Viramune (Nevirapine) - Indications and Dosage

INDICATIONS AND USAGE

VIRAMUNE is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on one principal clinical trial (BI 1090) that demonstrated prolonged suppression of HIV-RNA and two smaller supportive studies, one of which (BI 1046) is described below.

Additional important information regarding the use of VIRAMUNE for the treatment of HIV-1 infection:

• Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled studies, VIRAMUNE should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm³ or in adult males with CD4+ cell counts greater than 400 cells/mm³ unless the benefit outweighs the risk [ see Boxed Warning and Warnings and Precautions (5.1) ].
• The 14-day lead-in period with VIRAMUNE 200 mg daily dosing has been demonstrated to reduce the frequency of rash [ see Dosage and Administration (2.4) and Warnings and Precautions (5.2) ].
• If rash persists beyond the 14-day lead-in period, do not dose escalate to 200 mg twice daily.  The 200 mg once daily dosing regimen should not be continued beyond 28 days at which point an alternative regimen should be sought.

DOSAGE AND ADMINISTRATION

Adults

The recommended dose for VIRAMUNE is one 200 mg tablet daily for the first 14 days, followed by one 200 mg tablet twice daily, in combination with other antiretroviral agents. The lead-in period has been observed to decrease the incidence of rash. For concomitantly administered antiretroviral therapy, the manufacturer’s recommended dosage and monitoring should be followed.

Pediatric Patients

The recommended oral dose for pediatric patients 15 days and older is 150 mg/m² once daily for 14 days followed by 150 mg/m² twice daily thereafter. The total daily dose should not exceed 400 mg for any patient.

Table 1 Calculation of the Volume of VIRAMUNE Oral Suspension (50 mg/5 mL) Required for Pediatric Dosing Based on Body Surface and a Dose of 150 mg/m²

BSA range (m2)	Volume (mL)
0.06 – 0.12	1.25
0.12 – 0.25	2.5
0.25 – 0.42	5
0.42 – 0.58	7.5
0.58 – 0.75	10
0.75 – 0.92	12.5
0.92 – 1.08	15
1.08 – 1.25	17.5
1.25+	20

VIRAMUNE suspension should be shaken gently prior to administration. It is important to administer the entire measured dose of suspension by using an oral dosing syringe or dosing cup. An oral dosing syringe is recommended, particularly for volumes of 5 mL or less. If a dosing cup is used, it should be thoroughly rinsed with water and the rinse should also be administered to the patient.

Monitoring of Patients

Intensive clinical and laboratory monitoring, including liver enzyme tests, is essential at baseline and during the first 18 weeks of treatment with VIRAMUNE. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, would include monitoring of liver enzyme tests at baseline, prior to dose escalation, and at two weeks post dose escalation. After the initial 18 week period, frequent clinical and laboratory monitoring should continue throughout VIRAMUNE treatment [ see Warnings and Precautions (5) ]. In some cases, hepatic injury has progressed despite discontinuation of treatment.

Dosage Adjustment

Patients with Rash

VIRAMUNE should be discontinued if a patient experiences severe rash or any rash accompanied by constitutional findings [ see Boxed Warning, Warnings and Precautions , and Patient Counseling Information ]. A patient experiencing mild to moderate rash without constitutional symptoms during the 14-day lead-in period of 200 mg/day (150 mg/m²/day in pediatric patients) should not have their VIRAMUNE dose increased until the rash has resolved [ see Warnings and Precautions and Patient Counseling Information ]. The total duration of the once daily lead-in dosing period should not exceed 28 days at which point an alternative regimen should be sought.

Patients with Hepatic Events

If a clinical (symptomatic) hepatic event occurs, VIRAMUNE should be permanently discontinued. Do not restart VIRAMUNE after recovery [ see Warnings and Precautions ].

Patients with Dose Interruption

Patients who interrupt VIRAMUNE dosing for more than 7 days should restart the recommended dosing, using one 200 mg tablet daily (150 mg/m²/day in pediatric patients) for the first 14 days (lead-in) followed by one 200 mg tablet twice daily (150 mg/m² twice daily for pediatric patients).

Patients on Dialysis

An additional 200 mg dose of VIRAMUNE following each dialysis treatment is indicated in patients requiring dialysis. Nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known [ see Clinical Pharmacology ]. Patients with CrCL ≥20 mL/min do not require an adjustment in VIRAMUNE dosing.

DOSAGE FORMS AND STRENGTHS

Tablets: 200 mg, white, oval, biconvex, tablets embossed with 54 193 on one side
Oral suspension: 50 mg/5 mL, white to off-white oral suspension

HOW SUPPLIED/STORAGE AND HANDLING

VIRAMUNE tablets, 200 mg, are white, oval, biconvex tablets, 9.3 mm x 19.1 mm. One side is embossed with "54 193", with a single bisect separating the "54" and "193". The opposite side has a single bisect.

VIRAMUNE Tablets are supplied in bottles of 60 (NDC 0597-0046-60).

VIRAMUNE oral suspension is a white to off-white preserved suspension containing 50 mg nevirapine (as nevirapine hemihydrate) in each 5 mL. VIRAMUNE suspension is supplied in plastic bottles with child-resistant closures containing 240 mL of suspension (NDC 0597-0047-24).

Storage

Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature]. Store in a safe place out of the reach of children.