HIVManagement.org

 
Quick Menu / Table of Contents
Introduction Principles Management NRTI Key NRTI Info
NNRTI Key NNRTI Info PI Key PI Info Fusion Inhibitors
Drug Summary Investigational Adherence Lab Evaluation Resistance Tests
PEP Antiretroviral Tables OI Prevention Vaccinations TB Therapy
Hepatitis Therapy OI Diagnosis OI Therapy Bibliography Links
| Palliative Care | Presentations |

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)

Detailed Prescribing Information

April 2005

 

 

Direct Links to NNRTI Info
Key Points
Generic Brand
Delavirdine Rescriptor
Nevirapine Viramune
Efavirenz Sustiva
NNRTI Summary Information

 

 

Delavirdine = Rescriptor
Forms Available 100 mg tabs
Dosing 4x100 mg three times a day
Contraindication Concomitant rifampin, alprazolam, midazolam, triazolam, pimozide, or ergot derivative therapy

St John's Wort is expected to decrease delavirdine levels and therefore should not be used

Simvastatin, lovastatin
Severe hypersensitivity to nevirapine

Adverse Effects

33% incidence of rash, usually mild and NONPROGRESSIVE with continued treatment

5% of persons with rash will develop, mucosal involvement, and/or

Stevens-Johnson syndrome (aka erythema multiforme major)

Hepatitis which may be severe

Interactions

Increases PI levels

Antacids and proton pump inhibitors inhibit absorption of delavirdine

Suggested lab follow-up  Liver profile at 14 days, 30 days, and monthly x 3 months, then q3months
Warning Low barrier to one-step mutation.  Use only with other potent agents.
Complete prescribing information http://www.rescriptor.com

 

 

Nevirapine = Viramune
Forms Available 200 mg tabs
Dosing 200 mg daily x 14 days, then increase to 200 mg twice a day or 2x200 mg once a day
Contraindication Concomitant rifampin therapy

Previous progressive hypersensitivity or moderate or greater hypersensitivity to nevirapine

Avoid nevirapine use in antiretroviral-naive women with CD4-lymphocyte counts > 250 or men with CD4-lymphocyte counts > 400
Adverse Effects

33% incidence of rash, usually mild and NONPROGRESSIVE with continued treatment

5% of persons with rash will develop, mucosal involvement, and/or

Stevens-Johnson syndrome (aka erythema multiforme major)

Hepatitis which may be severe and more likely in the setting of higher CD4-lymphocyte counts, female gender, pre-existing hepatitis, single daily dosing.

Interactions

Nevirapine decreases protease inhibitor levels (compensate by increasing PI dosage 25-33%). Compensate for this interaction by the following dose modifications:

Increase indinavir to 1000 mg q8h

Increase lopinavir/ritonavir to 4 x 133mg/33mg caps twice a day
Increase nelfinavir to 1500 mg twice a day with food

Nevirapine effects levels of other drugs:
Decreases caspofungin levels (consider increasing dose of caspofungin to 70 mg/day)

Decreases oral contraceptive pill (OCP) efficacy

Decreases methadone, fentanyl, imidazole antifungal drug levels

Decreases warfarin efficacy

Unknown interactions with atazanavir, fosamprenavir: avoid nevirapine use with these protease inhibitors until further information is available
Suggested lab follow-up  Liver profile at 14 days, 30 days, and monthly x 3 months, then  every 3 months
Warning Low barrier to one-step mutation.  Use only with other potent agents.

Nevirapine should not be used in postexposure prophylaxis due to reports of fatal hepatotoxicity.

Women who start nevirapine therapy with CD4 cells counts greater than 250 (and possibly men with CD4 counts > 400) have a 12x greater risk of hepatitis due to nevirapine.  The risk is greatest for the first 6 weeks of therapy but patients should be monitored carefully for at least the first 18 weeks of therapy.
Sudden discontinuation of nevirapine-containing antiretrovirals may result in prolonged subtherapeutic serum levels of nevirapine in the setting of viral replication.  Subtherapeutic drug levels may be associated with the development of mutational resistance and loss of activity for nevirapine and the NNRTI class as it exists currently (May 2004).  See Administration Protocol below for further information on discontinuation strategies.
Administration
Protocol
Initiation of antiretroviral regimens containing nevirapine

1.  Check for possible drug interactions closely prior to prescribing nevirapine

2.  Monitor closely for hypersensitivity and hepatitis after initiation with a clinical evaluation and laboratory at 2 weeks and 4 weeks
3.  Discontinue drug for progressive rash or hepatitis

Discontinuation of antiretrovirals including nevirapine: (select one option below)

1.  Discontinue nevirapine for 5 days prior to discontinuation of NRTI backbone
2.  Substitute another short-acting antiretroviral such as lopinavir/ritonavir for nevirapine for two weeks prior to discontinuation of the antiretrovirals

Complete prescribing information http://www.viramune.com

 

 

Efavirenz = Sustiva
Forms Available 50 mg, 100mg, 200 mg capsules; 600 mg tablets
Dosing 3x200 mg or 600 mg daily

Usually taken at bedtime but if too much stimulation or dreaming, dosing can be done in the AM

Meal dependence High fat meals elevate Cmax of capsule by 40% and tablets by 80% which may result in increased CNS stimulation and adverse events.
Consider initiating therapy on an empty stomach and if tolerated administer with low fat and then regular feeds.
Contraindication Pregnancy or desire to become pregnant or inadequate birth control precautions

Do not use with saquinavir as the sole protease inhibitor

Midazolam, triazolam, and ergot derivatives are not to be used with Sustiva.

