Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

Figures & data

Table 1 Drugs in which plasma concentrations may be decreased by coadministration with nevirapine

Drug class	Type of drug
Antiarrhythmics	Amiodarone, disopyramide, lidocaine
Antibiotics	Clarithromycin, rifampin
Anticonvulsants	Carbamazepine, clonazepam, ethosuximide
Antifungals	Ketoconazole, itraconazole, voriconazole
Antithrombotics	Warfarin
Calcium-channel blockers	Diltiazem, nifedipine, verapamil
Cancer chemotherapy	Cyclophosphamide
Ergot alkaloids	Ergotamine
Immunosuppressants	Cyclosporin, tacrolimus, sirolimus
Motility agents	Cisapride
Opiate agonists	Fentanyl, methadone
Oral contraceptives	Ethinyl estradiol
Statins	Lovastatin, simvastatin, atorvastatin

Table 2 Summary of most relevant randomized clinical trials on nevirapine efficacy

Trial	Population	Intervention	Outcome	Follow-up
P1060 study^Citation19 2012	Children (85% had oral documentation of prior single-dose nevirapine exposure to prevent mother-to-child transmission) n = 288	Nevirapine-IR vs ritonavir-boosted lopinavir, both with zidovudine and lamivudine	HIV-1 RNA concentration of fewer than 400 copies per mL; 75.0% vs 84.9%, respectively; risk difference (RD) 9.72% (95% confidence interval [CI], −19.0 to 0.5; P = 0.06)	48 weeks
OCTANE^Citation22 2010	Women with single-dose exposure to nevirapine to prevent mother-to-child transmission n = 241	Nevirapine-IR vs ritonavir-boosted lopinavir, both with tenofovir disoproxil fumarate/ emtricitabine	HIV-1 RNA concentration of fewer than 400 copies per mL; 77% vs 92%, respectively; RD, 15.0% (95% CI, −24.3 to −5.9; P = 0.001)	24 weeks
ARTEN^Citation25 2011	Adult antiretroviral treatment–naïve patients n = 569	Nevirapine-IR vs ritonavir-boosted atazanavir, both with tenofovir disoproxil fumarate/ emtricitabine	HIV-1 RNA concentration of fewer than 50 copies per mL; 66.8% vs 64.8%, respectively; RD, 2.1% (95% CI, −6.0 to 10.6; P = 0.61)	48 weeks
NEWART^Citation27 2011	Adult antiretroviral treatment–naïve patients n = 152	Nevirapine-IR vs ritonavir-boosted atazanavir, both with tenofovir disoproxil fumarate/ emtricitabine	HIV-1 RNA concentration of fewer than 50 copies per mL; 61.3% vs 64.9%, respectively; RD, −2.6% (95% CI, −17.8 to 12.7; P = 0.74)	48 weeks
VERxVE^Citation13 2011	Adult antiretroviral treatment–naïve patients n = 1011	Nevirapine-XR vs nevirapine-IR, both with tenofovir disopropil fumarate/emtricitabine	HIV-1 RNA concentration of fewer than 50 copies per mL; 81.0% vs 75.9%, respectively; RD, 5.1% (95% CI, 0.02 to 10.2; P = 0.04)	48 weeks
TRANxITION^Citation38 2010	Adult antiretroviral treatment–experienced patients n = 443	Switching from nevirapine-IR to nevirapine-XR (2:1) in patients with HIV-1 RNA of fewer than 50 copies/mL, combined with either abacavir/lamivudine, tenofovir disoproxil fumarate/emtricitabine or zidovudine/emtricitabine	HIV-1 RNA concentration of fewer than 50 copies per mL; 88.8% vs 88.5%, respectively; RD, 0.3% (95% CI −5.6 to 7.3; P = 0.90)	48 weeks

