Table of Contents
FDA Consumer magazine
March-April 1999
Reviewing petitions for food additives designed to decrease the risk of food-borne illness, including diseases caused by E. coli, Salmonella, Campylobacter, Cyclospora, and Listeria, will become a top priority under a new FDA guidance.
While the food supply in the United States is among the safest in the world, every year millions of Americans become ill and thousands die from infections caused by these and other food-borne pathogens.
Expedited review is designed to give manufacturers an incentive to develop products to fight food-borne illness and ensure the products are marketed as soon as possible. These petitions will have to meet the same approval standards as other food additive petitions, including the need for valid scientific evidence, satisfaction of the safety standard, and presentation of supporting data.
Examples of petitions that could receive expedited review are those that propose the use of radiation or chemicals such as chlorine dioxide to reduce harmful bacteria.
The "Food Additive Petition Expedited Review--Guidance for Industry and Center for Food Safety and Applied Nutrition Staff" was published in the Jan. 5, 1999, Federal Register. Written comments may be submitted at any time to the Dockets Management Branch, Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.
Labels of certain tofu, soy milk, and other products containing soy protein would be allowed to carry a claim about how the product may help reduce the risk of coronary heart disease, under an FDA proposed rule.
If the proposal, published in the Nov. 10, 1998, Federal Register, is finalized, the new health claim would state that foods containing protein from soybeans, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease by lowering total blood cholesterol and LDL (low-density lipoprotein) cholesterol. High levels of total blood and LDL cholesterol levels are proven risk factors for coronary heart disease, the No. 1 cause of death in the United States.
Studies show that 25 grams of soy protein a day have a cholesterol-lowering effect. FDA has concluded that a soy product could qualify for the health claim only if it contained at least 6.25 grams of soy protein a serving because soy protein occurs in or can be added to a variety of foods and beverages, making it possible to eat as many as four servings of soy-protein-containing products a day. If each serving contained at least 6.25 grams of soy protein, four servings a day would provide the requisite 25 grams of soy protein.
(For more on health claims, see "Staking a Claim to Good Health" in the November-December 1998 FDA Consumer.)
Teens lean toward healthier eating ... The average total cholesterol level for today's teens is 160, down from 167 in the late 1960s, according to a 1998 federal government study. Although the 4 percent drop doesn't appear to be substantial, the National Institutes of Health says the findings indicate that a trend toward healthier eating habits may give young people a better start at healthy adulthood and decrease their chances of heart disease. (Journal of Preventive Medicine, December 1998)
User-friendly thermometers ... The U.S. Department of Agriculture is sponsoring a nationwide campaign to increase the use of food thermometers in the home. The campaign includes helping consumers learn what methods are most reliable for ensuring that temperatures are sufficient to destroy food-borne bacteria. A 1998 USDA-FDA food safety survey of the American population found that less than half of the people surveyed owned a thermometer and, of those, only 3 percent used one often when cooking hamburgers at home.
Arthritis patients now have another weapon in their fight against the painful and deteriorating effects of this disease: a new nonsteroidal anti-inflammatory drug that may not have the same side effects as other NSAIDs.
Celebrex (celecoxib), approved by FDA in December for rheumatoid arthritis and osteoarthritis, was found in several studies to substantially lower the risk of stomach and upper intestinal ulcers compared with other NSAIDs. However, FDA believes that additional studies are needed to see how the overall risks of Celebrex actually compare with those of other NSAIDs. Until such studies are done, FDA is requiring the drug's labeling to include the standard warning about the risks of gastrointestinal ulcers, bleeding and perforation associated with all NSAIDs.
The drug's labeling will advise patients taking Celebrex to be alert for signs of ulcers and bleeding, which can occur without warning, and to promptly report to their doctors such signs or symptoms as skin rash, unexplained weight gain, and swelling.
Another potential advantage of Celebrex is that it does not affect platelet aggregation (clumping), an important part of the blood clotting process. Many other NSAIDs can interfere with this platelet function, increasing the risk of bleeding complications in some patients.
Celebrex is made by G.D. Searle & Co., Chicago.
The first vaccine to help prevent Lyme disease, an infection transmitted to people through infected ticks, has been licensed by FDA.
Lymerix was approved in December for people 15 to 70 years old who live or work in grassy or wooded areas where ticks are present. More than 16,000 cases were reported by 45 states to the national Centers for Disease Control and Prevention in 1996, the last year for which complete statistics are available.
