VIRAMUNE

What it is

VIRAMUNE is available as extended-release VIRAMUNE XR tablets or as a suspension for oral administration. Each VIRAMUNE XR extended-release tablet contains 400 mg of nevirapine. Each 5 mL of the VIRAMUNE oral suspension contains 50 mg of nevirapine (as nevirapine hemihydrate).

Approved indications

— VIRAMUNE oral suspension in combination with antiretroviral agents is indicated for the treatment of HIV-1 infection in adults and children over the age of 2 months. — VIRAMUNE XR extended-release tablets in combination with antiretroviral agents is indicated for the treatment of HIV-1 infection in adults and children over the age of three years.

Dosing overview

VIRAMUNE should always be administered in combination with at least two additional antiretroviral agents. For oral suspension in adults aged 16 years and older: the recommended dose is VIRAMUNE 200 mg 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 200 mg twice daily, in combination with at least two additional antiretroviral agents. For extended-release tablets in adults aged 16 years and older: patients should initiate therapy with one 200 mg tablet of nevirapine immediate-release 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 one 400 mg tablet of VIRAMUNE XR extended-release once daily. Patients already on a regimen of nevirapine immediate-release 200 mg twice daily in combination with other antiretroviral agents can be switched to VIRAMUNE XR extended-release 400 mg once daily in combination with other antiretroviral agents without a lead-in period of nevirapine immediate-release. For paediatric patients aged 2 months to 15 years using oral suspension: the total daily dose should not exceed 400 mg of VIRAMUNE. Dosing may be calculated by body surface area (150 mg/m² once daily for two weeks followed by 150 mg/m² twice daily) or by weight (4 mg/kg once daily for 2 weeks followed by 7 mg/kg twice daily for patients up to 8 years of age, or 4 mg/kg twice daily thereafter).

Key safety warnings

The first 18 weeks of therapy with VIRAMUNE 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 and toxic epidermal necrolysis) and serious hepatitis/hepatic failure. The greatest risk of hepatic events and skin reactions occurs in the first 6 weeks of therapy. Severe and life-threatening skin reactions, including fatal cases, have occurred in patients treated with VIRAMUNE mainly during the first 6 weeks of therapy. These have included cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and hypersensitivity reactions characterised by rash, constitutional findings and visceral involvement. VIRAMUNE 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/swelling, muscle or joint aches, or general malaise), including SJS, or TEN. Severe or life-threatening hepatotoxicity, including fatal fulminant hepatitis, has occurred in patients treated with VIRAMUNE. The risk of hepatic events is greatest in the first 6 weeks of therapy. However, the risk continues past this period and monitoring should continue at frequent intervals throughout treatment. VIRAMUNE should not be initiated in adult females with CD4+ cell counts greater than 250 cell/mm³ or in adult males with CD4+ cell counts greater than 400 cells/mm³ who have a detectable plasmatic HIV-1 RNA unless the benefit outweighs the risk.

Contraindications

VIRAMUNE is contraindicated in patients with clinically significant hypersensitivity to the active ingredient or any of the excipients in the tablet or oral suspension. VIRAMUNE should not be administered to patients with severe hepatic dysfunction (Child-Pugh C) or pretreatment AST or ALT >5x Upper Limit of Normality (ULN) until baseline AST/ALT are stabilised (<5x ULN). VIRAMUNE should not be readministered to patients who have required permanent discontinuation for severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine; or patients who previously had AST or ALT > 5 x ULN during nevirapine therapy and had recurrence of liver function abnormalities upon readministration of nevirapine. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take the extended-release tablets. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take the oral suspension. Herbal preparations containing St John's Wort (Hypericum perforatum) must not be used while taking VIRAMUNE due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine.

PBS listing

The oral suspension 50 mg (as hemihydrate) per 5 mL in 240 mL is listed on the PBS with one item, under streamlined restriction, at an ex-manufacturer price of A$135.00.

Regulatory history

VIRAMUNE oral suspension was first listed on the ARTG on 2 August 2000. VIRAMUNE XR extended-release tablets were first listed on the ARTG on 4 January 2012. An AusPAR was issued on 19 December 2011, in which the TGA approved VIRAMUNE XR (nevirapine) extended-release tablets for the treatment of HIV-1 infection in adults and children over three years of age.