Non-nucleoside RTIs Flashcards
Non-nucleoside Reverse Transcriptase Inhibitors
NNRTIs
EFV- efavirenz
ETR- etravirine
RPV- rilpivirine
NVP- nevirapine
Atripla- efavirenz, tenofovir, emtricitabine
Complera- rilpivirine, tenofovir, emtricitabine
Inhibit same enzyme as NRTIs but work through different mechanism
Greatly different pharmacologic properties
Only current clinical use is HIV
Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs) MOA
Instead of pretending to be a regular nucleoside, bind to a different part of RT enzyme- this causes a change in the conformation of the enzyme that interferes with its ability to form the viral DNA chain
Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs) Adverse Effects
CNS
Efavirenz- broad spectrum of CNS effects (dizziness, drowsiness (sometimes insomnia), and abnormal and especially vivid dreams)
Less common- depression, psychosis, suicidal ideation
Onset usually very rapid (first few doses); often subsides after a several weeks
May be minimized by taking on empty stomach; at bedtime or 2-3 hours prior
History of mental illness or depression is relative contraindication
Dermatologic
Rashes with all; nevirapine is biggest offender
Some mild forms can be treated with antihistamines
Any lesions involving mucous membranes (suggests SJS or similar eruptions) must be managed urgently and represents absolute contraindication to rechallenge
Hepatotoxicity
All can cause a spectrum of hepatotoxicity, from asymptomatic transaminase elevations to clinical hepatitis to fulminant hepatic failure
Nevirapine induced hepatotoxicity may manifest as hypersensitivity reaction
Monitor liver enzymes and S/S hepatitis
Hypersensitivity
Nevirapine induced- characterized by flu like symptoms, fever, jaundice, abdominal pain with or without rash
Fulminant hepatic failure and severe rash (TEN) are most feared manifestations
Appears to be more frequent in patients who are less immunocompromised (have higher CD4 counts) when starting nevirapine
This reaction may be reduced by using a reverse taper upon initiation- start with lower dose and escalate to full dose over 2 weeks (when risk is highest)
Metabolic
Lipohypertrophy- manifests as gradual accumulation of fat in the abdomen, chest, and neck (as buffalo hump); may occur with all
Efavirenz and nevirapine have been linked to hyperlipidemia
Compared to efavirenz, rilpivirine showed less effect on lipid profiles
Pregnancy/Lactation
Efavirenz catD; do not offer to pregnant or conceiving women
Rilpivirine catB
Others catC
Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs) Important Facts
Key barrier is low genetic barrier to resistance
Single point mutation can lead to high level resistance in the entire class
Very strict adherence needed
Advanced generation agents- etravirine, rilpivirine possess activity against viruses with some NNRTI mutations
Have much broader interaction profiles than NRTIs
Nevirapine- inducer
Efavirenz and Etravirine- mixed properties
Rilpivirine- does not yet appear to show effects
The NNRTIs can be affected by other drugs that cause interactions
Important to counsel about skin and hepatotoxicity reactions that could happen in first few weeks and strict adherence
Dose titration of nevirapine
CNS effects of efavirenz
Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs) Good For
Efavirenz with tenofovir and emtricitabine is one of recommended alternative regimens for initial treatment of naive patients (Atripla)- first one pill once daily regimen
New integrase agent combos now offer this option (with lesser toxicity and possibly lower genetic barrier to resistance)
Other ones tend to be used as second line therapy in experienced patients
