FDA Logo links to FDA home page
U.S. Food and Drug Administration
HHS Logo links to Department of Health and Human Services website

FDA Home Page | Search FDA Site | FDA A-Z Index | Contact FDA

horizonal rule

Updates

Topics in This Issue:

Companies Warned About Unapproved Accutane

The FDA has sent letters to several firms warning them to stop illegally selling an unapproved, mislabeled version of the acne drug Accutane (isotretinoin). The agency believes that this illegal practice may pose a serious health risk, and urges people not to use illegal foreign versions of the drug.

The illegal drugs include a gel version of Accutane, designed to be applied to the skin, which is sold only with foreign language labeling to American consumers through the Internet. Companies have sold the drug, which purports to be equivalent to Accutane, without requiring a prescription. Accutane can cause birth defects if taken by pregnant women, and is subject to a restrictive distribution program known as the System to Manage Accutane Related Teratogenicity (SMART) program. The term "teratogenicity" refers to the potential to cause birth defects.

Under the SMART program, only certain physicians may legally prescribe Accutane. In addition, the prescription must be filled within seven days, and it must have a yellow sticker that certifies the patient is not pregnant. Before starting the treatment regimen, the patient must be educated about the dangerous side effects associated with this drug product when it is improperly used.

Illegal Internet sales of Accutane reflect the dangers that Americans face when they buy foreign versions of U.S. drugs online. These sites are inherently risky because they bypass the strong risk-management program that the FDA has established to protect consumers.

New Drug to Lower Cholesterol

Crestor (rosuvastatin) is the latest addition to the class of cholesterol-lowering drugs known as statins (HMG-CoA reductase inhibitors). These drugs work by partially blocking the synthesis of cholesterol in the liver, which helps remove cholesterol from the blood.

The most frequent side effects seen in people treated with Crestor include muscle aches, stomach pain, constipation, nausea, and weakness. In rare instances, severe muscle pain and muscle weakness resulting in kidney damage have been associated with statin drugs. If general muscle aches persist, people taking these drugs should call their physicians. Patients should be monitored for abnormalities of liver function before treatment, at 12 weeks following initial therapy, and with any elevation of dose. Monitoring is recommended periodically after that.

In clinical trials, most people reached target low-density lipoprotein (LDL), or "bad" cholesterol, levels as recommended by the National Cholesterol Education Program on either the 5-milligram or 10-milligram starting dose. The 20-milligram dose may be prescribed as the starting dose for people with very high cholesterol levels. A 40-milligram dose also is available.

Crestor is marketed by AstraZeneca Pharmaceuticals LP of Wilmington, Del.

Labeling Updates to Genital Herpes Drug

The FDA has revised the labeling for the drug Valtrex (valacyclovir hydrochloride) to include using it to reduce the risk of transmitting genital herpes to heterosexual partners with healthy immune systems.

Genital herpes is a common sexually transmitted infection caused by herpes simplex viruses (HSV). Many individuals have no or minimal symptoms from genital HSV infection and may transmit the virus during sexual contact when they show no signs of genital lesions.

The FDA based its decision to allow this additional use for Valtrex on the results of a placebo-controlled study conducted by the manufacturer, GlaxoSmithKline of Research Triangle Park, N.C. Researchers found that the risk of transmission is reduced when Valtrex is taken daily to suppress outbreaks and when safe sex practices are followed.

At the beginning of the study of 1,500 heterosexual couples, only one member of each couple had evidence of genital herpes. Study results showed a 48 percent reduction in the transmission of genital herpes from the infected partner to the uninfected partner among those taking Valtrex.

The following safe sex practices lower the chances of passing genital herpes to a partner:

The FDA had previously approved Valtrex to be taken episodically--when a person has a genital herpes outbreak or feels one coming on, or suppressively--daily to help suppress the recurrence of outbreaks. Valtrex is also approved to help heal the lesions and to lessen the pain of an initial episode of genital herpes.

Valtrex may cause kidney and nervous system problems in individuals who already have kidney disease and in older people who have age-related kidney problems. People with kidney problems or other medical conditions should consult their health care providers before taking Valtrex.

FDA Approves First Injectable Solution for Dog Sterilization

The FDA has approved the first product for chemical sterilization of 3- to 10-month-old male puppies. The drug, Neutersol Injectable Solution (zinc gluconate neutralized by arginine), provides an alternative to surgical castration and may prove to be a valuable aid in efforts to control dog overpopulation.

Neutersol is injected by a veterinarian directly into each testicle of the puppy. The drug works by either causing the testes and prostate to shrink or preventing movement of sperm from the testes, making the puppy sterile. Neutersol does not require the use of general anesthesia, though sedation is recommended to prevent the dog from moving during injection.

