Boehringer Ingelheim, producers of the UK's top-selling antiretroviral nevirapine, have issued new guidance to doctors on managing the risk of serious side-effects. This follows the publication by the European Agency for the Evaluation of Medicinal Products (EMEA) of a statement on serious skin and liver reactions associated with nevirapine two weeks previously.
The new management guidelines place particular emphasis on the first eight weeks of treatment, a time when close patient monitoring is required. A number of cases of severe rash have occurred where there has been a failure to follow the prescribed 14 day lead-in dose escalation. In this period, nevirapine should be dosed at 200mg/day, followed by a switch to 400mg/day thereafter.
In addition, Boehringer now recommend two weekly liver function tests during the first two months of nevirapine therapy, at the third month of treatment, and then on a three to six monthly basis. However, any occurrence of symptoms of hepatitis, or of a hypersensitivity reaction, should also prompt an assessment of liver function. Examples of the clinical symptoms of a nevirapine hypersensitivity reaction include rash, fever, arthralgia, myalgia, lymphadenopathy, hepatitis, eosinophilia, granulocytopenia, and renal dysfunction.
Where liver function tests show ASAT or ALAT to be greater than five times the upper limit of normal, regardless of clinical symptoms, nevirapine should be stopped immediately. When liver function normalises, the drug may be re-introduced using the standard 14 day lead-in dose escalation. If any significant liver function abnormalities recur, nevirapine should be permanently discontinued.
Where liver transaminases are greater than twice the upper limit of normal, and where the patient does not have symptoms suggestive of hepatitis or a hypersensitivity reaction, the drug may be continued provided the patient is closely monitored. If symptoms are present, however, nevirapine should be stopped and not re-administered.
Patients who are taking nevirapine are advised to report any symptoms which may be the result of liver damage to their doctor immediately. These include loss of appetite, nausea, vomiting and jaundice.
The EMEA's public statement on nevirapine is available at the EMEA's website in pdf form.