All prescription drugs that desire to be marketed in the U.S. must gain the approval of the Food and Drug Administration (FDA). Through the Center for Drug Evaluation and Research (CDER), which assures that safe and effective drugs are available to the American people, a prescription drug must pass a series of trials. Please understand that the FDA does not develop, manufacture or test drugs. Drug manufacturers submit full reports of a drug’s studies to the CDER so that the Center can evaluate its data. The studies answer the question, “Does this drug work for the proposed use?” By analyzing the data, CDER reviewers assess the benefit-to-risk relationship and determine if the drug will be approved. Once the drug has been placed on the market, the FDA continues to monitor it through post-marketing reports sent in by the manufacturer and through the MedWatch program – an FDA program that allows consumers and health care professionals to report serious side effects, quality control issues, and medical errors associated with drugs and products regulated by the FDA.

Sometimes, an unanticipated side effect manifests itself once the drug has been made available to the U.S. market. If the side effect is serious enough, the FDA may issue a warning to the public and request that changes be made to the drug’s label. If the side effect is extremely serious and the FDA decides that the risks of the drug outweigh its benefits, then the FDA may recall the drug.

Speak to a Lawyer

Each year, thousands of people die from or are seriously injured by prescription drugs, over-the-counter drugs and medical devices they believe to be safe. If you or a loved one have taken a defective drug, experienced problems with a defective medical device or used a defective product, then contact our law firm immediately. Consult an attorney privately to learn your legal rights. All information is held in the strictest of confidence.

Contact a Drug Lawsuit Lawyer & Attorney

For a free and confidential consultation, fill out our online case evaluation form or call us toll free at: 1-800-883-9858.

Legal help: Contact an Attorney

On 7-13-2011, the FDA issued an update to warn of further complications and adverse effects connected to the transvaginal placement of surgical mesh. A previous warning was issued in 2008, but the emergence of new complications in numerous patients necessitated an official update to the original warning. The most up to date FDA warning also acknowledges that the complications associated with transvaginal mesh are not rare, which is a modification from the previous warning. The number of complaints regarding vaginal mesh almost tripled in the past 3 years, and is currently approaching a shocking 3000. Vaginal mesh has been found to expose patients to greater risk than other more traditional forms of non-mesh methods of vaginal repair. According to the FDA warning, the use of vaginal mesh is “an area of continuing serious concern.”

Vaginal Mesh Erosion Lawsuits

• ObTape Lawsuit
• Vaginal Mesh Erosion Warning by the FDA
• Bladder Sling Mesh Erosion Lawsuits
• ObTape Mesh Erosion Lawsuits
• Vaginal Mesh, Bladder Slings and ObTape Lawsuits
• Transvaginal Mesh Lawsuits

What is Vaginal Mesh?

Vaginal mesh and bladder slings along with ObTape are medical device composed of synthetic material implanted surgically for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapsed (POP). Vaginal mesh treats stress urinary incontinence by supporting the urethra to prevent unexpected bladder leakage, and strengthens weakened vaginal walls for the treatment of pelvic organ prolapse. The mesh is supposed to be a permanent solution to these conditions, however for many women the distressing consequences result in further surgery for its removal. Often times, these patients were not adequately warned of the possible complications and had they been aware, they might have chosen an alternative device or treatment method. In many cases stress urinary incontinence and pelvic organ prolapsed can be treated successfully without the use of mesh. Furthermore, using vaginal mesh, bladder slings and Ob Tape can make further surgical repairs more challenging.

Vaginal Mesh Erosion

Vaginal mesh erosion happens when the vaginal mesh, bladder sling and Ob Tape actually grinds through the fragile tissue of the vaginal walls. Also referred to as extrusion or protrusion, mesh erosion is the most regular and repeatedly reported mesh-related concern. According to the FDA warning, expulsion is a complication limited to transvaginal mesh and can be avoided through the use of conventional non-mesh surgical methods. Mesh erosion can require multiple invasive surgeries to fix and can be incapacitating for some women. In a number of severe cases, multiple surgeries will not even fully resolve the complication. Other potential risks associated with vaginal mesh include, but are not limited to, pain during sexual intercourse, recurring vaginal discharge, and persistent vaginal bleeding.

Talk to a Vaginal Mesh Lawyer Today

Many patients suffering from vaginal mesh, bladder sling or Ob Tape complications wish that they had been adequately warned of the risks and potential complications before undergoing the operation. If you or a loved one is suffering from vaginal mesh injuries please call the Willis Law Firm. We have female consultants standing by, trained to discuss these sensitive issues confidentially. We are currently accepting vaginal mesh injury lawsuits nationwide. Our product liability law team at the Willis Law Firm is committed to getting you answers and financial compensation for your medical expenses, loss of income, physical pain, and emotional suffering. These cases are handled on a Contingency Fee Basis, which means that no attorney’s fees or any other expenses will be charged unless we recover for you. Call us toll free at 1-800-883-9858 for a free case evaluation about Filing a Lawsuit.

