In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Drug-Induced Liver Injury Impacts on the FDA

Robert Temple, M.D., Associate Director for Medical Policy
Center for Drug Evaluation and Research, FDA

Slide Presentation [PDF]

Abstract: Hepatotoxicity has been, over the years, the most important single cause of withdrawals and marked limitations of use of drugs or refusal to approve them. In the 1950’s, iproniazid (Marsilid) was probably the most hepatotoxic drug ever marketed, but isoniazid, from the same period, has been found to cause serious hepatotoxicity in about 0.1% of recipients. Benoxaprofen (Oraflex), ticrynafen (Selacryn), bromfenac (Duract) and troglitizone (Rezulin) all were withdrawn because of hepatotoxicity, and ibufenac, perhexilene and dilevalol, all marketed abroad, were never approved in the United States. Hepatotoxicity has caused important limitations of use for many drugs, including isoniazid, labetalol, dantrolene, felbamate, pemoline, tolcapone, and trovafloxacin.

In most cases, the hepatotoxicity of these drugs was recognized late, as neither animal nor human experience before marketing yielded recognizable (or recognized) signals of hepatotoxic potential. Yet most of the drugs did cause a greater rate of transaminase elevation than controls and most also were associated with at least a few instances of transaminase elevation accompanied by elevated bilirubin or jaundice.

Post-marketing surveillance now detects serious hepatotoxins in months (bromfenac, tolcapone, troglitizone, trovafloxacin), in marked contrast to the years of delay in the past (iproniazid, isoniazid), but it is obviously preferable to discover them before marketing.

It is critical to evaluate the predictive ability (sensitivity, specificity) of various potential signals of injury, notably transaminase elevations of various degrees (3 fold, 5 fold, etc.) and frequencies (2%, 3%, etc.) and serum transaminase elevations accompanied by elevated bilirubin, a particularly troublesome combination that seems to predict a roughly 10% rate of serious injury, as noted by Zimmerman in 1978. This pattern has been seen recently with dilevalol (not approved in U.S.), bromfenac, and troglitizone, and may have predicted the ultimate serious injury rate. For example, the approximately 0.1% rate of that combination with troglitizone is not far from one tenth of the annual rate of 1/10-50,000 of serious trogitizone injury. Refinement of these possible pre-marketing signals of injury is a major regulatory and public health task.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, on February 14, 2011 in an FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our firm. Fill out our free online evaluation form to the right and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Drug-Induced Liver Injury: A National and Global Problem

John R. Senior, M.D., Food & Drug Administration (FDA)

Slide Presentation [PDF]

Abstract: This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.

More and more drugs are being taken by more and more people, not only prescription products but also over-the-counter remedies, herbal agents and dietary supplements, in addition to alcohol in various forms and amounts. The liver is the principal organ for metabolizing, inactivating, and disposing of them. Their metabolites may injure the liver cells, and complex drug-drug interactions complicate the situation. It has become clear that certain individuals are much more susceptible to drug-induced liver damage than are most people, and uncommon but severe idiosyncratic liver damage requires special consideration as a safety problem. Not only are people genetically diverse, which affects the way they metabolize drugs and other chemicals, but each person’s life experience is different. Drug-induced liver injury has become the leading cause of acute liver failure among patients presenting for evaluation at liver transplant centers in the United States, and the leading single cause for having to remove approved drugs from the market.

These harsh facts have had major negative impacts on the Agency, the pharmaceutical industry, and the practice of medicine, as will be delineated by spokespersons from the three sponsoring organizations. We shall then assess the state-of-the-art with respect to pre-clinical, clinical, and post-marketing activities that have been and could be employed to attack the problems. The meeting is not intended to profess what should be done, but to provide an opportunity to work together to ask what more might be done. We shall explore the relationships between members of the sponsoring organizations and a new construct for the public concept of drug safety.

