Drug-Drug Interactions

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

Table 21b. Drug Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Other Drugs

This table provides information on the known or predicted interactions between NNRTIs and non-ARV drugs. For information regarding interactions between NNRTIs and other ARV drugs, including dosing recommendations, refer to Tables 21c, 22a, and 22b. 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. In cases where an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgement to select the most appropriate alternative medication to use.

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

Table 21b. 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 ↓ RPV expected when given simultaneously Give antacids at least 2 hours before or at least 4 hours after RPV.
H2 Receptor Antagonists DOR, ETR, NVP ↔ NNRTI expected No dose adjustment needed.
EFV ↔ EFV AUC No dose adjustment needed.
RPV 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.
PPIs DOR DOR AUC ↓ 17% and Cmin ↓ 16% No dose adjustment needed.
EFV, NVP ↔ EFV and NVP expected
ETR ↔ ETR AUC
RPV With Omeprazole 20 mg Daily:
  • RPV AUC ↓ 40% and Cmin ↓ 33%
Contraindicated.
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin, Doxazosin, Silodosin DOR, RPV ↔ 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 ↔ tamsulosin expected No dose adjustment needed.
EFV, ETR, NVP ↓ tamsulosin expected Monitor for therapeutic effectiveness of tamsulosin after 2–4 weeks. May need to increase dose to tamsulosin 0.8 mg once daily for patients who fail to respond to the 0.4 mg dose.
Antibacterials
Antimycobacterials
Bedaquiline DOR, RPV ↔ bedaquiline expected No dose adjustment needed.
EFV, ETR ↓ bedaquiline possible Do not coadminister.
NVP ↔ bedaquiline AUC No dose adjustment needed.
Rifabutin DOR DOR AUC ↓ 50% Increase DOR dose to 100 mg twice daily. No dose adjustment needed for rifabutin.
EFV Rifabutin ↓ 38% The recommended dosing range is rifabutin 450–600 mg per day.
ETR ↔ rifabutin and metabolite AUC

ETR AUC ↓ 37%
Do not coadminister ETR plus PI/r with rifabutin.

Use rifabutin 300 mg once daily if ETR is administered without PI/r.
NVP Rifabutin AUC ↑ 17% and metabolite AUC ↑ 24%

NVP Cmin ↓ 16%
No dose adjustment needed.
RPV Rifabutin plus RPV 50 mg Once Daily Compared to RPV 25 mg Once Daily Alone:
  • ↔ RPV AUC and Cmin
Increase RPV dose to 50 mg once daily. No dose adjustment for rifabutin needed.
Rifampin DOR DOR AUC ↓ 88% Contraindicated.
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 RPV AUC ↓ 80% Contraindicated.
Rifapentine DOR, RPV ↓ NNRTI expected Contraindicated.
EFV ↔ EFV concentrations No dose adjustment needed.
ETR, NVP ↓ NNRTI possible Do not coadminister.
Macrolides
Azithromycin All NNRTIs ↔ azithromycin expected No dose adjustment needed.
Clarithromycin DOR, RPV ↔ clarithromycin expected

↑ DOR and RPV possible
Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
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.
Erythromycin DOR, RPV ↑ DOR and RPV 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.
Anticoagulants
Apixaban DOR, RPV ↔ apixaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ apixaban possible Consider alternative ARV or anticoagulant therapy.
Betrixaban All NNRTIs ↔ betrixaban expected No dose adjustment needed.
Dabigatran All NNRTIs ↔ dabigatran expected No dose adjustment needed.
Edoxaban All NNRTIs ↔ edoxaban expected No dose adjustment needed.
Rivaroxaban DOR, RPV ↔ rivaroxaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ rivaroxaban possible Consider alternative ARV or anticoagulant therapy.
Warfarin DOR, RPV ↔ warfarin expected No dose adjustment needed.
EFV, ETR, NVP ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose accordingly.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin DOR, RPV ↓ NNRTI possible Contraindicated.
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.
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 ↓ 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 ↔ anticonvulsant expected No dose adjustment needed.
EFV, ETR, NVP ↓ anticonvulsant possible Monitor seizure control and consider anticonvulsant therapeutic drug monitoring.
Lamotrigine DOR, ETR, NVP, RPV ↔ lamotrigine expected No dose adjustment needed.
EFV ↓ lamotrigine possible Monitor seizure control and plasma concentrations of lamotrigine.
Antidepressants, Anxiolytics, and Antipsychotics
Antidepressants
Bupropion DOR, ETR, RPV ↔ bupropion expected No dose adjustment needed.
EFV Bupropion AUC ↓ 55% Titrate bupropion dose based on clinical response.
NVP ↓ bupropion possible
Citalopram, Escitalopram DOR, RPV ↔ 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 ↔ paroxetine expected No dose adjustment needed.
EFV, ETR ↔ paroxetine expected No dose adjustment needed.
Nefazodone DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ nefazodone expected

