GSK Purinethol Labeling Should Mention Tests For TPMT Enzyme Activity
Executive Summary
GlaxoSmithKline's Purinethol (6-mercaptopurine) labeling should mention the availability of tests for TPMT enzyme deficiency but should not specify how and when they should be used, FDA's Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee said at its July 15 meeting
|
GlaxoSmithKline's Purinethol (6-mercaptopurine) labeling should mention the availability of tests for TPMT enzyme deficiency but should not specify how and when they should be used, FDA's Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee said at its July 15 meeting. Subcommittee members said that the label could state that genotypic and phenotypic tests are available to determine if a patient has homozygous, heterozygous or wild-type thiopurine S-methyltransferase (TPMT) deficiency/activity. "You make statements that laboratory tests are available, but there is no contingency in the label on how to interpret those tests, you leave that up to the reference labs and to the information that is available," Committee Chair Victor Santana, MD, St. Jude Children's Hospital, said. Purinethol is indicated for remission induction and maintenance therapy in patients with acute lymphatic leukemia, but is used off-label extensively for irritable bowel disease. Use of 6-MP in TMPT-deficient patients can lead to neutropenia and, in some cases, secondary malignancies. The transplant immunosuppressant azathioprine (Prometheus' Imuran and generics), also used off-label for irritable bowel, is also metabolized by TPMT, but was not part of the labeling discussions at the meeting. Specifics about the timing of tests and dose reduction in TPMT-deficient patients should not be included in 6-MP labeling since not enough is known to make such recommendations, the subcommittee said. "There should be a statement, but not specific recommendations, that these patients do require serious considerations of dose adjustments and monitoring," Santana said. "This should be a test you should consider in the context of the patient having a toxicity, particularly myelosuppression," Santana noted. The subcommittee was concerned that requiring testing prior to initiation of therapy could delay treatment. While TPMT genotype tests are available commercially, none have gone through the FDA approval process. TPMT testing information in 6-MP labeling has also been recommended by FDA's Clinical Pharmacology Subcommittee (1 (Also see "Pharmacogenetic Test Should Be Added To 6-MP Label, FDA Cmte. Says" - Pink Sheet, 4 Nov, 2002.), p. 37). |