Proper injection technique and post-injection care are critical for the safe use of the product. According to FDA veterinarian Elizabeth Luddy, "The most serious reaction we saw in laboratory and field testing was ulceration of the scrotum at the injection site, associated with incorrect injection technique, movement of the needle during injection or the dog licking or biting the area after injection." To help educate veterinarians and dog owners about these and other safety issues and to prevent the occurrence of serious side effects, the approved labeling includes an instructional videotape demonstrating the proper injection technique, and a client information sheet explaining the importance of post-injection monitoring and care.

Unlike surgical castration, dogs treated with Neutersol become sterile without removal of the testicles and, therefore, testosterone is not completely eliminated. Testosterone-related diseases, such as prostate disease and tumors located near the testicles and anus, may not be prevented with this procedure. As with surgical castration, secondary male characteristics (roaming, marking, aggression, or mounting) may still occur.

Neutersol is manufactured by Meridian Medical Technologies Inc. for Technology Transfer Inc. of Columbia, Mo., and is available for use only by or on the order of a licensed veterinarian.

Photofrin to Treat Precancerous Lesions in Barrett's Esophagus

Photofrin (porfimer sodium), a drug approved in 1995 to treat esophageal cancer, has been approved by the FDA for a new use: to destroy precancerous lesions in people with Barrett's esophagus who do not undergo surgery to remove the esophagus (esophagectomy).

Barrett's esophagus is a condition in which the esophagus, the tube that carries food and saliva from the mouth to the stomach, changes so that some of its lining is replaced by a type of tissue similar to that normally found in the intestine. Barrett's esophagus is estimated to affect about 700,000 adults in the United States, and is linked to the common condition gastroesophageal reflux disease (GERD).

Although Barrett's esophagus may cause no symptoms, a small number of people with this condition develop precancerous lesions that progress to an often-deadly type of cancer of the esophagus.

Photofrin is a light-activated drug (photosensitizing agent) used in photodynamic therapy (PDT), a treatment for some cancers. PDT destroys cancer cells with a laser light used in combination with a photosensitizing agent.

Research supporting the expanded use of Photofrin showed that patients receiving Photofrin PDT were more likely to have a complete reversal of their precancerous lesions in Barrett's esophagus compared to those who did not receive the treatment. Photofrin PDT patients also had an 80 percent chance of being cancer-free two years later; those who did not receive Photofrin PDT had a 50 percent chance of being cancer-free. Photofrin PDT's effectiveness in reducing the long-term risk of esophageal cancer is not known.

Side effects of Photofrin PDT treatment include esophageal narrowing (strictures) and photosensitivity reactions (swelling, redness or blistering of the body if exposed to direct sunlight). The drug's labeling includes information on precautions that should be taken to avoid exposure of skin and eyes to bright light.

Photofrin is distributed by Axcan Scandipharm Inc. of Birmingham, Ala.

FDA Warns Consumers About Star Anise Teas

People are being advised not to consume teas brewed from star anise after the FDA determined that such beverages have been associated with illnesses in people and infants. The illnesses range from serious neurological effects such as seizures, to vomiting, jitteriness and rapid eye movement.

Teas brewed from star anise are popular with some who believe that the brew helps to protect against colic in infants. However, the FDA says that it is unaware of any scientific evidence to support those beliefs. According to the FDA, consumers should not drink star anise teas or give them to infants and children.

The initial reported illnesses were identified through a record review after a resident physician from Miami Children's Hospital treating an infant with seizures associated with the ingestion of a star anise-containing tea reported his findings to the Florida Poison Information Center (FPIC). The FPIC then reported the findings to the FDA. All the affected individuals, including infants, recovered without complications.

The FDA has since learned of similar reports from Florida, Illinois, New Jersey, Texas, and Washington as well as the Netherlands, France, and Spain.

First in a New Class of Antibiotics

The FDA has approved Cubicin (daptomycin for injection) to treat complicated skin and skin structure infections. These serious infections usually occur in people who are hospitalized and include major abscesses, post-surgical skin wound infections, and infected ulcers.

Cubicin, which fights infections by inhibiting the production of protein, DNA and RNA in the cells of bacteria, causing the cells to die, is the first approved product in a new class of antibiotics called cyclic lipopeptide antibacterial agents.

The FDA based its decision in September 2003 to approve Cubicin on a review of clinical studies involving more than 1,400 adults. The studies showed Cubicin was equivalent to standard treatments (such as vancomycin or a semi-synthetic penicillin such as oxacillin or nafcillin) in the treatment of complicated skin and skin structure infections.

Most reported side effects were mild to moderate in intensity. The most common adverse events included gastrointestinal disorders, injection site reactions, fever, headache, insomnia, dizziness, and rash. People receiving Cubicin should be monitored for the development of muscle pain or weakness, and blood tests measuring creatine phosphokinase (CPK) levels should be monitored weekly. Those who develop unexplained elevations in CPK while on Cubicin should be monitored more frequently.

