Table of Contents
FDA Consumer magazine
May-June 2000
FDA has issued an approvable letter for a drug regimen that is being evaluated for termination of early pregnancy. FDA sent the letter in February to the Population Council, an international nonprofit research institution, for the drug mifepristone used in combination with misoprostol. Mifepristone is better known as the French drug RU-486.
FDA issues approvable letters to manufacturers when questions remain to be resolved before final marketing approval can be granted. An approvable letter does not give a company permission to begin marketing the drug. FDA issued a prior approvable letter for mifepristone to the Population Council in September 1996, indicating that the agency believed the drug to be safe and effective, but that unresolved issues remained, including questions about manufacturing. The organization has filed a response to the outstanding issues.
Children should receive polio shots instead of the oral vaccine because of the very small chance that the oral dose can lead to polio infection, says the Centers for Disease Control and Prevention (CDC). CDC accepted the advice of an advisory panel that decided the benefits of the oral polio vaccine no longer outweigh the risks. CDC's recommended immunization schedule is published each January as a guide for state and local health departments and pediatricians.
Dietary supplement manufacturers should not make any pregnancy-related claims based on FDA's recent structure function rule until the agency considers recently raised concerns, FDA has advised.
The rule, published in the Jan. 6, 2000, Federal Register, was written to clarify the types of claims that are considered to relate to the "structure or function" of the body and so may be made without prior review by FDA. Claims that a product diagnoses, treats, prevents, cures, or mitigates diseases ("disease claims") do require prior FDA authorization.
The rule stated that certain conditions associated with pregnancy are diseases if they are recognizable to consumers or health professionals as abnormal, but that ordinary morning sickness associated with pregnancy, for example, does not cause significant or permanent harm and is not a disease.
FDA plans to give further guidance on these claims, but only after fully reviewing the pregnancy-related safety concerns, issuing a Federal Register notice describing the issues, and evaluating the results of a public meeting that was held on the topic March 30.
FDA urges all pregnant women to consult their health-care providers before taking any dietary supplements or medication.
Early complications of sickle cell disease can help doctors predict which infants most likely will die or suffer a stroke later in life, allowing physicians to tailor individual therapies based on disease-related risks, say researchers from the Cooperative Study of Sickle Cell Disease. After studying the records of 392 children from infancy to about 10 years, doctors found that three early complications‹painful swelling of hands and feet before the age of 1, early severe anemia, and an elevation of white blood cell counts‹were associated with more dire complications later in life such as stroke and death. (New England Journal of Medicine, January 2000)
For the first time, a vaccine is available to help protect infants and toddlers from so-called "invasive pneumococcal" diseases that can cause brain damage and even death.
The Prevnar Pneumococcal 7-valent Conjugate Vaccine (diphtheria CRM197 protein) was approved in February for preventing diseases caused by the organism Streptococcus pneumoniae (also known as pneumococcus). The bacteria can cause an infection of the bloodstream called bacteremia as well as meningitis, an infection of the lining of the brain or spinal cord.
This first-of-a-kind vaccine for children under 2 targets the seven most common strains of pneumococcus, which account for about 80 percent of invasive diseases (mostly blood infections) in infants.
Generally, infants will receive the vaccine in a series of four inoculations given at ages 2, 4, and 6 months, and again between 12 and 15 months of age. If children can't get the vaccine starting at 2 months, parents should see their health-care providers for alternative schedules.
Each year, in the United States, there are an estimated 16,000 cases of pneumococcal bacteremia and 1,400 cases of pneumococcal meningitis among children under 5. Children under 2 are at highest risk for infection. As many as half of meningitis cases result in brain damage and hearing loss, and about 10 percent of cases are fatal.
In a scientific study involving some 38,000 children, participants received either Prevnar or a different investigational vaccine, along with other recommended childhood vaccines. Prevnar was 100 percent effective in preventing invasive pneumococcal disease caused by the seven strains of pneumococcus in the vaccine and was about 90 percent effective against invasive diseases caused by all pneumococcal types.
Side effects were generally mild and included local reactions at the place of injection, irritability, drowsiness and decreased appetite. About 21 percent of children receiving Prevnar developed fevers over 100.3 degrees Fahrenheit, compared with about 14 percent of those in the control group.
Prevnar is not approved for use in adults or as a substitute for other approved pneumococcal vaccines for high-risk children older than 2. FDA has not evaluated the vaccine's effectiveness in preventing ear infections caused by pneumococcus.
Prevnar is marketed by a unit of Wyeth-Ayerst Laboratories, a division of American Home Products Corp., Philadelphia.
Routine flu shots should be considered for healthy infants and toddlers, say researchers, following two studies that showed these young children can suffer serious complications from an influenza infection. The studies found few deaths but lots of hospital stays and doctor visits. It also found unnecessary treatment with antibiotics in healthy children younger than 2, as well as in older, high-risk children with asthma, diabetes or other chronic conditions.
