Appendix A: Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors

The following table includes dose recommendations for U.S. Food and Drug Administration (FDA)–approved non-nucleoside reverse transcriptase inhibitor (NNRTI) products for adults with HIV. For information regarding the use of these medications in adolescents with HIV, including weight limitations and additional dosage forms, please consult FDA product labeling or Appendix A in the Pediatric Antiretroviral Guidelines. The older NNRTIs delavirdine (DLV) and nevirapine (NVP) are not listed in this table; DLV has been discontinued and NVP is no longer commonly used in clinical practice in the United States.

Generic Name (Abbreviation) Trade Name	Formulations	Dosing Recommendations^a	Elimination/ Metabolic Pathway	Serum Half-Life	Adverse Events^b
Doravirine (DOR) Pifeltro	Pifeltro 100-mg tablet STRs That Contain DOR^c Delstrigo (DOR/TDF/3TC)	DOR 100 mg PO once daily See Appendix A, Table 1 for dosing information for Delstrigo.	CYP3A4/5 substrate	15 hours	Rash, including Stevens-Johnson syndrome Nausea Dizziness Abnormal dreams
Efavirenz (EFV) Note: Generic only	Efavirenz (generic) 600-mg tablet STRs that Contain EFV^c EFV/TDF/FTC (generic) Symfi (EFV/TDF/3TC)	EFV 600 mg PO once daily on an empty stomach, preferably at or before bedtime See Appendix A, Table 1 for dosing information for STRs that contain EFV.	Metabolized by CYP2B6 (primary), 3A4, and 2A6 CYP3A4 mixed inducer/inhibitor (more an inducer than an inhibitor) CYP2B6 and 2C19 inducer	40–55 hours	Rash, inclding Stevens-Johnson syndrome Neuropsychiatric symptoms^d Serum transaminase elevations Hyperlipidemia QT interval prolongation Use of EFV may lead to false-positive results with some cannabinoid and benzodiazepine screening assays.
Etravirine (ETR) Intelence Note: Generic products are available.	Intelence 100-mg and 200-mg tablets Generic 100-mg and 200-mg tablets	ETR 200 mg PO twice daily following a meal.	CYP3A4, 2C9, and 2C19 substrate CYP3A4 inducer CYP2C9 and 2C19 inhibitor	41 hours	Rash, including Stevens-Johnson syndrome HSRs, characterized by rash, constitutional findings, and sometimes organ dysfunction (including hepatic failure), have been reported. Nausea
Rilpivirine (RPV) Edurant	Edurant 25-mg tablet STRs that Contain RPV^c Complera (RPV/TDF/FTC) Juluca (DTG/RPV) Odefsey (RPV/TAF/FTC) Copackaged IM Regimen Cabenuva (CAB plus RPV)	RPV 25 mg PO once daily with food. See Appendix A, Table 1 for dosing information for coformulated and copackaged regimens that contain RPV.	CYP3A4 substrate	PO: 50 hours IM: 13-28 weeks	Rash, including Stevens-Johnson syndrome Depression, insomnia, headache Hepatotoxicity QT interval prolongation IM Formulation Only Injection-site reactions (pain, induration, swelling, nodules) Rare postinjection reaction (dyspnea, agitation, abdominal cramps, flushing) occurring within a few minutes after RPV IM injection; possibly associated with inadvertent IV administration.
^a For dose adjustments in people with renal or hepatic insufficiency, see Appendix B. When no food restriction is listed, the antiretroviral drug can be taken with or without food. ^b Also see Table 21. ^c See Appendix A, Table 1 for information about these formulations. ^d Adverse events can include dizziness, somnolence, insomnia, abnormal dreams, depression, suicidality (e.g., suicide, suicide attempt or ideation), confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. Approximately 50% of people who are receiving EFV may experience any of these symptoms. Symptoms usually subside spontaneously after 2–4 weeks, but discontinuation of EFV may be necessary in a small percentage of people. Late-onset neurotoxicities, including ataxia and encephalopathy, have been reported. Key: 3TC = lamivudine; ARV = antiretroviral; CAB = cabotegravir; CD4 = CD4 T lymphocyte; CYP = cytochrome P; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; FTC = emtricitabine; HSR = hypersensitivity reaction; IM = intramuscular; IV = intravenous; NNRTI = non-nucleoside reverse transcriptase inhibitor; PO = orally; RPV = rilpivirine; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Generic Name (Abbreviation) Trade Name

