FDA Approves Simponi to Treat Ulcerative Colitis

The U.S. Food and Drug Administration today approved a new use for Simponi (golimumab) injection to treat adults with moderate to severe ulcerative colitis.

Simponi works by blocking tumor necrosis factor (TNF), which plays an important role in causing abnormal inflammatory and immune responses. Previously approved to treat rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis (arthritis affecting the joints in the spine and the pelvis), Simponi is now approved to treat adults with moderate to severe ulcerative colitis that is resistant (refractory) to prior treatment or requires continuous steroid therapy. [Read more…]

New Tool to Help Prevent Intentional Food Contamination

The U.S. Food and Drug Administration has released a new tool to help bolster the food industry’s defense measures against an act of intentional food contamination. The Food Defense Plan Builder is a comprehensive, easy-to-use software program designed to help owners and operators of food facilities—ranging from primary production and manufacturing to retail and transportation—develop customized plans to minimize the risk of intentional contamination at their individual food facilities.

The FDA does not require food facilities to implement food defense plans, but many facilities have voluntarily put such plans into place to safeguard their products. [Read more…]

FDA Orders Post-Market Surveillance of Some TMJ Implants

Today the U.S. Food and Drug Administration ordered three manufacturers of temporomandibular joint (TMJ) implants to conduct postmarket surveillance studies to determine the length of time before the implants are removed or replaced due to pain or other reasons.

The TMJ connects the lower jaw (mandible) to the temporal bone in the skull. A person may have an implant to replace the socket in the temporal bone or the rounded edge of the lower jaw that glides in the temporal bone socket because of an injury, arthritis, physical abnormality, or lost mobility. [Read more…]

Asclera Approved by FDA for Varicose Vein Treatment

The U.S. Food and Drug Administration today approved Asclera (polidocanol) injection for the treatment of small types of abnormally swollen or twisted veins called varicose veins.

Although they usually occur in the legs, varicose veins also can form in other parts of the body. Factors such as genetics, age, female gender, pregnancy, obesity, and prolonged periods of standing may increase the risk for varicose veins.

“Varicose veins are a common condition,” said Norman Stockbridge, M.D., Ph.D., director of the Division of Cardiovascular and Renal Products at the FDA’s Center for Drug Evaluation and Research. “Asclera is indicated for the treatment of small types of varicose veins when the aim of treatment is to improve appearance.”

Asclera is approved to close spider veins (tiny varicose veins less than 1 millimeter in diameter) and reticular veins (those that are 1 to 3 millimeters in diameter). Asclera acts by damaging the cell lining of blood vessels. This causes the blood vessel to close, and it is eventually replaced by other types of tissue.

Common adverse reactions to Asclera include leakage and collection of blood from damaged blood vessels at the injection site (hematoma), bruising, irritation, discoloration, and pain at the injection site.

Asclera is distributed by BioForm Medical Inc. of Franksville, Wis., and manufactured by Chemische Fabrik Kreussler & Co. of Wiesbaden, Germany.

Source: FDA, March 30, 2010

FDA Reports Outbreak Related to Raw Milk

Latest outbreak of campylobacteriosis in Midwest is linked to unpasteurized product.

The U.S. Food and Drug Administration, along with several state agencies, is alerting consumers to an outbreak of campylobacteriosis associated with drinking raw milk. At least 12 confirmed illnesses have been recently reported in Michigan. Symptoms of campylobacteriosis include diarrhea, abdominal pain and fever.

The FDA is collaborating with the Michigan Department of Community Health (MDCH), the Illinois Department of Public Health, the Indiana State Board of Animal Health and the Indiana State Health Department, to investigate the outbreak. MDCH reports that, as of March 24, 2010, it received reports of 12 confirmed cases of illness from Campylobacter infections in consumers who drank raw milk. The raw milk originated from Forest Grove Dairy in Middlebury, Ind.

