Efavirenz, manufactured under the trade name Sustiva by DuPont Pharmaceuticals, Wilmington, Del., was granted early approval to treat HIV-1 infection in combination with other HIV drugs.
FDA approved the drug after 24-week studies showed it effectively suppressed human immunodeficiency virus. The drug's effect on HIV beyond that period has not been demonstrated.
Dizziness, insomnia, impaired concentration, abnormal dreams, drowsiness, and other nervous system symptoms were reported in more than half of patients treated with efavirenz, but often stopped after the first or second day of treatment. Skin rash was also reported in some patients treated with efavirenz, but the rash was rarely severe enough to require patients to stop using the drug. Skin rash was more common and severe in pediatric patients than in adults, but otherwise adverse reactions were similar in the two groups.
Delusions and severe acute depression were also reported, mostly in patients with a history of mental illness or substance abuse. If these symptoms occur, efavirenz treatment should be discontinued.
As stated in the drug's labeling, health professionals should monitor patients' cholesterol and liver enzyme levels. Several AIDS drugs are associated with increased cholesterol and liver enzyme levels.
Because efavirenz appeared to cause birth defects in some laboratory studies, women should be tested for pregnancy before starting treatment and should use effective contraception.
An early approval such as that granted to efavirenz is based on blood tests or other laboratory tests, rather than clinical endpoints such as delay in death or reduction in opportunistic infections. If postmarketing studies fail to verify the drug's clinical benefits, FDA may withdraw approval.
Cleared for marketing Oct. 16, the QuickScreen at Home Drug Test, manufactured by Pharmatech, San Diego, Calif., comes in two models: one tests for cocaine, marijuana, opiates, amphetamine, and phencyclidine (PCP); the other tests for cocaine, marijuana, opiates, amphetamine, and methamphetamine.
The QuickScreen kit consists of an instructional insert, a question-and-answer handbook, a urine collection cup, a test strip that contains antibodies against specific drugs, and a mailer for laboratory submissions.
The test strip is placed in the urine immediately after it has been collected in the cup. After 10 minutes, color bands on the test strip indicate that either no drugs are present ("negative") or that one or more of the five drugs are possibly present ("inconclusive--need laboratory analysis"). The home test does not specify which drugs may be present in the urine; this information is available only after confirmatory testing by a laboratory establishes that the sample is positive.
If the initial QuickScreen results are negative, nothing further needs to be done with the urine sample. If the results are inconclusive, the urine sample is placed into a mailer provided with the kit and sent to a designated laboratory for testing. This confirmatory testing by the lab is essential because QuickScreen cannot determine with certainty that drugs are present. The final results should be available in three to seven business days by calling a help line and providing a special identification number.
Not every positive result means that illegal drugs have been used. For example, certain foods and medicines may cause a positive test result. Likewise, not every negative result means that illegal drugs were not used. It could mean that no illegal drugs were used within the past few days, that an amount too small to be detected was used, that the urine sample was tampered with, or that an illegal drug was used that is not tested with the QuickScreen kit.
The test kit will be sold in drugstores, pharmacies and other places that sell over-the-counter drugs.
More help for herpes ... People who suffer from recurrent outbreaks of genital herpes can benefit significantly from a new drug that can suppress the lesions, says a study by Children's Hospital of Eastern Ontario. Famvir (famciclovir) is only the third oral antiviral drug to be approved by FDA to reduce the number of outbreaks. Nearly three-quarters of the 455 patients treated with Famciclovir for one year had no recurrences for the entire year. Study participants had experienced 10 or more outbreaks in the two-year period before the study. Reducing outbreaks is significant because HIV can be transmitted through genital herpes sores. (Journal of the American Medical Association, September 1998)
The rule, published in the Oct. 23, 1998, Federal Register, will allow for full prescribing information on the use of aspirin in men and women who have had a heart attack or stroke or have certain other cardiovascular or rheumatologic conditions. It does not recommend or suggest aspirin for healthy people who want to lower their risk of heart attack or for people with peripheral vascular disease, such as those experiencing intense leg pain due to blockage of blood flow to that area of the body.
The approved labeling is designed for practitioners licensed to prescribe drugs. FDA determined that the supervision of a health-care provider is needed when aspirin is used for heart disease, stroke or rheumatologic diseases. The agency cautioned patients interested in taking aspirin for such diseases to consult with a doctor or other health-care professional first.
The new labeling, which is based on FDA's evaluation of multiple U.S. and foreign studies, will specify that:
The warning will state that people who drink three or more alcoholic beverages every day should consult their doctors before taking the product because an ingredient in it may cause stomach bleeding or liver damage, depending on the product.