↑ NNRTI possible
Monitor antidepressant effect and titrate dose as necessary based on clinical response.
Sertraline DOR, RPV ↔ sertraline expected No dose adjustment needed.
EFV Sertraline AUC ↓ 39% Monitor the antidepressant effect and titrate dose as necessary based on clinical response.
ETR, NVP ↓ sertraline possible
Trazodone DOR, RPV ↔ trazodone expected No dose adjustment needed.
EFV, ETR, NVP ↓ trazodone possible Monitor for therapeutic effectiveness of trazodone and titrate dose as necessary.
Anxiolytics (Benzodiazepines)
Alprazolam, Triazolam DOR, RPV ↔ benzodiazepine expected No dose adjustment needed.
EFV, ETR, NVP ↓ benzodiazepine possible Monitor for therapeutic effectiveness of benzodiazepine.
Diazepam DOR, RPV ↔ 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 ↔ lorazepam expected No dose adjustment needed.
EFV ↔ lorazepam AUC No dose adjustment needed.
Midazolam DOR, RPV ↔ midazolam expected 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.
Antipsychotics
Aripiprazole DOR, RPV ↔ 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 ↔ 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 ↔ cariprazine expected No dose adjustment needed.
EFV, ETR, NVP ↓ cariprazine and ↑ or ↓ active metabolite possible Do not coadminister.
Lurasidone DOR, RPV ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Olanzapine DOR, ETR, NVP, RPV ↔ olanzapine expected No dose adjustment needed.
EFV ↓ olanzapine possible Monitor for therapeutic effectiveness of olanzapine.
Pimavanserin DOR, RPV ↔ pimavanserin expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimavanserin expected Do not coadminister.
Pimozide DOR, RPV ↔ pimozide expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimozide possible Monitor for therapeutic effectiveness of pimozide.
Quetiapine DOR, RPV ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Antifungals
Fluconazole DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV ↔ fluconazole expected

↔ EFV AUC expected
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 possible with this combination.
Isavuconazole DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ isavuconazole possible Monitor isavuconazole concentration and antifungal response. Dose adjustments for isavuconazole may be necessary.
Itraconazole DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV Itraconazole and OH-itraconazole AUC, Cmax, and Cmin ↓ 35% 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.
Posaconazole DOR, ETR, NVP, RPV ↑ 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.
Voriconazole DOR, RPV ↑ NNRTI 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 antiretroviral tolerability and antifungal response and/or voriconazole concentration.
Antimalarials
Artemether/ Lumefantrine DOR, RPV ↔ antimalarial expected No dose adjustment needed.
EFV Artemether AUC ↓ 79%

DHA AUC ↓ 75%

Lumefantrine AUC ↓ 56%
Consider alternative ARV or antimalarial drug. If used in combination, monitor closely for antimalarial efficacy.
ETR Artemether AUC ↓ 38%

↔ DHA AUC

↔ lumefantrine AUC

↔ ETR AUC
Clinical significance of the reduced antimalarial drug concentrations unknown. If used in combination with ETR, monitor for antimalarial efficacy.
NVP Artemether AUC ↓ 67% to 72%

