FDA approves genotype test for drug response

The Food and Drug Administration approved the first DNA microarray test that indicates whether a patient is more or less likely to experience side effects from several common heart drugs, antidepressants and chemotherapy agents.

The agency last month gave its nod to the AmpliChip Cytochrome P450 Genotyping test for use with the Affymetrix GeneChip Microarray Instrumentation system.

"Physicians can use the genetic information from this test to prevent harmful drug interactions and to assure drugs are used optimally, which in some cases will enable patients to avoid less effective or potentially harmful treatment choices," said Acting FDA Commissioner Lester M. Crawford, DVM, PhD.

Experts praised the agency's action for providing a uniform tool that may lead to more personalized prescribing. P450 testing is carried out currently, usually in a research setting, but standards vary widely.

"It's a great step forward," said Floyd Sallee, MD, PhD, vice chair of psychiatry at the University of Cincinnati. Dr. Sallee authored a case study in the spring 2000 Journal of Child and Adolescent Psychopharmacology about a 9-year-old boy who died from an overdose of fluoxetine. Postmortem testing revealed polymorphisms in his P450 gene family.

But while the FDA decision received praise, many questions persist about exactly how this new tool should be used and whether testing would be most appropriate when making a prescribing decision or just when side effects appear.

"How to integrate a new test into ongoing standard of care is always a struggle," said Dr. Sallee. "You can have the best tool in the world, but, if no one knows how to use it properly, it makes no sense."

American Medical Association policy states that genetic tests should be performed only with comprehensive pre- and post-test counseling and that physicians should refer to specialists as appropriate.

In regard to this test, the results do not indicate definitively whether a patient will benefit from one of these drugs or be harmed, and the FDA approval includes the caveat that it should not be used as a stand-alone tool. The agency has cleared the test for use in conjunction with clinical evaluation and other tools to determine the best options.

Experts expect that, at least initially, this test will primarily offer a reason why a patient is responding in one way or another. For example, in a paper published in the January issue of the Journal of Clinical Psychiatry, patients prescribed risperidone, which is often used to treat schizophrenia and related disorders, were more likely to experience adverse drug reactions and discontinue those drugs if they had a certain genotype.

"If you have somebody with repeated side effects with different medications, it's helpful to test them," said Jose de Leon, MD, lead author and associate professor of psychiatry at the University of Kentucky in Lexington. Dr. de Leon is also researching whether such testing is cost-effective. The research is funded by this test's manufacturer, the National Alliance for Research on Schizophrenia and the Eli Lilly Research Foundation.

Genetic medicine experts say, however, that this test has the most promise to be used prospectively to reduce the chance of these types of problems ever occurring.

"You can use this information directly to adjust the drug dose right from the start rather than spending a lot of time titrating or running the risk that you have somebody who is particularly sensitive to the 'normal' starting dose of a drug and developing a side effect," said Reed E. Pyeritz, MD, PhD, chief of medical genetics at the University of Pennsylvania in Philadelphia.