Nevirapine dosing

Dosage adjustment Discontinue nevirapine if patients experience severe rash or a rash accompanied by constitutional findings (see Warnings). Patients experiencing rash during the 14-day lead-in period of 200 mg/day (4 mg/kg/day in children) should not have their nevirapine dose increased until the rash has resolved. 

Missed doses Patients who interrupt nevirapine dosing for more than 7 days should restart the recommended dosing, using one 200 mg tablet daily (4 mg/kg/day in children) for the first 14 days (lead-in), followed by one 200 mg tablet twice daily (4 or 7 mg/kg twice daily, according to age, for children). 

Renal function impairment An additional 200 mg dose of nevirapine following each dialysis treatment is indicated in patients requiring dialysis. Patients with Ccr 20 mL/min or greater do not require an adjustment in nevirapine dosing. 

At a nevirapine dose of 400 mg/day, 32—48% of patients develop skin rash versus 9% with a dose of 200 mg (Taiwo 2006). In female Brown Norway rats treated with nevirapine at a dose of 150 mg/kg/day, all developed a skin rash, while only half the rats developed the rash when dosed at 100 mg/kg/day. No rat developed a rash at doses of <75 mg/kg/day (Shenton et al. 2003). 

Starting with the second week of nevirapine treatment, progressive infiltration of T cells into the rat skin dermis was observed. To assess the specific role of the T cell populations in triggering the onset of skin rash, Shenton et al. transferred splenocyte T cells from rechallenged rats into naive recipients. Spleen CD4 T and CD8 T cells were isolated from the nevirapine-rechallenged rats, purified, and intravenously injected into naive recipients, which were then started on a full (150 mg/kg/day) nevirapine dose (Shenton et al. 2005). Recipients of CD4 T cells developed skin rash 9 days later, while CDS" T cell recipients behaved as nevirapine naive rats, only developing red ears by day 7 and skin rash by day 21... 

Eshleman SH, Hoover DR, Chen S, Hudelson SE, Guay LA, Mwatha A, Fiscus SA, Mmiro F, Musoke P, Jackson JB et al, (2005a) Nevirapine (NVP) resistance in women with HIV-1 sub-type C, compared with subtypes A and D, after the administration of single-dose NVP. J Infect Dis 192 30-36... 

Lee EJ, Kantor R, Zijenah L, Sheldon W, Emel L, Mateta P, Johnston E, Wells J, Shetty AK, Coovadia H et al. (2005) Breast-mUk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine. J Infect Dis 192 1260-1264... 

Seth RB, Sun L, Chen ZJ (2006) Antiviral innate immunity pathways. Cell research 16 141-147 Shapiro RL, Thior I, Gilbert PB, Lockman S, Wester C, Smeaton LM, Stevens L, Heymann SJ, Ndung u T, Gaseitsiwe S et al. (2006) Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-chUd HIV transmission in Botswana. Aids 20 1281-1288... 

Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior 1, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van WE, Mazhani L, Novitsky V, Lagakos S, Essex M (2007) Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 356 135-147... 

Conversely buprenorphine metabolism could by increased by carbamazepine, phenytoin, St. John s wort, efavirenz, and nevirapine, or any other CYP3A4 inducer the effects may be less than expected may need to increase buprenorphine dose. 

Nervirapine is an HIV drug that is a CYP3A4 inducer in a small sample, nevirapine caused a 50% reduction in methadone blood levels, resulting in complaints of methadone withdrawal symptoms in patients receiving methadone maintenance may need to increase methadone dose in patients who have nevirapine added to their drug regimen. 

Concomitant therapy with efavirenz, nevirapine, fosamprenavir, or nelfinavir-Consider a dose increase to 533/133 mg lopinavir/ritonavir (4 capsules or 6.5 mL) twice daily taken with food when used in combination with efavirenz, nevirapine, amprenavir, or nelfinavir, or 600/150 mg (3 tablets) twice daily with or without food when used in combination with efavirenz, nevirapine, fosamprenavir without ritonavir, or nelfinavir in treatment-experienced patients where decreased susceptibility to lopinavir is clinically suspected (by treatment history or laboratory evidence). 