DHA:
  • Study results are conflicting. DHA AUC ↓ 37% in one study, no difference in another.
Lumefantrine:
  • Study results are conflicting. Lumefantrine AUC ↓ 25% to 58% in two studies but ↑ 56% in another.
Clinical significance unknown. If used in combination, monitor closely for antimalarial efficacy and lumefantrine toxicity.
Atovaquone/ Proguanil DOR, ETR, NVP, RPV 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 ↔ 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 ↔ ticagrelor expected No dose adjustment needed.
EFV, ETR, NVP ↓ ticagrelor expected Consider alternative ARV or anticoagulant therapy.
Vorapaxar DOR, NVP, RPV ↔ 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, RPV, NVP No data Monitor for therapeutic effectiveness of atovaquone.
EFV Atovaquone AUC ↓ 44% to 47% Consider alternative ARV or agent for PCP or toxoplasmosis treatment or prophylaxis. If coadministration is necessary, monitor for therapeutic effectiveness of atovaquone.
Cardiac Medications
Dihydropyridine CCBs DOR, RPV ↔ CCBs expected No dose adjustment needed.
EFV, ETR, NVP ↓ CCBs possible Titrate CCB dose based on clinical response.
Diltiazem, Verapamil DOR, RPV ↔ 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 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 ↔ 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, RPV ↔ metformin expected No dose adjustment needed.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir DOR, RPV No data No dose adjustment needed.
EFV, ETR, NVP Daclatasvir 120 mg Once Daily plus EFV 600 mg Daily Compared with Daclatasvir 60 mg Alone:
  • Daclatasvir Cmin ↓ 17% and AUC ↑ 37%
The recommended dose is daclatasvir 90 mg once daily.
Dasabuvir plus Paritaprevir/ Ombitasvir/ RTV DOR ↑ DOR possible No dose adjustment needed.
EFV No data Contraindicated.
ETR, NVP ↓ DAAs possible Do not coadminister.
RPV RPV AUC ↑ 150% to 225% Do not coadminister, due to potential for QT interval 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 ↔ 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
NVP ↓ glecaprevir and pibrentasvir possible Consider alternative ARV or HCV regimen. If coadministration is necessary, monitor for HCV treatment efficacy.
RPV ↔ glecaprevir and pibrentasvir

RPV AUC ↑ 84%
No dose adjustment needed.
Ledipasvir/ Sofosbuvir DOR, RPV ↔ ledipasvir and sofosbuvir

↔ DOR

↔ RPV
No dose adjustment needed.
EFV Ledipasvir AUC, Cmin, and Cmax ↓ 34%

↔ sofosbuvir
ETR, NVP No significant effect expected
Sofosbuvir/ Velpatasvir DOR, RPV 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 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, RPV ↓ NNRTI expected Contraindicated.
EFV, ETR, NVP ↓ EFV, ETR, and NVP expected Do not coadminister.
Hormonal Therapies
Contraceptives– Injectable
Depot MPA
DOR, ETR, RPV ↔ 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 ↔ ethinyl estradiol

↔ norethindrone
No dose adjustment needed.
Contraceptives– Subdermal Implant
Etonogestrel
DOR, RPV ↔ 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
Levonorestrel
DOR, RPV ↔ levonorgestrel expected No dose adjustment needed.
EFV Levonorgestrel AUC ↓ 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– Vaginal Ring
Etonogestrel/ Ethinyl Estradiol
DOR, RPV ↔ 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 ↔ segesterone and ethinyl estradiol expected No dose adjustment needed.
EFV, ETR, NVP ↓ segesterone and ethinyl estradiol possible Consider alternative ARV or contraceptive method.
Emergency Contraceptives
Levonorgestrel (oral)
DOR, RPV ↔ 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 ↔ hormonal concentrations expected No dose adjustment needed.
EFV, ETR, NVP ↓ estradiol possible

