Removal of Rezulin from the Market
Troglitazone (Rezulin), a drug used in the treatment of type 2 diabetes mellitus (formerly non–insulin-dependent diabetes mellitus), was recently removed from the market at the request of the U.S. Food and Drug Administration (FDA).
The withdrawal occurred after the FDA reviewed recent safety data on troglitazone and two similar drugs, rosiglitazone (Avandia) and pioglitazone (Actos), and found that troglitazone is more toxic to the liver than the other drugs. Current data show that rosiglitazone and pioglitazone provide the same benefits as troglitazone without the same risk.
Since 1997, severe liver toxicity has been associated with troglitazone. The manufacturer, in consultation with the FDA, has strengthened the labeling of troglitazone several times and has recommended close monitoring of liver function in patients using the drug.
In March 1999, the Endocrine and Metabolic Drugs Advisory Committee of the FDA reviewed the status of troglitazone and its risk of liver toxicity. The committee recommended continued availability of the drug in a select group of patients—those whose diabetes is not well-controlled by other drugs.
Since that time, the FDA has monitored adverse events associated with troglitazone, as well as rosiglitazone and pioglitazone. After monitoring the two newer drugs for about a year, it became clear that they have less risk of severe liver toxicity than troglitazone.
For more information on the removal of troglitazone, contact the FDA at 888-INFO-FDA (888-463-6332). This information can also be accessed on the FDA Web site (http://www.fda.gov).
Increased Risk of Mortality with the Use of Cisapride
Cisapride (Propulsid), a prescription drug used in the treatment of severe nighttime heartburn in patients with gastroesophageal reflux disease, will be voluntarily removed from the U.S. market as of July 14, 2000. The effective date should allow enough time for patients and physicians to make alternative treatment decisions. After July 14, the manufacturer will continue to make the drug available to patients who meet specific clinical eligibility criteria for a limited-access protocol.
As of December 31, 1999, the use of cisapride has been associated with 341 reports of heart rhythm abnormalities, including 80 reports of mortality. Most of these adverse events occurred in patients who were taking other medications or had underlying conditions known to increase the risk of cardiac arrhythmia associated with cisapride.
Since cisapride was approved in 1993, the labeling has been revised several times to inform patients and physicians about the possible adverse effects. Despite these risk management efforts, the manufacturer has decided that access to the drug poses unacceptable risks and will remove it from the U.S. market.
Patients who are using cisapride should contact their physicians to discuss alternative treatment options. Physicians who are treating patients with severely debilitating conditions for whom they believe the benefits of cisapride may still outweigh the risks are encouraged to contact Janssen at 800-JANSSEN (800-526-7736). More information on the voluntary removal of cisapride from the U.S. market can be obtained by calling the FDA at 888-INFO-FDA (888-463-6332). This information can also be accessed on the FDA Web site (http://www.fda.gov).
Marijuana Use Among Children and Adolescents
The Committee on Substance Abuse of the American Academy of Pediatrics (AAP) has issued a statement about the growing number of children and adolescents who use marijuana. Marijuana is the most common illicit drug used by children and adolescents in the United States. Survey data show that use is on the rise among this group as they become less concerned about the dangers of the drug. Physicians must develop a reasoned approach to dealing with marijuana use among young persons so that they can provide appropriate care and counsel. The AAP statement appears in the October 1999 issue of Pediatrics.
According to the AAP committee, regular use of marijuana is associated with cardiovascular, pulmonary, reproductive and immunologic problems. Marijuana use may cause an accelerated heart rate and a minimal rise in blood pressure. Heavy use of marijuana may be dangerous for adolescents during puberty and is associated with diminished sperm motility, decreased sperm counts, decreased circulating testosterone levels, irregular ovulation and decreased gonadotrophin levels. Marijuana also influences the immune system and affects antitumor activities in the body.
In the past two decades, the average potency of marijuana has increased fivefold, states the AAP.“Casual use” of low-potency marijuana several decades ago has given way to compulsive use of high-potency marijuana today. Persons under the influence of marijuana show impaired problem-solving skills and difficulty in organizing thoughts and conversing. They have trouble with coordination; the ability to judge elapsed time, speed and distance; the ability to track a moving object; and reaction time. Marijuana contributes significantly to accidental death and injury among adolescents, especially those associated with motor vehicle crashes. Regular use affects short-term memory, learning and attention span. Finally, marijuana use often leads to the use of other more dangerous illicit drugs.
The AAP committee urges physicians to counsel young patients against the use of marijuana. Counsel should focus on health concerns, including the relationship of marijuana use to trauma associated with intoxication and the effect of the drug on memory and learning during this important period of development. Physicians can also discuss the potential harm that marijuana use may cause to adolescents during a period of rapid change in hormonal secretion, possible teratogenicity and the known consequences of long-term use.
Routine discussion of drug use should be part of health care for all young persons. Assessing potential drug use will allow the physician to offer anticipatory guidance before the onset of use, to intervene and minimize consequences if drug use has begun, and to detect and address issues of long-term or heavy use. The AAP committee states that teenagers who are dependent on marijuana should be offered treatment options, rather than simply punishment, for their illness.
