Public Statement on Viramune (Nevirapine) - Severe and Life-Threatening Cutaneous and Hepatic Reactions
News
The European Medicines Evaluation Agency's (EMEA) scientific committee, the Committee for Proprietary Medicinal Products (CPMP), has recently been made aware of additional reports of serious cutaneous and hepatic reactions, sometimes fatal, associated with Viramune1 (nevirapine). This has led to a re-assessment the benefit risk profile of nevirapine.
This assessment confirmed that severe and life-threatening cutaneous (including cases of Stevens- Johnson syndrome and toxic epidermal necrolysis) and hepatic reactions are the major clinical toxicity of nevirapine. The first 8 weeks of therapy with nevirapine therapy are a critical period which therefore require a close monitoring of the patients to disclose the potential appearance of severe and life-threatening skin reactions or serious hepatitis/hepatic failure. Some of the severe cutaneous reactions were associated with risk factors such as not following the dose escalation regimen or delaying seeking medical attention when the symptoms appeared. Furthermore, most of the cases of hepatitis were reported to be within the first 8 weeks of treatment, some of them were associated with hypersensitivity reactions (such as fever, rash, arthralgia, myalgia, hypereosinophilia or acute renal failure).
Following a review of the above information, the EMEA wishes to draw attention to the following:
- Concerning cutaneous reactions, the initial dosing of nevirapine of 200 mg daily and for patients 2 months up to 8 years 4 mg/kg once daily during the 14-days lead-in period must be STRICTLY adhered to.
- Patients should be intensively monitored during the first 8 weeks of treatment. Nevirapine must be permanently discontinued in patients developing a serious cutaneous reaction i.e. Stevens-Johnson syndrome, a toxic epidermal necrolysis or a severe rash accompanied by hypersensitivity reactions (characterised by rash, constitutional symptoms such fever, arthralgia, myalgia and lymphadenopathy, and visceral involvement such as hepatitis, eosinophilia, granulocytopenia and renal dysfunction).
- Concerning hepatic reactions, a close liver monitoring of patients must be performed especially during the first 8 weeks of therapy (see below). Nevirapine should be stopped and never readministered in patients with ASAT or ALAT greater than 2ULN associated with hypersensitivity reactions (characterised by rash, constitutional symptoms such fever, arthralgia, myalgia and lymphadenopathy, and visceral involvement such as hepatitis, eosinophilia, granulocytopenia and renal dysfunction) or hepatitis.
As an urgent measure, the prescribing and patient information has been modified through a rapid procedure at the request of the marketing authorisation holder. The EMEA thought it necessary to provide this new information to the public. The complete revised product information is available in the European Public Assessment Report of Viramune published on the EMEA Website.