Taking it

The standard dose of nevirapine (Viramune) is 200mg per day for the first 14 days on therapy and afterwards 200mg twice daily.

During the first two weeks on nevirapine, only one tablet should be taken twice a day, to allow the body to establish safe levels of the drug, so reducing the risk of developing a serious rash or other side-effects. Nevirapine can be taken with or without food and at the same time as other anti-HIV drugs.

Some studies have found a once-daily 400mg dose of the standard formulation of nevirapine 400mg comparably effective to twice-daily dosing 1 2 while others have not.3 One concern with once-daily dosing is that trough levels are well below levels seen with standard dosing. Peak levels may also be much higher than with standard dosing.4,5 A newer extended-release formulation of nevirapine (Viramune XR) appears to perform at least as well as the standard twice-daily version, with comparable safety and tolerability.6

Nevirapine is also available as an oral suspension at a dose of 10mg/ml, which can be used by children weighing less than 50kg, and patients who cannot take tablets.

United States FDA now recommends that if a rash with constitutional symptoms or a severe rash develops, treatment with nevirapine should be stopped. If a mild to moderate rash occurs without constitutional symptoms during the lead-in period, the nevirapine dose should not be doubled to the full dosage until the rash is gone. The lead in period of once-daily dosing should also not exceed 28 days. If the rash has not subsided, an alternative treatment should be used.7

Those who wish to interrupt or stop nevirapine-based treatment should stop taking the nevirapine component of their regimen five days before the nucleoside reverse transcriptase inhibitor (NRTI) backbone. Since nevirapine has a long half-life and a low genetic barrier to resistance, stopping all the drugs at the same time could cause diminishing effects of nevirapine to persist much longer than those of the NRTIs, leading to the emergence of NNRTI resistance mutations.8 9 10

If nevirapine therapy is stopped for any reason for more than seven days, the lead-in dosing of 200mg a day for 14 days should be used when the drug is resumed.

Patients with hepatitis C/HIV co-infection may have elevated levels of nevirapine in the blood.11 Nevirapine is not advised for use in patients with moderate or severe liver impairment.

Despite previous toxicity issues that emerged when looking at once-daily nevirapine dosing, Boehringer Ingelheim is moving forward with a 48-week, international study of treatment-naive patients, intended to include 1000 participants. The VERXVE study will compare twice-daily dosing with once-daily dosing of a new, extended release formulation comprising one nevirapine tablet. All participants will receive Truvada alongside nevirapine.

The study will also need to put to rest concerns regarding the efficacy of combinations which combine nevirapine and tenofovir. The DAUFIN study, reported on in 2007, found a high risk of treatment failure using the combination of tenofovir, 3TC and nevirapine and was prematurely halted, while an Italian study also had a high failure rate in recipients with a high viral load who were on a regimen of Truvada (tenofovir and FTC) with twice-daily nevirapine.12 3 13

In 2007, Boehringer-Ingelheim opened VERxVE, a phase III, 48-week study in 1000 treatment-naive patients to compare twice-daily dosing of nevirapine with once-daily dosing of an extended release formulation. Participants in both arms will receive Truvada. The study is no longer recruiting and results are not yet available.

References

  1. Allavena C et al. Experience with nevirapine taken once daily in 93 HIV-infected patients. Pathol Biol (Paris) 47: 563-565, 1999
  2. Garcia F et al. Comparison of twice-daily stavudine plus once- or twice-daily didanosine and nevirapine in early stages of HIV infection: the SCAN study. AIDS 14: 2485-2494, 2000
  3. Rey D et al. Early virologic non-response to once daily combination of lamivudine, tenofovir, and nevirapine in ART-naive HIV-infected patients: preliminary results of the DAUFIN Study. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 503, 2007
  4. van Heeswijk RPG et al. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals. AIDS 14: F77-F82, 2000
  5. Kappelhoff BS et al. Pharmacokinetics of nevirapine: once-daily versus twice-daily dosing in the 2NN study. HIV Clin Trials 6: 254-261, 2005
  6. Gathe J et al. Comparison of 48 week efficacy and safety of 400 mg QD nevirapine extended release formulation (Viramune XR) versus 200 mg BID nevirapine immediate release formulation (Viramune IR) in combination with Truvada® in antiretroviral (ARV) naïve HIV-1 infected patients (VERxVE). Eighteenth International AIDS Conference, Vienna, abstract THLBB202, 2010
  7. Klein R et al. Important changes to Viramune (nevirapine) oral solution and tablets. FDA release, 27 June 2008, 2008
  8. Mackie NE et al. Clinical implications of stopping nevirapine-based antiretroviral therapy: relative pharmacokinetics and avoidance of drug resistance. HIV Med 5: 180-184, 2004
  9. Yeni PG et al. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA panel. JAMA 292: 251-265, 2004
  10. Muro E et al. Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine. Implications for intervention studies. J Acquir Immune Defic Syndr 39: 419-421, 2005
  11. de Maat MM et al. Population pharmacokinetics of nevirapine in an unselected cohort of HIV-1-infected individuals. Br J Clin Pharmacol 54: 378-385, 2002
  12. Podzamczer D et al. Low hepatotoxicity in patients randomized to switching to nevirapine QD vs continuing with nevirapine BID. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 960, 2008
  13. Lapadula G et al. Risk of early virological failure to tenofovir/emtricitabine once daily plus nevirapine twice daily in HIV-infected patients naïve to antiretroviral therapy. Eleventh European AIDS Conference, Madrid, abstract P7.3/10, 2007
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