Only a week after officials in both France and Germany began restricting the prescriptions of the diabetes drug Actos made by Takeda Pharmaceuticals, the US Food and Drug Administration (FDA) will now require additional warnings that the use of Actos for more than a year might be linked with an increased risk of developing bladder cancer. Only a week prior, a French study with similar findings propelled French officials to suspend the use of Actos and officials in Germany have recommended that doctors not prescribe Actos to new patients.

The statement by the FDA is in response to a 5-year interim analysis of an ongoing 10-year study of Actos risk of bladder cancer. The FDA’s analysis claims that while they don’t see any overall increase risk of bladder cancer with the use of Actos, they noted an increased Actos bladder cancer risk among patients taking Actos for more than a year as well as those taking higher dosages of Actos. French and German studies, however, did claim that there is an overall increased risk of bladder cancer with Actos as well as an even higher risk the longer Actos is taken.

The French decision was made by its version of the FDA, the AFSSAPS which based their move on a study conducted by a national French insurer which examined results of more than 1.5 million individuals between the ages 40 and 79 years old being treated with Actos between 2006 and 2009. France’s move on Actos has triggered a study by the European Medicines agency, the umbrella drug regulatory agency of Europe. Their study is currently ongoing. A further report in an issue of Diabetes Care, reported 93 incidences of bladder cancer among Actos patients in the FDA Adverse Event Reporting system databases spanning between 2004 and 2009.

Between January 2010 and October 2010 more than 2.3 million patients filled a prescription for diabetes drug Actos. Actos has enjoyed great results following the restrictions placed on sister drug Avandia. Actos has been perceived as the ‘safer’ of the two diabetes drug, but new results linking Actos to bladder cancer might change that perception. In addition to being linked with bladder cancer, Actos has also been recently linked to increased heart failure and bone fractures.

Actos Bladder Cancer Lawsuit

If you or a family member took Takeda Pharmaceutical’s drug Actos (pioglitazone) and you have developed bladder cancer, we encourage you to contact a pharmaceutical lawyer at our firm immediately. An experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action in a potential Actos bladder cancer lawsuit against the makers of the drug.

Please fill out our online legal evaluation form to the right or call us and we will contact you within 4-12 hours for a free confidential case review. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

[04/22/2011]

FDA has updated the Tysabri (natalizumab) Prescribing Information to give new information about the size of the risk of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection, associated with use of Tysabri for the treatment of multiple sclerosis (MS) and Crohn’s disease. The update includes new safety information about patients who have taken other drugs that suppress the immune system, who may be at a higher risk for PML. Tysabri, in a class of medications called immunomodulators, has been approved by the FDA for the treatment of relapsing forms of multiple sclerosis since November 2004 and for the treatment of moderately to severely active Crohn’s disease since January 2008. The revised label includes a table summarizing rates of PML with Tysabri use according to the number of infusions (how long the drug is taken or duration of exposure) and information on a newly identified PML risk factor.

[02/05/2010]

FDA notified healthcare professionals and patients that the risk of developing progressive multifocal leukoencephalopathy (PML) increases with the number of Tysabri infusions received. This new safety information, based on reports of 31 confirmed cases of PML received by the FDA as of January 21, 2010, will now be included in the Tysabri drug label and patient Medication Guide. Information about the occurrence of immune reconstitution inflammatory syndrome (IRIS) in patients who have developed PML and subsequently discontinued Tysabri has also been added to the drug label. IRIS is a rare condition characterized by a severe inflammatory response that can occur during or following immune system recovery, causing an unexpected decline in a patient’s condition after return of immune function.

Based on the available information, FDA believes that the clinical benefits of Tysabri continue to outweigh the potential risks. Revisions to the drug label and patient Medication Guide, with the continued use of the TOUCH Prescribing Program, are intended to maximize the safe use of Tysabri and the identification of new PML cases.

Here is an important new warning about the heart drug Multaq (generic name: dronedarone), which is linked to severe liver injury. See also: Multaq Liver Failure Lawsuits,

The FDA has just classified this medication as a DO NOT USE medication.

Do not discontinue use of any medication without talking to your doctor first.

On January 14, 2011, the Food and Drug Administration (FDA) issued a safety announcement to health professionals and consumers about cases of rare, but severe liver injury in patients taking the anti-arrhythmic drug Multaq. The agency cited the cases of two patients who experienced liver failure and required liver transplants.

Then, on March 10, 2011, the maker of Multaq, Sanofi-aventis and Health Canada sent Canadian health professionals and patients much more comprehensive letters reporting that, in the 16 months from the launch of Multaq in July 2009 through November 2010, Sanofi-aventis had received 155 cases of liver injury (87 of these serious) including hepatic failure.

