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.
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:
|
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:
|
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:
Phenytoin plus EFV:
|
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:
|
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:
|
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:
|
|
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.
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:
|
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:
|
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:
Phenytoin plus EFV:
|
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:
|
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:
|
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:
|
|
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 |
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