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

Last Updated: October 25, 2018; Last Reviewed: October 25, 2018

This table provides information relating to PK interactions between NNRTIs and non-ARV drugs. For interactions between ARV agents and for dosing recommendations, refer to Tables 19c, 20a, and 20b. 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.

Note: DLV is not included in this table. Please refer to the DLV FDA package insert for information regarding drug interactions. The term “All NNRTIs” in this table refers to all NNRTIs except for DLV.

^a Approved dose for RPV is 25 mg once daily. Most PK interaction studies were performed using 75 to 150 mg per dose.
^b Norbuprenorphine is an active metabolite of buprenorphine.
^c R-methadone is the active form of methadone.

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

Key to Acronyms: ARV = antiretroviral; AUC = area under the curve; BID = twice daily; CCB = calcium channel blocker; C_max = maximum plasma concentration; C_min = minimum plasma concentration; DAA = direct-acting antiviral; DHA = dihydroartemisinin; DMPA = depot medroxyprogesterone acetate; DOR = doravirine; EFV = efavirenz; ETR = etravirine; HMG-CoA = hydroxy-methylglutaryl-coenzyme A; INR = international normalized ratio; MAC = Mycobacterium avium complex; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; OH-itraconazole = active metabolite of itraconazole; PCP = Pneumocystis jirovecii pneumonia; PDE5 = phosphodiesterase type 5; PI = protease inhibitor; PI/r = protease inhibitor/ritonavir; PK = pharmacokinetic; PPI = proton pump inhibitor; RPV = rilpivirine; RTV = ritonavir

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Antacids	RPV	↓ RPV expected when given simultaneously	Give antacids at least 2 hours before or at least 4 hours after RPV.
H2 Receptor Antagonists	RPV	↓ RPV	Give H2 receptor antagonists at least 12 hours before or at least 4 hours after RPV.
PPIs	RPV	With Omeprazole 20 mg Daily: RPV AUC ↓ 40% and C_min ↓ 33%	Contraindicated. Do not coadminister.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Alfuzosin, Doxazosin, Silodosin	EFV, ETR, NVP	↓ alpha antagonist expected	Consider alternative therapy. If coadministration is necessary, monitor for therapeutic effectiveness of alpha antagonist.
Tamsulosin	EFV, ETR, NVP	↓ tamsulosin expected	Monitor for therapeutic effectiveness of tamsulosin after 2 to 4 weeks of dosing. May need to increase to tamsulosin 0.8 mg once daily for patients who fail to respond to the 0.4 mg dose.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Apixaban	EFV, ETR, NVP	↓ apixaban possible	Consider alternative therapy.
Betrixaban	All NNRTIs	↔ betrixaban expected	No dose adjustment necessary.
Clopidogrel	EFV, ETR	↓ activation of clopidogrel possible	ETR may prevent metabolism of clopidogrel (inactive) to its active metabolite. Avoid coadministration, if possible.
Clopidogrel	DOR, NVP, RPV	↔ clopidogrel expected	No dose adjustment necessary.
Dabigatran	All NNRTIs	↔ dabigatran expected	No dose adjustment necessary.
Edoxaban	All NNRTIs	↔ edoxaban expected	No dose adjustment necessary.
Prasugrel	All NNRTIs	↔ prasugrel expected	No dose adjustment necessary.
Rivaroxaban	EFV, ETR, NVP	↓ rivaroxaban possible	Consider alternative therapy.
Ticagrelor	EFV, ETR, NVP	↓ ticagrelor expected	Consider alternative therapy.
Warfarin	EFV, ETR, NVP	↑ or ↓ warfarin possible	Monitor INR and adjust warfarin dose accordingly.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Carbamazepine, Phenobarbital, Phenytoin	EFV	Carbamazepine plus EFV: Carbamazepine AUC ↓ 27% EFV AUC ↓ 36% Phenytoin plus EFV: ↓ EFV ↓ phenytoin possible	Monitor anticonvulsant and EFV concentrations or, if possible, use alternative anticonvulsant to those listed.
