The recommendations, developed jointly by FDA, the national Centers for Disease Control and Prevention, and the National Institutes of Health and published in the Nov. 14 Morbidity and Mortality Weekly Report, followed the drugs' removal from the market in September. The drugs' manufacturer and marketer, Wyeth-Ayerst Laboratories and Interneuron Pharmaceuticals, withdrew the products at FDA's request after heart tests in five surveys indicated that about 30 percent of patients who took the drugs had heart valve abnormalities, even though most had no symptoms.
The Department of Health and Human Services advises people who have ever taken one or both of these drugs to see their doctors for a medical history and physical examination to check for a heart murmur, shortness of breath, or other signs of heart or lung disease. Patients who show such signs should undergo an echocardiogram, a test that uses sound waves to examine the inside of the heart.
Even if a patient has no symptoms of heart or lung disease, HHS advises an echocardiogram for all former fenfluramine and dexfenfluramine users before they undergo an invasive procedure for which the American Heart Association recommends antibiotic treatment for preventing bacterial endocarditis--a serious and potentially fatal infection of the heart's lining.
The radiation, from radioactive or machine sources, will help control disease-causing bacteria, such as Escherichia coli O157:H7 and Salmonella, in fresh or frozen beef, lamb and pork. The process does not make food radioactive or noticeably change taste, texture or appearance.
After reviewing a substantial number of studies that looked at the chemical, nutritional, toxic, and bacterial effects of irradiation on various meat products, the agency concluded that irradiation is safe in reducing disease-causing microbes in or on meat and that it does not compromise meat's nutritional value.
FDA has already approved irradiation for these products: poultry to control pathogens; pork to control the trichina parasite; fruits, vegetables and grains to control insects; and spices, seasonings and dry enzymes to control microorganisms.
FDA considers irradiation a complement to, not a replacement for, proper food-handling practices by meat producers and processors and consumers.
The adverse events involved patients treated with Lovenox (enoxaparin sodium) Injection. The agency said that similar reactions could be expected with other drugs of this type, known as low molecular weight heparins, as well as heparinoids. The other drugs are Fragmin (dalteparin sodium injection), Normiflo (ardeparin sodium) Injection, and Orgaran (danaparoid sodium) Injection.
The problems with these drugs may occur when they are used at the same time as spinal or epidural anesthesia, or spinal puncture. The combinations may cause bleeding or hematomas (collection of blood) in the spinal column that could result in permanent paralysis if not treated immediately.
FDA has asked the manufacturers of these drugs to add a boxed warning to the labeling discussing the risks.
Health-care professionals should report adverse events to the drug manufacturer or to FDA's MedWatch program by calling 1-800-FDA-1088 or faxing 1-800-FDA-0178.
Key provisions of the law include:
Managed-care health insurance programs hire PBMs to determine what medicines the plan will pay for. The proposal, published in the Jan. 5 Federal Register, applies to PBMs owned or influenced by manufacturers or distributors of medical products.
While PBMs can be useful tools for managing health-care costs, the agency says, practices such as "switching" medications based on financial incentives could have serious health implications for patients.
The deadline for comments on this proposal is April 6. Submit written comments to: Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Drive, Room 1-23, Rockville, MD 20857.
The warnings added to Posicor's labeling include advice to doctors not to prescribe the drug to patients at high risk of developing dangerously low heart rates. This includes those whose heart rates are already relatively low and those taking another drug that slows heart rate.
In addition, doctors are warned against giving the drug to patients who are also taking some statin drugs to reduce cholesterol. Doctors should not prescribe Posicor to patients on lovastatin or simvastatin because of the increased risk of muscle injury that can cause potentially life-threatening kidney and heart damage. Also, pending further information, doctors are strongly discouraged from prescribing Posicor to those on atorvastatin or cerivastatin. Fluvastatin and pravastatin, however, are metabolized differently from the other statins and, therefore, combining these drugs with Posicor is not expected to increase the risk of muscle injury.