Read the full letters:

• Multaq FDA Warning: Multaq Dear Patient Letter
• Multaq FDA Warning: Multaq Dear Doctors Letter

What You Should Do

Sanofi-aventis provided the following guidance for consumers:

Patients need to discuss this new safety information with their healthcare professionals.

Patients should immediately report to their doctors any symptoms that suggest possible liver injury, such as “loss of appetite, nausea, vomiting, unusual tiredness, right upper stomach area pain or discomfort, yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, or itching.”

Patients should discuss with their healthcare professionals the need for periodic liver function tests.

We have had previous concerns about other safety problems with Multaq. We opposed its initial approval. We are now classifying Multaq as a DO NOT USE drug. You should discuss with your health care providers what alternative medication or procedure would be best for you.

Do not discontinue use of any medication without talking to your doctor first.

Although the drug is not recommended for patients with severe heart failure, a black box warning on the label of the drug states that:

“In a placebo-controlled study in patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms, patients given dronedarone [Multaq] had a greater than two-fold increase in mortality. Such patients should not be given dronedarone.”

Report any adverse effects to the FDA Medwatch program.

Here is an important new warning about the heart drug Multaq (generic name: dronedarone), which is linked to severe liver injury. See also: Multaq Liver Failure Lawsuits.

Subject: Updated Safety Information for Multaq® (dronedarone) related to liver injury

Sanofi-aventis Canada Inc., in collaboration with Health Canada would like to inform patients of new important safety information related to liver injury, reported in patients treated with Multaq. Multaq helps control abnormal heart rate and rhythm called atrial fibrillation and can lower the risk of having to go into the hospital for heart problems.

• Patients should discuss with their healthcare professionals this new safety information regarding Multaq treatment.
• Patients treated with Multaq should immediately report to their doctors symptoms possibly suggesting liver injury (such as: Loss of appetite, nausea, vomiting, unusual tiredness, right upper stomach area pain or discomfort, yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, or itching) and patients should consider obtaining periodic liver function tests.

Sanofi-aventis has been working with Health Canada, and the Multaq Product Monograph was revised to include this new safety information.

Please speak with your doctor or pharmacist if you have any related concerns or if you experience any other unexpected effects while taking Multaq.

Here is an important new warning about the heart drug Multaq (generic name: dronedarone), which is linked to severe liver injury. See also: Multaq Liver Failure Lawsuits.

Subject: Updated Safety Information for Multaq® (dronedarone) in regards to hepatocellular liver injury

Dear Health Care Professional,

Sanofi-aventis Canada Inc. in collaboration with Health Canada, would like to inform you of important new safety information regarding Multaq (dronedarone).

During the 16 months following the initial launch of Multaq (July 20th, 2009), 155 post-marketing cases (87 serious cases) reporting hepatobiliary adverse events, including rare cases of hepatic failure, have been received. Some cases were suspected of drug-induced hepatic injury with a predominant hepatocellular pattern of injury, including two foreign post-marketing case reports of acute hepatic failure requiring transplantation. A definitive causal relationship between Multaq and these cases has not been established.

Exposure to Multaq through September 2010 was estimated at 79,503 patient-years.

Multaq is indicated for the treatment of patients with a history of, or current atrial fibrillation to reduce the risk of cardiovascular hospitalization due to atrial fibrillation.

• Healthcare professionals should discuss with their patients this new important safety information regarding Multaq treatment.
• Patients treated with Multaq should be advised to immediately report symptoms suggesting hepatic injury (such as anorexia, nausea, vomiting, fatigue, right upper abdominal quadrant pain, jaundice, dark urine, or itching).
• It has not been established that routine periodic monitoring of hepatic enzymes would enable early detection of severe liver injury. However, healthcare professionals should consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment.
• If hepatic injury is suspected, Multaq should be discontinued immediately and followed by necessary blood tests.
• The safety of restarting Multaq in patients who have sustained liver injury from any cause is unknown; accordingly, its use in such patients is not recommended.

The two cases of acute hepatic failure requiring transplantation occurred at 4.5 and 6 months after initiation of Multaq in patients with previously normal hepatic serum enzymes. Both patients were female and approximately 70 years of age.

In the first case, the patient had underlying intermittent atrial fibrillation, arterial hypertension and stable coronary artery disease. She was treated with Multaq for 4.5 months. Two weeks prior to hospitalization she reported increased exhaustion and tiredness. One week prior to admission she discontinued Multaq, and at the time of admission she was noted to have jaundice, coagulopathy, transaminitis and hyperbilirubinemia, which progressed to hepatic encephalopathy over the next nine days. A pre-transplant workup did not reveal another etiology of liver failure.