	ETR	↓ anticonvulsant and ETR possible	Do not coadminister. Consider alternative anticonvulsant.
	NVP	↓ anticonvulsant and NVP possible	Monitor anticonvulsant and NVP concentrations and virologic responses or consider alternative anticonvulsant.
	DOR, RPV	↓ NNRTI possible	Contraindicated. Do not coadminister. Consider alternative anticonvulsant.
Eslicarbazepine	All NNRTIs	↓ NNRTI possible	Monitor virologic outcomes and consider monitoring plasma concentrations of ARVs, or consider alternative anticonvulsant or ARV drug.
Oxcarbazepine	DOR, RPV	↓ NNRTI possible	Contraindicated. Do not coadminister.Consider alternative anticonvulsant.
Ethosuximide, Lacosamide, Tiagabine, Zonisamide	EFV, ETR	↓ anticonvulsant possible	Monitor seizure control and plasma concentrations of anticonvulsants (when available).
Lamotrigine	EFV	↓ lamotrigine possible	Monitor seizure control and plasma concentrations of lamotrigine.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Bupropion	EFV, NVP	Bupropion AUC ↓ 55% ↓ bupropion possible	Titrate bupropion dose based on clinical response.
Citalopram, Escitalopram	EFV, ETR, NVP	↓ antidepressant possible	Titrate antidepressant dose based on clinical response.
Fluoxetine, Fluvoxamine	All NNRTIs	↔ antidepressant expected	No dose adjustment necessary.
Paroxetine	EFV, ETR	↔ paroxetine observed with EFV or ETR	No dose adjustment necessary.
Paroxetine	DOR, NVP, RPV	↔ expected with DOR, NVP or RPV	No dose adjustment necessary.
Nefazodone	EFV, ETR, NVP	↓ nefazodone expected ↑ NNRTI possible	Monitor the antidepressant effect and titrate dose as necessary. Monitor for ARV-related adverse events.
Nefazodone	DOR, RPV	↑ NNRTI possible	Monitor for ARV-related adverse events.
Sertraline	EFV	Sertraline AUC ↓ 39%	Titrate sertraline dose based on clinical response.
Trazodone	EFV, ETR, NVP	↓ trazodone possible	Monitor the therapeutic effect of trazodone and titrate dose as necessary.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Fluconazole	EFV	↔ fluconazole or EFV	No dose adjustment necessary.
	ETR	ETR AUC ↑ 86%	No dose adjustment necessary. Use with caution.
	NVP	NVP AUC ↑ 110%	Increased risk of hepatotoxicity possible with this combination. Monitor NVP toxicity or use alternative ARV agent.
	DOR, RPV	↑ NNRTI possible	No dose adjustment necessary.
Isavuconazole	EFV, ETR, NVP	↓ isavuconazole possible	Dose adjustments for isavuconazole may be necessary. Consider monitoring isavuconazole concentration and antifungal response.
Isavuconazole	DOR, RPV	↑ NNRTI possible	No dose adjustment necessary.
Itraconazole	EFV	Itraconazole and OH-itraconazole AUC, C_max, and C_min ↓ 35% to 44%	Failure to achieve therapeutic itraconazole concentrations has been reported. Avoid this combination if possible. If coadministered, 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	Avoid this combination if possible. If coadministered, monitor itraconazole concentration and adjust dose accordingly.
	DOR, RPV	↑ NNRTI possible	No dose adjustment necessary.
Posaconazole	EFV	Posaconazole AUC ↓ 50% ↔ EFV	Avoid concomitant use unless the benefit outweighs the risk. If coadministered, monitor posaconazole concentration and adjust dose accordingly.
Posaconazole	DOR, ETR, NVP, RPV	↑ NNRTI possible	Monitor for NNRTI toxicities.