We aim to call attention of the medical profession and the public to the scope of the problem of drug hepatotoxicity. We hope to find better ways to detect it and identify risk factors. We shall seek to develop consensus among the respective constituencies on how they may work cooperatively on constructive research, improved procedures, and communications.

Learning Objectives: After listening to this presentation participants should be able to state two reasons why the problem of drug-induced liver injury has arisen; list consequences of it to the FDA, PhRMA, and the AASLD; explain the derivation and exact meaning of “idiosyncracy.”

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Looking for Hepatotoxicity, Working Up Patients, and Assessing Causality

James W. Freston, M.D., Ph.D.
University of Connecticut Heath Center, Farmington, CT

Slide Presentation [PDF]

The best time to look seriously for evidence of hepatotoxicity is in Phase II and III clinical trials. The setting is optimal for obtaining the data necessary to establish the clinical profile of the reaction and to determine causality with better precision than is ordinarily the case after the drug is approved. Of course, uncommon idiosyncratic reactions can usually be detected only after the drug is used broadly in the population. In designing clinical trials of new drugs, sponsors and investigators often face the issue of excluding or including patients with abnormal LFTs. Subject with severe liver disease usually are excluded. However, subjects with mild LFT elevations, for example, ALT values less than 2-3 times the upper limit of normal, should be included. This will enable the trial results to be applicable to the general populations, about 2 % of which harbor such abnormalities, usually due to ethanol use, hepatitis C and, possibly, NASH. Such patients are not at increased risk of suffering idiosyncratic drug reactions, although their hepatic response to an idiosyncratic reaction may be exaggerated. While they may be more susceptible to dose-related hepatic reactions, such are usually reversible upon discontinuation of the drug, and there is a large margin between these mild abnormalities and those associated with hepatocellular reactions that result in hyperbilirubinemia, a prolonged INR and other clinical indicators of severe hepatic dysfunction. Trial protocols must, of course, provide for LFT measurements at intervals that are sufficiently frequent to detect significant increases in LFTs before serious hepatic dysfunction has occurred. There also is value in determining if mild liver abnormalities worsen or improve during drug therapy. Improvements might occur, for example, in diabetics with NASH when they are treated with an experimental drug that improves glucose control. This may have been the case in clinical trials of rosiglitazone and pioglitazone, although the appropriate tests were not done to determine if the improvements in mild LFT abnormalities were due to improvements in NASH. Such studies are underway, which may not have been the case if patients with abnormal LFTs had been excluded from the large Phase III trials, thereby obviating the opportunity to document improved LFTs with improved glucose control. Thus, by including subjects with mild LFT abnormalities in trials, other potential benefits of a drug can be uncovered and more precise labeling can be developed to aid clinicians in optimizing the drug’s benefits and reducing its risks.

Detecting hepatic abnormalities at an early stage and assessing their causality appropriately are challenging. Data safety monitoring boards (DSMBs) are increasingly used in non-hepatology fields, particularly cardiology. DSMBs typically consist of experts in clinical medicine, biostatistics and epidemiology, operate independently from the sponsor, and provide interim reviews of accumulating safety data. Properly organized and functioning, they define in advance statistically valid study discontinuation rules, detect serious safety issues, and provide feedback to the sponsor about a range of areas of concern, including reasons for slow patient accrual, excessive dropouts, and non-compliance with protocols. DSMBs and more informal safety assessment committees can also assess causation. This requires the consistent application of a validated system for determining if the observed hepatic reaction was likely due to the test drug. The pattern of abnormal LFTs should be determined, e.g. hepatocellular, cholestatic, or mixed. The severity should be assessed, e.g. mild, moderate, severe, and causality assessed, usually on the basis of temporal exposure, lack of confounding causes, and positive dechallenge. The value of this assessment is critically dependent on a supply of accurate data, which often requires access to the clinician/investigator and the opportunity obtain follow up tests. This is facilitated if the protocols include specific language about steps to take at the study site when LFT abnormalities of a certain type and severity are detected. Typically, hepatitis serologies and a hepatocellular ultrasound exam should be obtained immediately upon confirmation of LFT rises beyond the limits specified in the protocol. The LFTs should be followed after drug discontinuation until they return to normal. If they are abnormal after 3-6 months, an evaluation for chronic liver disease should be undertaken to include serum protein electropheresis, if not already obtained, antinuclear antibody titer, and LKM antibody. Liver biopsy should also be obtained to better assess the cause and nature of the liver reaction.