In the second case, the patient had a medical history of paroxysmal atrial fibrillation and Sjögren’s syndrome. Following 6 months of treatment with Multaq, she developed weakness, abdominal pain, coagulopathy, transaminitis and hyperbilirubinemia. She was transplanted 1 month later; no alternate etiology for liver failure was identified in the transplant work-up. In both cases, the explanted liver showed evidence of extensive hepatocellular necrosis.

Sanofi-aventis has been working with Health Canada, and the Multaq Product Monograph was revised to include this new safety information.

FDA Drug Safety Communication:

Risk of Oral Clefts in Children Born to Mothers Taking Topamax (topiramate)

The U.S. Food and Drug Administration (FDA) is informing the public of new data that show that there is an increased risk for the development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy.

The benefits and the risks of topiramate should be carefully weighed when prescribing this drug to women of childbearing age, particularly for conditions not usually associated with permanent injury or death. Alternative medications that have a lower risk of oral clefts and other adverse birth outcomes should be considered for these patients. If the decision is made to use topiramate in women of childbearing age, effective birth control should be used. Oral clefts occur in the first trimester of pregnancy before many women know they are pregnant.

Topiramate was previously classified as a Pregnancy Category C drug, which means that data from animal studies suggested potential fetal risks, but no adequate data from human clinical trials or studies were available at the time of approval. However, because of new human data that show an increased risk for oral clefts, topiramate is being placed in Pregnancy Category D. Pregnancy Category D means there is positive evidence of human fetal risk based on human data but the potential benefits from use of the drug in pregnant women may be acceptable in certain situations despite its risks.

Additional Topamax (topiramate) Information for Patients

• If you take topiramate during pregnancy, there is a higher risk that your baby will develop a cleft lip and/or cleft palate. Oral clefts happen early in pregnancy, before many women even know they are pregnant. For this reason, women of childbearing age should talk to their healthcare professionals about other treatment options.
• Women of childbearing age who do decide to take topiramate and are not planning a pregnancy should use effective birth control (contraception) while taking topiramate. Women should talk to their healthcare professionals about the best kind of birth control to use while taking topiramate.
• Before you start topiramate, you should tell your healthcare professional if you are pregnant or are planning to become pregnant. Healthcare professionals may discuss other treatment options with you.
• You should tell your healthcare professional right away if you become pregnant while taking topiramate. You and your healthcare provider should decide if you will continue to take topiramate while you are pregnant.
• Topiramate should not be stopped without talking to a healthcare professional, even in pregnant women. Stopping topiramate suddenly can cause serious problems. Not treating epilepsy during pregnancy can be harmful to women and their developing babies.
• If you become pregnant while taking topiramate, you should talk to your healthcare professional about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect additional information about the safety of antiepileptic drugs during pregnancy.
• Topiramate passes into breast milk, but its effects on developing babies remain unknown. You should talk to your healthcare professional about the best way to feed your baby if you take topiramate.
• You should report any side effects you experience to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of the page.
• You should read the Medication Guide when picking up a prescription for topiramate. It will help you understand the potential risks and benefits of this medication.

Additional Information on Topamax (topiramate) for Healthcare Professionals

• You should inform women of childbearing age of the increased risk for oral clefts when topiramate is used in the first trimester of pregnancy.
• You should weigh the benefits and risks of topiramate when prescribing this drug to women of childbearing age, particularly when treating a condition not usually associated with permanent injury or death. Alternative medications that have a lower risk of oral clefts and other adverse birth outcomes should be considered. Healthcare professionals should discuss the relative risks and benefits of appropriate alternative therapies.
• If the decision is made to prescribe topiramate to women of childbearing age, healthcare professionals should recommend use of effective contraception for women who are not planning a pregnancy, keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.
• You should inform patients of the North American Antiepileptic Drug (NAEED) Pregnancy Registry and encourage patients who become pregnant to enroll by calling 1-888-233-2334.
• You should report adverse events involving topiramate to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of the page.

Data Summary on Topamax (topiramate)

Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry indicate an increased risk of oral clefts in infants exposed to topiramate monotherapy during the first trimester of pregnancy. The prevalence of oral clefts was 1.4% compared to a prevalence of 0.38% – 0.55% in infants exposed to other antiepileptic drugs (AEDs), and a prevalence of 0.07 % in infants of mothers without epilepsy or treatment with other AEDs. The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 21.3 as compared to the risk in a background population of untreated women (95% Confidence Interval:7.9 – 57.1). The UK Epilepsy and Pregnancy Register reported a similarly increased prevalence of oral clefts (3.2 %) among infants exposed to topiramate monotherapy, a 16-fold increase in risk compared to the risk in their background population (0.2%).

