Drug Injury Watch

Diet Drug Meridia Has Possible Cardiovascular Risks, Including Stroke, Heart Attack, And Cardiac Death

FDA Early Communication About Meridia (Sibutramine) Side Effects Issued by Agency In November 2009

(Posted by Tom Lamb at DrugInjuryWatch.com)

________________________________________________________________________________________

UPDATE:  Abbott Pulls Meridia in U.S. Amid FDA Safety Concerns (10/8/10, Bloomberg)

Abbott Laboratories agreed to pull its 13-year-old diet pill Meridia off the U.S. market because of heart attack and stroke risks.

The company announced the removal today at the request of the Food and Drug Administration after a study linked Meridia to 16 percent more major cardiovascular side effects among 10,000 high-risk patients who were followed for as long as six years....

_____________________________________________________________________________

UPDATE: Visit the Meridia Information page at our Drug Injury Law web site for more recent developments.

_____________________________________________________________________________

On November 20, 2009 the FDA issued an "Early Communication about an Ongoing Safety Review of Meridia (sibutramine hydrochloride)" to let patients and their doctors know about a possible increased risk for adverse cardiovascular events associated with the obesity drug Meridia.

As background, Meridia was approved by FDA in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet.  Meridia is marketed by Abbott Laboratories in the U.S.

A November 21, 2009 article, "Early Data Link Diet Drug to MI, Stroke, and Cardiac Death", published online by MedPage Today, provides a good summary of the basis for this Meridia safety alert:

Preliminary analysis of data from a placebo-controlled study of sibutramine (Meridia) suggested an excess risk of cardiovascular events including myocardial infarction and cardiac death among patients taking the diet drug, according to the FDA.

The findings come from a trial of 10,000 high-risk patients who were randomized to sibutramine or placebo. The FDA said there was a 1% absolute difference in the rate of heart attack, stroke, resuscitated cardiac arrest, or death with 11% of the sibutramine patients reaching that endpoint versus 10% of the placebo patients.

The difference, while small, "is higher than expected, suggesting that sibutramine is associated with an increased cardiovascular risk in the study population," the FDA said....

The findings come from the SCOUT trial (Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event) which had a combined primary endpoint of heart attack, stroke, resuscitated cardiac arrest, or death.

The study, begun in 2002, was conducted as part of a postapproval agreement with the agency that oversees drug approvals for the European Union.

We last wrote about cardiovascular side effects being associated with Meridia use back in October 2007, when Health Canada provided an update on reports of suspected Meridia adverse reactions.

P.S.  An update by means of this December 3, 2009 Reuters article: "US consumer group asks FDA to ban Abbott diet drug -- Public Citizen says Meridia increases heart risks".  (12/4/09)

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

November 2009 Medical Journal Article Describes Large Ongoing Study About Safety Of YAZ

INAS-OC Study: Intended To Evaluate Risk Of Developing Cardiovascular Side Effects For Women Who Use YAZ (DRSP/EE 24d)

(Posted by Tom Lamb at DrugInjuryWatch.com)

In May 2009 we first wrote about the International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC Study), which is intended to evaluate the risk of developing cardiovascular side effects for women who use YAZ, a popular birth control containing a unique progestin, drospirenone (DRSP), and a relatively low dose of an estrogen, ethinylestradiol (EE).  We reported, then, that this YAZ safety study had started in August 2005 and was ongoing as of May 2009.

We recently learned more about the current status of this INAS-OC Study in an article published November 18, 2009 by BMC Medical Research Methodology-- which is an open access journal publishing original peer-reviewed research articles in methodological approaches to healthcare research.

The November 2009 medical journal article about this ongoing YAZ safety study is called "International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC Study)".

From the Abstract for this INAS-Study article we get this information:

BACKGROUND: A 24-day regimen of contraceptive doses of drospirenone and ethinylestradiol (DRSP/EE 24d) was recently launched. This regimen has properties which may be beneficial for certain user populations (e.g., women suffering from premenstrual dysphoric disorder or acne). However, it is unknown whether this extended regimen has an impact on the cardiovascular risk associated with the use of oral contraceptives (OCs). The INternational Active Surveillance study of women taking Oral Contraceptives (INAS-OC) is designed to investigate the short- and long-term safety of the new regimen in a population which is representative for the typical user of oral contraceptives. Methods / Design A large, prospective, controlled, non-interventional, long-term cohort study with active surveillance of the study participants has been chosen to ensure reliable and valid results. More than 2,000 gynecologists in the US and 5 European countries (Austria, Germany, Italy, Poland, and Sweden) will recruit more than 80,000 OC users. The two to five year follow-up of these women will result in at least 220,000 documented women-years. The main clinical outcomes of interest for the follow-up are deep venous thrombosis, pulmonary embolism, acute myocardial infarction and cerebrovascular accidents....