The labeling also warns against the simultaneous use of Posicor, any statin drug, and either of the immunosuppressants tacrolimus or cyclosporine.
Health-care providers should report any adverse events to the manufacturer, Roche Laboratories, at 1-800-526-6367, or to FDA at 1-800-332-1088, by fax at 1-800-332-0178, or by mailing in a MedWatch form available on the agency's Website at http://www.fda.gov/medwatch/report/hcp.htm.
Laser pointers are generally safe when used as intended by teachers and lecturers to highlight areas on a chart or screen. However, price reductions have led to wider marketing, and FDA is concerned about promotion and use of the products as children's toys.
Light energy from a laser pointer aimed into the eye can be more damaging than staring directly into the sun. Federal law requires a warning on the product label about this potential hazard from lasers. Momentary exposure, as from an inadvertent sweep of the light across a person's eyes, causes only temporary flash blindness. But even this can be dangerous to someone who is driving or performing some other activity for which vision is critical.
In one study, researchers from FDA's Center for Biologics Evaluation and Research and the University of Sydney have discovered a key mechanism by which proteins called chemokines direct the traffic of immune cells in response to attacks on the body from disease or infections. Published in the Dec. 1, 1997, issue of the Journal of Experimental Medicine, this discovery may have potential implications for the treatment of AIDS, cancer, heart disease, and other serious medical conditions.
Researchers with the same center, in collaboration with scientists at the National Institutes of Health, also have detected factors that may make certain strains of HIV-1 more likely than others to be transmitted through sexual contact. These findings, published in the December 1997 issue of Nature Medicine, may further the development of HIV vaccines and treatment.
Evista (raloxifene), one of a new class of drugs called selective estrogen receptor modulators (SERMs), can help prevent bone thinning from osteoporosis primarily in postmenopausal women. Clinical data on Evista indicate that it acts like estrogen, though to a lesser degree, in increasing bone density and lowering blood lipids, and it did not adversely affect breast and uterine tissue. Unlike estrogen, however, it does not increase "good cholesterol" levels.
The most serious side effect associated with Evista is increased risk of blood clots. Women with a history of blood clots in their veins should not use the drug. Also, women who are pregnant or may become pregnant should not use the drug because of its potential danger to fetuses.
Manufacturer: Eli Lilly and Co., of Indianapolis.
Fortovase (saquinavir) is a new formulation of a protease inhibitor for treatment of HIV infection. Fortovase comes in a soft gelatin capsule and delivers more drug through the body than its predecessor, Invirase.
In a clinical study, twice as many patients who took Fortovase had undetectable virus levels in the blood at 16 weeks of treatment compared with those who took Invirase.
Fortovase was the first HIV drug approved after an FDA advisory committee recommended a more stringent reporting system for clinical study results.
Manufacturer: Hoffmann-La Roche Inc. of Nutley, N.J.
Meridia (sibutramine) is an appetite suppressant to be used along with a reduced-calorie diet to help manage obesity, a chronic disease that contributes to 300,000 deaths annually in this country.
The drug works by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. During clinical trials, there were no reports of pulmonary hypertension, a rare but serious side effect of the anti-obesity drugs fenfluramine and dexfenfluramine, which were taken off the market in September 1997. Also, echocardiograms showed no more valve disease in patients on Meridia than those on placebo.
Manufacturer: Knoll Pharmaceutical Co., of Mount Olive, N.J. Neumega (interleukin eleven) reduces the need for frequent platelet transfusions following high-dose chemotherapy. Platelet transfusions, while very safe, carry small risks of infectious disease transmission and bacterial contamination.
Neumega is injected daily under the skin when chemotherapy ends. In clinical studies, 28 percent of patients treated with Neumega avoided platelet transfusions, compared with 3 percent in the untreated group. Possible side effects include fluid retention, which can be a serious problem for some patients, and abnormal heart rhythms, which in studies returned to normal when the treatment ended.