Table 3 Nevirapine for preventing mother-to-child HIV-1 transmission

Trial	Population	Intervention	Outcome	Follow-up
Kesho Bora^Citation41 2011	Pregnant women with HIV-1 infection, n = 824	Pregnant women starting therapy at 28–36 weeks; zidovudine twice daily until delivery and a dose of 600 mg zidovudine plus 200 mg nevirapine at the onset of labor vs ritonavir-boosted lopinavir with zidovudine plus lamivudine until cessation of breastfeeding or to a maximum of 6.5 months postpartum	HIV-1 transmission at 6 weeks; 9.5% vs 5.4%, respectively; RD, 4.1% (95% CI, 0.5 to 7.8; P = 0.029)	12 months
HPTN 046^Citation42 2012	Breastfed infants without HIV-1 infection, n = 1527	Once-daily infant nevirapine-IR from age 6 weeks to 6 months or until breastfeeding cessation vs placebo	HIV-1 infection in infants at 6 months; incidence of HIV-1 infection 1.1% vs 2.4%; RD, 1.3% (95% CI, 0 to 2.6; P = 0.049)	6 months
SWEN^Citation43 2011	Pregnant women with HIV-1 infection who chose to breastfeed, n = 1890	Single-dose nevirapine IR vs extended-dose nevirapine IR through 6 weeks of age	HIV-1 infection in infants at 12 months; incidence of HIV-1 infection 10.4% vs 8.9%; RD, 1.5% (95% CI, −1.1 to 4.2; P = 0.15)	12 months

Table 4 Nevirapine XR safety (there are no new adverse drug reactions for nevirapine-XR that have not been previously identified for nevirapine-IR)

Disorder	Very common (frequency > 10%)	Common (frequency 1%–10%)	Uncommon (frequency 0.1%–1%)	Rare (frequency 0.01%–0.1%)
Gastrointestinal		Nausea, vomiting, abdominal pain, diarrhea
Hematologic		Granulocytopenia	Anemia
Hepatobiliary		Hepatitis (1.2%); liver function tests abnormal	Jaundice	Liver failure/fulminant hepatitis (may be fatal)
Immune system		Hypersensitivity (including anaphylactic reaction, angioedema, urticaria)	Drug rash with eosinophilia and systemic symptoms, anaphylactic reaction
Musculoskeletal, connective tissue and bone		Myalgia	Arthralgia
Nervous system		Headache
Skin and subcutaneous tissue	Exanthematous reaction		Stevens–Johnson syndrome (0.3%), toxic epidermal necrolysis (may be fatal), urticaria, angioedema
General symptoms		Fatigue, pyrexia	Fever
Laboratory investigations		Liver-function test abnormal (ALT/AST increased; GGT increased)	Blood phosphorus decreased, blood pressure increased

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; GGT, gamma glutamyl transpeptidase.

ViolariALindseyJCHughesMDNevirapine versus ritonavir-boosted lopinavir for HIV-infected childrenN Engl J Med2012366252380238922716976

 PubMed Web of Science ®Google Scholar

LockmanSHughesMDMcIntyreJAntiretroviral therapies in women after single-dose nevirapine exposureN Engl J Med2010363161499150920942666

 PubMed Web of Science ®Google Scholar

DominguezSGhosnJPeytavinGImpact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE studyJ Antimicrob Chemother201065112445244920813809

 PubMed Web of Science ®Google Scholar

ManosuthiWSungkanuparphSTantanathipPA randomized trial comparing plasma drug concentrations and efficacies between 2 non-nucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R StudyClin Infect Dis200948121752175919438397

 PubMed Web of Science ®Google Scholar

GatheJAndrade-VillanuevaJSantiagoSEfficacy and safety of nevirapine extended-release once daily versus nevirapine immediate-release twice daily in treatment-naive HIV-1-infected patientsAntivir Ther201116575976921817198

 PubMed Web of Science ®Google Scholar

ArastehKWardDPlettenbergA24 Wk efficacy and safety of transitioning virologically stable HIV-1 patients from IR nevirapine 200 mg BID to nevirapine XR 400 mg QD (TRANxITION)50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)September 12–15, 2010Boston, MAAbstract H-207

 Google Scholar

Kesho Bora Study Groupde VincenziITriple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trialLancet Infect Dis201111317118021237718

 PubMed Web of Science ®Google Scholar

CoovadiaHMBrownERFowlerMGEfficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trialLancet2012379981222122822196945

 PubMed Web of Science ®Google Scholar

OmerSBSix Week Extended Dose Nevirapine (SWEN) Study TeamTwelve-month follow-up of Six Week Extended Dose Nevirapine randomized controlled trials: differential impact of extended-dose nevirapine on mother-to-child transmission and infant death by maternal CD4 cell countAIDS201125676777621330912

 PubMed Web of Science ®Google Scholar