The benefits and the risks of topiramate should be carefully weighed when prescribing this drug for women of childbearing age, particularly when topiramate is considered for a condition not usually associated with permanent injury or death. Appropriate alternative treatment should be considered. Inform women of childbearing age of the increased risk for having a baby with an oral cleft if they become pregnant while using topiramate.

Cleft lip and cleft palate range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking and ear infections. Surgery is often used to close the lip and palate. With treatment, most children with cleft lip or palate do well.³

1. U.S. National Library of Medicine. National Institutes of Health. Topiramate monograph.
2. SDI, Vector One^®: National (VONA) and Total Patient Tracker (TPT). January 2007-December 2010.
3. U.S. National Library of Medicine. National Institutes of Health. Cleft Lip and Palate health topic.

Speak to a Topamax Lawyer about a Topamax Lawsuit

If you took Topamax (topiramate) or any other anti-seizure drug during pregnancy and your child was born with a cleft palate, cleft lip or any other congenital cranio-facial birth defect, we encourage you to contact a Topamax Litigation Attorney at our law firm immediately. It may be too late to recover from all of the devastating effects of Topamax but an experienced products liability pharmaceutical lawsuit lawyer at the Willis Law Firm can assist you in legal action against Johnson & Johnson (JNJ) and Ortho-McNeil Pharmaceutical LLC, the makers of Topamax. You are not alone. Join other birth defect victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

FDA Drug Safety Communication:

Severe liver injury associated with the use of dronedarone (marketed as Multaq)

Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals

Data Summary

Safety Announcement

[1-14-2011] The U.S. Food and Drug Administration (FDA) is alerting healthcare professionals and patients about cases of rare, but severe liver injury, including two cases of acute liver failure leading to liver transplant in patients treated with the heart medication dronedarone (Multaq).

Dronedarone is a drug used to treat abnormal heart rhythm in patients who have had an abnormal heart rhythm (atrial fibrillation or atrial flutter) during the past 6 months. Dronedarone (Multaq) can reduce the risk of being hospitalized for these heart problems. Since dronedarone’s (Multaq) approval in July 2009 through October 2010, around 492,000 dronedarone prescriptions were dispensed and around 147,000 patients filled dronedarone prescriptions at outpatient retail pharmacies in the United States.1 Additional usage can occur in the hospital setting.

Dronedarone (Multaq) was approved with a Risk Evaluation and Mitigation Strategy (REMS) with a goal of preventing its use in patients with severe heart failure or who have recently been in the hospital for heart failure. In a study of patients with these conditions, patients given dronedarone had a greater than two-fold increase in risk of death.

Information about the potential risk of liver injury from dronedarone (Multaq) is being added to the WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS sections of the dronedarone labels.

Today’s communication is in keeping with FDA’s commitment to inform the public about its ongoing safety review of drugs. FDA is continuing to review reports of possible adverse events and drug interactions with dronaderone submitted to our Adverse Event Reporting System.

Additional Information for Patients:

• Contact your healthcare professional if you develop itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools. These may be signs of liver injury.
• Talk to your healthcare professional about any concerns you have with this medication.
• Do not stop taking dronedarone unless told to do so by your healthcare professional.
• Report any side effects you experience to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of the page.
• Read the Medication Guide when picking up a prescription for dronedarone. It will help you understand the potential risks and benefits of this medication.

Additional Information for HCPs:

Advise patients to contact a healthcare professional immediately if they experience signs and symptoms of hepatic injury or toxicity (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, or itching) while taking dronedarone.

Consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment. However, it is not known whether routine periodic monitoring of serum liver enzymes (ALT, AST, and alkaline phosphatase) and bilirubin in patients taking dronedarone (Multaq) will prevent the development of severe liver injury.

If hepatic injury is suspected, dronedarone should be promptly discontinued and testing of serum liver enzymes and bilirubin should be performed. If hepatic injury is found, appropriate treatment should be initiated.

Dronedarone should not be restarted in patients who experience hepatic injury without another explanation for the observed liver injury.

Report adverse events involving dronedarone to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of the page.

Data Summary

FDA has received several case reports of hepatocellular liver injury and hepatic failure in patients treated with dronedarone, including two post-marketing reports of acute hepatic failure requiring transplantation. Because these reactions are reported voluntarily from a treatment population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The two cases of acute hepatic failure requiring transplantation occurred at 4.5 and 6 months after initiation of dronedarone (Multag) in patients with previously normal hepatic serum enzymes. Both patients were female and approximately 70 years of age. In the first case, the patient had underlying intermittent atrial fibrillation, arterial hypertension and stable coronary artery disease. She was treated with dronedarone (Multag) for 4.5 months. Two weeks prior to hospitalization she reported increased exhaustion and tiredness. One week prior to admission she discontinued dronedarone, and at the time of admission she was noted to have jaundice, coagulopathy, transaminitis and hyperbilirubinemia, which progressed to hepatic encephalopathy over the next nine days. A pre-transplant workup did not reveal another etiology of liver failure. In the second case, the patient had a medical history of paroxysmal atrial fibrillation and Sjogren’s syndrome. Following 6 months of treatment with dronedarone she developed weakness, abdominal pain, coagulopathy, transaminitis and hyperbilirubinemia. She was transplanted 1 month later; no alternative etiology for liver failure was identified in the transplant work-up. In both cases, the explanted liver showed evidence of extensive hepatocellular necrosis.

