NEVIRAPINE ACCORD

Nevirapine prolonged-release tablets should be administered by physicians who are experienced in the treatment of HIV infection. Posology Adults The recommended dose of nevirapine for patients initiating nevirapine therapy is one 200 mg immediate-release tablet 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 one 400 mg prolonged-release tablet once daily, in combination with at least two additional antiretroviral agents.

Patients currently on a nevirapine immediate-release twice daily regimen:

Patients already on a regimen of nevirapine immediate-release twice daily in combination with other antiretroviral agents can be switched to Nevirapine prolonged-release tablets once daily in combination with other antiretroviral agents without a lead-in period of nevirapine immediate-release.

Nevirapine prolonged-release tablets should be combined with at least two additional antiretroviral agents. For concomitantly administered therapy, the manufacturers recommended dose should be followed. If a dose is recognized as missed within 12 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 12 hours later, the patient should only take the next dose at the usual time. 17 m2 or above according to the Mosteller formula. g. 50 mg and 100 mg prolonged-release tablets, should be checked for their availability.

Children less than three years old The safety and efficacy of nevirapine prolonged-release tablets in children aged less than 3 years has not been established. No data are available. For patients less than 3 years and for all other age, weight and BSA groups, an immediate-release oral suspension dosage form should be checked for availability (please refer to the respective Summary of Product Characteristics).

Dose management considerations The total daily dose at any time during treatment should not exceed 400 mg for any patient. Patients should be advised of the need to take Nevirapine prolonged-release tablets every day as prescribed. Patients experiencing rash during the 14-day lead-in period of 200 mg/day should not initiate treatment with Nevirapine prolonged-release tablets until the rash has resolved.

1486 (VERxVE) were rash, nausea, liver function test abnormal, headache, fatigue, hepatitis, abdominal pain, diarrhoea and pyrexia. There are no new adverse drug reactions for nevirapine prolonged-release tablets that have not been previously identified for nevirapine immediate-release tablets and oral suspensions The nevirapine 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 nevirapine prolonged-release tablets have been reported. 1486 with 1,068 patients exposed to nevirapine on a backbone of tenofovir/emtricitabine.

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) Table 1: Lead-in phase with nevirapine immediate-release Blood and lymphatic system disorders Uncommon granulocytopenia Rare anaemia Immune system disorders Uncommon hypersensitivity (incl.

anaphylactic reaction, angioedema, urticaria), drug reaction with eosinophilia and systemic symptoms, anaphylactic reaction Nervous system disorders Common headache Gastrointestinal disorders Common abdominal pain, nausea, diarrhoea Uncommon vomiting Hepatobiliary disorders Uncommon jaundice, hepatitis fulminant (which may be fatal) Rare hepatitis (incl.

2 %), angioedema, urticaria Musculoskeletal and connective tissue disorders Uncommon arthralgia, myalgia General disorders and administration site conditions Common fatigue, pyrexia Investigations Uncommon liver function test abnormal (alanine aminotransferase increased; Transaminases increased; aspartate aminotransferase increased; gamma-glutamyltransferase increased; hepatic enzyme increased; hypertransaminasaemia), blood phosphorus decreased, blood pressure increased Table 2: Maintenance phase of nevirapine prolonged-release Blood and lymphatic system disorders Uncommon anaemia, granulocytopenia Immune system disorders Uncommon hypersensitivity (incl.

1). Nevirapine prolonged-release tablets 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. 4) Coadministration with herbal preparations containing St. 5).