Cubicin is manufactured by Abbott Laboratories of McPherson, Kan., for Cubist Pharmaceuticals Inc. of Lexington, Mass.

FDA Approves New Oral Contraceptive

The FDA has approved Seasonale, a 91-day oral contraceptive regimen that reduces expected menstrual periods from once a month to about once every three months. Seasonale contains active ingredients that are already approved in oral contraceptives--progestin (levonorgestrel) and estrogen (ethinyl estradiol).

Tablets containing the active hormones are taken for 12 weeks, followed by one week of placebo (inactive) tablets. Conventional oral contraceptive use is based on a 28-day regimen (21 days of active tablets followed by 7 days of placebo tablets). As with the conventional 28-day regimen, women who take Seasonale will have menstrual periods while taking the placebo tablets.

Though Seasonale users have fewer scheduled menstrual cycles, data from clinical trials show that many women had more unplanned bleeding and spotting between the expected menstrual periods than women taking a conventional 28-day cycle oral contraceptive.

The risks of using Seasonale are similar to the risks of conventional oral contraceptives and include an increased risk of blood clots, heart attack, and stroke. The labeling also warns that cigarette smoking increases the risk of serious cardiovascular side effects.

Because Seasonale users can expect to have fewer periods, the label advises women to consider the possibility that they may be pregnant if they miss scheduled periods. Women should discuss contraceptive use, along with precautions and warnings, with their doctors.

Seasonale is manufactured by Barr Laboratories of Pomona, N.Y.

Hormone-free Claims to be Removed From Labeling

Four manufacturers of whole milk, reduced-fat milk, and ice cream received warning letters from the FDA in September 2003, informing them that their products are misbranded. The products' labeling contains the false statements "No Hormones" or "Hormone Free."

The warning letters explain that the statements make false claims because all milk contains naturally occurring hormones, and milk cannot be processed in a manner that renders it free of hormones.

The FDA also cautioned the firms that the agency could pursue further action such as seizure or injunction, or both, if they fail to take prompt action to correct the labels.

New Treatment for Hemophilia

People with hemophilia A now have another treatment available. The FDA has licensed a new clotting factor, the first one produced to treat the disorder without using human or animal blood additives in the manufacturing process.

Hemophilia is an inherited disorder that prevents blood from clotting normally. People with hemophilia are at risk for serious and sometimes life-threatening bleeding episodes. Individuals with hemophilia A, the most common of these disorders, are deficient in a specific blood clotting component called factor VIII.

The new product, ADVATE Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method, is produced using genetically engineered Chinese hamster ovary cells that have been altered to produce the deficient factor VIII. ADVATE is approved to prevent and control bleeding episodes or to prepare people with hemophilia for surgery.

The FDA has previously approved a number of products to treat hemophilia A, all containing human factor VIII made with additives derived from human or animal blood. These products and the new ADVATE require intravenous injections to prevent or treat bleeding episodes.

Factor VIII products that use human or animal components are considered very safe as a result of advances during the last two decades. These include viral inactivation and steps in manufacturing that are believed to effectively prevent transmission of hepatitis B, hepatitis C and HIV from these products. Since 1987, none of these products has been proved to transmit any of these infections. The manufacture of ADVATE without using human or animal components provides additional safeguards against any infectious risks that may arise from the use of these components.

ADVATE is manufactured by Baxter Healthcare Corp. of Westlake Village, Calif.

Olestra Labeling Change

The labeling requirement advising consumers about potential abdominal problems for foods containing the zero-calorie fat substitute olestra is no longer warranted, the FDA says.

The FDA announced in the Aug. 5, 2003, Federal Register that manufacturers will no longer need to include the label statement, required since olestra's approval in 1996. The statement informs consumers that olestra may cause abdominal cramping and loose stools in some people, that it inhibits the body's absorption of vitamins A, D, E, and K and other nutrients, and that these vitamins have been added to compensate for olestra's effects on these nutrients. Consumption studies of products containing olestra showed the fat substitute caused only infrequent, mild gastrointestinal effects in amounts that reflected typical dietary habits.

However, the FDA will require manufacturers to continue adding vitamins A, D, E, and K to such products.

Olestra was approved in 1996 for use in potato chips, cheese puffs, and other savory snacks. While the label changes are effective immediately, consumers can expect that there may be a period of time before companies introduce the new product label.

Growth Hormone for Short Stature

A brand of growth hormone has been approved for long-term treatment of children with short stature of unknown origin. This new indication for Humatrope (somatropin, rDNA origin, for injection) is the first approval for use of growth hormone in children that restricts the therapy to children under a specified height.

The American Association of Clinical Endocrinologists and the Growth Hormone Research Society define short stature as height more than two standard deviations (SD) below the mean for age and sex. This corresponds to the shortest 2.3 percent of children.