Lyme disease is rarely fatal, typically producing a "bull's eye" rash and flu-like symptoms in its early stages, and occasionally facial weakness and heart problems. As the disease progresses, months or years later, some patients experience chronic arthritis or neurological problems.
The vaccine may provide protection for most people but it does not prevent all cases of Lyme disease. Therefore, FDA recommends that people continue to take standard preventive measures against infection such as wearing protective clothing, using tick repellent, and removing attached ticks.
The vaccine's effectiveness depends on people getting three doses over a one-year period. The time of year the vaccination is given may be important. In a clinical trial in the northeast United States, safety and efficacy were shown when the vaccine doses were given between January and April, shortly before the peak tick season in that area. It is not known how long protection against Lyme disease lasts after vaccination.
Lymerix, marketed by SmithKline Beecham Pharmaceuticals, Philadelphia, Pa., contains a genetically engineered protein from an outer surface of the spiral-shaped bacterium responsible for Lyme disease. The protein stimulates antibodies that appear to disable the bacterium's ability to infect people.
A new product for cancer patients with severe pain that breaks through regular narcotic therapy has been approved by FDA.
Actiq is a form of fentanyl citrate, an opioid narcotic more powerful than morphine. The medicine is in the form of a flavored sugar lozenge that dissolves in the mouth while held by an attached handle.
Many cancer patients experience persistent pain that is treated with oral narcotics. But these patients can experience acute breakthrough pain, with sudden onset that occurs spontaneously or as a result of activity.
Actiq is dissolved slowly in the mouth until the drug is consumed, about 15 minutes. Pain relief may last several hours, starting while the drug is still being consumed.
During clinical trials, side effects included sleepiness, dizziness, nausea, and constipation.
Because Actiq may be fatal to children, as well as adults not already taking opioid narcotics, FDA approved the new drug under special regulations that restrict its distribution. A risk management plan is in place to minimize the opportunity for misuse of the potent narcotic.
Anesta Corporation, Salt Lake City, markets Actiq with partner Abbott Laboratories.
Under a new FDA regulation finalized in November, health-care providers will get specific information on the safe pediatric use of certain new drugs and biologics.
Every year, more than half of newly approved drugs and biologics that are likely to be used in children lack information to permit safe and effective use, such as how the drugs affect children and what doses are age-appropriate, according to FDA. Without adequate information, the agency says, doctors may be reluctant to prescribe certain drugs for children, or they may prescribe them inappropriately.
The regulation requires pediatric use information for new drugs and biologics that are commonly used in children or are otherwise important in their treatment. Also, the rule allows FDA to require pediatric testing of already-marketed products in certain circumstances, such as when the absence of adequate labeling could pose significant risks.
Pediatric data could be submitted after a drug has already been approved if FDA has safety concerns about testing a drug on children before testing it on adults. However, FDA will not delay the approval of a drug for adults because the pediatric studies are not yet completed.
The pediatric study requirement could be waived entirely in the following cases:
An at-home laser treatment recently cleared by FDA offers diabetics a way to penetrate the skin and draw blood without using traditional razor-sharp lancets.
As many as 5.3 million Americans with diabetes have had to draw blood samples at home for daily blood glucose level analysis by pricking their fingers with lancets, a particularly difficult process for children.
Cleared for marketing in December, the Cell Robotics' Lasette, manufactured by Cell Robotics Inc., Albuquerque, N.M., is a first-of-its-kind portable laser, which can be used at home by both adults and children who have received a prescription and training from their health-care providers. Clinical testing has shown that adequately trained patients can perform finger pinpricks with the laser device as accurately as with lancets.
Sweet change ... After being suspected since 1981 as a possible cause of cancer, saccharin may be headed for a new status. The Executive Committee of the national Toxicology Program has recommended that the artificial sweetener be dropped from the program's list of suspected carcinogens. The Department of Health and Human Services still must approve the change. Saccharin accounts for about one-third of the artificial sweeteners sold in the United States.
