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The FDA has cleared for marketing the first laboratory test system that will allow physicians to consider unique genetic information in selecting medications and doses of medications for a variety of common conditions, including heart disease, psychiatric disease, and cancer.
"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," says Acting FDA Commissioner Dr. Lester M. Crawford.
Manufactured by Roche Molecular Systems Inc. of Pleasanton, Calif., the AmpliChip Cytochrome P450 Genotyping Test is the first DNA microarray test to be cleared by the FDA. A microarray is similar to a computer microchip, but instead of tiny circuits, the chip contains millions of tiny DNA molecules. The test is performed using DNA that is extracted from a patient's blood.
The new test analyzes one of the genes from a family of genes called cytochrome P450. The enzymes produced from these genes are active in the liver to break down certain drugs and other compounds. Variations in this family of genes can cause a patient to metabolize certain drugs more quickly or more slowly than average, or, in some cases, not at all. The specific gene that is analyzed by this test plays an important role in the body's ability to metabolize some commonly prescribed drugs, including antidepressants, antipsychotics, beta blockers, and some chemotherapy drugs.
Cleared for use with the Affymetrix GeneChip Microarray Instrumentation System manufactured by Affymetrix Inc. of Santa Clara, Calif., the test is not intended to be used by itself to determine the optimum drug dosage. The test should be used along with clinical evaluation and other tools to determine the best treatment options for patients.
Labels for Strattera (atomoxetine) will now carry a bolded warning about the potential for severe liver injury. Strattera is a drug approved by the FDA for attention-deficit hyperactivity disorder (ADHD) in adults and children. The labeling update follows the reports of severe liver injury in one teen-ager and one adult, both of whom recovered, who had been treated with Strattera for several months.
The labeling warns that severe liver injury may progress to liver failure resulting in death or the need for a liver transplant in a small percentage of people who take Strattera.
The warning also indicates that the medication should be discontinued in people who develop a yellowing of the skin or whites of the eyes (jaundice) or laboratory evidence of liver injury.
Strattera has been on the market since 2002 and has been used in more than 2 million people. In clinical trials involving 6,000 patients, no signal of liver problems (hepatotoxicity) had emerged.
The FDA has asked the manufacturer, Eli Lilly and Company of Indianapolis, to add the bolded warning about severe liver injury to the labeling. Eli Lilly has agreed to alert health care professionals about the new information in a "Dear Health Care Professional" letter. The company will also update the patient package insert with information about the signs and symptoms of liver problems, which include itchy skin, jaundice, dark urine, upper right-sided abdominal tenderness, and unexplained "flu-like" symptoms.
Painful sores and ulcers in the lining of the mouth are a common complication of the high-dose chemotherapy and radiation therapy regimens associated with bone marrow transplants. Patients suffering from the complication, called mucositis, have difficulty eating and swallowing. In the most severe form of mucositis, patients cannot eat or drink at all and must receive nutrition and fluid replacement through their veins.
The FDA has approved a treatment called Kepivance (palifermin) to help prevent mucositis. The drug also shortens the duration of the condition.
Kepivance is a synthetic version of a naturally occurring human protein called keratinocyte growth factor (KGF) that stimulates the growth of cells in the skin and on the surface layer of the mouth, stomach, and colon. Kepivance, like the natural KGF, also stimulates cells on the surface layer of the mouth to grow. This is thought to lead to faster replacement of these cells when killed by the cancer treatments and is believed to speed up the healing process of mouth ulcers.
Kepivance, which has been shown to be safe and effective only in those being treated for leukemia and lymphoma, is manufactured by Amgen Inc. of Thousand Oaks, Calif.
The FDA has issued a warning to people who may have used imported ginseng from FCC Products Inc., based in Livingston, N.J. The ginseng products are considered adulterated under the Federal Food, Drug, and Cosmetic Act because they contain unsafe chemical residues from the pesticides procymidone and quintozene.