↔ goserelin, leuprolide acetate, and spironolactone expected

↓ dutasteride and finasteride possible
Monitor feminizing effects of estrogen and antiandrogen therapy and titrate dose as necessary to achieve therapeutic goals.
EFV, ETR, NVP ↓ testosterone possible Monitor masculinizing effects of testosterone and titrate testosterone dose as necessary to achieve therapeutic goals.
Menopausal Replacement Therapy DOR, RPV ↔ 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 for other progestin-NNRTI interactions
Monitor menopausal symptoms. Titrate to the dose of hormonal therapy that achieves menopausal symptom relief.
Immunosuppressants
Cyclosporine DOR, RPV ↔ 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 ↔ 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, RPV ↔ 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.
Fluvastatin DOR, NVP, RPV ↔ 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 ↔ lovastatin and simvastatin expected No dose adjustment needed.
EFV Simvastatin AUC ↓ 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 ↔ pitavastatin expected No dose adjustment needed.
EFV ↔ pitavastatin AUC No dose adjustment needed.
Pravastatin DOR, NVP, RPV ↔ 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 ↔ rosuvastatin expected No dose adjustment needed.
Narcotics/Treatments for Opioid Dependence
Buprenorphine
Sublingual or buccal
DOR, RPV ↔ 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 ↔ 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 ↔ lofexidine expected No dose adjustment needed.
Methadone DOR, ETR No significant effect No dose adjustment needed.
EFV Methadone AUC ↓ 52% Opioid withdrawal common; monitor and increase methadone dose as necessary.
NVP Methadone AUC ↓ 37% to 51%

↔ NVP
Opioid withdrawal common; monitor and increase methadone dose as necessary.
RPV 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 ↔ sildenafil AUC and Cmax No dose adjustment needed.
Tadalafil DOR, RPV ↔ 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 ↔ 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.
a R-methadone is the active form of methadone.

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

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

Drug-Drug Interactions

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

Table 21b. Drug Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Other Drugs

This table provides information on the known or predicted interactions between NNRTIs and non-ARV drugs. For information regarding interactions between NNRTIs and other ARV drugs, including dosing recommendations, refer to Tables 21c, 22a, and 22b. 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. In cases where an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgement to select the most appropriate alternative medication to use.

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

Table 21b. 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 ↓ RPV expected when given simultaneously Give antacids at least 2 hours before or at least 4 hours after RPV.
H2 Receptor Antagonists DOR, ETR, NVP ↔ NNRTI expected No dose adjustment needed.
EFV ↔ EFV AUC No dose adjustment needed.
RPV 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.
PPIs DOR DOR AUC ↓ 17% and Cmin ↓ 16% No dose adjustment needed.
EFV, NVP ↔ EFV and NVP expected
ETR ↔ ETR AUC
RPV With Omeprazole 20 mg Daily:
  • RPV AUC ↓ 40% and Cmin ↓ 33%
Contraindicated.
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin, Doxazosin, Silodosin DOR, RPV ↔ 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 ↔ tamsulosin expected No dose adjustment needed.
EFV, ETR, NVP ↓ tamsulosin expected Monitor for therapeutic effectiveness of tamsulosin after 2–4 weeks. May need to increase dose to tamsulosin 0.8 mg once daily for patients who fail to respond to the 0.4 mg dose.
Antibacterials
Antimycobacterials
Bedaquiline DOR, RPV ↔ bedaquiline expected No dose adjustment needed.
EFV, ETR ↓ bedaquiline possible Do not coadminister.
NVP ↔ bedaquiline AUC No dose adjustment needed.
Rifabutin DOR DOR AUC ↓ 50% Increase DOR dose to 100 mg twice daily. No dose adjustment needed for rifabutin.
EFV Rifabutin ↓ 38% The recommended dosing range is rifabutin 450–600 mg per day.
ETR ↔ rifabutin and metabolite AUC

ETR AUC ↓ 37%
Do not coadminister ETR plus PI/r with rifabutin.

Use rifabutin 300 mg once daily if ETR is administered without PI/r.
NVP Rifabutin AUC ↑ 17% and metabolite AUC ↑ 24%

NVP Cmin ↓ 16%
No dose adjustment needed.
RPV Rifabutin plus RPV 50 mg Once Daily Compared to RPV 25 mg Once Daily Alone:
  • ↔ RPV AUC and Cmin
Increase RPV dose to 50 mg once daily. No dose adjustment for rifabutin needed.
Rifampin DOR DOR AUC ↓ 88% Contraindicated.
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 RPV AUC ↓ 80% Contraindicated.
Rifapentine DOR, RPV ↓ NNRTI expected Contraindicated.
EFV ↔ EFV concentrations No dose adjustment needed.
ETR, NVP ↓ NNRTI possible Do not coadminister.
Macrolides
Azithromycin All NNRTIs ↔ azithromycin expected No dose adjustment needed.
Clarithromycin DOR, RPV ↔ clarithromycin expected