Even the best of detection and assessment methodologies commonly fail to establish causality, but at least the observed reactions can be categorized according to probability, e.g. definitely related, probably related, possibly related, probably not related, definitely related. In comparative trials this approach should distinguish between the study drug and the comparator in terms of the frequency of reactions. The approach is also useful in the absence of a comparator group although it may be exceedingly difficult to separate a drug effect from other causes operating in the background in a given population, e.g. diabetics, patients with congestive heart failure.

Learning Objectives: after hearing this presentation, listeners should be able to

• describe the rationale for including patients with mildly abnormal serum tests of liver function or injury in clinical trials;
• outline a cost-effective and ethically acceptable program for assessing causality;
• apply a methodology for establishing causality.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Emerging Trends in Acute Liver Failure in the United States

William M. Lee, MD
University of Texas Southwestern

Slide Presentation [PDF]

Abstract: Acute liver failure (ALF) is a rare condition in which a variety of agents cause severe and sudden liver cell dysfunction. Sometimes termed fulminant hepatic failure, ALF is thought to affect about 2,000 in the U.S. per year. This overwhelming catastrophe leads to coma, multi-organ dysfunction, and death, primarily affecting young and previously healthy people. Over the past 30 years, the most frequent causes of ALF worldwide have been viral hepatitis, and drug-induced liver injury, with smaller numbers of cases due to a variety of etiologies. Until recently, little data have been available on ALF in the United States, the relative rarity of cases and lower population density in the U.S. limiting clinical studies. The ALF Study Group was formed in 1997 as a consortium of centers with experience in ALF from around the United States. The current report describes in detail the demographic profile, clinical features and outcome of patients developing ALF in the U.S. between 1998 and 2000, based on data collected prospectively by the ALF Study Group. Between January 1998 and October 2000, 258 patients were enrolled from 17 academic liver units around the United States. To be admitted to the study, patients met standard entry criteria for acute liver failure, i.e., coagulopathy (PT > 15 seconds or INR 1.5) and hepatic encephalopathy within 8 weeks of the first symptoms or jaundice without previous underlying liver disease.

Of the 258 patients, 190 (74%) were female. The reasons for the preponderance of women in this series have not been elucidated, as the underlying etiologies encountered do not share a female preponderance. Whether genetic or hormonal differences are important has not been explored. The impact of drug hepatotoxicity is exemplified by the finding that ALF due to acetaminophen or due to idiosyncratic drug reactions accounted for 52% of the total. Acetaminophen (ACM) poisoning was the most common cause of ALF, accounting for 98 (38%) cases. Although 79% of the ACM group were women, similar percentages were seen for the idiosyncratic drug reactions (74%) and for other causes of ALF.

A dose-related toxin, acetaminophen is the single most common etiology for ALF in the U.S., Europe and Australia, although acetaminophen is rarely implicated in Asia. Only 12% of acetaminophen-related hospital admissions reach the threshold of developing symptoms of ALF, suggesting that the 98 cases observed in this study represent only a small fraction of the acetaminophen burden. The proportion of accidental cases in the present series was 60%% while 38% were thought to be overt suicidal ingestions. Accidental toxicity due to acetaminophen occurs when patients consume large amounts of drug over several days seeking pain relief, without realizing its possible harmful effects. Acetaminophen intoxication represents an acute event limited to a single-time-point ingestion or to a brief interval of exposure. As a result, ALT levels are extraordinarily high, bilirubin levels low and evidence of acute renal insufficiency and acidosis characterize the most severe cases, whose severity in terms of coma grade on admission equals that of other forms of ALF. Remarkably, these patients have a high spontaneous survival, perhaps attributable to the brevity of their drug exposure. Idiosyncratic drug reactions were responsible for another 35 (14%) cases, and included cases of troglitazone (4), bromfenac (4) and isoniazid (5).