Absorption - Nevirapine is readily absorbed (more than 90%) after oral administration. Peak plasma nevirapine concentrations of 2 mcg/mL (7.5 micromolar) were attained within 4 hours following a single 200 mg dose. Following multiple doses, nevirapine peak concentrations appear to increase... 

Nevirapine has been shown to be an inducer of hepatic cytochrome P450 metabolic enzymes 3A4 and 2B6. The pharmacokinetics of autoinduction are characterized by an approximately 1.5- to 2-fold increase in the apparent oral clearance of nevirapine as treatment continues from a single dose to 2 to 4 weeks of dosing with 200 to 400 mg/day. Auto-induction also results in a corresponding decrease in the terminal phase half-life of nevirapine in plasma from approximately 45 hours (single dose) to approximately 25 to 30 hours following multiple dosing with 200 to 400 mg/day. 

The majority of rashes associated with nevirapine occur within the first 6 weeks of initiation of therapy. Instruct patients not to increase the 200 mg/day (4 mg/kg/day in children) dosage if any rash occurs during the 2-week lead-in dosing period until the rash resolves. 

Efavirenz is given orally at a dose of one 600-mg tablet per day. As an important part of the AIDS cocktail, efavirenz is administered with the same protease inhibitors and NRTIs as described in the nevirapine section. The half-hfe of efavirenz after a single dose is 52-76 h, and multiple doses lower the half-life to 40-55 h. Treatment with efavirenz has been associated with the development of serious psychiatric side-effects, including severe depression, suicidal thoughts, aggressive behavior, and paranoid and manic reactions. 

The NNRTIs efavirenz and nevirapine interact with a number of drugs metabolized in the liver. The doses of protease inhibitors may need to be increased when they are given with efavirenz or nevirapine. Nevirapine is associated with a high incidence of... 

One large randomised controlled trial demonstrates that nevirapine given to mothers as a single dose at the onset of labour and to babies as a single dose within 72 hours of birth is more effective than an intrapartum and post-partum regimen of zidovudine. However this regimen can cause NNRTI resistant virus in mother and child. 

Nevirapine Possibly Data are insufficient to assess whether dose adjustments are necessary when rifampicin is co administered with nevirapine. Therefore, rifampicin and nevirapine should be used only in combination if clearly indicated and with careful monitoring... 

HIV infection (in combination with other antiretrovirals) PO 800 mg (two 400-mg capsules) q8h. Dosage adjustments when given concomitantly Delavirdine, itraconazole, ketoconazok Reduce dose to 600 mg q8h. Efavirenz-. Increase dose to 1,000 mg q8h. Lopinavir/ritonavir Reduce dose to 600 mg twice a day. Nevirapine-. Increase dose to 1,000 mgqSh. Rifabutin-. Reduce rifabutin by lA and increase indinavir to 1,000 mg q8h. Ritonavir 100-200 mg twice a day and indinavir 800 mg twice a day or ritonavir 400 mg twice a day and indinavir 400 mg twice a day. 

Space drug doses evenly around the clock and continue nevirapine therapy for the full course of treatment... 

Nevirapine NNRTI 200 mg bid. Adjust dose in hepatic insufficiency Dose-escalate from 200 mg daily over 14 days to decrease frequency of rash Rash, hepatitis (occasionally fulminant), nausea, headache See footnote 4 for contraindicated medications... 

A single dose of nevirapine (200 mg) is effective in the prevention of transmission of HIV from mother to newborn when administered to women at the onset of labor and followed by a 2-mg/kg oral dose to the neonate within 3 days after delivery. There is no evidence of human teratogenicity. However, resistance has been documented after this single dose. 

Havlir D, Murphy R, Saag M, Kaul I, Johnson V, Richman DD. Nevirapine further dose escalation of monotherapy (600 mg/daily) and combination therapy with zidovudine. In The First National Conference on Human Retroviruses and Related Infections, Washington D.C., 1993 101. 

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