Earlier HIV treatment for Women ... Women infected with the AIDS virus may need to begin treatment sooner and at lower viral levels than men, says a new study. Research found that when groups of men and women infected with HIV had similar white blood cell counts, the average viral level in the women was only about half the level found in men, yet they progressed to full-blown AIDS at the same rate. Researchers fear that with the current guidelines, women may be undertreated or treated late. (The Lancet, November 1998)
Overused implants ... Some cardiologists believe that doctors are using stents--tubular metal implants that help reopen clogged arteries--needlessly in heart patients who could benefit from simpler, less expensive treatments. About 800,000 stents were implanted in more than 500,000 Americans in 1998 alone. Stents work best in patients with clogging in a short section of a major heart artery. They are not recommended for patients with extensive clogging, problems in smaller arteries, or clogging where vessels branch. (New England Journal of Medicine, December 1998)
Health professionals can report serious adverse reactions or other product problems to FDA's MedWatch program by:
Call the 800 number or visit the Website for forms or for further assistance.
FDA encourages consumers to report through their doctors, but if they prefer, they may submit the MedWatch form themselves.
The maker of the impotence drug Viagra (sildenafil) has updated the product's labeling in response to adverse reaction reports the company and FDA have received since the drug went on the market last year.
The new labeling, revised in consultation with FDA, addresses postmarketing reports of heart attacks, sudden cardiac death, and high blood pressure. A causal relationship has not been established from these reports. The new information is intended to keep consumers and doctors fully informed about the risks and benefits of Viagra, a drug that the agency says is safe and effective if used according to the updated labeling.
The new labeling advises doctors that treatments for impotence, including Viagra, generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. Also, it advises doctors to be especially cautious in prescribing Viagra to patients who have had:
Also, the labeling now warns about the risk of painful, prolonged erections in men who use the drug and advises patients to seek immediate medical attention if their erection lasts longer than four hours.
The new label information augments the original label information, which warned against the joint use of Viagra and nitrates.
FDA encourages health-care professionals to report unexpected adverse and serious reactions associated with Viagra use to the drug's manufacturer, Pfizer Inc., at 1-800-438-1985 or to FDA's MedWatch program.
FDA and the maker of Tasmar (tolcapone), a drug for treating Parkinson's disease, have warned doctors about three fatal liver injuries associated with the drug and have recommended significant changes in how it is used.
Worldwide, about 60,000 patients have taken Tasmar, a drug approved in 1997 to augment treatment with two other Parkinson's drugs, levadopa and carbidopa. The three deaths amount to a rate of about one reported death for every 20,000 patients using the drug.
Last November, Tasmar manufacturer Hoffmann-La Roche Inc. alerted doctors that the drug's labeling had changed to limit its use to patients who do not have severe movement abnormalities and who do not respond to or who are not appropriate candidates for other available treatments.
The new warning calls for liver monitoring every two weeks, more frequently than previously recommended. Doctors also should advise patients to monitor themselves for signs of liver disease such as jaundice, fatigue, or loss of appetite. If patients fail to show substantial benefit within the first three weeks of treatment, they should be withdrawn from the drug.
FDA emphasizes that patients should not stop taking Tasmar without first speaking to their doctors. Abrupt withdrawal or reduction in dose can lead to a return of symptoms or other, more serious, complications. All cases of serious liver injury occurring in Parkinson's patients, whether on Tasmar or another drug, should be reported to FDA's MedWatch program, or to Roche Laboratories at 1-800-526-6367.
For more information about Parkinson's, see "Parkinson's Disease: New Treatments Slow Onslaught of Symptoms" in the July-August 1998 FDA Consumer.
A new drug that can help reduce the amount of human immunodeficiency virus when combined with other anti-HIV medications has received approval from FDA.
Ziagen (abacavir), approved last December, is taken twice daily to treat HIV, a virus that mutates rapidly and may become resistant to current treatments. The drug, one of a class called nucleoside analogue reverse transcriptase inhibitors (NRTIs), is approved for adults and children older than three months.
The drug, however, has been associated with a potentially fatal allergic reaction in at least 5 percent of patients. Possible symptoms include skin rash, fever, nausea, abdominal pain, and severe tiredness. Patients experiencing such a reaction should stop taking the drug and call their doctors right away. Ziagen should not be taken again after a reaction occurs because more severe symptoms could arise within hours that may include life-threatening low blood pressure or death.
Physicians can register patients developing symptoms of hypersensitivity by calling 1-800-270-0425.
All NRTIs can cause lactic acidosis, a fatal metabolic disorder that causes an abnormal buildup of lactic acid. Symptoms may include an enlarged liver. Other reported side effects of Ziagen include nausea, vomiting, fatigue, headache, diarrhea, and loss of appetite.
Ziagen received accelerated approval, and, at present, there are no results from controlled trials showing the long-term effectiveness of Ziagen to suppress HIV infection or AIDS.
