible	Adjust lovastatin or simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Pitavastatin	DOR, ETR, RPV IM, RPV PO	↔ pitavastatin expected	No dose adjustment needed
Pitavastatin	EFV	↔ pitavastatin AUC	No dose adjustment needed
Pravastatin	DOR, 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, 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
Buprenorphine Implant	DOR, RPV IM, RPV PO	↔ buprenorphine expected	No dose adjustment needed
Buprenorphine Implant	EFV, ETR	No data	Clinical monitoring is recommended when NNRTI is initiated after insertion of buprenorphine implant.
Lofexidine	DOR, EFV, ETR, 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
	RPV IM	↓ methadone AUC expected	No dose adjustment needed; monitor for withdrawal symptoms.
	RPV PO	↔ R-methadone^a AUC	No dose adjustment needed; monitor for withdrawal symptoms.
PDE5 Inhibitors
Avanafil, Tadalafil, Vardenafil	DOR, RPV IM, RPV PO	↔ PDE5 inhibitor expected	No dose adjustment needed
Avanafil, Tadalafil, Vardenafil	EFV, ETR	↓ PDE5 inhibitor possible	May need to titrate dose based on clinical effect.
Sildenafil	DOR	↔ sildenafil expected	No dose adjustment needed
	EFV	↓ 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 C_max	No dose adjustment needed
Sedative/Hypnotics
Benzodiazepines
Alprazolam, Triazolam	DOR, RPV IM, RPV PO	↔ alprazolam or triazolam expected	No dose adjustment needed
Alprazolam, Triazolam	EFV, ETR	↓ alprazolam or triazolam possible	Monitor for therapeutic effectiveness of benzodiazepine.
Diazepam	DOR, RPV IM, RPV PO	↔ diazepam expected	No dose adjustment needed
	EFV	↓ 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, RPV IM, RPV PO	↔ lorazepam expected	No dose adjustment needed
Lorazepam	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 C_max ↑ 57%	Monitor for therapeutic effectiveness of midazolam.
	RPV IM, RPV PO	↔ midazolam expected	No dose adjustment needed
Orexin Receptor Antagonists
Daridorexant	DOR, RPV IM, RPV PO	↔ daridorexant expected	No dose adjustment needed
	EFV	Daridorexant AUC ↓ 61%	Do not coadminister.
	ETR	↓ daridorexant possible	Do not coadminister.
Lemborexant, Suvorexant	DOR, RPV IM, RPV PO	↔ lemborexant expected	No dose adjustment needed
Lemborexant, Suvorexant	EFV, ETR	↓ lemborexant possible	Do not coadminister.
Other Sedatives
Eszopiclone, Zolpidem	DOR, RPV IM, RPV PO	↔ eszopiclone or zolpidem expected	No dose adjustment needed
Eszopiclone, Zolpidem	EFV, ETR	↓ eszopiclone or zolpidem possible	Monitor for therapeutic effectiveness of sedative and titrate to clinical effect.
Miscellaneous
Finerenone	DOR, RPV IM, RPV PO	↔ finerenone expected	No dose adjustment needed
Finerenone	EFV, ETR	↓ finerenone expected	Consider alternative ARV or alternative to finerenone. If coadministration is necessary, monitor finerenone efficacy.
Praziquantel	DOR, RPV IM, RPV PO	↔ praziquantel expected	No dose adjustment needed
	EFV	R-praziquantel and S-praziquantel AUC ↓ 74% to 75%	Do not coadminister. If coadministration is necessary, consider alternative ARVs.
	ETR	↓ praziquantel possible	Do not coadminister. If coadministration is necessary, consider alternative ARVs.
^aR-methadone is the active form of methadone. Key to Symbols: ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC Key: ARV = antiretroviral; AUC = area under the curve; C_max = maximum plasma concentration; C_min = minimum plasma concentration; CAB = cabotegravir; CCB = calcium channel blocker; DAA = direct-acting antiviral; DHA = dihydroartemisinin; DOAC = direct oral anticoagulants; DOR = doravirine; EFV = efavirenz; ETR = etravirine; IM = intramuscular; INR = international normalized ratio; isoniazid = isonicotinic acid hydrazide; MAC = Mycobacterium avium complex; MPA = medroxyprogesterone acetate; CMV = cytomegalovirus; NNRTI = non-nucleoside reverse transcriptase inhibitor; 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