Formulations

Dosing Recommendations^a

Elimination/ Metabolic Pathway

Serum Half-Life

Adverse Events^b

Doravirine
(DOR)
Pifeltro

Pifeltro

100-mg tablet

STRs That Contain DOR^c

Delstrigo (DOR/TDF/3TC)

DOR 100 mg PO once daily

See Appendix A, Table 1 for dosing information for Delstrigo.

CYP3A4/5 substrate

15 hours

Rash, including Stevens-Johnson syndrome

Nausea

Dizziness

Abnormal dreams

Efavirenz
(EFV)

Note: Generic only

Efavirenz (generic)

600-mg tablet

STRs that Contain EFV^c

EFV/TDF/FTC (generic)
Symfi (EFV/TDF/3TC)

EFV 600 mg PO once daily on an empty stomach, preferably at or before bedtime

See Appendix A, Table 1 for dosing information for STRs that contain EFV.

Metabolized by CYP2B6 (primary), 3A4, and 2A6

CYP3A4 mixed inducer/inhibitor (more an inducer than an inhibitor)

CYP2B6 and 2C19 inducer

40–55 hours

Rash, inclding Stevens-Johnson syndrome

Neuropsychiatric symptoms^d

Serum transaminase elevations

Hyperlipidemia

QT interval prolongation

Use of EFV may lead to false-positive results with some cannabinoid and benzodiazepine screening assays.

Etravirine
(ETR)
Intelence

Note: Generic products are available.

Intelence

100-mg and 200-mg tablets

Generic

100-mg and 200-mg tablets

ETR 200 mg PO twice daily following a meal.

CYP3A4, 2C9, and 2C19 substrate

CYP3A4 inducer

CYP2C9 and 2C19 inhibitor

41 hours

Rash, including Stevens-Johnson syndrome

HSRs, characterized by rash, constitutional findings, and sometimes organ dysfunction (including hepatic failure), have been reported.

Nausea

Rilpivirine
(RPV)
Edurant

Edurant

25-mg tablet

STRs that Contain RPV^c

Complera (RPV/TDF/FTC)
Juluca (DTG/RPV)
Odefsey (RPV/TAF/FTC)

Copackaged IM Regimen

Cabenuva (CAB plus RPV)

RPV 25 mg PO once daily with food.

See Appendix A, Table 1 for dosing information for coformulated and copackaged regimens that contain RPV.

CYP3A4 substrate

PO: 50 hours

IM: 13-28 weeks

Rash, including Stevens-Johnson syndrome

Depression, insomnia, headache

Hepatotoxicity

QT interval prolongation

IM Formulation Only

Injection-site reactions (pain, induration, swelling, nodules)
Rare postinjection reaction (dyspnea, agitation, abdominal cramps, flushing) occurring within a few minutes after RPV IM injection; possibly associated with inadvertent IV administration.

^a For dose adjustments in people with renal or hepatic insufficiency, see Appendix B. When no food restriction is listed, the antiretroviral drug can be taken with or without food.

^b Also see Table 21.

^c See Appendix A, Table 1 for information about these formulations.

^d Adverse events can include dizziness, somnolence, insomnia, abnormal dreams, depression, suicidality (e.g., suicide, suicide attempt or ideation), confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. Approximately 50% of people who are receiving EFV may experience any of these symptoms. Symptoms usually subside spontaneously after 2–4 weeks, but discontinuation of EFV may be necessary in a small percentage of people. Late-onset neurotoxicities, including ataxia and encephalopathy, have been reported.

Key: 3TC = lamivudine; ARV = antiretroviral; CAB = cabotegravir; CD4 = CD4 T lymphocyte; CYP = cytochrome P; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; FTC = emtricitabine; HSR = hypersensitivity reaction; IM = intramuscular; IV = intravenous; NNRTI = non-nucleoside reverse transcriptase inhibitor; PO = orally; RPV = rilpivirine; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Back to Appendix A

Appendix A, Table 4. Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors