U.S. Food and Drug Administration
FDA Consumer magazine
July-August 2002
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The FDA has approved the use of Vioxx (rofecoxib) for rheumatoid arthritis. Vioxx previously had been approved for osteoarthritis and pain.
The agency also approved new label text and precautions that are based on the results of a one-year study. The study demonstrated that Vioxx was associated with a lower incidence of serious upper gastrointestinal (GI) adverse events, including major bleeding, perforation, and obstruction. However, the study also found that Vioxx was associated with a higher rate of heart attacks and other adverse cardiovascular events, compared with other medications approved for the same uses.
The FDA has cleared the first dialysis system that is specifically designed for home use by people with chronic or acute kidney disease. The Personal Hemodialysis (PHD) System, made by Aksys Ltd., Lincolnshire, Ill., automates the dialysis process, allowing people with kidney failure to perform daily dialysis at home or in a clinic. In either setting, the system requires a prescription from a physician and training for the user.
Hemodialysis works by circulating blood through special filters to remove waste from the body, much like a fully functioning kidney does. The PHD System includes equipment that purifies water, prepares a chemical solution to help remove toxins, pumps blood, and delivers the dialysis solution. A computer-like touch screen prompts the operator through each step of the procedure. Between treatments, the system automatically cleans and disinfects the fluid pathways.
The PHD System is designed to be used five or six days per week, in shorter dialysis sessions than the conventional dialysis regimen of three days per week. In clinical tests, the PHD System was found to be similar to conventional hemodialysis equipment in effectiveness, accuracy, and safety.
The FDA has approved the marketing of Lotronex (alosetron hydrochloride) with restrictions, nearly two years after its manufacturer removed it from the market. Lotronex is the only medication proven effective in treating the symptoms of irritable bowel syndrome (IBS).
GlaxoSmithKline (GSK) of Research Triangle Park, N.C., voluntarily withdrew Lotronex in November 2000 after the FDA received reports of serious and life-threatening intestinal complications, including severe constipation and ischemic colitis. These conditions resulted in hospitalization, blood transfusions, surgery, and even death.
Lotronex slows the movement of stools through the bowels. It does not cure IBS and it will not help every person who takes it. For those with IBS who are helped, Lotronex reduces lower abdominal pain and discomfort, urgency to have a bowel movement, and diarrhea.
The FDA recognizes the need to carefully balance making effective therapies available with protecting the public from drug-related adverse events. As a result, the agency worked together with GSK to develop a Risk Management Plan (RMP) that allows market reintroduction of Lotronex, but only with limited access to women suffering with severe diarrhea-predominant IBS that is disabling.
This restricted marketing program ensures not only that patients and physicians are fully informed of the risks and benefits of Lotronex prior to using it, but also that only appropriate patients are prescribed the drug. The program enrolls only qualified physicians who agree to accept certain responsibilities.
The RMP brings together active participation by the doctor, the patient and the pharmacist. It includes the following components:
GSK will establish a prescribing program for Lotronex to enroll physicians who plan to prescribe the drug.
GSK will enroll physicians who agree to educate patients on the risks and benefits of Lotronex treatment, and to provide patients a copy of the FDA-approved Medication Guide.
Patients will be asked to read and sign a Patient-Physician Agreement before receiving their initial prescription for Lotronex.
Pharmacists will be asked to fill only prescriptions that display a prescribing program sticker affixed by an enrolled physician, and to give patients a copy of the FDA-approved Medication Guide every time they dispense the drug.
Enrolled physicians will have agreed to report serious adverse events to GSK or to the FDA.
GSK will conduct an ongoing assessment of the RMP, including a study of the prescribing and actual use of Lotronex.
The June 7 action follows an April 23, 2002, recommendation by the FDA's Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee.
IBS is a disorder of the intestine that shows no sign of disease that can be seen or measured, but doctors know that the intestine isn't functioning normally. Abdominal pain, cramps, gas, bloating, diarrhea and constipation are among the symptoms.
Additional information on Lotronex, including the revised professional and patient labels and physician and patient agreement documents, can be found on the FDA's Web site.
The FDA has issued a health alert warning that people who receive blood products, particularly plasma-containing products, may be at risk for developing transfusion-related acute lung injury (TRALI). This serious pulmonary syndrome may lead to death if not recognized and treated appropriately.
TRALI can occur when white blood cell antibodies in the donor's blood react with the recipient's white blood cells, causing a change in the lung tissue that allows fluid to enter. Most donors implicated in TRALI reactions are women with more than two children or donors who have had multiple transfusions. If not treated immediately and appropriately, TRALI may cause respiratory or breathing problems that can lead to death.
The FDA's Center for Biologics Evaluation and Research (CBER) has received reports of more than 45 TRALI-related deaths since the early 1990s. The condition is a leading cause of transfusion-related death.
Symptoms of TRALI include fever, shortness of breath, and a drop in blood pressure. X-rays often show the recipient's lungs as completely white. Symptoms typically begin one to two hours after a transfusion, but may be delayed up to six hours. Health-care professionals should be alert that any respiratory distress or breathing problems during or following a blood transfusion could be caused by TRALI.
Deaths from TRALI must be reported to CBER according to FDA regulations.
The FDA encourages voluntary reporting of non-fatal TRALI reactions. Reports can be filed via the FDA's MedWatch reporting program, by phone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; by e-mail; or by mail at MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852.
Biogenics Inc. of St. George, Utah, has signed a consent decree that prohibits the firm from manufacturing and distributing its ephedrine-containing AMP II Pro Drops, any other product containing ephedrine hydrochloride, any synthetic ephedrine alkaloid, or any new drug not approved by the FDA. The consent decree was signed on April 12, 2002.
The decree also gives the FDA authority to order the firm, doing business as E'OLA International, to recall and discontinue the marketing of any products that violate the law in the future.
On October 30, 2001, at the request of the FDA, U.S. Marshals seized $2.8 million worth of E'OLA's AMP II Pro Drops. Previous FDA inspections found that the products contain a drug, ephedrine hydrochloride, but are labeled as a dietary supplement for use in weight loss. These E'OLA products violate the law because drug ingredients are prohibited for use in dietary supplements.
Ephedrine hydrochloride has been approved as a drug by the FDA since 1948, and therefore cannot be legally marketed as a dietary supplement. E'OLA also marketed its products as a treatment for obesity. Products marketed to treat diseases are drugs. In addition, the labeling failed to bear adequate directions for its intended use.
Three pharmacies that sold nicotine lollipops and lip balm over the Internet have agreed to quit making and marketing the products after being warned by the FDA that they are illegal. Based on statements from the pharmacies' Internet sites, the products were promoted as aids to stop smoking or to treat nicotine addiction.
The FDA is concerned about the health risk of these products because they appear to be custom-made (compounded) and dispensed without a doctor's prescription, and they contain a form of nicotine that is not used in FDA-approved smoking cessation products. In addition, their candy-like characteristics present a risk of accidental use by children.
In April, the FDA issued warning letters to the pharmacies, informing them that their nicotine lollipops and lip balm were illegal. The letters also stated that continued marketing of these drug products may result in further regulatory action, potentially including a seizure or injunction.
The products cited in the letters included compounds using nicotine salicylate, natural sweeteners, and flavorings in a sugar-free base and were available in four different dosages. The claims on the Web sites included that the products helped alleviate the "hand-to-mouth fixation" associated with smoking and were a "convenient, tasty way" to replace the cigarette habit. After investigating and carefully assessing these Web sites, the FDA determined that the pharmacies' nicotine lollipops and nicotine lip balm were intended for use as "drugs" and appeared to be illegal for the following reasons:
They are compounded and dispensed without a doctor's prescription.
They are unapproved new drugs, which need, but do not have, FDA approval.
They are made from a drug substance, nicotine salicylate, which is not permitted for use by pharmacists in compounding drugs. The FDA-approved smoking cessation products are made from different forms of nicotine.
They are misbranded because their labeling does not have adequate directions for the uses for which they are being offered and does not have adequate warnings against use by children.
Within the 15 days required for a response, all three pharmacies notified the FDA in writing that they had stopped making or distributing the products in question. The FDA continues to monitor Web sites for products that may endanger public health.
In April 2002, the FDA approved Faslodex (fulvestrant) for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women whose disease progresses following anti-estrogen therapy.
In this type of breast cancer, estrogen can stimulate the growth of tumors by entering cells at multiple sites called estrogen receptors. Faslodex inhibits this action of estrogen and appears to reduce the number of estrogen receptors in breast cancer cells.
Faslodex was found to be as effective as the drug anastrozole in two randomized, controlled clinical trials in postmenopausal women with locally advanced or metastatic breast cancer that progressed following treatment with tamoxifen. Anastrozole is another drug used to decrease estrogen production and suppress the growth of tumors that need estrogen to grow. Faslodex is administered as a monthly injection into the buttocks.
The most commonly reported side effects were nausea, headache, back pain, vomiting, constipation, diarrhea, abdominal pain, hot flushes, and pharyngitis (inflammation of the throat), regardless of whether patients were treated with Faslodex injections or anastrozole tablets. Pain at the site of the injection was reported in about 10 percent of patients treated with Faslodex.
Faslodex is indicated for postmenopausal women and should not be given to pregnant women because of the risk of harm to a fetus.
Faslodex is distributed in the United States by AstraZeneca Pharmaceuticals LP, Wilmington, Del.
A new type of implantable cardioverter defibrillator (ICD) that also has the ability to deliver cardiac resynchronization therapy (CRT) was recently approved by the FDA. The device, called Contak CD CRT-D, can be used to treat symptoms of advanced heart failure in certain people who already need an ICD.
The Contak system is intended to treat people who already need an implantable defibrillator, whose heart timing is off and who, despite taking heart failure medication, have symptoms of advanced heart failure, such as fatigue, shortness of breath, and difficulty performing daily activities.
The defibrillator component of the product detects and treats life-threatening heart rhythms. The CRT component coordinates the beating of the left and right ventricles of the heart so that they work together more effectively to pump blood throughout the body.
The FDA based its approval on the results of two multicenter clinical studies conducted in the United States by the device's manufacturer, Guidant Corp. of Indianapolis. In the first study, 581 people received the Contak system; in the second study, 127 people received it. In half the people, only the defibrillator component was turned on; in the other half, both the defibrillator and the CRT components were turned on. Both groups were studied for six months.
The studies showed that the Contak system is safe and that it effectively coordinates the beating of the heart's ventricles, resulting in an improvement in some of the symptoms of heart failure. People in whom both components were turned on had a better quality of life and improved exercise capacity than those in whom just the defibrillator was turned on. The studies did not show whether or not the device ultimately affected patient survival.
The FDA is requiring Guidant to conduct a postmarketing study of 1,000 people over three years to determine the product's safety and effectiveness.
The FDA has approved SecreFlo (secretin) for injection to help confirm the diagnosis of pancreatic dysfunction and the presence of a pancreatic tumor (gastrinoma) that may be cancerous. SecreFlo is a synthetic formulation of the naturally occurring porcine hormone secretin.
Patients with pancreatic dysfunction are unable to digest food properly. Thick mucus obstructs the pancreas and prevents essential enzymes from breaking down food. Left untreated, this condition can cause patients to become severely malnourished and dehydrated.
SecreFlo helps confirm the diagnosis of pancreatic dysfunction by stimulating the pancreas to secrete pancreatic juice and bicarbonate, which is used to measure the functioning of the pancreas. SecreFlo helps confirm the presence of a pancreatic tumor by stimulating the stomach to release a hormone called gastrin, which is further tested to confirm the diagnosis.
ChiRhoClin, Inc. of Silver Spring, Md., is the sponsor of SecreFlo. The product is manufactured by Chesapeake Biological Laboratories of Baltimore for RepliGen Corporation of Needham, Mass.
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