By comparison with the ACM cases, idiosyncratic reactions are characterized by slower onset, lower ALT, higher bilirubin levels, normal renal function but much poorer spontaneous survival. Hepatitis A and B caused 11 (4%) and 21 (8%) cases respectively. Seventy-three (28%) patients underwent hepatic transplantation, 61 of whom survived (84% short-term survival). One hundred and twelve (43%) patients survived without transplantation (spontaneous survivors). Seventy-three (28%) patients died without transplantation. Overall survival in the group was 67%. Only 6% of acetaminophen patients were transplanted, 69% surviving spontaneously, while 25 died without receiving a liver graft. By contrast, 54% of the idiosyncratic group received a transplant, 20% died and 26% recovered spontaneously.

Drug-induced liver injury leading to acute liver failure accounts for 52% of all acute liver failure in the U.S. and is a disease of the developed world, since virtually no cases are found in developing countries. As such, developed nations should be able to institute preventive measures for this newly evolving crisis. With regard to acetaminophen, limitation of package size and better patient and physician education might help alleviate this burgeoning health problem.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Clinical Picture & Issues in Clinical Phases of Drug Development

Neil Kaplowitz, M.D.
University of Southern California, Los Angeles

Slide Presentation [PDF]
Slide:  Risk of Hepatotoxicity [PDF]

Drug-induced liver disease can mimic all forms of acute and chronic hepatic diseases. However, the predominant clinical presentations resemble acute icteric hepatitis or cholestatic liver disease. The former is of grave significance as the mortality approximates 10% due to acute liver failure. Hepatitis-like reactions are accompanied by systemic symptoms, jaundice, markedly increased serum transaminases, and, in more severe cases coagulopathy and encephalopathy. Cholestatic reactions, although not usually life threatening, present with jaundice, disproportionate increased serum alkaline phosphatase and pruritus: these reactions may resolve slowly and lead to vanishing bile duct disease and rarely biliary cirrhosis.

Some presumptive mechanistic information can be deduced from the frequency and the latency of adverse events. High frequency and short latency suggest that the parent drug or metabolite is directly toxic. Low frequency and longer latency suggest either immune-mediated (within 4-6 weeks), or metabolic idiosyncratic toxicity (variable but delayed). Irrespective of the mechanism, i.e. immune-mediated or “idiosyncratic”, and notwithstanding low incidence, these reactions often occur on the background of more frequent anicteric, transient milder liver injury. The relationship between the frequent mild injury and rare severe injury is unclear. Does the mild injury reflect a propensity or signal for serious problems? Does severe injury reflect impaired adaptation – in other words is it the handling of the drug or of the injury or both which determines the occurrence of overt or severe liver injury?

The pre-approval clinical phases of drug development represent a key arena for identification of hepatotoxic potential. At this stage drugs with significant toxic potential are easily recognized but those with low toxic potential may be less easily recognized, particularly if identification of overt (symptomatic jaundice) or serious injury is used as the marker. The rule of three’s predicts that to insure not missing an overt adverse event occurring in 1 per 1000 requires studying 3000 individuals. Thus, the absence of overt disease in 3000 study patients (typical pre-approval cohort) does not prove it will not occur and only predicts an incidence of overt disease of less than 1 per 1000 and life threatening disease of less than 1 per 10,000. Furthermore, if the adverse reaction is of the delayed idiosyncratic type, the clinical trials may have included a far smaller number of subjects at risk for sufficient duration. Furthermore, the frequency of testing and rules for stopping may confound the identification of a significant signal. Despite the low incidence of over liver injury, less severe injury may be found more frequently and constitute a possible or probable indicator. What then is a significant and specific signal for concern during the clinical phase of drug development? – increased incidence of ALT >3X ULN versus matched controls?, ALT > 8-10X ULN?, hyperbilirubinemia?

