Adult Antiretroviral Guidelines

US DHHS Guidelines with Australian Commentary

NNRTI interactions

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

DHHS Last Updated: September 2022Australian Commentary Last Updated: July 2023

Despite there being no direct effect on RPV plasma concentration, high doses of oral supplements may modify gastric pH, thereby affecting RPV absorption – subsequent potential impact on maintenance of viral suppression.

in the context of between-class ARV switches, clinicians may need to factor in enzyme induction of some NNRTIs, time to induction dissipation, and potential impact on ARV being introduced.

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 24c24e24f25a, 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
AntacidsDOR, EFV, NVP↔ NNRTI AUCNo dose adjustment needed.
ETR↔ ETR expectedNo dose adjustment needed.
RPV IM↔ RPV expectedNo dose adjustment needed.
RPV PO↓ RPV expected when given simultaneouslyGive antacids at least 2 hours before or at least 4 hours after RPV.
H2 Receptor AntagonistsDOR, NVP↔ NNRTI expectedNo dose adjustment needed.
EFV↔ EFV AUCNo dose adjustment needed.
ETR ↔ ETR AUCNo dose adjustment needed.
RPV IM↔ RPV expectedNo dose adjustment needed.
RPV PORPV AUC ↓ 76% when famotidine 40 mg is taken 2 hours priorGive H2 receptor antagonists at least 12 hours before or at least 4 hours after RPV.
Proton Pump Inhibitors
DORDOR AUC ↓ 17% and Cmin ↓ 16%No dose adjustment needed.
EFV, NVP↔ EFV and NVP expected
ETRWith Omeprazole 40 mg Daily

  • ETR AUC ↑ 41%

RPV IM↔ RPV expectedNo dose adjustment needed.
RPV POWith 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 expectedNo dose adjustment needed.
EFV, ETR, NVP↓ alpha-adrenergic antagonists expectedConsider alternative ARV or alpha-antagonist therapy. If coadministration is necessary, monitor for therapeutic effectiveness of alpha antagonist.
Tamsulosin
DOR, RPV IM, RPV PO↔ tamsulosin expectedNo dose adjustment needed.
EFV, ETR, NVP↓ tamsulosin expectedMonitor 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 possibleDo not coadminister.
NVP↔ bedaquiline AUCNo dose adjustment needed.
Rifabutin
DORDOR AUC ↓ 50%Increase DOR dose to 100 mg twice daily. No dose adjustment is needed for rifabutin.
EFVRifabutin ↓ 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 expectedContraindicated.
RPV PORifabutin 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
DORDOR AUC ↓ 88%Contraindicated. After stopping rifampin, wait 4 weeks before initiating DOR.
EFVEFV AUC ↓ 26%Do not use EFV 400 mg with rifampin. Maintain EFV dose at 600 mg once daily and monitor for virologic response.
ETRSignificant ↓ ETR possibleDo not coadminister.
NVPNVP ↓ 20% to 58%Do not coadminister.
RPV IM↓ RPV expectedContraindicated.
RPV PORPV AUC ↓ 80%Contraindicated.
Rifapentine
DORDOR 100 mg Twice Daily plus Once-Weekly Rifapentine and Isoniazid Compared to DOR 100 mg Twice Daily Alone
OR AUC ↓ 29%, Cmin ↓ 31%
Contraindicated. After stopping rifapentine, wait 4 weeks before initiating DOR.
EFV↔ EFV concentrationsNo dose adjustment needed.
ETR↓ ETR possibleDo not coadminister.
NVPNVP Cmin ↓ 27%Do not coadminister.
RPV IM, RPV PO↓ RPV expectedContraindicated.
Antibacterials—Macrolides
Azithromycin
All NNRTIs↔ azithromycin expectedNo dose adjustment needed.
Clarithromycin
DOR↔ clarithromycin expected

↑ DOR possible
Monitor for ARV tolerability if used in combination.
EFVClarithromycin AUC ↓ 39%Monitor for effectiveness, or consider alternative agent (e.g., azithromycin) for MAC prophylaxis and treatment.
ETRClarithromycin AUC ↓ 39%