Voriconazole	EFV	Voriconazole AUC ↓ 77% EFV AUC ↑ 44%	Contraindicated at standard doses. Dose Adjustment: Voriconazole 400 mg BID, EFV 300 mg daily
	ETR	↔ Voriconazole AUC ETR AUC ↑ 36%	No dose adjustment necessary.
	NVP	↓ voriconazole possible ↑ NVP possible	Monitor for toxicity and antifungal response and/or voriconazole concentration.
	DOR, RPV	↑ NNRTI possible	No dose adjustment necessary.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Canagliflozin, Dapagliflozin, Empagliflozin, Sitagliptin	All NNRTIs	↔ antihyperglycemic expected	No dose adjustment necessary.
Linagliptin, Saxagliptin	EFV, ETR, NVP	↓ antihyperglycemic possible	Monitor glycemic control.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Artemether/ Lumefantrine	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 2 studies but ↑ 56% in another.	Clinical significance unknown. If used, monitor closely for antimalarial efficacy and lumefantrine toxicity.
Atovaquone/ Proguanil	EFV	Atovaquone AUC ↓ 75% Proguanil AUC ↓ 43%	No dose recommendation. Consider alternative drug for malaria prophylaxis, if possible.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Bedaquiline	EFV, ETR	↓ bedaquiline possible	Do not coadminister.
Bedaquiline	NVP	↔ bedaquiline AUC	No dose adjustment necessary.
Clarithromycin	EFV	Clarithromycin AUC ↓ 39%	Monitor for effectiveness or consider alternative agent, such as azithromycin, for MAC prophylaxis and treatment.
	ETR	Clarithromycin AUC ↓ 39% ETR AUC ↑ 42%	Consider alternative agent, such as azithromycin, for MAC prophylaxis and treatment.
	NVP	Clarithromycin AUC ↓ 31% NVP AUC ↑ 26%	Monitor for effectiveness or use alternative agent, such as azithromycin, for MAC prophylaxis and treatment.
	RPV	↔ clarithromycin expected ↑ RPV possible	Consider alternative macrolide, such as azithromycin, for MAC prophylaxis and treatment.
Rifabutin	DOR	DOR AUC ↓ 50%	Increase DOR dose to 100 mg twice daily. No dose adjustment for rifabutin.
	EFV	Rifabutin ↓ 38%	Dose: Rifabutin 450–600 mg/day; or Rifabutin 600 mg 3 times/week ifEFV is not coadministered with a PI
	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 C_min ↓ 16%	No dose adjustment necessary. Use with caution.
	RPV	Rifabutin plus RPV 50 mg Once Daily Compared to RPV 25 mg Once Daily Alone: ↔ RPV AUC and C_min	Increase RPV dose to 50 mg once daily. No dose adjustment for rifabutin.
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	EFV	↔ EFV concentrations	No dose adjustment necessary.
	ETR, NVP	↓ NNRTI possible	Do not coadminister.
	DOR, RPV	↓ NNRTI expected	Contraindicated.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Atovaquone	EFV	Atovaquone AUC ↓ 44% to 47%	Consider alternative agent for PCP or toxoplasmosis treatment or use alternative ARV drug. If used in combination, monitor therapeutic efficacy of atovaquone.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Aripiprazole	EFV, ETR, NVP	↓ aripiprazole expected	Monitor effectiveness of antipsychotic. Consider doubling usual dose of aripiprazole over 1–2 weeks. Refer to aripiprazole prescribing information for dosing recommendations.
Brexpiprazole	EFV, ETR, NVP	↓ brexpiprazole expected	Monitor effectiveness of antipsychotic. Consider doubling the usual dose of brexpiprazole and making further adjustments based on clinical response. Refer to brexpiprazole prescribing information.
Cariprazine	EFV, ETR, NVP	↓ cariprazine and ↑ or ↓ active metabolite possible	Coadministration is not recommended.