We look forward to eventually seeing the results obtained from this INAS-OC Study, which is reportedly funded by an unconditional grant from Bayer Schering Pharma AG, Berlin.

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

Drug Industry Document Archive (DIDA) Adds 15 More Pharma-Related Documents To Collection In November 2009

This Archive Contains Some "Secret" Documents Only Made Public In The Course Of Lawsuits Filed Against Pharmaceutical Companies

(Posted by Tom Lamb at DrugInjuryWatch.com)

Created and maintained by the University of California at San Francisco (UCSF), the Drug Industry Document Archive (DIDA) contains over 1500 documents, many of which were previously secret and only made public as a result of lawsuits filed against drug companies.

In September 2009 Kim Klausner, who is the Tobacco Digital Library Manager at UCSF, kindly sent us an email notification about the addition of some Wyeth ghostwriting documents to the DIDA collection.

Now, a couple of months later, Kim Klausner has let us know about 15 new rather "revealing" pharma-related documents that have been added to this DIDA collection.  From her recent email:

I’m pleased to announce that we’ve added 15 new documents to the Drug Industry Document Archive (DIDA).  You can find them by typing in “ddu:20091112” without the quotation marks in the query box at http://dida.library.ucsf.edu.  (A few of the documents in this batch replace damaged ones so are not strictly “new.”)

The documents include:

-- Depositions from Karen Mittleman, the DesignWrite staffer who worked on Wyeth’s publication plan for Premarin products. She responds to questions about how academic authors, her medical communications company and the drug manufacturer implemented its plan. (Parts of these documents appear redacted because the version we received had highlighting which doesn’t OCR well.)

-- A letter from Thomas Sullivan, President of Rockpointe, a medical communications firm, spells out the terms under which his company does business with numerous drug company clients and clarifies his relationship with ACRE, the Association of Clinical Researchers and Educators. He also provides a list of payments from drug and medical device companies for Rockpointe services from 2006 to June 2009.

-- The 1999 Tactical Plan for Paxil which includes participation in ISAAC (Initiative for Social Anxiety Assessment and Care), a disease-based registry of potential patients/customers, for which physicians will be paid $100 for each person recruited.

-- The 2004 Lexapro Marketing Plan which includes this gem:  Bylined articles will allow us to fold Lexapro messages into articles on depression, anxiety and comorbidity developed by (or ghostwritten for) thought leaders (page 23).

Feel free to forward this announcement to anyone who might be interested. And please click on the Contact Us link at the bottom of DIDA’s pages if you want help searching.

Once again, we are grateful that Kim took the time to let us know about these additions to the DIDA collection, and we thank all the good folks at UCSF who are involved with the creation and growth of this project.

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

Consumers Union’s Safe Patient Project Forum Webcast: “To Err Is Human, To Delay Is Deadly”

Marks 10th Anniversary Of IOM Study On Medical Errors And Raises Concerns About Lack Of Progress

(Posted by Tom Lamb at DrugInjuryWatch.com)

The Consumers Union’s Safe Patient Project (formerly Stop Hospital Infections) is holding a forum, “To Err Is Human, To Delay Is Deadly,” in Washington, DC, today, Tuesday, November 17, 2009, from 10 a.m. to 3:30 p.m. EST. 

There is a free live webcast on this “To Err Is Human, To Delay Is Deadly” forum on the day of the event.  If you cannot tune in then, a recording of this forum webcast will be available up to a year after this date.

The forum marks the 10th anniversary of the IOM study on medical errors and raises concerns about the lack of progress over the past decade in preventing medical harm.  Speakers at this forum include:

Arthur Levin, Center for Medical Consumers, member of the original IOM committee and long-time consumer advocate for patient safety;
 
Dr. Richard Shannon, University of Pennsylvania Health System, successful advocate for patient safety from within the walls of the hospital, challenging those in the medical community who say it is too difficult to stop hospital-acquired infections;

Merrill Goozner, independent author, writer and active blogger on health issues, former director of the Integrity in Science project at the Center for Science in the Public Interest, who will speak about conflicts of interest and the influence of the medical industry on creating a safer and more patient oriented health care system; and,

U.S. Representative Bruce Braley of Iowa, a strong advocate for eliminating medical harm to save patients’ lives and to reduce costs to the health care system.

