Safety Announcement From FDA - High-Dose Zocor and Increased Risk of Muscle Injury

FDA Drug Safety Communication: Ongoing safety review of high-dose Zocor* (simvastatin) and increased risk of muscle injury

[3-19-2010] Based on review of data from a large clinical trial and data from other sources, the U.S. Food and Drug Administration (FDA) is informing the public about an increased risk of muscle injury in patients taking the highest approved dose of the cholesterol-lowering medication, Zocor (simvastatin) 80 mg, compared to patients taking lower doses of simvastatin and possibly other drugs in the "statin" class.

The clinical trial data being reviewed is from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial. The agency is also reviewing data from other clinical trials, observational studies, adverse event reports, and data on prescription use of simvastatin to better understand the relationship between high-dose simvastatin use and muscle injury (see Data Summary below).

The muscle injury, also called myopathy, is a known side effect with all statin medications. Patients with myopathy generally have muscle pain, tenderness or weakness, and an elevation of a muscle enzyme in the blood (creatine kinase). The higher the dose of statin used, the greater the risk of developing myopathy. The risk of myopathy is also increased when simvastatin, especially at the higher doses, is used with certain drugs (see Simvastatin Dose Limitations below).

The most serious form of myopathy is called rhabdomyolysis. It occurs when a protein (myoglobin) is released as muscle fibers break down. Myoglobin can damage the kidneys. Patients with rhabdomyolysis may have dark or red urine and fatigue, in addition to their muscle symptoms. Damage to the kidneys from rhabdomyolysis can be so severe that patients may develop kidney failure, which can be fatal.

Known risk factors for developing rhabdomyolysis include age (> 65 years), low thyroid hormone levels (hypothyroidism), and poor kidney function. Myopathy and rhabdomyolysis are listed as possible side effects in the simvastatin and other statin drug labels.

Healthcare professionals should:

· Understand that rhabdomyolysis is a rare adverse event reported with all statins.

· Be aware of the potential increased risk of muscle injury with the 80 mg dose of simvastatin compared to lower doses of simvastatin and possibly other statin drugs.

· Follow the recommendations in the simvastatin label regarding drugs that may increase the risk for muscle injury when used with simvastatin (see Simvastatin Dose Limitations below).

Patients should:

· Not stop taking simvastatin unless told to by their healthcare professional.

· Talk to their healthcare professional about any questions they have about the use of simvastatin.

· Call their healthcare professional if they experience any of the following: muscle pain, tenderness or weakness, urine that is dark or red-colored, or unexplained tiredness.

This communication is in keeping with FDA's commitment to inform the public about its ongoing safety review of drugs. The agency will update the public as soon as this review is complete.

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

Additional Information for Patients

Patients currently using 80 mg simvastatin should:

· Know that rhabdomyolysis is a rare side effect reported with all statin medications.

· Not stop taking simvastatin unless told to by their healthcare professional.

· Review their medical history and current medications with their healthcare professional to determine if they should continue using simvastatin.

· Talk to their healthcare professional about any questions or concerns they have about simvastatin.

· Call their healthcare professional if they have muscle pain, tenderness or weakness, dark or red colored urine, or unexplained tiredness.

· Report any side effects with simvastatin to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.

Additional Information for Healthcare Professionals

FDA recommends that healthcare professionals should:

· Understand that rhabdomyolysis is a rare adverse event reported with all statins.

· Be aware of the potential increased risk of muscle injury with the 80 mg dose of simvastatin compared to lower doses of simvastatin and possibly other statin drugs.

· Review patients' medical history and medications to determine if simvastatin is clinically appropriate.

· Discuss with patients the benefits and risks, including the risk of myopathy and rhabdomyolysis, of simvastatin therapy.

· Be aware of potential drug-drug interactions with simvastatin.

· Report any adverse events associated with the use of simvastatin to FDA's MedWatch program using the information in the "Contact Us" box at the bottom of the page.

Data Summary

FDA's review of the SEARCH trial is part of the agency's continuing effort to evaluate the risk of muscle injury with simvastatin; this review includes evaluating data from clinical trials, observational studies, and adverse event reports, as well as data on prescription use of simvastatin.

The SEARCH trial evaluated over 6.7 years the number of major cardiovascular events (heart attack, revascularization, and cardiovascular death) in 6031 patients taking 80 mg of simvastatin compared to 6033 patients taking 20 mg of simvastatin. All patients in the study had previously had a heart attack.

Preliminary SEARCH trial results revealed that more patients in the simvastatin 80 mg group developed myopathy compared to patients in the simvastatin 20 mg group (52 [0.9%] cases compared to 1 case [0.2%]). Further, FDA's preliminary analyses of the primary data suggest that 11 (0.02%) of the patients in the simvastatin 80 mg group developed rhabdomyolysis compared to no patients in the simvastatin 20 mg group.

In 2008, the agency alerted the public about an increased risk of developing rhabdomyolysis when doses greater than 20 mg of simvastatin are given with amiodarone. The agency also included information about this drug interaction in its Summer 2008 issue of the FDA Drug Safety Newsletter¹ and in its November 2008 Patient Safety News broadcast².

In March 2010, FDA approved a labeling revision for simvastatin based on interim results from an ongoing clinical trial – the Heart Protection Study 2 (HPS2). The revised label states that patients of Chinese descent should not receive simvastatin 80 mg with cholesterol-modifying doses of niacin-containing products. Further, the revised label recommends caution when such patients are treated with simvastatin 40 mg or less in combination with cholesterol-modifying doses of niacin-containing products. The interim HPS2 results showed that the incidence of myopathy was higher in patients of Chinese descent (0.43%) compared with patients not of Chinese descent (0.03%) taking 40 mg simvastatin plus cholesterol-modifying doses (≥1 g/day) of a niacin-containing product. It is not known if the increased risk for myopathy observed in these patients applies to other patients of Asian descent.

Moreover, FDA has requested that the sponsor of simvastatin change the product labeling to instruct healthcare professionals to avoid prescribing simvastatin doses greater than 40 mg daily when patients are taking the medication diltiazem, due to an increased risk for myopathy.

A 2010 review of prescription drug use data conducted by FDA found that, despite dose limitations and drug-drug interaction precautions included in the simvastatin drug label, patients are continuing to be prescribed higher doses of simvastatin with other medications that are known to increase the risk for rhabdomyolysis (see Simvastatin Dose Limitations below).

It is important for healthcare professionals to consider the potential risks and known benefits of simvastatin compared to other cholesterol-lowering therapies when deciding to use simvastatin. Healthcare professionals should also carefully review patients' medications for potential drug-drug interactions before prescribing or dispensing simvastatin.

This communication is in keeping with FDA's commitment to inform the public about its ongoing safety review of drugs. The agency will update the public as soon as this review is complete.

Ongoing Safety Review of High-dose Zocor (simvastatin) and Increased Risk of Muscle Injury http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204882.htm

FLOOD SAFETY: No matter what time of year it is, there is always a risk for flooding. There are many states being impacted by floods. Be sure to listen to your local news and weather for safety information specific to your area. For more information, visit the following sites:

• http://www.weather.gov/ahps/
• http://emergency.cdc.gov/disasters/floods/
• http://www.fema.gov/hazard/flood/index.shtm

Class I Recall: Baxter's HomeChoice Peritoneal Dialysis Cycler

FDA Classifies Baxter's January HomeChoice Peritoneal Dialysis Cycler Field Corrective Action as a Class I Recall

Baxter is Deploying Revised Labeling, Training and Upcoming Software Revisions to Further Assist Clinicians and Patients

DEERFIELD, Ill., March 2, 2010 – Baxter Healthcare Corporation announced today that the U.S. Food and Drug Administration (FDA) has classified Baxter’s recent Urgent Product Recall regarding Increased Intraperitoneal Volume (IIPV), or overfill of the abdominal cavity, associated with HomeChoice and HomeChoice Pro peritoneal dialysis cyclers as a Class I recall. This action has been classified as a Class I recall because of the risk of serious injury or patient death that could be associated with the use of this device. Over the last two years, Baxter has received serious injury reports and at least one patient death report associated with this issue.

About IIPV

IIPV may result in serious injury or death from conditions such as: abdominal wall and/or diaphragmatic hernias, hydrothorax, heart failure, acute hypertension, pulmonary edema, decreased pulmonary function and pericardial effusion. Children and non-verbal patients may be at increased risk because of their smaller size and/or inability to communicate. Increased monitoring of these patients is recommended. Other vulnerable populations include critically ill patients and patients with pulmonary and hemodynamic instability.

Patients and caregivers should watch for the potential signs of IIPV. These include: difficulty breathing; vomiting or spitting up; a child complaining of a “funny feeling” in the abdomen; a child crying during therapy without other apparent reasons; difficulties feeding; feeling full, bloated, or overfilled after treatment; abdominal pain or discomfort; expanded or tense abdomen; localized swelling around the genital area (labia, scrotum) or groin region, belly button, the tunnel tract of the peritoneal dialysis catheter or the PD catheter exit site; leakage of fluid from the PD catheter exit site; and unexpected increase in blood pressure.

If patients or caregivers notice any of these symptoms, they should stop the device, initiate manual drain, and contact their healthcare provider immediately. Additional information that will be relevant in assessing patients for IIPV includes: careful monitoring of pre- and post-treatment weight; evaluating vital signs including heart rate and blood pressure; review of the recorded ultrafiltration from the device; and development of symptoms of respiratory distress or increased effort in breathing. For patients in a clinic, hospital, or critical care setting, clinicians should consider increased monitoring. This would include evaluating oxygen saturation and evidence of abdominal tenseness.

Baxter is continuing to investigate the causes, fixes, and mitigations associated with IIPV and use of the HomeChoice device. Current mitigations under development and implementation include changes to device labeling and software, which are intended to address issues such as prescription and patient errors, including bypassing alarms. Patients will receive new Patient At-Home Guides, which contain expanded information about IIPV, the symptoms, warnings and cautions, and how to address IIPV, should it occur. Baxter has also developed and is validating a software modification to address this issue and plans to submit a 510(k) to the FDA midyear. The software update will include additional user interface messages and alarms, and change default settings and allowable ranges to reduce risk of excessive accumulation of fluid in the peritoneal cavity.

HomeChoice systems are intended for automatic control of dialysis solutions exchange in the treatment of adult and pediatric renal failure patients undergoing peritoneal dialysis. The recall notice does not require the physical return of HomeChoice units and patients may continue using them. Affected model numbers include: 5C4471, 5C4471R, 5C8310, 5C8310R, 5C4474, 5C4474R, R5C8320, R5C8320R, T5C4441, T5C4441R, T5C8300, T5C8300R, 5C4474D and 5C4474DR. It is important that clinicians rev the prescription settings for devices to help reduce prescription errors and weigh the risks and benefits of continued use of this device by their patients.

Baxter sent recall notices to clinicians and patients informing them of this action and identifying steps that are intended to reduce the harm associated with IIPV. These January 2010 letters contain more detailed information about device usage and are available at www.baxter.com. Customers or patients with questions regarding this notice may contact Baxter 24 hours a day, seven days a week at 1-800-553-6898. Any adverse reactions experienced with the use of this product, and/or quality problems, should be reported to Baxter’s Renal business at 1-888-736-2543, prompt 3, and the FDA's MedWatch Program at 1-800-FDA-1088 or www.fda.gov/MedWatch/report.htm .

“We are committed to providing peritoneal dialysis patients with the safest and most effective therapy possible,” said Bruce McGillivray, president of Baxter’s Renal business. “We stand ready to support our patients and the nephrology community as we develop and implement measures intended to reduce the occurrence of IIPV.” The company does not expect the corrections required to address the IIPV issue to be financially material.

Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

This release includes forward-looking statements concerning the company’s HomeChoice systems, including expectations with respect to the cost of addressing the IIPV issue identified in this release. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: future actions of regulatory bodies and other governmental authorities, including the FDA and foreign counterparts that could substantially affect the nature or timing of the company’s actions; additional product development steps, including software development; product quality or patient safety issues; and the other factors identified in the company’s most recent filing on Form 10-K and other SEC filings, all of which are available on the company’s web site. The company does not undertake to update its forward-looking statements.

March is National Kidney Month

http://www.nkdep.nih.gov/kidneymonth/

Kidneys filter your blood. They remove wastes and extra water. When the kidneys are diseased, they stop doing these jobs and wastes build up, damaging the body. If not treated, kidney disease can lead to kidney failure. But you can prevent kidney failure.

Early kidney disease has no symptoms. Most people don't know something is wrong until their kidneys are about to fail. The only way to tell if you have kidney disease is to get tested. Simple blood and urine tests are used to detect kidney disease.

RECALL: OneTouch SureStep Test Strips (LifeScan)

LifeScan and FDA notified healthcare professionals of a voluntary recall of eight lots of OneTouch SureStep Test Strips, used by people with diabetes to measure their blood glucose levels at home. The test strips are being recalled because they may provide falsely low glucose results when the glucose level is higher than 400 mg/dL. If patients use the falsely low test results to determine their insulin dose, they may give themselves too little insulin, which could result in poor blood glucose control. High blood glucose must be recognized and treated promptly to avoid serious complications, such as coma and death. The eight lots of consumer OneTouch SureStep Test Strips being recalled are identified in the firm's press release. Lot numbers are located on the outer carton and test strip vial. LifeScan estimates approximately fourteen thousand packages (50- and 100-count) of consumer OneTouch SureStep Test Strips were distributed nationwide between August 1, 2009 and January 28, 2010. It is important that patients with recalled test strips continue to test their blood glucose. Patients with access to a meter that does not use OneTouch SureStep Test Strips should use this other meter to test their blood glucose until replacement product from LifeScan arrives. If an alternate meter is not available, patients may continue to test using the recalled OneTouch SureStep Test Strips. However, if patients obtain results above 400 mg/dL, they should contact their healthcare professional for further instructions because their glucose may be significantly higher. Read the complete MedWatch 2010 Safety summary, including a link to the firm's press release.