The warning could apply to as many as 11 million Americans, the number of people who are heavy drinkers, according to the U.S. Substance Abuse and Mental Health Services Administration.
The rule expands a 1993 rule that required pain relievers and fever reducers newly approved for adult use to carry a warning to heavy alcohol users to consult with their doctors before using these type of medicines. The new rule, published in the Oct. 23, 1998, Federal Register, now applies to all OTC products and combination products intended for adult use that contain aspirin, other salicylates, acetaminophen, ibuprofen, naproxen sodium, and ketoprofen. Also, unlike the 1993 regulation, the new rule requires the specific risk to be stated.
FDA's rule is based on public comments and data on the effect of combining chronic alcohol consumption with use of various OTC pain relievers and fever reducers. It also follows the recommendations of FDA's Nonprescription Drugs Advisory Committee and the agency's Arthritis Drugs Advisory Committee, both of which concluded that chronic alcohol users should be warned that they may be at increased risk of liver damage or stomach bleeding when they use these drugs.
Arava was approved in September for slowing the progression of the disease after clinical studies showed that the drug was effective in relieving the painful, swollen joints of rheumatoid arthritis and retarding damage the disease causes to joints. Arava is not, however, a cure for rheumatoid arthritis.
Because animal studies suggested the drug may cause birth defects, its labeling will carry a special warning stating that Arava should never be used by pregnant women or women of childbearing age who are not using reliable contraception. Also, because the drug remains in the body for a long time, the drug's labeling will recommend that women who want to become pregnant after taking Arava undergo a drug-elimination procedure.
The drug's labeling also will caution doctors to monitor liver enzymes of patients using Arava because clinical studies identified liver toxicity as a possible side effect. The drug is not recommended for patients with significant liver disease. Other side effects include diarrhea, hair loss, and rash.
Arava will be marketed by Hoechst Marion Roussel, Kansas City, Mo.
Etanercept, licensed by FDA in November, helps reduce the pain and swollen joints of moderate to severe active rheumatoid arthritis in patients who have not responded well to other treatments. It can be used in combination with methotrexate for patients who did not benefit enough from methotrexate alone.
Etanercept is not approved to treat less severe symptoms of rheumatoid arthritis or for osteoarthritis or other forms of the disease.
Etanercept binds to, and inhibits the action of, tumor necrosis factor, a naturally occurring protein in the body that promotes inflammation and is present at elevated levels in the fluid surrounding the affected joints of rheumatoid arthritis patients.
In clinical trials, about 59 percent of patients treated with etanercept experienced a significant reduction in symptoms such as swollen and painful joints after six months of treatment, compared with 11 percent of untreated patients.
Some patients treated with the new product developed reactions at the injection site, such as itching, pain or swelling, but the reactions were generally mild to moderate and lasted only a few days.
In children with moderate to severe juvenile rheumatoid arthritis, studies have shown results similar to those in adults. When possible, children should be up-to-date with vaccine immunizations before starting therapy with etanercept because it is not known whether treatment will affect immunization responses.
While clinical studies so far have not shown an increase in serious infections or malignancies in patients using etanercept, studies are under way to look at the product's long-term safety.
Etanercept will be marketed by Immunex Corp., Seattle, and Wyeth-Ayerst Laboratories, Philadelphia.
Self-inflicted illnesses ... People trying to treat their own medical conditions using remedies from health-food stores have become severely ill, say six separate published reports. Lead poisoning, impotence, lethargy, abnormal heart rhythms, and other disorders have resulted from pills and powders sold as dietary supplements that are touted as "all natural" and free of drugs but which in fact contain powerful herbs, toxic contaminants, or potent drugs or hormones. The report stated that several children with cancer worsened when their parents rejected conventional therapy in favor of the alternative treatments. (New England Journal of Medicine, September 1998)
Herceptin (trastuzumab), manufactured by Genentech, Inc., San Francisco, Calif., was licensed in September for use alone in patients who have had little success with chemotherapy, or as a first-line treatment for use in combination with Taxol (paclitaxel).
Bioengineered from part of a mouse antibody altered to closely resemble a human antibody, Herceptin is the second monoclonal antibody approved to treat cancer.
Herceptin's benefits were shown in two clinical trials. One showed that women receiving chemotherapy plus Herceptin had less rapid tumor growth, more tumors with at least 50 percent reduction in size, and higher one-year survival rates. In the second trial, Herceptin was found to be effective when used alone in patients who had relapsed following chemotherapy for metastatic cancer. The tumor response rate was 14 percent among the 222 patients. In 3 percent of the patients, the tumors disappeared altogether.