The discussions at this conference should lead to the design of an approach to verifying liver abnormalities in drug development which constitute a possible or probable signal for concern and what to do with that information with respect to drug approval.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Impact of Hepatotoxicity on the Pharmaceutical Industry

Bert Spilker, Ph.D., M.D.
Senior Vice President, PhRMA, Washington, D.C.

Slide Presentation [PDF]

Abstract: A fundamental question for various stakeholders to address is “how rare or mild does hepatotoxicity have to be for a drug to be approved and to remain on the market?” At this meeting we will review the relevant factors that go into this decision. Regulatory agency, industry, and societal decisions depend on both sound science and balancing benefits and risks. But if the Food and Drug Administration (FDA) raises standards based on political pressures rather than sound science, it will deter some research and discourage new drug development, The FDA is sometimes pressured by the media to act in haste and set unreasonable standards. The media, in turn, are often responding to outspoken consumer extremists who have other interests than seeking sound scientific answers, and they spread disinformation.

Our challenge is to insure that claims or accusations of hepatotoxicity must be demonstrated with persuasive scientific evidence before a drug is removed from the market. We must be able to separate signals from noise, and anecdotes from facts.

The three goals for this meeting are to consider how to (1) create a sound research agenda that will improve scientific understanding and counter unsupported allegations of drug risk, (2) develop more approaches for extrapolating hepatic data and for using postmarketing data optimally, and (3) develop a mechanism to monitor progress on both the research agenda and development of extrapolation principles and postmarketing approaches. In addition, we must evaluate the various strategies for risk communication and risk management.

Industry is committed to working with all stakeholders on this issue to assure continued patient safety.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Impact of Drug-Induced Liver Injury on Hepatology & Practice of Medicine

William M. Lee, MD
Professor of Medicine, University of Texas Southwestern Medical Center

Slide Presentation [PDF]

Abstract: Among the joys of good health are digestion of food and elimination of internally-derived toxins, functions primarily supplied by the gastrointestinal tract and kidneys respectively. However, the processing and excretion of all absorbed xenobiotics (foreign substances) is the province of the liver. Building upon, but exceeding in complexity, the functions of the gut and kidney, normal hepatic function is a third essential for good health. Drug reactions that interfere with hepatic function and are life-threatening are extremely rare, given the number of xenobiotics ingested. The marvel is that a single liver can and does metabolize as many as 12 drugs at a time without evidence of injury or even of buildup of any one of the various compounds ingested. As a result, patients and physicians assume (or take for granted) that the liver will perform its job faithfully with never a complaint.

Metabolism of xenobiotics involves the creation of activated intermediate compounds that rarely bind to cell proteins with subsequent hepatocyte damage, either directly or by invoking immune responses. The final result is often massive and sudden necrosis of liver cells, multi-organ failure and death. This rare but catastrophic event finds clinicians and patients unaware of the potential disaster and un-prepared to deal with a rapidly deteriorating situation. The likelihood of drug toxicity varies among individual agents and among drug classes. Many physicians are not familiar these varying propensities for drug toxicity. Even if they are aware of the possible consequences, physicians seldom give patients specific instructions that might be life-saving such as what to do should dark urine or jaundice develop. The very rarity of severe liver injury due to drugs represents its fundamental virtue and problem. We cannot develop an appropriate cost-effective response for events as infrequent as 1:50,000 prescriptions. How much instruction should a patient receive for such events? If a toxic reaction is recognized with a given agent, how much advertising in the post-marketing period should be directed at education of physicians to potential but rare events that seldom occur? Fear of drugs by physicians or patients limits their use. Withdrawal of drugs due to rare toxicity deprives patients of potential benefits. Caution, particularly in regard to drugs with known hepatotoxicity such as isoniazid, may lead to closer supervision, monitoring of liver function tests, or limitation of use to the least susceptible patients.