Raw milk is unpasteurized milk from hoofed mammals, such as cows, sheep, or goats. Raw milk may contain a wide variety of harmful bacteria – including Salmonella, E. coli O157:H7, Listeria, Campylobacter and Brucella — that may cause illness and possibly death. Public health authorities, including FDA and the Centers for Disease Control and Prevention, have expressed concerns about the hazards of drinking raw milk for decades.

Symptoms of illness caused by various bacteria commonly found in raw milk may include vomiting, diarrhea, abdominal pain, fever, headache and body ache. Most healthy individuals recover quickly from illness caused by raw milk. However, some people may have more severe illness, and the harmful bacteria in raw milk can be especially dangerous for pregnant women, the elderly, infants, young children and people with weakened immune systems.

If consumers of raw milk are experiencing one or more of these symptoms after consuming raw milk or food products made from raw milk, they should contact their health care provider immediately.

Since 1987, the FDA has required all milk packaged for human consumption to be pasteurized before being delivered for introduction into interstate commerce. Pasteurization, a process that heats milk to a specific temperature for a set period of time, kills bacteria responsible for diseases, such as listeriosis, salmonellosis, campylobacteriosis, typhoid fever, tuberculosis, diphtheria and brucellosis. FDA’s pasteurization requirement also applies to other milk products, with the exception of a few aged cheeses.

From 1998 to 2008, 85 outbreaks of human infections resulting from consumption of raw milk were reported to CDC. These outbreaks included a total of 1,614 reported illnesses, 187 hospitalizations and 2 deaths. Because not all cases of foodborne illness are recognized and reported, the actual number of illnesses associated with raw milk likely is greater.

Proponents of drinking raw milk often claim that raw milk is more nutritious than pasteurized milk and that raw milk is inherently antimicrobial, thus making pasteurization unnecessary. There is no meaningful nutritional difference between pasteurized and raw milk, and raw milk does not contain compounds that will kill harmful bacteria.

Source: FDA (March 26, 2010)

Xifaxan Approved by FDA for Patients with Liver Disease

The U.S. Food and Drug Administration (FDA) today approved the use of Xifaxan for reduction in the risk of the recurrence of overt hepatic encephalopathy (HE) in patients with advanced liver disease. This is a new use for Xifaxan (rifaximin), a drug that has been approved for the treatment of traveler’s diarrhea.

Hepatic encephalopathy is a worsening of brain function that can occur in patients whose liver can no longer remove toxins from the blood. Increased levels of ammonia in the blood are thought to play a role in the development of HE, and Xifaxan works by reducing these levels.

“The approval of Xifaxan for this new indication provides an additional treatment option for patients with liver disease,” said Joyce Korvick, M.D., deputy director for safety of FDA’s Division of Gastroenterology Products. “Hepatic encephalopathy occurs commonly in patients with liver disease, and there are few effective treatments for this serious condition.”

The efficacy of Xifaxan was established in a randomized placebo-controlled clinical trial of adult patients from the United States, Canada, and Russia. Patients with liver disease who entered the trial had no or mild symptoms of HE. Patients treated with Xifaxan were less likely to develop HE during the trial, compared to placebo-treated patients.

Xifaxan was not studied in patients with the most severe forms of liver disease. Since most patients were also taking lactulose (a synthetic sugar which helps prevent absorption of ammonia from the intestine) during the trial, the efficacy of Xifaxan as a stand-alone treatment for HE could not be assessed.

The most common adverse reactions reported with the use of Xifaxan in patients with liver disease include swelling of the arms and legs (peripheral edema), nausea, gas, and headache.

Xifaxan received a priority review under FDA’s new drug application process and was granted orphan designation status. Xifaxan is manufactured by Salix Pharmaceuticals Inc. of Morrisville, N.C.

Source: Food and Drug Administration (March 24, 2010)

Zocor May Increase Muscle Injury Risk

The U.S. Food and Drug Administration today warned patients and healthcare providers about the potential for increased risk of muscle injury from the cholesterol-lowering medication Zocor (simvastatin) 80 mg.