Currently, pediatric vaccination guidelines (established by the Advisory Committee on Immunization Practices) call for annual flu shots only for high-risk children 6 months and older and others in their household, and reports show that only about 10 percent of high-risk children actually get the shots. Flu shots cannot be given to children less than 6 months old. (New England Journal of Medicine, January 2000)
Women smokers may be more than twice as likely to develop lung cancer as male smokers, say researchers at Pennsylvania State University who recently discovered that a gene linked to the abnormal growth of lung cells is not as active in men. The study showed that the action of the gastrin-releasing peptide receptor, or GRPR, which plays a key role in the development of the lungs, increased lung cancer risk in both women and men smokers. But that risk was much higher for women smokers compared with their male counterparts. Differences in the action of the gene in women made the risk associated with GRPR 12 times higher for women and only 2.4 times higher for men smokers. Researchers say that GRPR becomes active in men only in the presence of tobacco smoke or some other respiratory attack, but remains active in women whether they smoke or not. (Journal of the National Cancer Institute, January 2000)
A common antibiotic given to newborns with whooping cough is causing a severe stomach disorder, according the Centers for Disease Control and Prevention (CDC). The report marks the first time that the antibiotic, erythromycin, has been strongly linked to pyloric stenosis, an illness among newborns that blocks digestion and causes projectile vomiting. While CDC urges physicians and parents to be aware of this potentially serious side effect of the drug, the agency does not recommend that physicians stop prescribing it for whooping cough, which can be fatal. An average of about 1,900 cases of whooping cough a year was found among infants in the United States between 1994 and 1996.
The first mammography system to produce digital images instead of the standard analog images on x-ray film has been approved by FDA.
The Senographe 2000D proved to be as effective as x-rays in a study of 625 women, 44 of whom had breast cancer. In that study, five qualified radiologists compared digital mammography with analog mammography and found comparable effectiveness in the screening and diagnosis of breast cancer.
The study results did not show that the digital images were more effective in finding cancer than the x-ray film images. The digital technology, however, offers several potential advantages over the current film/screen method for mammography. Unlike film images, digital images:
The Senographe 2000D, approved in January, is made by General Electric Medical Systems. Currently, only facilities certified to practice film mammography may use the Senographe 2000D for mammography.
A new test that can be done without a pelvic exam may help detect cervical cancer in women who can't, don't or won't get Pap smears. Two recent studies report that a DNA test can detect cervical cancer just as well as Pap smears, and that women can collect the samples for the test themselves. FDA approval of the DNA test could be several years away. If approved, the test could be administered at home or by a general practitioner. (Journal of the American Medical Association, January 2000)
Women with breast cancer associated with two genetic mutations may live up to four years longer by having their healthy breast and ovaries removed, say researchers. The BRCA1 and BRCA2 gene mutations were identified a few years ago and are known to raise the risk of breast cancer. The study does not advocate surgery for women in early stages of breast cancer without the gene mutations. It does, however, suggest that some women may be more concerned with sexual and reproductive functions and self-image than with gaining a few years in life expectancy. (Journal of the American Medical Association, February 2000)
The rate of salmonella illness from eating raw or undercooked eggs dropped by more than one-third between 1996 and 1998, according to the Centers for Disease Control and Prevention (CDC) in Atlanta. This represents a turn-around from the soaring rate of egg-related salmonella sicknesses reported in the 1980s and early 1990s. CDC says the annual rate went from 0.6 cases per 100,000 people in 1976 to 3.6 in 1996, but that the number of cases per year dropped to 2.2 per 100,000 between 1996 and 1998. CDC credits the decrease with better safety measures for egg production and preparation.
For the first time, FDA has used the Internet to reach Website operators who may be violating U.S. law. The agency sent letters by e-mail last winter to a dozen operators of foreign-based Internet sites selling prescription drugs that may be illegal.
While similar to traditional warning letters sent to those the agency believes may be violating the law, the "cyber" letters represent a new stage in FDA's efforts to protect the public against illegal and potentially dangerous products sold through Websites. FDA sent the letters to Website domain holders that the agency determined may be offering to sell prescription drugs to U.S. citizens without valid (or any) prescriptions. The agency is concerned that these drugs could pose a serious risk to patients, particularly if used without proper medical supervision.
The letters warned the Website operators that they may be in violation of the Federal Food, Drug, and Cosmetic Act and informed them of the laws governing prescription drug sales in the United States. In addition, the letters warned Website operators that future shipments of their products to this country may be automatically detained and refused entry.
FDA also sent paper copies of the letters to the Website operators, as well as to the U.S. Customs Service and to regulatory officials in countries where the Websites are based.