Physicians want to know how to avoid the risks and how to become educated regarding drug toxicity. They want safe drugs but realistically know that universal safety cannot be guaranteed. Yet they seldom participate in the efforts to monitor drug reactions; adverse events are reported to FDA less than 10% of the time. Improved methods of post-marketing surveillance should result in more rapid identification of potential toxins whose initial clinical assessments did not identify drug events. Education directed at recognition of the symptoms of acute liver failure might lead to earlier withdrawal of toxins and prompt institution of intensive care.

The three constituencies represented at this conference should dedicate their efforts to greater education of physicians and patients concerning drug toxicity and severe liver injury with the goal of identifying harmful effects more reliably and preventing these potentially avoidable events.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Pharmacogenomics: Dangerous Drug or Susceptible Patient?

Paul B. Watkins, M.D.
University of North Carolina at Chapel Hill

Slide Presentation [PDF]

The rapid application of pharmacogenomics to drug discovery will have many implications for the future of the pharmaceutical industry, including development of drugs that will work optimally only in subsets of patients with a given disease. To identify responders, molecular diagnostic testing will need to become standard medical practice. One anticipated advantage of genotype-tailored medications is that clinical testing could be limited to those with the appropriate genotype, greatly reducing the sample sizes required to show efficacy. However, sample size reductions will increase the chance that potential for serious idiosyncratic toxicity, such as irreversible liver injury, will go unrecognized during clinical development. There is, therefore, increasing urgency to understand the molecular basis for drug induced liver injury, particularly irreversible idiosyncratic injury.

The number of genes potentially involved in idiosyncratic severe liver injury due to drugs is very large and involve many pathways. One approach taken to identify these genes has been to collect genomic DNA from patients experiencing serum alanine aminotransferase (ALT) elevations during clinical trials. The DNA is then screened for known mutations in potentially relevant genes, or subjected to “shot gun” screening for single nucleotide polymorphisms (SNPs). The mutation frequencies found in the patients experiencing ALT elevation are then compared to the corresponding frequencies found in patients who did not manifest ALT elevations. This line of research should allow development of molecular diagnostic tests that could be used to exclude from treatment most patients susceptible to ALT elevations. This practice would obviate the need for routine ALT monitoring of all treated patients and, based on current thinking, would be expected to generally reduce the incidence of severe idiosyncratic liver injury. However, the insight obtained into the basis for severe idiosyncratic liver injury will be limited because only a very small subset of patients manifesting ALT elevations generally go on to develop progressive liver injury, even with continued administration of the drug. This subset can generally not be identified in clinical trials since treatment is usually promptly discontinued in patients experiencing ALT elevations. There is now a pressing need for development of a bank of tissue and genomic DNA obtained from patients who have experienced well-documented severe adverse reactions to specific medications. Such a bank would serve as a critical resource for all researchers in this area.

Learning Objectives:

• The number of genes potentially involved in idiosyncratic severe liver reactions to drugs is very large and involve many pathways.
• Current efforts to associate genetic mutations with ALT elevations observed in clinical trials will probably provide limited insight in the mechanisms underlying idiosyncratic liver injury.
• There is an urgent need to establish a bank of tissue and genomic DNA obtained from patients who have experienced severe liver injury due to drugs.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Pre-Clinical Issues in Drug Development

 François Ballet M.D., Ph.D.
Aventis, Paris

Slide Presentation [PDF]

Abstract: Despite considerable progress in the understanding of the mechanisms of liver toxicity, we are not yet able to design non-hepatotoxic drugs rationally. Also there are no “ universal ” high throughput molecular or cellular screening approaches that could be apply systematically at the hit or lead generation phase of drug development to screen for hepatotoxicity. Therefore it is not surprising that in most cases hepatotoxicity is detected at later stages of drug development when animal (usually rat and dog) toxicity studies are performed, during the course of clinical trials or even at a later stage when a drug is on the market.

Very few studies have been conducted on the incidence of hepatotoxicity in drug development and on the predictive value of animal toxicity studies. Based on available data the liver appears to be the most common target organ for toxicity encountered during the course of drug development. Also, based on available surveys, the predictive value of animal hepatotoxicity studies appears to be limited. Idiosyncratic hepatotoxicity cannot be detected by conventional animal toxicity studies. Interspecies differences in bioavailability, distribution and metabolism may also explain a number of false positives and false negatives. There is clearly a need to better understand the drug metabolism enzyme profile of the most commonly used non-rodent species i.e. the dog and the monkey. Some false negative results may be related to insufficient exposure of the animals either because the doses tested were too low or because intestinal absorption was poor. Certain liver abnormalities may occur only in diseased models (e.g. drug-induced hyperbilirubinemia in severe infection) and therefore cannot be detected in healthy laboratory animals. Finally certain liver changes, e.g. liver hyperplasia, are common findings in laboratory animals butb are considered to be of no clinical significance in man.

A number of criteria are being used to assess the clinical significance of animal toxicity data : (a) type/severity of injury (b) reversibility (c) mechanism of toxicity (d) interspecies differences (e) availability of sensitive biomarkers of toxicity (e) safety margin (non toxic dose/pharmacologically active dose) (f) therapeutic potential. Contrary to other target organs (e.g. kidney, adrenal, heart), minimal and reversible liver injury can be detected in early clinical trials by monitoring liver enzymes. Therefore in certain cases it may be justified to test in man a drug found to be hepatotoxic in pre-clinical studies, especially when the therapeutic value is high.

In recent years toxicogenomic and proteomic approaches have been tested with the aim of developing more efficient in vitro screening assays. It is important to realize that these technologies are based on cellular models with intrinsic limitations in term of in vivo relevance. Also they represent a formidable challenge in term data management and interpretation. Based on current experience the most valuable use of these “transcript expression profile” approaches appears to be “secondary” screening for back-up selection and investigation of toxicity mechanisms.

A better understanding in the molecular mechanisms of hepatotoxicity in man is a critical prerequisite for any improvement in the detection of hepatotoxicity during the pre-clinical phase of drug development. Identification of critical molecular toxicity targets can lead to the design of pertinent molecular or cellular screening assays or to the development of new biomarkers/endpoints for in vivo studies. Pharmacogenetic techniques should be more systematically applied to patients with idiosyncratic toxicity in order to identify critical suceptibility genes which could lead secondarily to identification of mechanisms. Also a more systematic/prospective analysis of animal and human hepatotoxicity data encountered during the course of drug development should be carried-out as a joint effort between industry and regulatory agencies to improve the toxicology strategy.

Finally another important aspect is the need to improve communication and to foster exchanges between toxicologists (Ph.Ds/DVMs) and clinicians (M.Ds) in industry and in academia. Indeed, in the opinion of the author, an inter-disciplinary and more integrated approach is a key factor to improve the testing strategy for hepatotoxicity in the pre-clinical phase of drug development.

Learning objectives:   After hearing this presentation, listeners should be able to list or outline

• The different steps of the drug discovery and development process
• Main principles of animal toxicology studies
• How to use data from animal toxicology studies for go/no go decision
• Specific issues related to hepatotoxicity in animals (liver hyperplasia, enzyme induction…)
• Predictive value of animal toxicity studies. Causes for false-negatives and false-positives
• Screening strategy for hepatotoxicity
• Role of mechanistic studies
• New approaches (toxicogenomics, proteomics, pharmacogenetics…)
• How to improve predictivity of animal toxicity studies ?

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 damage, liver toxicity, acute hepatic failure or acute liver 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.