Although muscle injury (called myopathy) is a known side effect with all statins, today’s warning highlights the greater risk of developing muscle injury, including rhabdomyolysis, for patients when they are prescribed and use higher doses of this drug. Rhabdomyolysis is the most serious form of myopathy and can lead to severe kidney damage, kidney failure, and sometimes death.

“Review of simvastatin is part of an ongoing FDA effort to evaluate the risk of statin-associated muscle injury and to provide that information to the public as it becomes available,” said Eric Colman, M.D., Deputy Director of FDA’s Division of Metabolism and Endocrinology Products (DMEP). “It’s important for patients and healthcare professionals to consider all the potential risks and known benefits of any drug before deciding on any one therapy or dose of therapy.”

Simvastatin is sold as a single-ingredient generic medication and as the brand-name Zocor. It also is sold in combination with ezetimibe as Vytorin, and in combination with niacin as Simcor.

FDA’s review of new information on the risk of muscle injury is derived from clinical trials, observational studies, adverse event reports, and prescription use data. The agency also is reviewing data from the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial, which evaluated major cardiovascular events, such as heart attack, revascularization and cardiovascular death, in patients taking 80 mg compared to 20 mg of simvastatin. SEARCH also included data on muscle injury in patients taking simvastatin.

FDA is committed to informing the public about its ongoing safety review of drugs and will update the public as soon as the review of simvastatin is complete.

Source: FDA, March 19. 2010

Onglyza, a New Type 2 Diabetes Drug Approved by FDA

The U.S. Food and Drug Administration (FDA) today approved Onglyza (saxagliptin), a once-daily tablet to treat Type 2 diabetes in adults. The medication is intended to be used with diet and exercise to control high blood sugar levels.

The hormone insulin keeps blood sugar (glucose) levels within a narrow range in people who don’t have diabetes. People with Type 2 diabetes are either resistant to insulin or do not produce enough insulin to maintain normal blood sugar levels.

Onglyza is in a class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors which stimulate the pancreas to make more insulin after eating a meal.

“Keeping blood sugar levels in adequate control is essential to the good health of the 24 million people in the United States with Type 2 diabetes,” said Mary Parks, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “High blood sugar levels can cause blurry vision and excessive urination and eventually result in such serious conditions as kidney and eye disease.”

The most common side effects observed with Onglyza are upper respiratory tract infection, urinary tract infection, and headache. Other side effects include allergic-like reactions such as rash and hives.

Approval of Onglyza was primarily based on the results of eight clinical trials. The application seeking FDA approval was submitted before December 2008 when the agency recommended that manufacturers of new diabetes drugs carefully design and evaluate their clinical trials for cardiovascular safety. Although Onglyza was not associated with an increased risk for cardiovascular events in patients who were mainly at low risk for these events, the FDA is requiring a postmarket study that will specifically evaluate cardiovascular safety in a higher risk population.

Onglyza is manufactured by Bristol-Myers Squibb Co. of Princeton, N.J., and marketed by Bristol-Myers and AstraZeneca Pharmaceuticals LP, of Wilmington, Del.

Source: FDA, July 31, 2009

FDA Warns of Potential Dangers of Botox and Botox Cosmetic

The U.S. Food and Drug Administration today notified the public that Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B) have been linked in some cases to adverse reactions, including respiratory failure and death, following treatment of a variety of conditions using a wide range of doses.

In an early communication based on the FDA’s ongoing safety review, the agency said the reactions may be related to overdosing. There is no evidence that these reactions are related to any defect in the products.

The adverse effects were found in FDA-approved and nonapproved usages. The most severe adverse effects were found in children treated for spasticity in their limbs associated with cerebral palsy. Treatment of spasticity is not an FDA-approved use of botulism toxins in children or adults.