Consumers who want information about online pharmacies, or who want to report Websites that may be selling FDA-regulated products illegally, can contact FDA through its Website at www.fda.gov/oc/buyonline/.
To order single copies of this FDA Consumer article, use the contact information listed after the title. To order 2 to 50 copies, write to FDA (HFI-40), Rockville, MD 20857.
"Sugar Substitutes: Americans Opt for Sweetness and Lite"
(FDA) 00-2330
Write to FDA (HFS-555), Washington, DC 20204
Women with irritable bowel syndrome (IBS) whose primary symptom is diarrhea now have another option for treating their condition.
Alosetron hydrochloride (Lotronex) was approved by FDA in February to treat irritable bowel syndrome symptoms such as chronic or recurrent abdominal pain, diarrhea and constipation, and the sudden, urgent need to go to the bathroom.
IBS is a functional abnormality of the gastrointestinal tract that is estimated to affect up to 15 percent of Americans--women three times more often than men. Alosetron was not approved for and is not recommended for men.
Although how the drug works is not completely understood, alosetron slows intestinal movement and may provide relief by targeting the underlying neurological activity associated with the condition.
Alosetron's approval was based on two 12-week studies of 1,273 women who met specific pain and stool consistency criteria. In both studies, the drug was significantly more effective than a placebo in providing relief from IBS pain and discomfort and in reducing the number of days that women experienced an urgent bathroom need. Treatment with alosetron also resulted in firmer stools and a significant decrease in stool frequency.
The most common side effect was constipation. The drug's labeling recommends managing this adverse effect by temporarily stopping drug treatment and giving customary care, including laxatives and fiber.
Four patients taking alosetron developed acute colitis, a potentially serious inflammation of the large intestine, which subsided when the drug was discontinued. Whether a causal relationship exists between the drug and this effect is being studied. Health-care providers should stop treatment immediately in patients with symptoms of acute colitis (such as bloody diarrhea and sudden, significant worsening of abdominal pain) to allow a prompt evaluation of their condition. And, FDA encourages health care providers to report any such cases to the agency's MedWatch program.
Alosetron is marketed by Glaxo Wellcome Inc., Research Triangle Park, N.C.
Two prescription drugs--Propulsid, used to treat severe heartburn, and the diabetes drug Rezulin--have been taken off the market by their manufacturers following decisions that they pose unacceptable risks to patients.
The manufacturer of the prescription drug Propulsid (cisapride), Janssen Pharmaceutica Inc., Titusville, N.J., announced in March that it was voluntarily withdrawing the drug from the U.S. market. Propulsid is a prescription drug treatment for severe nighttime heartburn experienced by patients with gastroesophageal reflux disease (GERD) that does not adequately respond to other therapies.
Propulsid has been associated with a significant number of reports of heart rhythm abnormalities and several deaths. Most adverse events have occurred while patients were taking other medications or suffering from underlying conditions known to increase risk.
Since the drug's approval in 1993, its label has been revised several times to inform health care professionals and patients about the risks. But despite these risk management efforts and additional steps that have been under consideration, the firm decided in consultation with FDA that continued prescription access to the drug poses unacceptable risks. The company will, however, continue to make the drug available to patients with severely debilitating conditions for whom the benefits may outweigh its risks, and who meet specific clinical eligibility criteria for limited access.
Patients currently taking Propulsid are urged to promptly contact their health care providers to discuss alternative treatments. Physicians who are treating patients with severely debilitating conditions are encouraged to contact Janssen at 1-800-JANSSEN.
Rezulin (troglitazone), a drug used to treat Type 2 diabetes mellitus, was removed from the market at FDA's request following a review of recent safety data showing that the drug is more toxic to the liver than two other similar drugs, Avandia (rosiglitazone) and Actos (pioglitazone). Both of these drugs offer the same benefits as Rezulin, but without the same risks.
Severe liver toxicity has been known to occur with Rezulin since 1997, prompting manufacturer Parke-Davis/Warner-Lambert to both strengthen its labeling several times and recommend close monitoring of liver function in patients taking the drug.
Patients should not discontinue taking Rezulin or other treatments for diabetes without discussing alternative therapies with their physicians.
The prognosis for most people with Lyme disease who receive conventional treatment is excellent, says a study by Yale University researchers and a team of Connecticut doctors. In the largest long-term study of the effects of the disease, patients who received conventional treatment suffered no more long-term health problems than individuals who never had Lyme disease. (Journal of the American Medical Association, February 2000)
Table of Contents | How to Subscribe | Back Issues | FDA Home Page
Questions concerning the editorial content of FDA Consumer should be directed to FDA's Office of Public Affairs.
(Hypertext created by clb 2000-APR-14)