Olanzapine	EFV	↓ olanzapine possible	Monitor effectiveness of olanzapine.
Olanzapine	DOR, ETR, NVP, RPV	↔ olanzapine expected	No dose adjustment necessary.
Pimozide	EFV, ETR, NVP	↓ pimozide possible	Monitor therapeutic effectiveness of pimozide.
Lurasidone, Pimavanserin, Quetiapine, Thioridazine	EFV, ETR, NVP	↓ antipsychotic possible	Monitor effectiveness of antipsychotic.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Alprazolam	EFV, ETR, NVP	↓ alprazolam possible	Monitor for therapeutic effectiveness of alprazolam.
Diazepam	EFV, NVP	↓ diazepam possible	Monitor for therapeutic effectiveness of diazepam.
Diazepam	ETR	↑ diazepam possible	Decreased dose of diazepam may be necessary. Monitor for diazepam toxicity.
Lorazepam	EFV	↔ lorazepam AUC	No dose adjustment necessary.
Lorazepam	ETR, NVP	↔ lorazepam expected	No dose adjustment necessary.
Midazolam	EFV	↑ or ↓ midazolam possible	Monitor therapeutic effectiveness and toxicity of midazolam.
	ETR	Midazolam AUC ↓ 31% Midazolam active metabolite C_max ↑ 57%	Monitor therapeutic effectiveness of midazolam.
	NVP	↓ midazolam possible	Monitor therapeutic effectiveness of midazolam.
Triazolam	EFV, ETR, NVP	↓ triazolam possible	Monitor therapeutic effectiveness of triazolam.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Dihydropyridine CCBs	EFV, ETR, NVP	↓ CCBs possible	Titrate CCB dose based on clinical response.
Diltiazem, Verapamil	EFV	Diltiazem AUC ↓ 69% ↓ verapamil possible	Titrate diltiazem or verapamil dose based on clinical response.
Diltiazem, Verapamil	ETR, NVP	↓ diltiazem or verapamil possible

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Dexamethasone	DOR, EFV, ETR, NVP	↓ NNRTI possible	Consider alternative corticosteroid for long-term use. If dexamethasone is used with NNRTI, monitor virologic response.
Dexamethasone	RPV	Significant ↓ RPV possible	Contraindicated with more than a single dose of dexamethasone.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Daclatasvir	EFV, ETR, NVP	Daclatasvir 120 mg Once Daily plus EFV 600 mg Daily Compared with Daclatasvir 60 mg Alone: Daclatasvir C_min↓ 17%, AUC ↑ 37%	The recommended dose is daclatasvir 90 mg once daily.
Daclatasvir	DOR, RPV	No data	No dose adjustment necessary.
Dasabuvir plus Paritaprevir/ Ombitasivir/ RTV	DOR	↑ DOR possible	No dose adjustment necessary.
	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	EFV	Elbasvir AUC ↓ 54% Grazoprevir AUC ↓ 83% EFV ↔ by grazoprevir EFV ↔ AUC by elbasvir	Contraindicated.
	ETR, NVP	↓ elbasvir and grazoprevir expected	Do not coadminister.
	DOR, RPV	↔ Elbasvir, grazoprevir ↔ DOR, RPV	No dose adjustment necessary.
Glecaprevir/ Pibrentasvir	DOR	↑ DOR expected	No dose adjustment necessary.
	EFV	↓ glecaprevir and pibrentasvir expected	Do not coadminister.
	ETR, NVP	↓ glecaprevir and pibrentasvir possible	Do not coadminister.
	RPV	↔ glecaprevir, pibrentasvir RPV AUC ↑ 84%	No dose adjustment necessary.
Ledipasvir/ Sofosbuvir	EFV	Ledipasvir AUC, C_min, and C_max ↓ 34% ↔ sofosbuvir	No dose adjustment necessary.