New Drug to Reduce the Risk of Stroke
The U.S. Food and Drug Administration (FDA) has approved a medication that combines two active ingredients—aspirin and dipyridamole—into one pill to reduce the risk of stroke in patients who have already had transient ischemic attacks or completed ischemic strokes caused by blood clots in the brain. According to the FDA, each year in the United States, approximately 500,000 persons have strokes and about 150,000 die from them. Of these strokes, 400,000 are ischemic, caused by a blood clot that reduces or blocks blood flow to the brain.
The new drug will be marketed as Aggrenox. The clinical trial of Aggrenox was called the European Stroke Prevention Study. The double-blind, placebo-controlled study lasted 24 months. Of the 6,602 patients included in the trial, 76 percent had an ischemic stroke and 24 percent had a transient ischemic attack within three months of entry into the trial. Trial results showed that the combination medication reduced the risk of stroke by 36.8 percent and the cumulative risk of stroke and death by 24.2 percent, compared with placebo.
The trial also compared the use of the combination drug with the single use of each active ingredient. Results revealed that the combination drug was more effective in reducing the risk of stroke than each active ingredient alone.
Patients with hypersensitivity to dipyridamole, aspirin or any of the other components of the products should not take Aggrenox. Adverse effects related to the use of Aggrenox include headache, abdominal pain, dizziness and nausea.
For more information on Aggrenox for the treatment of stroke, visit the FDA Web site at http://www.fda.gov or call 888-INFO-FDA (888-463-6332).
FDA Warning on Use of Dietary Supplement
The U.S. Food and Drug Administration (FDA) has issued a warning about a new dietary supplement called Triax Metabolic Accelerator. The product is being marketed as a dietary supplement for the purpose of weight loss, but the FDA has determined that the product is not a dietary supplement. Rather, it is an unapproved new drug that contains a potent thyroid hormone. This hormone may cause serious health problems, such as myocardial infarction and stroke. The active ingredient in the product is triiodothyroacetic acid.
Through the MedWatch reporting system, the FDA has learned of several persons who were found to have abnormal results on thyroid function tests while they were using Triax. These persons sought medical attention after experiencing symptoms that included severe diarrhea, fatigue, lethargy and profound weight loss.
The FDA warns consumers not to purchase or consume the product, which is being sold through retail stores and on the Internet. All persons who have used the product are urged to consult their physician immediately if they experience any adverse effects, including insomnia, nervousness, sweating and diarrhea.
The manufacturer of Triax has agreed to stop distributing any product that contains triiodothyroacetic acid. Further action by the FDA is being considered. For more information, call the FDA at 888-INFO-FDA (888-4636-332) or visit the FDA Web site (http://www.fda.gov).
Safe Transportation for Children with Special Needs
The Committee on Injury and Poison Prevention of the American Academy of Pediatrics (AAP) has released a statement on the safe transportation of children with special needs. The statement provides important considerations for transporting such children in motor vehicles and reviews the current guidelines for the protection of children with specific health care needs. The statement appears in the October 1999 issue of Pediatrics.
According to the AAP committee, important considerations for transporting a child with special needs include the following:
The rear seat of the motor vehicle is the safest place for all children to ride. Rear-facing safety seats should never be placed in the front seat of a vehicle that has front passenger or side air bags.
For a child with special needs who requires frequent observation and must ride in the front seat, the vehicle should be equipped with an on/off switch for the air bag.
Instructions that are provided by the manufacturers of the vehicle and car safety seat must be followed.
The committee also recommends planning for appropriate vehicle restraints and accessing the most current information on transporting children with special needs.
Guidelines for the selection of an appropriate occupant protection system and the proper positioning of a child with special needs are also included in the statement. The general recommendations are divided into two categories: infants and young children, and older children and adolescents.
The statement also gives recommendations on the transportation of children with specific health care needs, including those with a tracheostomy, a spica cast, challenging behaviors and muscle tone abnormalities; those who must lie in a prone or supine position after surgery; and those who must be transported in wheelchairs.
For assistance in identifying local community resources for the procurement of specific restraint systems, the committee suggests contacting the National Easter Seal Society at 800-221-6827.
Effect of Caffeine on Exercise Performance
The American College of Sports Medicine (ACSM) has released an official statement on caffeine and exercise performance. The statement covers the effects of caffeine on endurance and short-term exercise performance, and discusses the practical aspects of caffeine ingestion. The statement appears in ACSM's Current Comments, July 1999.
In the laboratory, ingestion of caffeine (3 to 9 mg per kg) before exercise increased performance during prolonged exercise and short-term intense exercise that lasted about five minutes. Because such results are usually reported in well-trained elite or recreational athletes, field studies are required to test the ergogenic potency of caffeine, reports the ACSM. Caffeine does not appear to enhance athletic performance during sprinting that lasts less than 90 seconds, although research in this area is limited.
