Fatal progressive multifocal leukoencephalopathy (PML) in a patient taking rituximab (Rituxan) for rheumatoid arthritis prompted the drug's manufacturers to revise the Warnings section of the product labeling. Rituximab is approved for use in non-Hodgkin's lymphoma and rheumatoid arthritis, and its labeling already bears a warning that it can induce PML in patients with hematologic malignancies and autoimmune diseases the drug is not approved for. Patients taking rituximab who have new neurologic symptoms (clumsiness; progressive weakness; or changes in vision, speech, or personality) should be given a neurologic workup for PML. Upon confirmation of the diagnosis, rituximab should be discontinued (any concomitant immunosuppressive therapy should also be reduced or discontinued).

Erlotinib (Tarceva) is used to treat locally advanced or metastatic non-small cell lung cancer and, in combination with gemcitabine, locally advanced, unresectable, or metastatic pancreatic cancer. A pharmacokinetic study involving 15 patients with moderate hepatic impairment according to the Child-Pugh criteria who were taking erlotinib indicates that there is a risk of serious hepatotoxicity associated with its use. One patient in the study died of hepatorenal syndrome, one died of rapidly progressing liver failure, and eight died of progressive disease. Six of the 10 patients who died had baseline total bilirubin levels of more than three times the upper limit of normal, suggesting that they had severe hepatic impairment, rather than the moderate impairment indicated by the Child-Pugh scores. Erlotinib's product labeling has been revised to place greater emphasis on the risk of hepatotoxicity. Nurses should closely monitor total bilirubin and liver enzyme (transaminase) levels in patients taking erlotinib. Findings of a total bilirubin level of more than three times the upper limit of normal, transaminase levels of more than five times the upper limit of normal, or both in patients with normal levels prior to treatment warrant either suspension or discontinuation of drug therapy, as do the doubling of total bilirubin, the tripling of transaminases, or both in patients with levels outside the normal range prior to treatment.

OSI Pharmaceuticals Inc. and Genentech Inc. Dear healthcare professional [letter]: Tarceva (erlotinib). September 2008. http://www.fda.gov/medwatch/safety/2008/tarceva_dhcp_etter.pdf; Genentech Inc. and Biogen Idec. Dear healthcare professional [letter]: Rituxan (rituximab). September 2008. http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf.