September 23, 2008 — Cases of fatal hepatotoxicity have been reported with use of erlotinib (Tarceva, OSI Pharmaceuticals, Inc, and Genentech, Inc), the US Food and Drug Administration (FDA) warned healthcare professionals today.
Patients with hepatic impairment should be closely monitored during erlotinib therapy, and particular caution is advised for those with total bilirubin levels greater than 3 times the upper limit of normal (ULN), according to an alert issued by MedWatch, the FDA's safety information and adverse event reporting program.
Dosing should be interrupted or discontinued for severe changes in liver function, such as doubling of total bilirubin and/or tripling of transaminases in baseline levels outside the normal range.
The warning was based on findings from a postapproval pharmacokinetic study (n = 15) of patients with solid tumors and moderate hepatic impairment (Child-Pugh class B), in which 2 of 10 deaths were attributed to hepatotoxicity. One patient died from hepatorenal syndrome, and the other from rapidly progressing liver failure.
"Six out of the 10 patients who died had baseline total bilirubin > 3 × ULN suggesting severe, rather than moderate, hepatic impairment," the company said in a communication to clinicians, highlighting the limitations of using Child-Pugh criteria in oncology patients with liver involvement.
Erlotinib is indicated as monotherapy for locally advanced or metastatic non–small cell lung cancer after failure of at least 1 prior chemotherapy regimen and in combination with gemcitabine HCl (Gemzar injection, Eli Lilly & Co) for the first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer.
Adverse events related to use of erlotinib should be reported to the manufacturer by telephone at 1-877-TARCEVA (1-877-827-2382). Alternatively, case data may be relayed to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.
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