St. John's Wort may decrease Sustiva levels and is therefore not to be used.

Voriconazole should not be used with efavirenz.

Adverse Effects

50% CNS stimulation including sleeplessness, confusion, nightmares: this may be debilitating over short-term or long-term

5% incidence of rash, usually mild and NONPROGRESSIVE with continued treatment

Hepatitis which may be severe

Interactions

Efavirenz decreases PI levels (compensate by increasing PI dosage 25-33%)

Increase indinavir to 1000 mg po q8h

Increase lopinavir/ritonavir to 4 x 133mg/33mg caps twice a day

Increase amprenavir to 8x150 twice a day or use ritonavir 100 mg twice a day

Decreases oral contraceptive pill efficacy

Decreases methadone, fentanyl, imidazole antifungal drug levels

Decreases warfarin efficacy

Decreases voriconazole levels to subtherapeutic

Suggested lab follow-up  Liver profile at 30 days and every 2-3 months and as indicated
Warning Low barrier to one-step mutation.  Use only with other potent agents.
Sudden discontinuation of efavirenz-containing antiretroviral regimens without substitution of other potent antiretroviral or antiretroviral combination may result in prolonged subtherapeutic serum levels of nevirapine.  These subtherapeutic drug levels may result in the development of mutational resistance and loss of activity for efavirenz and the NNRTI class as it exists currently (May 2004)  See Usage Suggestions below for further information.
Administration
Protocol
Initiation of efavirenz:

Initiate therapy during a period that is noncritical for CNS function in the patient's life (eg on a work weekend).  Dosing may be suggested either immediately before bedtime or in the AM, whichever is better tolerated by the patient.  Tolerance to these CNS effects (sleeplessness, nightmares, alteration of mentation, stimulation) may improve over the first two weeks of therapy.

Observe dosing interactions with protease inhibitors carefully (see above)

Discontinuation of efavirenz:
It is recommended that when antiretrovirals are discontinued that include nevirapine and
efavirenz, a potent and active protease inhibitor should be substituted first for the NNRTI.  This PI substitution therapy should then be continued for 2 weeks.  At that point when NNRTI serum and/or intracellular levels are essentially zero, the PI-based substitute antiretroviral therapy may be stopped.  Alternatively stop the efavirenz for 5 days prior to stopping the NRTI backbone.
Complete prescribing information http://www.sustiva.com

 

 

 

NNRTI Summary Information

Generic

Brand

Pill Burden
per day
Dosing
Frequency
per day
Rash PI Drug
Levels
Other High Level
Resistance Mutations
nevirapine
Viramune
2 1-2 33%  ↓ 25-33% hepatitis risk 12x higher
for women CD4>250
K103N, Y181C/I, Y188C/L/H, G190A/S, M230L
delavirdine
Rescriptor
12 3 33% ↑↑ hepatitis K103N, Y181C/I, Y188C/L/H, G190A/S, M230L, P236L
efavirenz
Sustiva
1 1 5%  ↓ 25-33% %50 CNS
stimulation

pregnancy contraindication

K103N, Y181C/I, Y188C/L/H, M230L

 

For detailed NNRTI Mutation information, please consult with HIVResistanceWeb.com or check the HIV Resistance Test section of this site.

 

 

Next Page Click HERE for Key Protease Inhibitor Information or HERE for Detailed PI Info

 

 

Links to Antiretroviral Sections
Nucleoside & Nucleothree times a daye Reverse Transcriptase Inhibitors (NRTI)
AZT  |  ddC  |  ddI  |  d4T  |  3TC  |  ABC  |  FTC  |  TDF  |  Combivir  |  Trizivir  |  Epzicom  |  Truvada
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI)
efavirenz  |  nevirapine  |  delavirdine
Protease Inhibitors (PI)  |  Boosted Protease Inhibitors
saquinavir  indinavir  |  ritonavir  |  nelfinavir  |  amprenavir  |  lopinavir + ritonavir  |  atazanavir  |  fosamprenavir  |  tipranavir
Fusion Inhibitors
enfuvirtide
 
Quick Menu / Table of Contents
Introduction Principles Management NRTI Key NRTI Info
NNRTI Key NNRTI Info PI Key PI Info Fusion Inhibitors
Drug Summary Investigational Adherence Lab Evaluation Resistance Tests
PEP Antiretroviral Tables OI Prevention Vaccinations TB Therapy
Hepatitis Therapy OI Diagnosis OI Therapy Bibliography Links
| Palliative Care | Presentations |
 

8.5.2005