↑ DOR and RPV possible
Consider alternative macrolide (e.g., azithromycin) for MAC prophylaxis and treatment.
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.
Erythromycin DOR, RPV ↑ DOR and RPV 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.
Anticoagulants
Apixaban DOR, RPV ↔ apixaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ apixaban possible Consider alternative ARV or anticoagulant therapy.
Betrixaban All NNRTIs ↔ betrixaban expected No dose adjustment needed.
Dabigatran All NNRTIs ↔ dabigatran expected No dose adjustment needed.
Edoxaban All NNRTIs ↔ edoxaban expected No dose adjustment needed.
Rivaroxaban DOR, RPV ↔ rivaroxaban expected No dose adjustment needed.
EFV, ETR, NVP ↓ rivaroxaban possible Consider alternative ARV or anticoagulant therapy.
Warfarin DOR, RPV ↔ warfarin expected No dose adjustment needed.
EFV, ETR, NVP ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose accordingly.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin DOR, RPV ↓ NNRTI possible Contraindicated.
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.
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 ↓ 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 ↔ anticonvulsant expected No dose adjustment needed.
EFV, ETR, NVP ↓ anticonvulsant possible Monitor seizure control and consider anticonvulsant therapeutic drug monitoring.
Lamotrigine DOR, ETR, NVP, RPV ↔ lamotrigine expected No dose adjustment needed.
EFV ↓ lamotrigine possible Monitor seizure control and plasma concentrations of lamotrigine.
Antidepressants, Anxiolytics, and Antipsychotics
Antidepressants
Bupropion DOR, ETR, RPV ↔ bupropion expected No dose adjustment needed.
EFV Bupropion AUC ↓ 55% Titrate bupropion dose based on clinical response.
NVP ↓ bupropion possible
Citalopram, Escitalopram DOR, RPV ↔ 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 ↔ paroxetine expected No dose adjustment needed.
EFV, ETR ↔ paroxetine expected No dose adjustment needed.
Nefazodone DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ nefazodone expected

↑ NNRTI possible
Monitor antidepressant effect and titrate dose as necessary based on clinical response.
Sertraline DOR, RPV ↔ sertraline expected No dose adjustment needed.
EFV Sertraline AUC ↓ 39% Monitor the antidepressant effect and titrate dose as necessary based on clinical response.
ETR, NVP ↓ sertraline possible
Trazodone DOR, RPV ↔ trazodone expected No dose adjustment needed.
EFV, ETR, NVP ↓ trazodone possible Monitor for therapeutic effectiveness of trazodone and titrate dose as necessary.
Anxiolytics (Benzodiazepines)
Alprazolam, Triazolam DOR, RPV ↔ benzodiazepine expected No dose adjustment needed.
EFV, ETR, NVP ↓ benzodiazepine possible Monitor for therapeutic effectiveness of benzodiazepine.
Diazepam DOR, RPV ↔ 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 ↔ lorazepam expected No dose adjustment needed.
EFV ↔ lorazepam AUC No dose adjustment needed.
Midazolam DOR, RPV ↔ midazolam expected 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.
Antipsychotics
Aripiprazole DOR, RPV ↔ 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 ↔ 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 ↔ cariprazine expected No dose adjustment needed.
EFV, ETR, NVP ↓ cariprazine and ↑ or ↓ active metabolite possible Do not coadminister.
Lurasidone DOR, RPV ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Olanzapine DOR, ETR, NVP, RPV ↔ olanzapine expected No dose adjustment needed.
EFV ↓ olanzapine possible Monitor for therapeutic effectiveness of olanzapine.
Pimavanserin DOR, RPV ↔ pimavanserin expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimavanserin expected Do not coadminister.
Pimozide DOR, RPV ↔ pimozide expected No dose adjustment needed.
EFV, ETR, NVP ↓ pimozide possible Monitor for therapeutic effectiveness of pimozide.
Quetiapine DOR, RPV ↔ antipsychotic expected No dose adjustment needed.
EFV, ETR, NVP ↓ antipsychotic possible Monitor for therapeutic effectiveness of antipsychotic.
Antifungals
Fluconazole DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV ↔ fluconazole expected