	ETR, NVP	No significant effect expected
	DOR, RPV	↔ Ledipasvir, sofosbuvir ↔ DOR, RPV
Simeprevir	DOR	No significant effect expected.	No dose adjustment necessary.
	EFV	Simeprevir AUC ↓ 71%, C_min ↓ 91% ↔ EFV	Do not coadminister.
	ETR, NVP	↓ simeprevir expected	Do not coadminister.
	RPV	↔ simeprevir and RPV	No dose adjustment necessary.
Sofosbuvir/ Velpatasvir	EFV	Velpatasvir AUC ↓ 43% , C_max ↓ 37%, and C_min ↓ 47%	Do not coadminister.
	ETR, NVP	↓ velpatasvir expected	Do not coadminister.
	DOR, RPV	No significant effect expected	No dose adjustment necessary.
Sofosbuvir/ Velpatasvir/ Voxilaprevir	EFV	Velpatasvir AUC ↓ 43% , C_max ↓ 37%, and C_min ↓47% ↓ voxilaprevir expected	Do not coadminister.
	ETR, NVP	↓ voxilaprevir expected ↓ velpatasvir expected	Do not coadminister.
	DOR, RPV	No significant effect expected	No dose adjustment necessary.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
St. John’s Wort	EFV, ETR, NVP	↓ EFV, ETR, and NVP expected	Do not coadminister.
St. John’s Wort	DOR, RPV	↓ NNRTI expected	Contraindicated.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Hormonal Contraceptives Oral	EFV	↔ Ethinyl estradiol Etonogestrel (metabolite of oral desogestrel) C_min ↓ 61% Levonorgestrel (metabolite of oral norgestimate) AUC ↓ 83% Norelgestromin (metabolite of oral norgestimate) AUC ↓ 64%	Use alternative or additional contraceptive methods.
	ETR	Ethinyl estradiol AUC ↑ 22% No significant effect on norethindrone	No dose adjustment necessary.
	NVP	Ethinyl estradiol AUC ↓ 29%, C_min ↓ 58% Norethindrone AUC ↓ 18% Etonogestrel (metabolite of oral desogestrel) C_min ↓ 22%	Based on clinical data demonstrating no change in effectiveness, no dose adjustment necessary.
	RPV	↔ Ethinyl estradiol ↔ Norethinodrone	No dose adjustment necessary.
	DOR	↔ Ethinyl estradiol ↔ Levonorgestrel	No dose adjustment necessary.
Depot Medroxy- progesterone Acetate (MPA) Injectable	EFV, NVP	DMPA: no significant change	No dose adjustment necessary.
Etonogestrel- Releasing Subdermal Implant	EFV	Etonogestrel AUC ↓ 63% to 82%	Use alternative or additional contraceptive methods.
Etonogestrel- Releasing Subdermal Implant	NVP	Etonogestrel: no significant change	No dose adjustment necessary.
Etonogestrel/ Ethinyl Estradiol Vaginal Ring	EFV	Ethinyl estradiol (intravaginal ring) AUC ↓ 56% Etonogestrel (intravaginal ring) AUC ↓ 81%	Use alternative or additional contraceptive methods.
Levonorestrel-Releasing Subdermal Implant	EFV	Levonorgestrel AUC ↓ 47%	Use alternative or additional contraceptive methods. Unintended pregnancies were observed in women who used EFV and levonorgestrel implant concomitantly.
Levonorestrel-Releasing Subdermal Implant	NVP	Levonorgestrel AUC ↑ 35%	No dose adjustment necessary.
Levonorgestrel For emergency contraception	EFV	Levonorgestrel AUC ↓ 58%	Effectiveness of emergency postcoital contraception may be diminished.
Menopausal Hormone Replacement Therapy	EFV, ETR, NVP	↓ estrogen possible with estradiol or conjugated estrogen (equine and synthetic) ↓ medroxyprogesterone possible ↓ micronized progesterone possible ↓ drospirenone possible See Hormonal Contraceptives for other progestin-NNRTI interactions	Monitor menopausal symptoms. Titrate to the dose of hormonal therapy that achieves menopausal symptom relief.