The Safe Patient Project campaign released a report earlier this year on the subject, which describes how this campaign covers the following issues:

• hospital-acquired infections
• medical errors and other medical harm
• physician accountability
• drug safety

We encourage those who are interested in medication mistakes and medical errors to take the time to view this “To Err Is Human, To Delay Is Deadly” forum webcast either live, today, or at your convenience in the weeks or months to come.  Of course, you should feel free to share this forum webcast information with others, also.

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

Anemia Drugs Procrit And Aranesp May Increase Twofold The Risk Of Potentially Fatal Blood Clots

Results From Large Long-Term Study Show Association Between These Erythropoiesis-Stimulating Agents And Venous Thromboembolism

(Posted by Tom Lamb at DrugInjuryWatch.com)

In late October 2009 we learned that the results from the Trial to Reduce Cardiovascular Events with Aransep Treatment (TREAT) indicated that the anemia drug Aranesp might cause an increased risk for stroke in patients with diabetes and chronic kidney disease.

Just a couple of weeks later we have been presented with a possible explanation as to why this might be so.

From a November 10, 2009 article by HealthDay reporter Steven Reinberg, "Anemia Drugs May Cause Deadly Blood Clots", we get this new information about erythropoiesis-stimulating agents (ESAs) such as Procrit (epoetin alfa) and Aranesp (darbepoetin alfa):

"These drugs hit the market in the mid-1990s, and by 2002, 50 percent of patients on chemotherapy were receiving them," said lead researcher Dr. Dawn Hershman, co-director of the breast program at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian Hospital/Columbia University Medical Center in New York City.

Initial testing of these drugs was done on only 12 weeks of use, she noted. "Right from the beginning, there was concern that these drugs would cause some side effects, but the initial studies did not find any risk of thrombosis."

Her longer study was more informative. "We confirmed that these agents can increase the risk of thrombosis by twofold," Hershman added.... [emphasis added]

Hershman thinks the findings raise questions about the drug's approval process and whether adequate post-marketing research was undertaken to ensure their long-term safety.

These drugs do have a place, she said. "But we have to figure out what the best indication is and use every agent with caution. We should think about the drugs that we give."

The underlying study, "Patterns of Use and Risks Associated With Erythropoiesis-Stimulating Agents Among Medicare Patients With Cancer", was published in the November 10, 2009 online edition of the Journal of the National Cancer Institute in advance of its print publication in the December 2 edition of this medical journal.

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

Aranesp Associated With Increased Risk For Stroke In Patients With Diabetes And Chronic Kidney Disease

TREAT Study Revealed, Also, That This Amgen Anemia Drug Was No Better Than Placebo In Reducing Deaths Or Cardiovascular Problems

(Posted by Tom Lamb at DrugInjuryWatch.com)

The anemia drug Aranesp (darbepoetin alfa) might cause an increased risk for stroke in patients with diabetes and chronic kidney disease, according to the results from the Trial to Reduce Cardiovascular Events with Aransep Treatment (TREAT), a new study that was published in the October 30, 2009 edition of the New England Journal of Medicine (NEJM) and presented recently at the annual meeting of the American Society of Nephrology.

As background, patients with type 2 diabetes and kidney disease often become anemic.  In turn, heart and kidney problems can be accelerated by anemia.  Accordingly, doctors have long prescribed Aranesp and other erythropoiesis-stimulating agent (ESA) drugs based on the belief that treating the anemia would improve patient’s prognosis.

In an October 31, 2009 Boston Globe article, "Researchers question anemia drug benefits", reporter Elizabeth Cooney provides a good summary of the unexpected results from this TREAT study and the implications of those results:

The study, led by Boston researchers, is the first trial to compare this class of anemia drugs with a placebo in the ability to prevent death and serious complications - even though the drugs have been in use for decades.

"The risks of the therapy were bigger than we thought, namely stroke, and the benefits were less than we thought, in quality of life," said Dr. Marc Pfeffer, a cardiologist at Brigham and Women’s Hospital who led an international group studying Aranesp, which raises red blood cell levels....