Ziagen is marketed by GlaxoWellcome Inc., Research Triangle Park, N.C.
Dogs diagnosed with separation anxiety or an age-related cognitive deterioration syndrome can now be treated with new veterinary drugs FDA recently approved.
Clomicalm Tablets (clomipramine hydrochloride) treat separation anxiety in dogs older than 6 months, and Anipryl Tablets (selegiline hydrochloride, L-deprenyl hydrochloride) control the clinical signs associated with canine cognitive dysfunction syndrome (CDS).
Separation anxiety occurs when the owner or someone the dog is attached to leaves the dog. Signs include barking, destructive behavior, excessive salivation, and loss of house training. In clinical trials, Clomicalm Tablets, used with behavior modification, reduced the signs of separation anxiety and increased the rate of improvement compared with behavior modification alone.
CDS is an age-related deterioration in the dog's ability to function normally. Behavioral changes associated with CDS include disorientation, decreased activity level, abnormal sleep-wake cycles, loss of house training, or changes in responsiveness to family members or in greeting behavior. While clinical trials showed Anipryl Tablets to be effective in controlling CDS symptoms, the degree of responsiveness varied among dogs.
While Clomicalm Tablets and Anipryl Tablets are safe for dogs at the recommended dosages, both products can cause side effects. The package inserts for both products carry important statements that should be considered before treatment. For example, a dog should not be taking both drugs at the same time.
Novartis Animal Health, Greensboro, N.C., sells Clomicalm Tablets, and Pfizer Animal Health Inc., Exton, Pa., sells Anipryl Tablets.
A guidance on FDA's "fast-track" approval programs and a final rule on distribution of "off-label" information are among FDA's accomplishments in the year since the Nov. 21, 1997, enactment of the Food and Drug Modernization Act.
The guidance on FDA's fast-track programs provides drug sponsors and researchers with information on how to facilitate the development and evaluation of new drugs and biologic products designed for serious and life-threatening illnesses.
The final rule on off-label use allows marketers of drugs, biologics and medical devices to distribute unapproved but sound and balanced information on their products if they commit to researching the unapproved use and submitting their findings to FDA for approval.
The 1997 law required FDA to complete 17 regulations, 11 guidances, six regulatory notices, nine reports, and at least 18 other tasks. By Nov. 23, the agency had issued 16 final rules and nine proposed rules, 36 guidances, 11 regulatory notices, and one report, meeting nearly all the deadlines under the law and beating many of them.
More information on the FDA Modernization Act is available on FDA's Website at www.fda.gov/opacom/7modact.html.
Internet rumors that call into question the safety of tampons are unfounded, according to FDA's Center for Devices and Radiological Health, which regulates tampons and other medical devices. There is no evidence, the agency says, to support unattributed allegations that tampons are contaminated with asbestos and dioxin and that rayon fibers in tampons cause toxic shock syndrome, or TSS.
One Internet claim is that U.S. tampon manufacturers add asbestos to their products to promote excessive menstrual bleeding in order to sell more tampons. Asbestos is not, and never has been, used to make tampon fibers, according to FDA, which reviews the design and materials for all tampons sold in the United States. The agency has no evidence of asbestos in tampons and no reports of increased menstrual bleeding following tampon use.
It is also alleged that some tampons contain the chemical dioxin. Tampons sold in the United States are made of cotton, rayon, or blends of the two materials. Although past methods of chlorine bleaching of rayon's cellulose fibers could lead to tiny amounts of dioxin (amounts that posed no health risk to consumers), today, cellulose undergoes a chlorine-free bleaching process resulting in finished tampons that have no detectable level of dioxin. More information on dioxin and tampons is available on FDA's Website at www.fda.gov/cdrh/ocd/tampons.html.
Another claim that appeared on the Internet is that rayon in tampons causes TSS, as well as dryness, ulcerations or lacerations in vaginal tissues that could make a woman more susceptible to other infections and diseases.
While there is a relationship between tampon use and toxic shock syndrome--about half of TSS cases today are associated with tampon use--there is no evidence that rayon tampons create a higher risk than cotton tampons with similar absorbency.
Toxic shock syndrome is a rare but potentially fatal disease caused by a bacterial toxin. TSS reports have decreased significantly in recent years, with only five confirmed menstrually related cases reported in 1997, compared with a high of 814 cases in 1980.