Herceptin binds to a protein called HER2, which is found on the surface of some normal cells and plays a role in regulating cell growth.
Only breast cancer patients who had tumors with excess amounts of HER2 were shown to benefit from Herceptin, with those with the highest levels of the protein responding best.
FDA in September approved a test called the DAKO HercepTest to measure HER2 protein in tumors.
Selection of patients who are most likely to benefit is important because of the possible serious risks from Herceptin. Some patients may experience weakening of the heart muscle that can lead to congestive heart failure. Because of the possible effects on the heart, certain cardiac precautions should be taken for all patients. Also, because of the seriousness of the risk in some cases, Herceptin is not approved for use in combination with certain types of chemotherapy.
Side effects that are more common in patients using Herceptin plus chemotherapy than in those using chemotherapy alone include reduction of white blood cells, anemia, diarrhea, abdominal pain, and infections. Other side effects, including chills, fever, pain, weakness, nausea, vomiting, and headache, are common during the first weekly infusion with Herceptin.
FDA approved Nolvadex (tamoxifen citrate) for reducing the incidence of breast cancer based on a National Cancer Institute study that showed that tamoxifen reduced the chance of getting breast cancer by 44 percent in women who were judged to be at increased risk for the disease.
The drug will not eliminate the risk completely, and its long-term effects are unknown. Also, the drug has potentially serious side effects, including endometrial cancer (cancer of the lining of the uterus) and blood clots in major veins and the lungs.
In approving the drug, FDA emphasized that tamoxifen should be used only in high-risk women following a medical evaluation of a woman's individual risk factors, such as age, personal health history, and family history of breast cancer.
The drug's labeling will provide information to help doctors identify women who should receive the drug. The labeling will specify, for example, that women 50 and older are at increased risk of breast cancer if they have at least two direct-line relatives who have had breast cancer, have been diagnosed with atypical hyperplasia on breast biopsy, delivered their first baby at age 30 or older, and started menstruating at age 11 or younger.
FDA's approval of tamoxifen for breast cancer prevention follows the September 1998 approval recommendation of the agency's Oncologic Drugs Advisory Committee.
The supplemental new drug application that FDA approved for tamoxifen's new use was submitted by the drug's manufacturer, Zeneca Pharmaceutical Inc., Wilmington, Del.
Reducing risk of colon cancer ... Women who take multivitamins for at least 15 years may cut their risk of colon cancer by 75 percent, says a study by Brigham and Women's Hospital in Boston. The study revealed that folic acid, the same vitamin women are urged to take to help prevent birth defects in babies, is likely the key ingredient. Women who got at least 400 micrograms of folic acid each day from supplements or foods such as green vegetables and fortified cereals had 31 percent fewer colon cancers than those who got less than 200 mcg. (Annals of Internal Medicine, October 1998)
The agency received at least 44 adverse event reports in the past 10 years, according to the Sept. 28 safety notification, in which antitheft systems (also called electronic article surveillance systems) and metal detectors appeared to interfere with implantable pacemakers, implantable cardioverter/defibrillators, and spinal cord stimulators. FDA believes that other electronic medical devices may also be affected.
Reported effects of interference have included chest pain in pacemaker users, unintended shocks to patients with implantable cardioverter/defibrillators, and pain and jolts--and in one case a fall that resulted in injury--due to overstimulation from spinal cord stimulators. Also reported were shifts in pacemakers' pulsing rates and unwanted changes of implantable cardioverter/defibrillators to "monitor only" mode.
In the letter, FDA recommended that doctors tell their patients about some precautions they can take:
FDA asks health-care practitioners to report any adverse events related to electromagnetic interference with electronic devices to FDA's MedWatch program.
The entire safety notification letter can be found on FDA's Website at www.fda.gov/cdrh/safety.html.
A MedWatch report can be made by:
FDA encourages consumers to report through their doctors, but if they prefer, they may submit the MedWatch form themselves.
The first devices of their kind, the HeartMate Vented Electric Left Ventricular Assist System and the Novacor LVAS help do the heart's work by pumping blood through the body. FDA cleared the devices last Sept. 29 for cardiac transplant candidates at risk of imminent death.
Both devices consist of a blood pump implanted in the abdominal area and connected by a cable through the skin to a small external computer worn at the waist. The computer can be powered by a base unit plugged into the wall or by batteries worn at the waist or, in the case of the HeartMate device, under the arms.
