Antiretroviral Agents: Nonnucleoside Reverse Transcriptase Inhibtors

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nevirapine

Detailed Prescribing Information

March 2007

Nevirapine = Viramune
Forms Available	200 mg tablets
Dosing	200 mg daily for 14 days, then increase to 200 mg twice a day or 2 x 200 mg once a day
Contraindication	Concomitant rifampin therapy Previous progressive hypersensitivity OR moderate or greater hypersensitivity to nevirapine
Contraindication	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
	Effects of other drugs on nevirapine levels: Fluconazole therapy significantly raises nevirapine trough levels (no significant clinical events) - no dose adjustments are necessary¹
	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
Administration Protocol	Discontinuation of antiretrovirals including nevirapine: (select one option below) 1. Discontinue nevirapine for 5 days prior to discontinuation of NRTI backbone, OR 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

Links to Antiretroviral Sections (click on anything)

Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI)

AZT | ddC | ddI | d4T | 3TC | ABC | FTC | TDF | Combivir | Trizivir | Epzicom | Truvada | Atripla

Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI)

efavirenz | nevirapine | delavirdine

Protease Inhibitors (PI) | Boosted Protease Inhibitors

Fusion Inhibitors

enfuvirtide

Quick Menu / Table of Contents
Introduction	Principles	Management	NRTI Info	NNRTI Info
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 Therapy

3.26.2007

1. W Manosuthi, C Athichathanabadi, S Uttayamakul, and others. Plasma nevirapine levels, adverse events and efficacy of antiretroviral therapy among HIV-infected patients concurrently receiving nevirapine-based antiretroviral therapy and fluconazole. BMC Infectious Diseases 7:14. March 12, 2007.