Multaq (dronedarone) is approved to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent history of AF/AFL and associated cardiovascular risk factors (age >70, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥ 50 mm or left ventricular ejection fraction <40%) who are in sinus rhythm or who will be cardioverted.

Dronedarone (Multag) is contraindicated in patients with NYHA Class IV heart failure or NYHA Class II – III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. In a placebo-controlled study in patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms (the ANDROMEDA Study), patients given dronedarone had a greater than two-fold increase in mortality. Such patients should not be given dronedarone. 

1. SDI, Vector One®: National (VONA) and Total Patient Tracker (TPT). July 2009-October 2010. Data extracted 12-14-10.
-
Related Information

FDA Drug Safety Podcast for Healthcare Professionals: Severe liver injury associated with the use of dronedarone (marketed as Multaq)1  1/20/2011  Multaq (dronedarone) Information2  

Contact Us Report a Serious Problem

1-800-332-1088
1-800-FDA-0178 Fax
MedWatch Online3
Regular Mail: Use postage-paid FDA Form 35004
Mail to: MedWatch 5600 Fishers Lane
Rockville , MD  20857

Department of Health and Human Services

 Sanofi Aventis Deutschland GmbH 2/9/11
   
Public Health Service
Food and Drug Administration – Silver Spring  MD 20993
 
Warning Letter
VIA UPS MAIL  
WL: 320-11-09
 
February 9, 2011
 
Mr. Martin Siewert, Chairman of the Board
Sanofi Aventis Deutschland GmbH
Industriepark Hochst, Building H550
Frankfurt am Main   65926
Germany
 
Dear Mr. Siewert:
 
During our September 6-10, 13-16, 2010 inspection of your pharmaceutical manufacturing facility, Sanofi Aventis Deutschland GmbH, Industriepark Hochst, Building H550, Frankfurt am Main, Germany, investigators from the Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
 
We have reviewed your firm’s responses in October 2010 and January 2011, however we continue to have concerns related to your firm’s compliance with CGMP.
 
Specific violations observed during the inspection include, but are not limited to the following:
 
1. Your firm has not established or followed appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile [21 C.F.R. § 211.113(b)]. For example,
 
For example, in June 2010, your firm failed to identify the organisms recovered from a sterility test for Apidra lot #OF100. Identification of microorganisms recovered from a sterility test is essential when conducting a sterility failure investigation. In addition, the identification of organisms is also a fundamental part of any investigation of environmental or personnel monitoring excursions.
 
Your firm’s failure to identify organisms recovered from a sterility test was also discussed during the December 2008 inspection.
 
We recognize that your firm voluntarily recalled the Apidra, Lot#0F151A, which was  part of the February 2010 production campaign in which there was a significant concern regarding environmental contamination levels. We expect all procedures related to the response for an out-of-limit environmental monitoring sample or a sterility failure to include the appropriate evaluation and remedial measures, as appropriate.
                                                                                                                               
2. Your firm has not established separate or defined areas or such other control systems as necessary to prevent contamination or mix-ups during aseptic processing. [21 C.F.R. § 211.42(c)]. For example,
 
a) The airflow velocity inside critical areas of the aseptic processing operations of Line (b)(4) was found unacceptable by FDA. The documentary evidence of in-situ air pattern analysis (e.g., smoke studies) reviewed during the inspection confirmed this condition.
                                                                
With respect to aseptic processing in critical areas, you should be able to demonstrate unidirectional airflow and sweeping action over and away from the product under dynamic conditions. Please note that proper design and control prevents turbulence and stagnant air in the critical areas. It is crucial that airflow patterns are evaluated for turbulence that can act as a channel for contamination, and that any deficient conditions are addressed.
 
b) Your environmental monitoring program does not give assurance that environmental contaminants are reliably detected. Your practice of collecting samples from the gloves of operators, from left and right hands on alternate days is unacceptable. In addition, your SOP fails to include instructions for the location and duration of samples collected in the critical aseptic processing areas.
                                                                      
An adequate environmental monitoring program should be established by your firm. It should capture meaningful data and act as an early warning system to detect possible environmental contaminants that may impact the sterility of drug products manufactured at your facility that purport to be sterile.
 
3. Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. [21 C.F.R. § 211.25(a)]. For example,
 
On September 6 and 9, 2010, operators involved in the cleaning operations and aseptic connections during filling, were observed demonstrating incorrect aseptic techniques to prevent product contamination. We expect that operators who conduct operations within aseptic processing areas be properly trained and monitored to ensure that proper aseptic techniques are utilized during all operations.
 
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility.  You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations.  If you wish to continue to ship your products to the United States, it is the responsibility of your firm to ensure compliance with all U.S. standards for CGMP and all applicable U.S. laws and regulations.
 
Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. In addition, FDA may be refusing admission of articles manufactured at Sanofi Aventis Deutschland GmbH, Industriepark Hochst, Building H550, Frankfurt am Main, Germany, into the United States. The articles are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)], in that, the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practice within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)].
                                                                                                              
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. Please identify your response with FEI # 3002807197.
 
If you have questions or concerns regarding this letter, contact Douglas Campbell, Compliance Officer, at the below address and telephone number.
 
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Division of Manufacturing and Product Quality
International Compliance Branch
White Oak, Building 51, Room 4224
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel: (301) 796-3201
Fax: (301) 847-8741                                                       
 
Sincerely,
/S/
Richard L. Friedman
Director
Division of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research

Speak to a Multaq Lawyer about a Multaq Liver Failure Lawsuit

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, acute liver failure or acute hepatic failure please contact a Multaq Liver Failure Lawsuit Attorney at our law firm immediately. It may be too late to recover from the devastating effects of Multaq, but an experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action against Sanofi-Aventis SA, the maker of this dangerous drug. You are not alone. Join other liver failure victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

Drug Safety Oversight Board Meeting, January 20, 2011

Public Summary

The Executive Director updated the Drug Safety Oversight Board (DSB or Board) on Drug Safety Communications posted and in development since the November 18, 2010 meeting. The following is a list of the posted risk communications:

Drug Safety Communications Posted since the November 18, 2010 DSB meeting:

• November 19, 2010: FDA recommends against the continued use of propoxyphene:¹ FDA issued a DSC notifying the public and healthcare professionals that it is recommending against continued prescribing and use of the pain reliever propoxyphene because new data show that the drug can cause serious toxicity to the heart, even when used at therapeutic doses. FDA has requested that companies voluntarily withdraw propoxyphene from the US market.
• December 14, 2010: Death resulting from overdose after accidental ingestion of Tessalon (benzonatate) by children under 10 years of age:² FDA issued a DSC warning the public that accidental ingestion of benzonatate by children under the age of 10 years can result in death from overdose. The DSC also announced that new information about accidental ingestion resulting in overdose and death in children below 10 years of age is being added to the Warnings and Precautions sections of labeling for benzonatate products to make healthcare professionals aware of this safety issue.
• December 17, 2010: Abnormal heart rhythms associated with use of Anzemet (dolasetron mesylate):³ FDA issued a DSC informing patients and healthcare professionals that the injection form of Anzemet (dolasetron mesylate) should no longer be used to prevent nausea and vomiting associated with cancer chemotherapy (CINV) in pediatric and adult patients. New data demonstrate that Anzemet injection can increase the risk of developing an abnormal heart rhythm (torsade de pointes), which in some cases can be fatal. Patients at particular risk are those with underlying heart conditions or those who have existing heart rate or rhythm problems. The DSC also announced that a contraindication against this use (CINV) is being added to the product label for Anzemet injection.Anzemet tablets may still be used to prevent CINV because the risk of developing an abnormal heart rhythm with the oral form of this drug is less than that seen with the injection form. However, a stronger warning about this potential risk is being added to the Warnings and Precautions sections of the Anzemet tablet label.
• December 22, 2010: Ongoing safety review of Recombinant Human Growth Hormone (somatropin) and possible increased risk of death:⁴ FDA issued a DSC informing the public that results from a study conducted in France—the Santé Adulte GH Enfant (SAGhE) study—found that persons with certain kinds of short stature (idiopathic growth hormone deficiency and idiopathic or gestational short stature) treated with recombinant human growth hormone during childhood and who were followed over a long period of time, were at a small increased risk of death when compared to individuals in the general population of France. FDA is currently reviewing all available information on this potential risk and will communicate any new recommendations once it has completed its review. At this time, FDA recommends that patients continue their recombinant human growth hormone treatment as prescribed by their healthcare provider.
• January 12, 2011: Update to ongoing safety review of Lantus (insulin glargine) and possible risk of cancer:⁵ FDA issued a DSC updating the public about its ongoing safety review of Lantus (insulin glargine) and a possible increased risk of cancer. In July 2009, FDA issued an Early Communication to inform the public that it was reviewing four published observational studies, three of which suggested an increased risk of cancer associated with the use of Lantus. FDA has reviewed the four studies and has determined that the evidence presented in the studies is inconclusive, due to limitations in how the studies were designed and carried out and in the data available for analysis.FDA also reviewed results from a five-year randomized clinical trial, which compared Lantus to Neutral Protamine Hagedorn (NPH) insulin in individuals with Type 2 diabetes. The results did not show an increased risk of cancer in subjects treated with Lantus compared to those treated with NPH insulin; however, this study was not specifically designed to evaluate cancer outcomes. At this time, FDA has not concluded that Lantus increases the risk of cancer. Our review is ongoing, including review of information from a current clinical trial, and the Agency will update the public when it has additional information.
• January 13, 2011: Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure:⁶ FDA issued a DSC notifying the public and healthcare professionals that it is asking drug manufacturers to limit the strength of acetaminophen in prescription drug products, which are predominantly combinations of acetaminophen and opioids. This action will limit the amount of acetaminophen in these products to 325 mg per tablet, capsule, or other dosage unit, making these products safer for patients.In addition, a Boxed Warning highlighting the potential for severe liver injury and a Warning highlighting the potential for allergic reactions (e.g., swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) are being added to the label of all prescription drug products that contain acetaminophen.
• January 14, 2011: Severe liver injury associated with the use of dronedarone (marketed as Multaq):⁷ FDA issued a DSC alerting healthcare professionals and patients about cases of rare, but severe liver injury, including two cases of acute liver failure leading to liver transplant in patients treated with the heart medication dronedarone (Multaq).Information about the potential risk of liver injury from dronedarone is being added to the WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS sections of the dronedarone labels.