The pump is connected to the left ventricle, the heart's main pumping chamber. From there, blood is pumped into the aorta, the main artery supplying blood to the body. Patients who are healthy enough to leave the hospital after the device is implanted should stay close to a facility that knows how to manage the device and must be trained to use the system.
Clinical studies by both manufacturers showed that each of the devices worked equally well inside and outside the hospital.
An estimated 15,000 to 20,000 people in the United States are potential candidates for heart transplants yearly, but there are only enough hearts for about 2,000 people. Some of the remaining patients could be candidates for the new devices.
The HeartMate system is made by Thermo Cardiosystems Inc., Woburn, Mass., and the Novacor LVAS is made by Baxter Healthcare Corp., Oakland, Calif.
Boston Scientific Corp., Natick, Mass., stopped distributing the NIR ON Ranger with Sox last Oct. 5. FDA urged hospitals to stop using the device immediately and distributed information to physicians to alert them to the potential danger.
The product was available for only two months before being recalled. About 36,000 of the devices had been distributed, and the company estimated that 25,000 had been used.
The device is an implanted stent that helps keep previously blocked coronary arteries open after the blockage has been cleared. The stent is positioned by threading it through an artery using a balloon delivery catheter containing a thin wire. At the previously blocked site, a tiny balloon is inflated, which expands the stent device up against the blood vessel wall. The balloon is then deflated and the delivery catheter is withdrawn, leaving the stent permanently in place to prop open the artery.
According to the company, the failure of the device is likely due to changes in the manufacturing process of the balloon portion of the catheter. However, FDA did not review or approve these changes.
The recall does not affect the NIR ON Ranger without Sox, a similar product also made by Boston Scientific.
Healthier people ... Americans may be eating 22 percent more fruit, 19 percent more vegetables, and 47 percent more grains than they did 25 years ago, says a study, but they still need to improve their diets to meet the goals of Healthy People 2000, a national initiative for improving the public health. The study also revealed that while alcohol consumption has declined significantly, consumers are drinking about the same amounts of beer and wine as was reported in 1970. (Cancer, October 1998)
The illegally promoted lenses are:
Only one orthokeratology lens for daily wear has been approved. That lens is not approved for overnight use. Overnight use of this type of lens may create a risk of corneal damage and infection, according to the agency.
Because of these safety concerns, FDA has recommended that eye-care professionals and contact lens dispensers and wearers use only tinted lenses that have FDA's approval or clearance and orthokeratology lenses that the agency has either cleared or approved for use in an investigational study.
FDA asked doctors to report any complaints or injuries associated with the use of tinted or orthokeratology contact lenses to the agency's MedWatch program.
The complete letter is available on FDA's Website at www.fda.gov/cdrh/safety.html.
(For more on contact lenses, see "Keeping an Eye on Contact Lenses" in the March-April 1998 FDA Consumer.)
Cool food ... Frozen produce is just as healthy as fresh fruits and vegetables, says a consensus by the American Frozen Food Institute, the National Food Processors Association, and FDA. Fresh foods such as spinach, grapes or carrots may spend a long time between being picked and being consumed, thus losing nutrients as they age. Produce that is frozen just after picking, however, doesn't lose those nutrients. Nevertheless, fresh or frozen, the overall goal is to get Americans to eat at least five servings a day of fruits and vegetables.
The need for vitamin C ... Americans aren't getting enough vitamin C, says a researcher from the Arizona State University, leaving them more vulnerable to a host of health problems. The worst conditions can develop into scurvy. It isn't easy to fortify food with vitamin C since its potency is weakened when exposed to heat and air, the study says, and some of America's favorite foods--such as bananas, apples, potatoes, and lettuce--are not high in vitamin C. Also, after 10 days in the refrigerator, fruits and vegetables may lose up to half of their vitamin and mineral content. Researchers recommend a 4-ounce glass of orange juice, which would provide an entire day's vitamin C requirements. (Journal of the American College of Nutrition, September 1998)
Award is not a mirage ... FDA's Office of Regulatory Affairs has received the 1998 Government Technology Leadership Award for its Operational and Administrative System for Import Support (OASIS) program. OASIS allows FDA to clear some imports electronically without sacrificing safety. The electronic system reduces costs for the import industry and allows FDA to focus resources on those import shipments that are considered to be of high health risk or that have had a history of noncompliance. The award, sponsored by Government Executive magazine, recognizes organizational accomplishments in all levels of government.
FDA Consumer magazine (January-February 1999)
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