This new indication for Humatrope restricts therapy to children who are even shorter, specifically more than 2.25 SD below the mean for age and sex, or the shortest 1.2 percent of children. For example, for 10-year-old boys and girls, this corresponds to heights of less than 4 feet 1 inch. This would correspond to heights of less than 5 feet 3 inches in adult men and 4 feet 11 inches in adult women.

The manufacturer, Eli Lilly and Company of Indianapolis, has advised the FDA that it will not engage in direct-to-consumer advertising of Humatrope. Lilly also says that the drug's distribution will be tightly controlled. The company will limit the marketing of Humatrope for this new use to pediatric endocrinologists to better ensure proper use of the product.

Labeling Changes for Asthma Drug Salmeterol

New safety information and warnings have been added to the labeling of drug products that contain salmeterol, a long-acting bronchodilator used to treat asthma and chronic obstructive pulmonary disease (COPD). The products affected are Serevent Inhalation Aerosol, Serevent Diskus, and Advair Diskus, all manufactured by GlaxoSmithKline of Research Triangle Park, N.C.

The new labeling consists of a boxed warning about a small, but significant, increased risk of life-threatening asthma episodes or asthma-related deaths observed in people taking salmeterol in a large study. The labeling changes are based on analysis of the Salmeterol Multi-Center Asthma Research Trial (SMART), which compared the effects of salmeterol with an inactive substance (placebo) for 28 weeks in people with asthma.

Although SMART intended to enroll 60,000 people, GlaxoSmithKline stopped the study after an interim analysis, which revealed that a higher number of asthma-related deaths and life-threatening experiences were observed in the Serevent group. Other analyses showed no increase in respiratory or asthma-related events in whites. But among blacks in the study, there was a statistically significant increase in respiratory or asthma-related events in the Serevent group. In addition, the occurrence of asthma-related death and life-threatening experience was greater in blacks treated with Serevent compared with the placebo.

The FDA emphasizes that, based on available data, the benefits of treatment with salmeterol in people with asthma and COPD continue to outweigh the potential risks when used according to the product labeling. The FDA strongly advises people that they should not stop taking products that contain salmeterol without first talking to their physicians. Abruptly stopping drugs that treat asthma and COPD can result in serious worsening of these diseases that could be life-threatening. The FDA also emphasizes that all asthma drugs should be prescribed as part of a comprehensive plan that provides education about the disease and its proper treatment and takes into account a person's asthma severity.

Wider Use for Enbrel

A genetically engineered protein, already licensed for treatment of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, and psoriatic arthritis, has now been approved to treat patients with a chronic inflammatory disease called ankylosing spondylitis (AS), which similarly affects the lower back and joints.

Enbrel (etanercept) binds to tumor necrosis factor (TNF), a naturally occurring protein in the body, and inhibits its action. TNF, which promotes inflammation in the body, is found at elevated levels in the blood and certain tissues of patients with AS. It is believed that interference with TNF plays a role in the beneficial effects of Enbrel for AS. Enbrel is manufactured by Immunex Corp. of Seattle, and is marketed by Amgen Inc. of Thousand Oaks, Calif. and Wyeth Pharmaceuticals of Philadelphia.

About 350,000 people in the United States have AS. The disease affects men more often than women. Symptoms may start in adolescence and are usually present by age 30. People often have lower back pain and stiffness, chest pain, joint pain and swelling, and tenderness due to the inflammation. In some people, the disease can cause significant pain and disability for many years.

Currently approved drugs to treat the symptoms of AS include some non-steroidal anti-inflammatory drugs (NSAIDs). Another type of drug, called disease modifying anti-rheumatic drugs (DMARDs), is approved for use in other inflammatory joint diseases. DMARDs are sometimes used to treat AS when NSAIDs are ineffective, although none is currently FDA-approved for this use.

Antimicrobial Spray Safe for Fighting E. coli

The FDA has allowed a Utah company to market an antimicrobial spray that, when applied to uncooked beef carcasses, helps fight E. coli O157:H7, an organism that can cause severe gastrointestinal disease or death in humans.

The company, aLF Ventures of Salt Lake City, submitted a notice to the FDA providing scientific data supporting the firm's conclusion that lactoferrin--an antimicrobial protein found in cow's milk and beef--is not required to be approved by the FDA because use of the substance in foods is considered "generally recognized as safe" (GRAS). This means its safety has been established by available scientific data that has led qualified experts to conclude that the use of the ingredient is safe for its intended purpose.

In addition, the information submitted to the FDA stated that the amount of added lactoferrin that remains on the beef after spraying is comparable to the amount that naturally occurs in the beef. The company also submitted data to the U.S. Department of Agriculture (USDA). The USDA is responsible for addressing labeling issues with lactoferrin-treated beef.

horizonal rule