Appendix B: Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors

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 Also available as part of the STR Delstrigo (DOR/TDF/3TC)^c STRs That Contain DOR^c Delstrigo (DOR/TDF/3TC)	Pifeltro DOR 100 mg PO once daily See Appendix B, Table 1 for dosing information for Delstrigo.	CYP3A4/5 substrate	15 hours	Nausea Dizziness Abnormal dreams
Efavirenz (EFV) Note: The branded product Sustiva has been discontinued.	Efavirenz (generic) 600-mg tablet STRs that Contain EFV^c Atripla (EFV/TDF/FTC) Symfi (EFV 600 mg/TDF/3TC) Symfi Lo (EFV 400 mg/TDF/3TC)	Efavirenz (generic) EFV 600 mg PO once daily on an empty stomach, preferably at or before bedtime See Appendix B, 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^d Neuropsychiatric symptoms^e 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	Intelence 100-mg, and 200-mg tablets	Intelence 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^d 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 Intramuscular Regimen Cabenuva (CAB plus RPV)	Edurant RPV 25 mg PO once daily with food. See Appendix B, Table 1 for dosing information for coformulated and copackaged regimens that contain RPV.	CYP3A4 substrate	PO: 50 hours IM: 13-28 weeks	Rash^d Depression, insomnia, headache Hepatotoxicity QT interval prolongation IM Formulation Only Injection-site reactions (pain, induration, swelling, nodules) Rare post-injection 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 patients with renal or hepatic insufficiency, see Appendix B, Table 12. When no food restriction is listed, the antiretroviral drug can be taken with or without food. ^b Also see Table 20. ^c See Appendix B, Table 1 for information about these formulations. ^d Rare cases of Stevens-Johnson syndrome have been reported with the use of most NNRTIs; the highest incidence of rash was seen among patients who were receiving NVP. ^e 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 patients 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 patients. 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; NVP = nevirapine; PO = orally; RPV = rilpivirine; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; XR = extended release

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

Also available as part of the STR Delstrigo (DOR/TDF/3TC)^c

STRs That Contain DOR^c

Delstrigo (DOR/TDF/3TC)

Pifeltro

DOR 100 mg PO once daily

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

CYP3A4/5 substrate

15 hours

Nausea

Dizziness

Abnormal dreams

Efavirenz
(EFV)

Note: The branded product Sustiva has been discontinued.

Efavirenz (generic)

600-mg tablet

STRs that Contain EFV^c

Atripla (EFV/TDF/FTC)
Symfi (EFV 600 mg/TDF/3TC)
Symfi Lo (EFV 400 mg/TDF/3TC)

Efavirenz (generic)

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

See Appendix B, 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^d

Neuropsychiatric symptoms^e

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

Intelence

100-mg, and 200-mg tablets

Intelence

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^d

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 Intramuscular Regimen

Cabenuva (CAB plus RPV)

Edurant

RPV 25 mg PO once daily with food.

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

CYP3A4 substrate

PO: 50 hours

IM: 13-28 weeks

Rash^d

Depression, insomnia, headache

Hepatotoxicity

QT interval prolongation

IM Formulation Only

Injection-site reactions (pain, induration, swelling, nodules)
Rare post-injection 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 patients with renal or hepatic insufficiency, see Appendix B, Table 12. When no food restriction is listed, the antiretroviral drug can be taken with or without food.

^b Also see Table 20.

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

^d Rare cases of Stevens-Johnson syndrome have been reported with the use of most NNRTIs; the highest incidence of rash was seen among patients who were receiving NVP.

^e 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 patients 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 patients. 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; NVP = nevirapine; PO = orally; RPV = rilpivirine; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; XR = extended release

Back to Appendix B

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