These residues are deemed unsafe because there has been no maximum amount of residues allowed (tolerance) established for them in ginseng. The FDA is responsible for enforcing pesticide tolerances and food additive regulations. A raw agricultural commodity or processed food or feed is deemed to be unsafe and adulterated if a pesticide chemical residue for which no tolerance has been set is present.
At the FDA's request, the U.S. District Court for the District of New Jersey issued a warrant for the seizure of these products. The U.S. Marshals Service, accompanied by an FDA investigator, seized the ginseng in December 2004.
The physicians' labeling of Depo-Provera Contraceptive Injection will now carry a "black box" warning to highlight that prolonged use of the drug may result in loss of bone density. The FDA has approved the injectable drug for use in women to prevent pregnancy.
Depo-Provera Contraceptive Injection has been used for decades for birth control throughout the world and it remains a safe and effective contraceptive. The FDA and New York City-based Pfizer Inc., the drug's manufacturer, are issuing the warning to ensure that patients and physicians have access to the important information.
The loss of bone density is greater the longer the drug is taken, and this loss may not be completely reversible after discontinuing the drug. The warning states that a woman should only use Depo-Provera Contraceptive Injection as a long-term birth control method, for example, longer than two years, if other birth control methods are inadequate.
Black box warnings are designed to highlight special or serious problems about an FDA-regulated product. The warnings help physicians to prescribe a drug that may be associated with serious side effects in a way that maximizes its benefits and minimizes its risks.
The warning is based on analyses by Pfizer and the FDA of data that clarified the drug's long-term effects on bone density.
The company will incorporate the new information in the patient information sheet distributed with the drug.
In December 2004, the FDA learned from AstraZeneca Pharmaceuticals that a large clinical trial comparing Iressa (gefitinib) with an inactive substance (placebo) showed no survival benefit from taking Iressa. The study involved people with non-small cell lung cancer who had failed other courses of cancer therapy.
People who take Iressa should consult their physicians as soon as possible, but they should not change their therapy without first talking to a health care professional.
Alternative therapies are available. The FDA has approved Taxotere (docetaxel) and Tarceva (erlotinib), both of which have been shown in studies to improve survival in people with non-small cell lung cancer whose cancer has progressed while on previous therapies.
The FDA approved Iressa on May 2, 2003, under the agency's accelerated approval program. This program allows the agency to approve a drug for marketing based on how it affects a surrogate endpoint--such as a sign of a disease or the results of a laboratory test--that is considered reasonably likely to predict clinical benefit, such as improved symptoms or survival.
Iressa was approved because the data from clinical trials showed that it caused significant shrinkage in tumors in about 10 percent of patients, and this was thought likely to increase patients' overall survival time.
One requirement for drugs approved under accelerated approval is that the sponsor must study them further to verify the expected clinical benefit. After the approval of Iressa, AstraZeneca, based in Wilmington, Del., conducted a study in about 1,700 patients to determine whether the drug would in fact prolong survival in comparison to patients taking a placebo. The results indicate that the drug did not prolong survival.
Under the FDA's accelerated approval program, the agency has the authority to remove a drug from the market if a postmarketing clinical study fails to verify clinical benefit. After the FDA has evaluated the recent study results, the agency will determine whether Iressa should be withdrawn from the market or if other regulatory actions are appropriate.
A new therapy to slow vision loss in people with wet age-related macular degeneration (AMD), an eye disease that destroys central vision, has been approved by the FDA.
Macugen (pegaptanib sodium injection) is the first in a new class of ophthalmic drugs to specifically target vascular endothelial growth factor (VEGF), a protein that acts as a signal in triggering the abnormal blood vessel growth and leakage that is the hallmark of wet AMD.
AMD is the leading cause of irreversible blindness in patients older than 50 in developed countries. According to a study in the April 2004 issue of Archives of Ophthalmology, AMD is the leading cause of blindness for white Americans, with 1.8 million cases reported in 2002.