The adverse reactions appear to be related to the spread of the toxin to areas distant from the site of injection, and mimic symptoms of botulism, which may include difficulty swallowing, weakness and breathing problems.

The FDA is not advising health care professionals to discontinue prescribing these products. The agency is currently reviewing safety data from clinical studies submitted by the drugs’ manufacturers, as well as post-marketing adverse event reports and medical literature. After completing a review of the data, the FDA will communicate to the public its conclusions, resulting recommendations, and any regulatory actions.

Early Communication from the FDA About Botox

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. Nor does it mean that FDA is advising healthcare professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the U.S.

These serious systemic adverse reactions occurred following treatment of a variety of conditions using a wide range of botulinum toxin doses. FDA is currently reviewing safety data from clinical studies submitted by the manufacturers of Botox, Botox Cosmetic and Myobloc, as well as post-marketing adverse event reports and the medical literature.

Botox (botulinum toxin type A) is approved for treatment of conditions such as blepharospasm (spasm of the eyelids), cervical dystonia (severe neck muscle spasms), and severe primary axillary hyperhydrosis (excess sweating). Botox Cosmetic, also botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines.

Myobloc (botulinum toxin Type B) is approved for the treatment of adults with cervical dystonia; the safety and effectiveness of Myobloc for cervical dystonia in children have not been established.

FDA is aware of the body of literature describing the use of botulinum toxins to treat limb spasticity in children and adults. The safety, efficacy and dosage of botulinum toxins have not been established for the treatment of limb spasticity of cerebral palsy or for use in any condition in children less than 12 years of age.

The current prescribing information (labeling) for Botox, Botox Cosmetic and Myobloc describes adverse reactions occurring in regions near the site of injection for each product’s approved uses, such as dysphagia (difficulty swallowing) after injections to treat cervical dystonia, or ptosis (drooping eye lids) after injections for glabellar frown lines or for strabismus and blepharospasm.

The Warnings sections of the labeling for both botulinum toxin products note that important systemic adverse effects, including severe difficulty swallowing and difficulty breathing have occurred in patients with neuromuscular disorders after local injection of typical doses of botulinum toxin. FDA now has evidence that similar, potentially life-threatening systemic toxicity from the use of botulinum toxin products can also result after local injection in patients with other underlying conditions such as those with cerebral palsy associated limb spasticity. Systemic toxicity has been reported in children, several of whom required feeding tubes and/or ventilation (breathing) support.

Until such time that FDA has completed its review, healthcare professionals who use medicinal botulinum toxins should:

  • Understand that potency determinations expressed in “Units” or “U” are different among the botulinum toxin products; clinical doses expressed in units are not comparable from one botulinum product to the next
  • Be alert to the potential for systemic effects following administration of botulinum toxins such as: dysphagia, dysphonia, weakness, dyspnea or respiratory distress
  • Understand that these effects have been reported as early as one day and as late as several weeks after treatment
  • Provide patients and caregivers with the information they need to be able to identify the signs and symptoms of systemic effects after receiving an injection of a botulinum toxin
  • Tell patients they should receive immediate medical attention if they have worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness

What does FDA know now about these data?

The FDA has reviewed post-marketing cases from its Adverse Event Reporting System (AERS) database and from the medical literature of pediatric and adult patients diagnosed with botulism following a local injection with a marketed botulinum toxin product.

The pediatric botulism cases occurred in patients less than 16 years old, with reported symptoms ranging from dysphagia to respiratory insufficiency requiring gastric feeding tubes and ventilatory support. Serious outcomes included hospitalization and death. The most commonly reported use of botulinum toxin among these cases was treatment of limb muscle spasticity associated with cerebral palsy. For Botox, doses ranged from 6.25 to 32 Units/kilogram (U/kg) in these cases. For Myobloc, reported doses were from 388 to 625 U/kg.