ETR AUC ↑ 42%
Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
NVPClarithromycin 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.
ErythromycinDOR↑ DOR possibleMonitor 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 possibleConsider 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 expectedNo dose adjustment needed.
EdoxabanAll NNRTIs↔ edoxaban expectedNo dose adjustment needed.
Rivaroxaban DOR, RPV IM, RPV PO↔ rivaroxaban expectedNo dose adjustment needed.
EFV, ETR, NVP↓ rivaroxaban possibleConsider alternative ARV or anticoagulant therapy.
Warfarin
DOR, RPV IM, RPV PO↔ warfarin expectedNo dose adjustment needed.
EFV, ETR, NVP↑ or ↓ warfarin possibleMonitor INR and adjust warfarin dose accordingly.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin
DOR↓ DOR possibleContraindicated. After stopping anticonvulsant, wait 4 weeks before initiating DOR.
EFVCarbamazepine 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 possibleDo not coadminister.
NVP↓ anticonvulsant and NVP possibleConsider alternative ARV or anticonvulsant. If coadministration is necessary, monitor anticonvulsant and NVP concentrations and virologic response.
RPV IM, RPV PO↓ RPV possibleContraindicated.
Eslicarbazepine
All NNRTIs↓ NNRTI possibleConsider 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 possibleContraindicated.
EFV, ETR, NVP↓ NNRTI possibleConsider 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 expectedNo dose adjustment needed.
EFV, ETR, NVP↓ anticonvulsant possibleMonitor seizure control. Consider anticonvulsant therapeutic drug monitoring.
Lamotrigine
DOR, ETR, NVP, RPV IM, RPV PO↔ lamotrigine expectedNo dose adjustment needed.
EFV↓ lamotrigine possibleMonitor seizure control and plasma concentrations of lamotrigine.
Antidepressants, Anxiolytics, and Antipsychotics
Also see the Sedative/Hypnotics section below.
BupropionDOR, ETR, RPV IM, RPV PO↔ bupropion expectedNo dose adjustment needed.
EFVBupropion AUC ↓ 55%Titrate bupropion dose based on clinical response.
NVP↓ bupropion possible
Citalopram, EscitalopramDOR, RPV IM, RPV PO↔ antidepressant expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antidepressant possibleTitrate antidepressant dose based on clinical response.
Fluoxetine, FluvoxamineAll NNRTIs↔ antidepressant expectedNo dose adjustment needed.
ParoxetineDOR, NVP, RPV IM, RPV PO↔ paroxetine expectedNo dose adjustment needed.
EFV, ETR↔ paroxetine expectedNo dose adjustment needed.
NefazodoneDOR, RPV IM, RPV PO↑ NNRTI possibleNo dose adjustment needed.
EFV, ETR, NVP↓ nefazodone expected

↑ NNRTI possible
Monitor antidepressant effect. Titrate dose as necessary based on clinical response.
SertralineDOR, RPV IM, RPV PO↔ sertraline expectedNo dose adjustment needed.
EFVSertraline AUC ↓ 39%Monitor the antidepressant effect. Titrate dose as necessary based on clinical response.
ETR, NVP↓ sertraline possible
TrazodoneDOR, RPV IM, RPV PO↔ trazodone expectedNo dose adjustment needed.
EFV, ETR, NVP↓ trazodone possibleMonitor for therapeutic effectiveness of trazodone and titrate dose as necessary.
Antipsychotics
AripiprazoleDOR, RPV IM, RPV PO↔ aripiprazole expectedNo dose adjustment needed.
EFV, ETR, NVP↓ aripiprazole expectedMonitor 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 expectedNo dose adjustment needed.
EFV, ETR, NVP↓ brexpiprazole expectedMonitor 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 expectedNo dose adjustment needed.
EFV, ETR, NVP↓ cariprazine and ↑ or ↓ active metabolite possibleDo not coadminister.
IloperidoneDOR, RPV IM, RPV PO↔ antipsychotic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antipsychotic possibleMonitor for therapeutic effectiveness of antipsychotic.
Lumateperone
DOR, RPV IM, RPV PO↔ antipsychotic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antipsychotic possibleDo not coadminister.
Lurasidone
DOR, RPV IM, RPV PO↔ antipsychotic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antipsychotic possibleMonitor for therapeutic effectiveness of antipsychotic.
OlanzapineDOR, ETR, NVP, RPV IM, RPV PO↔ olanzapine expectedNo dose adjustment needed.
EFV↓ olanzapine possibleMonitor for therapeutic effectiveness of olanzapine.
Other Antipsychotics

CYP3A4 substrates (e.g., clozapine, perphenazine, risperidone)
DOR, RPV IM, RPV PO↔ antipsychotic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antipsychotic possibleMonitor for therapeutic effectiveness of antipsychotic.
Pimavanserin
DOR, RPV IM, RPV PO↔ pimavanserin expectedNo dose adjustment needed.
EFV, ETR, NVP↓ pimavanserin expectedDo not coadminister.
Pimozide
DOR, RPV IM, RPV PO↔ pimozide expectedNo dose adjustment needed.
EFV, ETR, NVP↓ pimozide possibleMonitor for therapeutic effectiveness of pimozide.
QuetiapineDOR, RPV IM, RPV PO↔ antipsychotic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antipsychotic possibleMonitor for therapeutic effectiveness of antipsychotic.
Ziprasidone
DOR, RPV IM, RPV PO↔ antipsychotic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antipsychotic possibleMonitor for therapeutic effectiveness of antipsychotic.
Antifungals
FluconazoleDOR↑ DOR possibleNo dose adjustment needed.
EFV↔ fluconazole expected