Research by the national Centers for Disease Control and Prevention suggests that some high-absorbency tampons may increase the risk of TSS in menstruating women. There is no evidence, however, that the material from which a tampon is made contributes to TSS or to vaginal dryness, ulcerations or lacerations.
Women may avoid problems, the agency says, by choosing a tampon with the lowest absorbency needed to control menstrual flow. Also, women are encouraged to read the information about preventing and recognizing TSS provided in the labeling for tampons, and to ask their health-care providers about the condition. For more information on TSS, go to FDA's Website at www.fda.gov/oc/opacom/hottopics/tampons.html.
An injectable cement has been approved by FDA that can shorten the time patients with certain wrist fractures must wear a cast.
Normally, to heal a broken wrist, patients wear a cast for six to eight weeks. With the new product, the cast needs to be worn for only two weeks, followed by a removable splint for two to four weeks.
Though referred to as cement, the product is actually an injectable paste that can help hold broken wrist bones together. It sets quickly, helping to stabilize the fracture, and over time is replaced by bone. It does not eliminate the need for other stabilizing devices, such as hardware and pins, in patients who would normally need them.
Studies showed that the paste was similar in effectiveness to conventional treatments in healing the fractures, and complications with both treatments were about the same after one year. However, certain patients who received the injectable cement lost more bone length than patients treated conventionally.
The product, approved in December, is manufactured by Norian Corp., Cupertino, Calif. FDA is requiring the company to study the product's longer-range safety, including the long-term risk for re-fracture and arthritis.
Comments on tampon name ... FDA is seeking suggested names for a new, highly absorbent tampon. The new category would join the existing absorbency terms "junior," "regular," "super," and "super plus." The agency, which announced the search in the Jan. 21 Federal Register (www.fda.gov/ohrms/dockets/98fr/012199b.txt), is specifically seeking comments on the term "ultra," but suggestions for alternative terms are welcome. Submit proposed names by April 21, 1999, to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. All comments should be identified with docket number 98N-0970.
Inhaled corticosteroids used to treat asthma and intranasal corticosteroids used for allergy-related nasal symptoms--about a dozen products in all--will begin to carry new labeling to alert health-care providers that use of these drugs in children may reduce their rate of growth.
In studies, the average reduction in growth velocity (used to compare children's rate of growth) was about one centimeter, or a third of an inch, per year. The reduction appears to be related to dose and length of time taking the drug.
The long-term effects on final adult height are unknown, and it is also not known whether patients' growth will "catch up" if treatment is stopped. Drug manufacturers are continuing to monitor the drugs to learn more about their long-term effects on growth.
Patients should not stop using their inhaled or intranasal corticosteroids without first speaking to their health-care providers about the benefits of these drugs compared to the risks.
STDs still widespread ... Health officials have beaten back syphilis and gonorrhea to an all-time low in the United States, but 15 medium-to-large cities still report high rates of both, says a national Centers for Disease Control and Prevention study. While the United States spends more than $8 billion annually battling sexually transmitted diseases, CDC says many people don't get treated perhaps because of the shame associated with such diseases.
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Peptic ulcers know no gender ... Once affecting mostly men, peptic ulcer disease now strikes an equal number of women, says the national Centers for Disease Control and Prevention. Both men and women generally develop their first onset symptoms by age 35, and the risk of ulcer disease increases with age. Contrary to popular belief, ulcers are not caused by stress or spicy foods. A bacterial infection known as Helicobacter pylori (H. pylori) is responsible for 9 out of 10 cases of peptic ulcer disease, and the rest are caused by nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. CDC says that once detected, most H. pylori infections can be cured with 10 to 14 days of antibiotics.
No cancer from hair dye ... There is little convincing evidence of increased cancer risk with normal use of hair-color products, says an eight-year study. Researchers at the University of California in San Francisco found that though rising worldwide rates of cancer of the immune system have suggested a link to dye use, hair color products were not a factor. (American Journal of Public Health, November 1998)
Don't withhold herbal information ... Despite the growth in annual sales of herbal supplements to an estimated $27 billion, consumers are not telling their doctors that they use the products, says a study sponsored by the Beth Israel Deaconess Medical Center. The effects, say researchers, can be dangerous. Patients who have abruptly ended alternative medicines when hospital treatments are necessary have suffered devastating consequences such as delirium and racing heart, resulting in intensive care. If the patients had disclosed their self-treatments, many of the complications could have been prevented. (Journal of the American Medical Association, November 1998)
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