The reports of adult botulism cases described symptoms including patients experiencing difficulty holding up their heads, dysphagia and ptosis. Some reports described systemic effects that occurred distant from the site of injection and included weakness and numbness of the lower extremities. Among the adult cases that were serious, including hospitalization, none required intubation or ventilatory support. No deaths were reported. The doses for Botox ranged from 100 to 700 Units and for Myobloc from 10,000 to 20,000 U.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. FDA will communicate to the public its conclusions, resulting recommendations, and any regulatory actions after the review of the data are completed.

Report serious adverse events to FDA’s MedWatch reporting system by completing a form on line at http://www.fda.gov/medwatch/report/hcp.htm, by faxing (1-800-FDA-0178), by mail using the postage-paid address form provided online (5600 Fishers Lane, Rockville, MD 20853-9787),
or by telephone (1-800-FDA-1088)

Source: U.S. Food and Drug Administration (FDA)

FDA Warns of Possible Neuropsychiatric Side Effects to Pfizer’s Anti-Smoking Drug, Chantix (varenicline)

The U.S. Food and Drug Administration (FDA) has issued a Public Health Advisory to alert health care providers, patients, and caregivers to new safety warnings concerning Prfizer’s anti-smoking drug, Chantix (varenicline). The FDA’s "Early Communication" advises that the agency is evaluating adverse event reports on Chantix related to changes in behavior, agitation, depressed mood, suicidal ideation, and actual suicidal behavior.

As the agency’s review of the adverse event reports proceeds, it appears increasingly likely that there may be an association between Chantix and serious neuropsychiatric symptoms. As a result, FDA has requested that Pfizer, the manufacturer of Chantix, elevate the prominence of this safety information to the warnings and precautions section of the Chantix prescribing information, or labeling. In addition, FDA is working with Pfizer to finalize a Medication Guide for patients. This is an example of FDA working with drug manufacturers throughout products’ lifecycles to keep health care professionals and patients informed of new and emerging safety data.

"Chantix has proven to be effective in smokers motivated to quit, but patients and health care professionals need the latest safety information to make an informed decision regarding whether or not to use this product," said Bob Rappaport, M.D., director of the FDA’s Division of Anesthesia, Analgesia and Rheumatology Products. "While Chantix has demonstrated clear evidence of efficacy, it is important to consider these safety concerns and alert the public about these risks. Patients should talk with their doctors about this new information and whether Chantix is the right drug for them, and health care professionals should closely monitor patients for behavior and mood changes if they are taking this drug."

Chantix was approved by FDA in May 2006 as a smoking cessation drug. Chantix acts at sites in the brain affected by nicotine and may help those who wish to stop smoking by providing some nicotine effects to ease the withdrawal symptoms and by blocking the effects of nicotine from cigarettes if users resume smoking.

In the Public Health Advisory and a Health Care Professional Sheet that was also issued today, FDA emphasized the following safety information for patients, caregivers, and health care professionals:

Patients should tell their health care provider about any history of psychiatric illness prior to starting Chantix. Chantix may cause worsening of current psychiatric illness even if it is currently under control. It may also cause an old psychiatric illness to reoccur. FDA notes that patients with these illnesses were not included in the studies conducted for the drug’s approval.

Health care professionals, patients, patients’ families, and caregivers should be alert to and monitor for changes in mood and behavior in patients treated with Chantix. Symptoms may include anxiety, nervousness, tension, depressed mood, unusual behaviors and thinking about or attempting suicide. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of varenicline therapy.

Patients should immediately report changes in mood and behavior to their doctor.

Vivid, unusual, or strange dreams may occur while taking Chantix.

Patients taking Chantix may experience impairment of the ability to drive or operate heavy machinery.

FDA will continue to update health care professionals with new information from FDA’s continuing review or if new information is received on Chantix and serious neuropsychiatric symptoms. FDA may consider requesting further revisions to the labeling or taking other regulatory action as the agency’s continuing reviews and conclusions warrant.

Source: FDA, February 1, 2008