Gender-Affirming Hormone Therapy	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 dosing as necessary to achieve therapeutic goals.
Gender-Affirming Hormone Therapy	EFV, ETR, NVP	↓ testosterone possible	Monitor masculinizing effects of testosterone and titrate testosterone dose as necessary to achieve therapeutic goals.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Atorvastatin	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.
	DOR, RPV	↔ atorvastatin AUC	No dose adjustment necessary.
Fluvastatin	EFV, ETR	↑ fluvastatin possible	Dose adjustments for fluvastatin may be necessary. Monitor for fluvastatin toxicity.
Lovastatin, Simvastatin	EFV	Simvastatin AUC ↓ 68% Simvastatin active metabolite AUC ↓ 60%	Adjust simvastatin dose according to lipid response, but do not exceed the maximum recommended dose. If EFV is used with a PI/r, simvastatin and lovastatin should be avoided.
Lovastatin, Simvastatin	ETR, NVP	↓ lovastatin possible ↓ simvastatin possible	Adjust lovastatin or simvastatin dose according to lipid responses but do not exceed the maximum recommended dose. If ETR or NVP is used with a PI/r, simvastatin and lovastatin should be avoided.
Pitavastatin	EFV	↔ pitavastatin AUC	No dose adjustment necessary.
Pitavastatin	DOR, ETR, NVP, RPV	↔ pitavastatin expected	No dose adjustment necessary.
Pravastatin	EFV	Pravastatin AUC ↓ 44%	Adjust statin dose according to lipid responses, but do not exceed the maximum recommended dose.
Pravastatin	ETR	↓ pravastatin possible
Rosuvastatin	EFV, ETR, NVP	↔ rosuvastatin expected	No dose adjustment necessary.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Cyclosporine, Everolimus, Sirolimus, Tacrolimus	EFV, ETR, NVP	↓ immunosuppressant possible	Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Buprenorphine Sublingual or buccal	EFV	Buprenorphine AUC ↓ 50% Norbuprenorphine^bAUC ↓ 71%	No dose adjustment recommended; monitor for withdrawal symptoms.
	ETR	Buprenorphine AUC ↓ 25%	No dose adjustment necessary.
	NVP	No significant effect	No dose adjustment necessary.
Buprenorphine Implant	EFV, ETR, NVP	No data	Clinical monitoring is recommended if NNRTI is initiated after insertion of buprenorphine implant.
Methadone	EFV	Methadone AUC ↓ 52%	Opioid withdrawal common; increased methadone dose often necessary.
	DOR, ETR	No significant effect	No dose adjustment necessary.
	NVP	Methadone AUC ↓ 37% to 51% No significant effect on NVP	Opioid withdrawal is common; increased methadone dose is often necessary.
	RPV	R-methadone^c AUC ↓ 16%	No dose adjustment necessary, but monitor for withdrawal symptoms.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Sildenafil	DOR, RPV	↔ sildenafil expected	No dose adjustment necessary.
	ETR	Sildenafil AUC ↓ 57%	May need to titrate sildenafil dose based on clinical effect.
	EFV, NVP	↓ sildenafil possible
Tadalafil	EFV, ETR, NVP	↓ tadalafil possible	May need to titrate tadalafil dose based on clinical effect.
Tadalafil	RPV	↔ tadalafil	No dose adjustment necessary.
Avanafil, Vardenafil	EFV, ETR, NVP	↓ PDE5 inhibitor possible	May need to increase PDE5 inhibitor dose based on clinical effect.

Concomitant Drug Class/Name	NNRTI^a	Effect on NNRTI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Enzalutamide	All NNRTIs	↓ NNRTI expected	Contraindicated.
Mitotane	All NNRTIs	↓ NNRTI expected	Contraindicated.