VIRAMUNE

Viramune should be administered by physicians who are experienced in the treatment of HIV infection. Posology Patients 16 years and older The recommended dose for Viramune is 20 mL (200 mg) oral suspension once daily for the first 14 days (this lead-in period should be used because it has been found to lessen the frequency of rash), followed by 20 mL (200 mg) oral suspension twice daily, in combination with at least two additional antiretroviral agents.

25 m2. If a dose is recognized as missed within 8 hours of when it was due, the patient should take the missed dose as soon as possible. If a dose is missed and it is more than 8 hours later, the patient should only take the next dose at the usual time.

Dose management considerations Patients experiencing rash during the 14-day lead-in period of 200 mg/day (4 mg/kg/day or 150 mg/m2/day for paediatric patients) should not have their Viramune dose increased until the rash has resolved.

4). The 200 mg once daily dosing regimen should not be continued beyond 28 days at which point in time an alternative treatment should be sought due to the possible risk of underexposure and resistance. Patients who interrupt nevirapine dosing for more than 7 days should restart the recommended dosing regimen using the two week lead-in period.

4). Elderly Nevirapine has not been specifically investigated in patients over the age of 65. Renal impairment For patients with renal dysfunction requiring dialysis an additional 200 mg dose of nevirapine following each dialysis treatment is recommended.

2. 3). 2). Paediatric population The total daily dose should not exceed 400 mg for any patient. Viramune may be dosed in paediatric patients either by body surface area (BSA) or by body weight as follows: By BSA using the Mosteller formula the recommended oral dose for paediatric patients of all ages is 150 mg/m2 once daily for two weeks followed by 150 mg/m2 twice daily thereafter.

25+ 20 Mosteller Formula: ² = × () 3600 By weight the recommended oral dose for paediatric patients up to 8 years of age is 4 mg/kg once daily for two weeks followed by 7 mg/kg twice daily thereafter. For patients 8 years and older the recommended dose is 4 mg/kg once daily for two weeks followed by 4 mg/kg twice daily thereafter.

Calculation of the volume of Viramune oral suspension (50 mg/5 mL) required for paediatric dosing after the two weeks lead-in period. Weight Range (kg) for patients < 8 yrs of age on a body weight basis receiving 7 mg/kg. Weight Range (kg) for patients ≥ 8 years of age on a body weight basis receiving 4 mg/kg.

Summary of the safety profile The most frequently reported adverse reactions related to Viramune therapy, across all clinical studies, were rash, allergic reactions, hepatitis, abnormal liver function tests, nausea, vomiting, diarrhoea, abdominal pain, fatigue, fever, headache and myalgia.

The postmarketing experience has shown that the most serious adverse reactions are Stevens- Johnson syndrome/ toxic epidermal necrolysis, serious hepatitis/hepatic failure, and drug reaction with eosinophilia and systemic symptoms, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction.

4). Tabulated summary of adverse reactions The following adverse reactions which may be causally related to the administration of Viramune have been reported. The frequencies estimated are based on pooled clinical study data for adverse reactions considered related to Viramune treatment.

Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Blood and lymphatic system disorders Common granulocytopenia Uncommon anaemia Immune system disorders Common hypersensitivity (incl.

5%). Anaphylactic reaction was identified through post-marketing surveillance but not observed in randomised, controlled clinical studies. The frequency category was estimated from a statistical calculation based on the total number of patients exposed to nevirapine in randomised controlled clinical studies (n = 2 718).

Decreased blood phosphorus and increased blood pressure were observed in clinical studies with co-administration of tenofovir/emtricitabine. 4). The following adverse reactions have also been reported when nevirapine has been used in combination with other anti-retroviral agents: pancreatitis, peripheral neuropathy and thrombocytopaenia.

1). Viramune should not be used as the sole active antiretroviral, as monotherapy with any antiretroviral has shown to result in viral resistance. The first 18 weeks of therapy with nevirapine are a critical period which requires close monitoring of patients to disclose the potential appearance of severe and life-threatening skin reactions (including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) and serious hepatitis/hepatic failure.

The greatest risk of hepatic and skin reactions occurs in the first 6 weeks of therapy. However, the risk of any hepatic event continues past this period and monitoring should continue at frequent intervals. e. a concentration ≥ 50 copies/mL - at the initiation of nevirapine.

As serious and life threatening hepatotoxicity has been observed in controlled and uncontrolled studies predominantly in patients with a plasma HIV-1 viral load of 50 copies/mL or higher, nevirapine 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, who have a detectable plasma HIV-1 RNA unless the benefit outweighs the risk.

In some cases, hepatic injury has progressed despite discontinuation of treatment. Patients developing signs or symptoms of hepatitis, severe skin reaction or hypersensitivity reactions must discontinue nevirapine and seek medical evaluation immediately.

3). 2). Cutaneous reactions Severe and life-threatening skin reactions, including fatal cases, have occurred in patients treated with nevirapine mainly during the first 6 weeks of therapy. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity reactions characterised by rash, constitutional findings and visceral involvement.

Patients should be intensively monitored during the first 18 weeks of treatment. Patients should be closely monitored if an isolated rash occurs. Nevirapine must be permanently discontinued in any patient experiencing severe rash or a rash accompanied by constitutional symptoms (such as fever, blistering, oral lesions, conjunctivitis, facial oedema, muscle or joint aches, or general malaise), including Stevens-Johnson syndrome, or toxic epidermal necrolysis.

1. Readministration to patients who have required permanent discontinuation for severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine. Patients with severe hepatic impairment (Child-Pugh C) or pre-treatment ASAT or ALAT > 5 ULN until baseline ASAT/ALAT are stabilised < 5 ULN.

4). Coadministration with herbal preparations containing St. 5).