The DSB discussed two topics:
1.  An Update on Operating Room Fires and Alcohol Based Skin Preps
2.  Safe Injection Practice and Vial Fill Issues

The views expressed by non-CDER employees are those of the individual and not necessarily the opinion of their respective government agency.

Update on Operating Room Fires and Alcohol Based Skin Preps

The Board invited guest experts from the American Society of Anesthesiologists (ASA), Chip Amoe III, J.D., M.P.A. and Charles Cowles, Jr. M.D. Mr. Amoe is the Assistant Director of Federal Affairs for ASA, representing the organization’s regulatory policy and functioning as the primary liaison between ASA and the White House, HHS, CMS, FDA, DEA, and other administrative agencies. Dr. Cowles is an assistant professor of anesthesiology at the University of Texas, MD Anderson Cancer Center in Houston, TX. Dr. Cowles is a former firefighter and is currently a representative on the ASA Task Force of the management and prevention of operating room fires.

The Board discussed the following regarding operating room fires:

• Material presented on operating room (OR) fires at the April 2009 DSB meeting
• The role of the Safe Use Initiative in reducing OR fires
• The role of two FDA Centers, the Center for Drug Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH) in assessing and addressing the potential risk of OR fires
• Scope of the current safety issue: the fire triad of fuel, oxidizer, and ignition source
• The role of supplemental oxygen in the risk of OR fires
• A video discussing the potential risk of an OR fire: http://www.apsf.org/resources_video.php⁸
• Previous actions to minimize the risk of OR fires
• MedWatch reports received by FDA regarding OR fires
• Possible regulatory and non-regulatory actions to help address the safety issue

Safe Injection Practices and Vial Fill Issues

The Board invited a guest expert, Joseph Perz, DrPH, from the Centers for Disease Control and Prevention (CDC). Dr. Perz is a team leader for Ambulatory and Long Term Care in the Prevention and Response Branch of the Division of Healthcare Quality Promotion.

The Board discussed the following regarding Safe Injection Practices:

• The scope of the safety issue
• Examples of public health incidents that resulted from unsafe injection practices
• The injection practices that can result in transmission of infectious disease between patients and between providers and patients
• Provider misconceptions that lead to unsafe injection practices
• CDC initiatives for addressing the safety issue
• The role FDA’s Safe Use Initiative is planning in addressing this safety issue
• Possible regulatory and non-regulatory approaches to address the safety issue

Draft Drug Safety Communication

The Board discussed a draft DSC involving over the counter monograph products and related (unapproved) prescription products used as topical anesthetics. The products have been rarely associated with methemoglobinemia and death. The Board evaluated whether the draft DSC effectively communicated, without alarm, the important messages to consumers and healthcare professionals about proper use of the products, keeping it away from children, and disposing of leftover medication.

Speak to a Multaq Lawyer about a Multaq Liver Failure Lawsuit

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, acute liver failure or acute hepatic failure, please contact a Multaq Liver Failure Lawsuit Attorney at our law firm immediately. It may be too late to recover from the devastating effects of Multaq, but an experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action against Sanofi-Aventis SA, the maker of this dangerous drug. You are not alone. Join other liver failure victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.