Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Pifeltro:

• 100 mg tablet

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

Pifeltro:

• 1 tablet once daily

• Nausea
• Dizziness
• Abnormal dreams

Efavirenz 
(EFV) 
Sustiva 

Note: Generic product is available.

Sustiva:

• 50 and 200 mg capsules
• 600 mg tablet

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)

Sustiva:

• 600 mg once daily, at or before bedtime
• Take on an empty stomach to reduce side effects.

Metabolized by CYPs 2B6 (primary), 3A4, and 2A6 

CYP3A4 mixed inducer/inhibitor (more an inducer than an inhibitor) CYP2C9 and 2C19 inhibitor; 2B6 inducer

• Rash^c
•  Neuropsychiatric symptoms^d
• Increased transaminase levels
• Hyperlipidemia
• False-positive results with some cannabinoid and benzodiazepine screening assays reported
• QT interval prolongation

Atripla:

• (EFV 600 mg plus TDF 300 mg plus FTC 200 mg) tablet

Atripla:

• 1 tablet once daily on an empty stomach, preferably at bedtime

Symfi:

• (EFV 600 mg plus TDF 300 mg plus 3TC 300 mg) tablet

Symfi:

• 1 tablet once daily on an empty stomach, preferably at bedtime

Symfi Lo:

• (EFV 400 mg plus TDF 300 mg plus 3TC 300 mg) tablet

Symfi Lo:

• 1 tablet once daily on an empty stomach, preferably at bedtime

Intelence:

• 25, 100, and 200 mg tablets

Intelence:

• 200 mg BID
• Take following a meal.

CYP3A4, 2C9, and 2C19 substrate 

3A4 inducer; 2C9 and 2C19 inhibitor

• Rash, including Stevens-Johnson syndrome^c
• HSRs, characterized by rash, constitutional findings, and sometimes organ dysfunction (including hepatic failure) have been reported.
• Nausea

Nevirapine 
(NVP) 
Viramune or Viramune XR 

Note: Generic is available for 200 mg tablets and oral suspension.

• 200 mg tablet
• 400 mg XR tablet
• 50 mg/5 mL oral suspension

• 200 mg once daily for 14 days (lead-in period); thereafter, 200 mg BID, or 400 mg (Viramune XR tablet) once daily
• Take without regard to meals.
• 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 period until rash resolves, but do not administer for longer than 28 days total.

CYP450 substrate, inducer of 3A4 and 2B6; 80% excreted in urine (glucuronidated metabolites, <5% unchanged); 10% in feces 

Contraindicated in patients with moderate to severe hepatic impairment. 

Dose adjustment is recommended in patients on hemodialysis (see Appendix B, Table 8).

• Rash, including Stevens-Johnson syndrome^c
• Symptomatic hepatitis, including fatal hepatic necrosis, has been reported:
  • Rash reported in approximately 50% of cases.
  • Occurs at 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.

Edurant:

• 25 mg tablet

Edurant:

• 25 mg once daily
• Take with a meal.

• Rash^c
• Depression, insomnia, headache
• Hepatotoxicity
• QT interval prolongation

Juluca:

• (RPV 25 mg plus DTG 50 mg) tablet

Juluca:

• 1 tablet once daily
• Take with a meal.

Odefsey:

• (RPV 25 mg plus TAF 25 mg plus FTC 200 mg) tablet

Odefsey:

• 1 tablet once daily
• Take with a meal.

Complera:

• (RPV 25 mg plus TDF 300 mg plus FTC 200 mg) tablet

Complera:

• 1 tablet once daily
• Take with a meal.

^a For dose adjustments in patients with renal or hepatic insufficiency, see Appendix B, Table 8. 
^b Also see Table 15. 
^c Rare cases of Stevens-Johnson syndrome have been reported with most NNRTIs; the highest incidence of rash was seen with NVP. 
^d Adverse events can include dizziness, somnolence, insomnia, abnormal dreams, depression, suicidality (suicide, suicide attempt or ideation), confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. Approximately 50% of patients receiving EFV may experience any of these symptoms. Symptoms usually subside spontaneously after 2 to 4 weeks but may necessitate discontinuation of EFV in a small percentage of patients. 

Key to Acronyms: 3TC = lamivudine; ARV = antiretroviral; BID = twice daily; CD4 = CD4 T lymphocyte; CYP = cytochrome P; DLV = delavirdine; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; FTC = emtricitabine; HSR = hypersensitivity reaction; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; XR = extended release