↔ EFV AUC expected
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 possible with this combination.
Isavuconazole DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV, ETR, NVP ↓ isavuconazole possible Monitor isavuconazole concentration and antifungal response. Dose adjustments for isavuconazole may be necessary.
Itraconazole DOR, RPV ↑ NNRTI possible No dose adjustment needed.
EFV Itraconazole and OH-itraconazole AUC, Cmax, and Cmin ↓ 35% 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.
Posaconazole DOR, ETR, NVP, RPV ↑ 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.
Voriconazole DOR, RPV ↑ NNRTI 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 antiretroviral tolerability and antifungal response and/or voriconazole concentration.
Antimalarials
Artemether/ Lumefantrine DOR, RPV ↔ antimalarial expected No dose adjustment needed.
EFV Artemether AUC ↓ 79%

DHA AUC ↓ 75%

Lumefantrine AUC ↓ 56%
Consider alternative ARV or antimalarial drug. If used in combination, monitor closely for antimalarial efficacy.
ETR Artemether AUC ↓ 38%

↔ DHA AUC

↔ lumefantrine AUC

↔ ETR AUC
Clinical significance of the reduced antimalarial drug concentrations unknown. If used in combination with ETR, monitor for antimalarial efficacy.
NVP Artemether AUC ↓ 67% to 72%

DHA:
  • Study results are conflicting. DHA AUC ↓ 37% in one study, no difference in another.
Lumefantrine:
  • Study results are conflicting. Lumefantrine AUC ↓ 25% to 58% in two studies but ↑ 56% in another.
Clinical significance unknown. If used in combination, monitor closely for antimalarial efficacy and lumefantrine toxicity.
Atovaquone/ Proguanil DOR, ETR, NVP, RPV 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 ↔ 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 ↔ ticagrelor expected No dose adjustment needed.
EFV, ETR, NVP ↓ ticagrelor expected Consider alternative ARV or anticoagulant therapy.
Vorapaxar DOR, NVP, RPV ↔ 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, RPV, NVP No data Monitor for therapeutic effectiveness of atovaquone.
EFV Atovaquone AUC ↓ 44% to 47% Consider alternative ARV or agent for PCP or toxoplasmosis treatment or prophylaxis. If coadministration is necessary, monitor for therapeutic effectiveness of atovaquone.
Cardiac Medications
Dihydropyridine CCBs DOR, RPV ↔ CCBs expected No dose adjustment needed.
EFV, ETR, NVP ↓ CCBs possible Titrate CCB dose based on clinical response.
Diltiazem, Verapamil DOR, RPV ↔ 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 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 ↔ 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, RPV ↔ metformin expected No dose adjustment needed.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir DOR, RPV No data No dose adjustment needed.
EFV, ETR, NVP Daclatasvir 120 mg Once Daily plus EFV 600 mg Daily Compared with Daclatasvir 60 mg Alone:
  • Daclatasvir Cmin ↓ 17% and AUC ↑ 37%
The recommended dose is daclatasvir 90 mg once daily.
Dasabuvir plus Paritaprevir/ Ombitasvir/ RTV DOR ↑ DOR possible No dose adjustment needed.
EFV No data Contraindicated.
ETR, NVP ↓ DAAs possible Do not coadminister.
RPV RPV AUC ↑ 150% to 225% Do not coadminister, due to potential for QT interval 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 ↔ 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
NVP ↓ glecaprevir and pibrentasvir possible Consider alternative ARV or HCV regimen. If coadministration is necessary, monitor for HCV treatment efficacy.
RPV ↔ glecaprevir and pibrentasvir

RPV AUC ↑ 84%
No dose adjustment needed.
Ledipasvir/ Sofosbuvir DOR, RPV ↔ ledipasvir and sofosbuvir