The committee states that the mechanisms for improved endurance are not clear. After caffeine ingestion, muscle glycogen sparing happens early in endurance exercise. Researchers do not know if this is caused by increased fat mobilization and use by the muscle. During short-term exercise, the positive effect of caffeine is not related to the sparing of muscle glycogen.
The ergogenic effects of caffeine are present with urinary caffeine levels that are well below the allowable limit of the International Olympic Committee, raising ethical issues about the use of caffeine in athletes. ACSM asks whether the practice should be condoned because it is legal or discouraged because it may lead to more serious abuse. ACSM believes that one solution would be to add caffeine to the list of banned substances, requiring athletes to abstain from caffeine ingestion 48 to 72 hours before competition and discouraging its use to increase performance in the average population.
Current Comments are official statements by the ACSM concerning topics of interest to the public at large. More information may be obtained by calling 317-637-9200 or by writing the ACSM at P.O. Box 1440, Indianapolis, IN 46206-1440.
Information Packet on Viral Hepatitis
The National Digestive Diseases Information Clearinghouse, which is an information service of the National Institute of Diabetes and Digestive and Kidney Diseases, has released a new packet of publications on viral hepatitis for use by health professionals and the public.
Three illustrated, easy-to-read booklets are included in the folder. These patient information booklets, “What I Need to Know About Hepatitis A,” “What I Need to Know About Hepatitis B,” and “What I Need to Know About Hepatitis C,” are written in simple language and have been field tested for readability. The booklets explain the causes, risk factors, diagnosis, treatment and prevention of the virus. The booklets are also available in Spanish.
Two fact sheets for physicians are also included in the folder. “Vaccination for Hepatitis A and B” provides vaccination dosing schedules. “Chronic Hepatitis C: Current Disease Management,” which has been updated by the expert panelists from the 1997 Consensus Development Conference on Hepatitis C, includes the combination therapy (alpha interferon and ribavirin) that was approved by the U.S. Food and Drug Administration.
To receive one free copy of the hepatitis folder, the request may be faxed, along with the mailing address and telephone number, to the NDDIC at 301-907-8906 or mailed to NDDIC, 2 Information Way, Bethesda, MD 20892-3570.
New Booklets on Racial and Ethnic Issues in Health Care
Many racial and ethnic minorities experience unequal access to the many advances made in medical technology and basic health care services, reports the Kaiser Family Foundation. In response to this problem, the foundation has published three new booklets made up of materials that were presented at a recent forum on improving minority access to medical care.
“Key Facts: Race, Ethnicity & Medical Care” (publication no. 1523) provides information and corresponding charts on racial and ethnic disparities in the following areas: health; health coverage; access to preventive and primary care; and the use of medical care for specific conditions such as heart disease, cancer, asthma and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).
“A Synthesis of the Literature” (publication no. 1526) summarizes research that was conducted between 1985 and 1999 on racial and ethnic differences in health care. The research included racial differences in heart disease and stroke, cancer, diabetes, HIV/AIDS, mental health, and maternal and child health.
“Perceptions of How Race & Ethnic Background Affect Medical Care: Highlights from Focus Groups” (publication no. 1524) summarizes the findings of 12 separate focus groups that were conducted to better understand how race and ethnic background affect medical care. Seven of the focus groups were minority health care consumers and the other five groups were health care professionals and hospital administrators.
For additional copies of the booklets, contact the Kaiser Family Foundation publications request line at 800-656-4533. Copies may also be obtained on the Web at http://www.kff.org.
Role of Warfarin Therapy in Older Patients
Older persons especially are at risk for systemic thromboembolism, including stroke, and other conditions that are treated with oral anticoagulants. However, oral anticoagulant therapy is often underused in older patients, according to the American Geriatrics Society (AGS). In response, the Clinical Practices Committee of the AGS has developed clinical practice guidelines on the use of oral anticoagulants (warfarin) in older persons. The guidelines appear in the February 2000 issue of the Journal of the American Geriatrics Society.
The AGS guidelines outline the indications for warfarin therapy as shown by properly designed clinical trials; factors associated with an increased risk for bleeding during treatment; and general guidelines for dosing, monitoring and reversal of therapy in patients older than 65 years.
According to the AGS committee, the indications for anticoagulation include: prevention of venous thrombosis and thromboembolism; treatment of deep vein thrombosis and pulmonary embolism; nonvalvular atrial fibrillation; cardiomyopathy; valvular heart disease; tissue or mechanical prosthetic heart valves; and acute myocardial infarction. The AGS recommendations also cover the identification of bleeding risk, the initiation of anticoagulation, monitoring of anticoagulation, the intensity of anticoagulation and the reversal of anticoagulant therapy.
Conflicting factors, such as age of the patient, risks versus benefits of treatment and concurrent medical conditions, can make it difficult for practicing physicians to interpret the written guidelines and to decide whether anticoagulants are the best treatment option for their patients. As a result, the AGS states that physicians must communicate the risks and benefits of warfarin therapy to the patient, the family and/or the caregiver, and properly document the factors that lead to the clinical decision in the medical record.