↔ EFV AUC
No dose adjustment needed.
ETRETR AUC ↑ 86%No dose adjustment needed.
NVPNVP AUC ↑ 110%Consider alternative ARV or antifungal agent. Increased risk of hepatotoxicity is possible with this combination.
RPV IM, RPV PO↑ RPV possibleNo dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Isavuconazole
DOR↑ DOR possibleNo dose adjustment needed.
EFV, ETR, NVP↓ isavuconazole possibleMonitor isavuconazole concentration and antifungal response. Dose adjustments for isavuconazole may be necessary.
RPV IM, RPV PO↑ RPV possibleNo dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Itraconazole
DOR↑ DOR possibleNo dose adjustment needed.
EFVItraconazole 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.
NVPItraconazole 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 possibleNo dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
PosaconazoleDOR, ETR, NVP↑ NNRTI possibleNo dose adjustment needed.
EFVPosaconazole 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 possibleNo dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Voriconazole
DOR↑ DOR possibleNo dose adjustment needed.
EFVVoriconazole 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 possibleNo dose adjustment needed. If coadministered, consider monitoring for QTc prolongation.
Antimalarials
Artemether/LumefantrineDOR, RPV IM, RPV PO↔ antimalarial expected
No dose adjustment needed.
EFVArtemether 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.
ETRArtemether 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.
NVPArtemether 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 PONo data
Monitor for antimalarial efficacy.
EFVAtovaquone AUC ↓ 75%

Proguanil AUC ↓ 43%
No dose recommendation. Consider alternative drug for malaria prophylaxis, if possible.
Antiplatelets
ClopidogrelDOR, NVP, RPV IM, RPV PO↔ clopidogrel expected
No dose adjustment needed.
EFV, ETR↓ activation of clopidogrel possibleConsider alternative ARV or antiplatelet. ETR may prevent metabolism of clopidogrel to its active metabolite.
Prasugrel
All NNRTIs↔ prasugrel expectedNo dose adjustment needed.
Ticagrelor DOR, RPV IM, RPV PO↔ ticagrelor expectedNo dose adjustment needed.
EFV, ETR, NVP↓ ticagrelor expectedConsider alternative ARV or anticoagulant therapy.
VorapaxarDOR, NVP, RPV IM, RPV PO↔ vorapaxar expectedNo dose adjustment needed.
EFV, ETR↓ vorapaxar expectedInsufficient data to make a dose recommendation.
Antipneumocystis and Anti-Toxoplasmosis .Drugs
Atovaquone (oral solution)DOR, ETR, NVP, RPV IM, RPV PONo dataMonitor for therapeutic effectiveness of atovaquone.
EFVAtovaquone 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, Mpox)
Brincidofovir
All NNRTIs↔ brincidofovir expectedNo dose adjustment needed.
Cidofovir
All NNRTIs↔ cidofovir expectedNo dose adjustment needed.
TecovirimatDOR, RPV PO↓ DOR or RPV expected but not likely to be clinically relevantNo dose adjustment needed.
EFV, ETR, NVP↔ EFV, ETR, or NVP expectedNo dose adjustment needed.
RPV IM↓ RPV expected but not likely to be clinically relevantNo 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 possibleConsider 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 possibleConsider alternative ARV or alternative to bosentan. If coadministration is necessary, monitor virologic response.
Dihydropyridine CCBsDOR, RPV IM, RPV PO↔ CCBs expectedNo dose adjustment needed.
EFV, ETR, NVP↓ CCBs possibleTitrate 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
DexamethasoneDOR, EFV, ETR, NVP↓ NNRTI possible
Consider alternative corticosteroid for long-term use. If dexamethasone is used with NNRTI, monitor virologic response.
RPV IM, RPV POSignificant ↓ RPV possibleContraindicated with more than a single dose of dexamethasone.
Glucose-Lowering Agents
Canagliflozin, Dapagliflozin, Empagliflozin, Sitagliptin
All NNRTIs↔ antihyperglycemic expectedNo dose adjustment needed.
Linagliptin, Saxagliptin DOR, RPV IM, RPV PO↔ antihyperglycemic expectedNo dose adjustment needed.
EFV, ETR, NVP↓ antihyperglycemic possibleMonitor glycemic control.
Metformin
DOR
↔ metformin AUC

DOR AUC ↓ 26% and Cmax ↓ 24%
No dose adjustment needed.
EFV, ETR, NVP↔ metformin expectedNo dose adjustment needed.
RPV IM↔ metformin expectedNo dose adjustment needed.
RPV PO↔ metformin AUCNo dose adjustment needed.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir
DOR, RPV IM, RPV PO
No data
No dose adjustment needed.
EFV, ETR, NVPDaclatasvir 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/RTVDOR↑ DOR possibleNo dose adjustment needed.
EFVNo dataContraindicated.
ETR, NVP↓ DAAs possibleDo not coadminister.
RPV IM↑ RPV expectedDo not coadminister due to the potential for QTc prolongation with higher concentrations of RPV.
RPV PORPV AUC ↑ 150% to 225%Do not coadminister due to the potential for QTc prolongation with higher concentrations of RPV.
Elbasvir/GrazoprevirDOR↔ 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 expectedDo 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
↔ etonogestrelNo 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 expectedNo 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
AtorvastatinDOR↔ atorvastatin AUCNo dose adjustment needed.
EFV, ETRAtorvastatin 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.
EFVPravastatin 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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