↔ DOR

↔ RPV
No dose adjustment needed.
EFV Ledipasvir AUC, Cmin, and Cmax ↓ 34%

↔ sofosbuvir
ETR, NVP No significant effect expected
Sofosbuvir/ Velpatasvir DOR, RPV 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 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, RPV ↓ NNRTI expected Contraindicated.
EFV, ETR, NVP ↓ EFV, ETR, and NVP expected Do not coadminister.
Hormonal Therapies
Contraceptives– Injectable
Depot MPA
DOR, ETR, RPV ↔ 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 ↔ ethinyl estradiol

↔ norethindrone
No dose adjustment needed.
Contraceptives– Subdermal Implant
Etonogestrel
DOR, RPV ↔ 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
Levonorestrel
DOR, RPV ↔ levonorgestrel expected No dose adjustment needed.
EFV Levonorgestrel AUC ↓ 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– Vaginal Ring
Etonogestrel/ Ethinyl Estradiol
DOR, RPV ↔ 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 ↔ segesterone and ethinyl estradiol expected No dose adjustment needed.
EFV, ETR, NVP ↓ segesterone and ethinyl estradiol possible Consider alternative ARV or contraceptive method.
Emergency Contraceptives
Levonorgestrel (oral)
DOR, RPV ↔ 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 ↔ hormonal concentrations expected No dose adjustment needed.
EFV, ETR, NVP ↓ estradiol possible

↔ goserelin, leuprolide acetate, and spironolactone expected

↓ dutasteride and finasteride possible
Monitor feminizing effects of estrogen and antiandrogen therapy and titrate dose as necessary to achieve therapeutic goals.
EFV, ETR, NVP ↓ testosterone possible Monitor masculinizing effects of testosterone and titrate testosterone dose as necessary to achieve therapeutic goals.
Menopausal Replacement Therapy DOR, RPV ↔ 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 for other progestin-NNRTI interactions
Monitor menopausal symptoms. Titrate to the dose of hormonal therapy that achieves menopausal symptom relief.
Immunosuppressants
Cyclosporine DOR, RPV ↔ 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 ↔ 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, RPV ↔ 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.
Fluvastatin DOR, NVP, RPV ↔ 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 ↔ lovastatin and simvastatin expected No dose adjustment needed.
EFV Simvastatin AUC ↓ 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 ↔ pitavastatin expected No dose adjustment needed.
EFV ↔ pitavastatin AUC No dose adjustment needed.
Pravastatin DOR, NVP, RPV ↔ 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 ↔ rosuvastatin expected No dose adjustment needed.
Narcotics/Treatments for Opioid Dependence
Buprenorphine
Sublingual or buccal
DOR, RPV ↔ 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 ↔ 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 ↔ lofexidine expected No dose adjustment needed.
Methadone DOR, ETR No significant effect No dose adjustment needed.
EFV Methadone AUC ↓ 52% Opioid withdrawal common; monitor and increase methadone dose as necessary.
NVP Methadone AUC ↓ 37% to 51%

↔ NVP
Opioid withdrawal common; monitor and increase methadone dose as necessary.
RPV 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 ↔ sildenafil AUC and Cmax No dose adjustment needed.
Tadalafil DOR, RPV ↔ 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 ↔ 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.
a R-methadone is the active form of methadone.

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

Key: ARV = antiretroviral; AUC = area under the curve; CCB = calcium channel blocker; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; DAA = direct-acting antiviral; DHA = dihydroartemisinin; DLV = delavirdine; DOR = doravirine; EFV = efavirenz; ETR = etravirine; FDA = Food and Drug Administration; HCV = hepatitis C virus; INR = international normalized ratio; MAC = Mycobacterium avium complex; MPA = medroxyprogesterone acetate; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; OH-itraconazole = active metabolite of itraconazole; PCP = Pneumocystis jirovecii pneumonia; PDE5 = phosphodiesterase type 5; PI/r = protease inhibitor/ritonavir; PK = pharmacokinetic; PPI = proton pump inhibitor; RPV = rilpivirine; RTV = ritonavir
Updated
Reviewed
Dec. 18, 2019

Download Guidelines