In the printed abstract of the presentation below, sponsored by the US FDA at the Westfields Conference Center, Chantilly VA on February 12 -13, 2001, prescription drugs are cited by the medical community and the FDA repeatedly as one of the major causes of acute liver damage, acute liver failure and acute hepatic failure.

“This program is organized to include active participants from academia, the pharmaceutical industry, the regulatory Agency (FDA), and interested public persons. We welcome them to consider together the problems of drug-induced chemical injury to the liver, and how best we may work together to address, ameliorate, or solve those problems for the benefit of patients and consumers who are using products with medicinal effects.”

Subsequently, in a February 14, 2011 FDA Warning Letter published by the US Food and Drug Administration, the FDA warns patients and healthcare professionals of multiple instances of Multaq related cases of acute liver failure, which required liver transplants.

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

If you or a loved one took the heart medication Multaq (dronedarone) and experienced liver toxicity, liver damage, acute hepatic failure or acute liver failure, please contact a Multaq Liver Damage Lawsuit Attorney at our law firm immediately. Fill out our free online legal evaluation form on the right side of this page and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help.

Post-Marketing: State of the Art and Issues Defined

Peter K. Honig, MD, MPH
Director, Office of Postmarketing Drug Risk Assessment, FDA

Slide Presentation [PDF]

Abstract: Acute hepatic injury is one of the most common forms of pre-clinical and clinical toxicity encountered with drugs. Fortunately, most drugs with the potential for substantial hepatotoxicity will be identified during early testing. Yet, pre-approval testing cannot be relied upon to identify less common drug-related hepatotoxicity because of the recognized and accepted limitations of the safety database submitted in support of a drug licensing application. Phase 3 clinical trials are designed, powered, and reviewed to detect relatively common dose-related adverse drug reactions (ADR) whether or not these are predicted from the drug’s pharmacology. However, a database of several thousand patients, which is typical of most marketing applications, lacks the power to observe rare adverse reactions (i.e. those occurring at rate of 1 per 1000 exposures or less). Furthermore, short trial duration and, in some cases, specific patient selection criteria contribute to the inability of pre-marketing studies to detect the rare, drug-related adverse events that may occur when the drug is given to a larger numbers and a broader range of patients following approval. ADRs with a long induction period will not be detected in brief trials and adverse reactions resulting from specific interactions with personal characteristics, concurrent diseases and concomitant drug therapies will not be found. Therefore, it is critically important that new information regarding severe drug-induced hepatotoxicity appearing postmarketing regarding drug product safety be collected, analyzed, and acted upon in an expeditious manner.

One of the main objectives of post-marketing safety surveillance is to detect rare adverse events associated with the use of drugs, to assess the likelihood of a causal relationship of the event to the drug and, when a drug cause seems likely, estimate the rate of the event. This responsibility is shared by the regulatory authorities, drug manufacturers and by physicians, whose timely reports of adverse drug events are the main source of information about rare adverse effects. The strengths and limitations of the current tools and mechanisms for identifying signals of serious hepatoxicity of marketed drugs and the methods used to quantify the population risk and identification of risk factors that may confer individual susceptibility to drug-induced hepatic injury using population-based resources will be discussed. Additionally, regulatory considerations in the benefit:risk assessment of drugs that are identified as hepatotoxic and the strengths and limitations of existing risk management tools will be highlighted. Finally, knowledge gaps and issues requiring further research or development will be outlined for further discussion in the conference breakout groups. These include but are not limited to: 1) development of a standardized nomenclature and definitions for liver test abnormalities and liver injury, 2) improving the quality and quantity of voluntary reporting, 3) quantifying the frequency of LFT abnormalities and evaluating the usefulness of liver monitoring recommendations as a risk management strategy in preventing drug injury, 4) development of active and sentinel surveillance strategies for drug-induced liver injury, and 5) development of a nationwide research proposal to determine mechanisms of individual susceptibility to drug-induced hepatic injury.

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 damage, liver toxicity, acute hepatic failure or acute liver 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.