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

Generic Name (Abbreviation) Trade Name Formulations Dosing Recommendationsa Elimination/ Metabolic Pathway Serum Half-Life Adverse Eventsb



  • 100-mg tablet

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


  • DOR 100 mg PO once daily

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

CYP3A4/5 substrate

15 hours



Abnormal dreams


Note: The branded product Sustiva has been discontinued.

Efavirenz (generic)

  • 600-mg tablet

STRs that Contain EFVc

  • 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, at or before bedtime

Take on an empty stomach to reduce side effects.

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


Neuropsychiatric symptomse

Serum transaminase elevations


QT interval prolongation

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



  • 100-mg, and 200-mg tablets


  • ETR 200 mg PO twice daily

Take following a meal.

CYP3A4, 2C9, and 2C19 substrate

CYP3A4 inducer

CYP2C9 and 2C19 inhibitor

41 hours

Rash, including Stevens-Johnson syndromed

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


Viramune or Viramune XR

Note: Generic products are available.


  • 200-mg tablet
  • 50-mg/5-mL oral suspension

Viramune XR

  • 400-mg tablet


  • 200-mg tablet
  • 400-mg extended-release tablet

50-mg/5-mL oral suspension


  • NVP 200 mg PO once daily for 14 days (lead-in period); thereafter, NVP 200 mg PO twice daily, or
  • NVP 400 mg (Viramune XR tablet) PO once daily

Take without regard to food.

Repeat lead-in period if therapy is discontinued for >7 days.

In patients who develop mild-to-moderate rash without constitutional symptoms, continue lead-in dose until rash resolves, but do not extend lead-in period beyond 28 days.

CYP450 substrate

CYP3A4 and 2B6 inducer

Contraindicated in patients with moderate to severe hepatic impairment.

Dose adjustment is recommended in patients on hemodialysis (see Appendix B, Table 12).

25–30 hours

Rash, including Stevens-Johnson syndromed

Symptomatic Hepatitis

  • Symptomatic hepatitis, including fatal hepatic necrosis, has been reported.
  • Rash has been reported in approximately 50% of cases.
  • Symptomatic hepatitis occurs at a significantly higher frequency in ARV-naive female patients with pre-NVP CD4 counts >250 cells/mm3 and in ARV-naive male patients with pre-NVP CD4 counts >400 cells/mm3.
  • NVP should not be initiated in these patients unless the benefit clearly outweighs the risk.



  • 25-mg tablet

Coformulated STRs that Contain RPVc

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

Copackaged Intramuscular Regimen

  • Cabenuva (CAB plus RPV)


  • RPV 25 mg PO once daily

Take 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


Depression, insomnia, headache


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


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