The disease occurs in two forms: wet and dry. Wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula--located in the center of the retina. These new blood vessels tend to be fragile and often leak blood and fluid. The blood and fluid raise the macula from its normal place at the back of the eye, causing rapid damage to occur. An early symptom of wet AMD is straight lines that appear wavy.
Dry AMD occurs when the light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye. The most common symptom of this type is slightly blurred vision. Wet AMD, which makes up about 10 percent of AMD cases, is considered to be more severe than the dry form.
Approved for marketing in December 2004, Macugen is a single strand of nucleic acid that specifically binds to a particular protein that plays a critical role in the formation of new blood vessels and increased leakage from blood vessels--two of the primary pathological processes responsible for the vision loss associated with wet AMD.
Macugen therapy was co-developed by Eyetech Pharmaceuticals Inc. and Pfizer Inc., both of New York City.
The FDA is warning people not to buy or use Carbolith (lithium carbonate) 150-milligram capsules for treating bipolar disorder, also called manic-depressive illness, a serious psychiatric condition. Valeant Canada Ltd. of Montreal recalled the capsules after testing indicated that the product may not deliver adequate amounts of the drug to ensure effective treatment.
Health Canada recently advised people taking Carbolith 150 to continue taking their medicine and to consult with their health care professionals as soon as possible. Americans who have purchased the drug through the Internet and taken it for bipolar disorder could experience adverse events associated with lowered blood lithium levels, including a worsening of the illness.
In addition, people who may have taken the Carbolith product for several weeks or longer may experience toxic effects, such as confusion, muscle twitching, vomiting, and diarrhea, when they switch to a lithium carbonate product that delivers adequate amounts of the drug.
See the public advisory issued by Health Canada about this recall.
The FDA issued a public health advisory in December 2004 concerning use of non-steroidal anti-inflammatory drugs (NSAIDs), including those known as COX-2 selective agents. The public health advisory is an interim measure, pending further review of data that continue to be collected.
Recently released data from controlled clinical studies showed that the COX-2 selective agents Vioxx (rofecoxib), Celebrex (celecoxib), and Bextra (valdecoxib) may be associated with an increased risk of serious cardiovascular events, such as heart attack and stroke, especially when used for long periods or in very high-risk settings, such as immediately after heart surgery.
In addition, preliminary results from a long-term clinical trial--up to three years--suggest that long-term use of the non-selective NSAID Aleve (naproxen) may be associated with an increased cardiovascular risk compared to an inactive substance (placebo).
Specifically, the public health advisory recommends that
The FDA will continue to analyze all available information from new studies of Vioxx, Celebrex, Bextra, and naproxen and other data for non-selective NSAIDs and COX-2 selective products to determine whether additional regulatory action is needed.
The FDA has issued a final record-keeping rule to protect the U.S. human food and animal feed supply in the event of serious health threats. Under the authority of the Bioterrorism Act of 2002, the regulation requires people who manufacture, process, pack, transport, distribute, receive, hold, or import food to establish and maintain records.
The records identify the immediate previous source of all food received, as well as the immediate subsequent recipient of all food released. Records must be retained at the establishment where the activities covered in the records occurred or at an accessible location. Food companies may keep the information in any format, paper or electronic. All businesses covered by the rule must comply within 12 months from Dec. 9, 2004, the date the rule was published in the Federal Register, except small businesses, which have 18 months to comply, and very small businesses, which have 24 months.
When the FDA has a reasonable belief that an article of food is adulterated and presents a serious threat to humans or animals, any records or other information to which the FDA has access must be available for inspection and copying as soon as possible, and no later than 24 hours from the time an official request is made.
The Bioterrorism Act allows the FDA to bring civil action in federal court to enjoin the people who fail to comply with this rule. The FDA can also seek criminal actions in federal court to prosecute those who fail to establish and maintain records as required by the rule.