Neumega is not effective for patients undergoing bone marrow transplants.
Manufacturer: Genetics Institute Inc., of Cambridge, Mass.
Propecia is the first hair loss treatment in pill form. It is marketed for men only because, in women, it causes birth defects and has not otherwise been shown to be safe and effective.
The drug's active ingredient, finasteride, was first approved in a larger dose as a treatment for prostate enlargement.
Manufacturer: Merck and Co., of West Point, Pa. Regranex Gel (becaplermin) is the first biotechnology
product for treating and healing deep diabetic foot and leg ulcers. These ulcers, which about 15 percent of the country's 16 million diabetics develop, increase the risk of infection and amputation.
The gel is used topically, along with standard ulcer management measures.
Manufacturer: Ortho-McNeil Pharmaceutical, of Raritan, N.J.
Rituxan (rituximab) is the first biotechnology product to treat patients who have a cancer of the immune system called low-grade B-cell non-Hodgkin's lymphoma and who have not responded to chemotherapy or other standard treatments. FDA reviewed the license application in five months and approved the product in nine.
By targeting and destroying specific white blood cells involved in the disease, Rituxan shrinks tumors with less severe side effects than most cancer treatments.
Manufacturer: IDEX Pharmaceuticals Corp., of San Diego, and Genentech Inc., of San Francisco.
ThermaChoice is a uterine balloon catheter heat system alternative to hysterectomy or surgical destruction of the uterine lining when excessive, noncancerous menstrual bleeding can't be controlled by drugs. The outpatient procedure is usually done without general anesthesia and takes about a half hour. Studies showed it safely controlled bleeding for at least one year in more than 80 percent of participants.
As the balloon heat treatment also destroys the lining, it is not for use in women who still plan to have children. Pregnancy is possible after treatment if some lining cells survive. However, scientists believe such pregnancies would carry considerable risk to the mother and fetus, so treated women must use effective contraception or undergo sterilization.
Manufacturer: Gynecare-Ethicon Inc., of Menlo Park, Calif.
Tobi (tobramycin for inhalation) is the first inhaled antibiotic for people with cystic fibrosis, an inherited condition that can lead to diminished lung function and chronic lung infections. Tobi suppresses Pseudomonas aeruginosa bacteria, a potentially dangerous microorganism that affects the lungs or respiratory system of most people with cystic fibrosis.
A reformulation of the injectable form of tobramycin, which FDA approved in 1975, Tobi helped improve lung function and reduce bacteria in sputum in clinical trials. Side effects included voice alteration and ringing in the ears.
Manufacturer: PathoGenesis Corp., of Seattle.
Toronto SPV Valve is a new type of heart valve for adults with defective natural or prosthetic aortic valves. The tissue valve, taken from a pig, is supported by the patient's aorta, unlike previous tissue valves, which require metal or plastic supports called stents. With increased space from elimination of the stent, doctors can implant larger valves for improved blood flow.
In a study of about 600 patients ages 33 to 93 in the United States, Canada, and the United Kingdom, the new valve was safe and provided good blood flow.
Manufacturer: St. Jude Medical Inc., of Minneapolis.
Transderm Scop (scopolamine patch) is a small, tan-colored patch that is placed behind the ear before surgery to prevent the nausea and vomiting related to some pain relievers and anesthesia.
Each patch should be used only once and for no longer than three days. It should not be used by children.
Manufacturer: Novartis Consumer Health, of Summit, N.J.
Zenapax (daclizumab) is the first monoclonal antibody to help prevent acute kidney transplant rejection. Used with a standard course of immunosuppressive therapy, it helps prevent kidney rejection with minimal additional side effects.
FDA reviewed and approved the license application for this biologic in six months.
Manufacturer: Roche Laboratories Inc., of Nutley, N.J.
FDA Consumer magazine (March-April 1998)