The study confirmed that patients taking Aranesp required fewer blood transfusions and suffered less fatigue, but other hoped-for outcomes were not seen.

Dr. Steven Woloshin of the Dartmouth Institute for Health Policy and Clinical Practice said the findings reinforce a crucial message in medicine.

"This current study is an important reminder of how important it is not to assume the treatments work, but to prove them," said Woloshin, who was not involved in the study. Aranesp, made by California-based Amgen, was approved by the Food and Drug Administration in 2001 for use in kidney patients, but a similar drug also made by Amgen has been prescribed for 20 years.

The NEJM article about this TREAT study concerning Aranesp, "A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease", was accompanied by an editorial, "Treatment of Anemia in Chronic Kidney Disease — Strategies Based on Evidence", from Philip A. Marsden, M.D. 

Amgen, the drug company that makes Aranesp, issued a press release about the TREAT study results, "Large Study of Anemia Treatment in Chronic Kidney Disease Patients Not on Dialysis Published in the New England Journal of Medicine Failed to Meet Primary Efficacy Endpoints", which includes this statement:

Amgen has shared this information with global regulatory authorities and anticipates that the TREAT results will be included in labeling once discussions are complete.

We will be watching for this revised package insert, or label, for Aranesp which may or may not be announced by means of a so-called "Dear Doctor" letter.

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

Diabetes Drug Byetta Linked To Kidney Problems And Cases Of Renal Failure

October 2009 Byetta Label Change Follows Earlier Alert From U.K. About Kidney-Related Side Effects

(Posted by Tom Lamb at DrugInjuryWatch.com)

In March 2009 the Drug Safety Update Newsletter alerted us about reports of kidney-related side effects associated with the use of the diabetes drug Byetta (exenatide) from the U.K.

About eight months later, in early November 2009, the FDA informed doctors and other healthcare providers in the U.S. that it had approved revisions to the Byetta package insert, or label, so that it will now include information about numerous post-marketing reports of altered kidney function, including acute renal failure and insufficiency.

This move seemingly was prompted by reports of 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal insufficiency) in patients using Byetta that were received by the FDA from April 2005 through October 2008.

From the Information for Healthcare Professionals: Reports of Altered Kidney Function in patients using Exenatide (Marketed as Byetta) issued by the FDA on November 2, 2009, and the Data Summary part of that document in particular, we get these details:

FDA has completed a review of 78 cases of altered kidney function reported in patients with diabetes using Byetta. The cases were reported to FDA’s Adverse Event Reporting System (AERS) between April 28, 2005 and October 29, 2008. Sixty-two of the cases were classified as acute renal failure and 16 cases were classified as renal insufficiency. Cases of acute renal failure or insufficiency occurred as soon as 3 days and up to 2 years after initiation of Byetta. The patient ages ranged from 23 to 83 years, with an average age of 60 years.

The majority of patients, 74/78 (95%), had at least one contributory risk factor for altered kidney function, such as cardiac insufficiency, hypertension, pancreatitis, rhabdomyolysis, and urinary tract infection, as well as concomitant medications such as antiretrovirals, antihypertensives, diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs)....

Hospitalization was required in 71 of 78 (91%) patients and there were 4 deaths reported in the cases reviewed. Eighteen patients required dialysis and two patients required kidney transplantation after initiation of Byetta. Of those patients who required dialysis, six had no prior history of altered kidney function, two had a prior history of altered kidney function, and the remaining 10 patients reported no information regarding prior renal history.

Byetta was discontinued in 63 of 78 (80%) patients, with 39 (50%) patients reporting improved signs and symptoms after discontinuation of the drug. One patient experienced recurrent altered kidney function after re-initiation of Byetta....

Due to the serious potential consequences of altered kidney function and temporal relationship between the development of renal effects and initiation of Byetta, FDA has approved revisions to the drug label for Byetta to describe this risk.

___________________________________________________________________

 

Free Byetta Case Evaluation 

Strictly Confidential, No Obligation.

___________________________________________________________________________

For the drug-company perspective concerning this Byetta label change about kidney-related side effects, we direct you to the October 2009 "Dear Doctor" letter from Amylin Pharmaceuticals Inc. and Eli Lilly and Co. which includes, as an enclosure, the "BYETTA® (exenatide) injection Full Prescribing Information (October 2009)".

We will continue to monitor and report about this emerging drug safety issue involving the diabetes medication Byetta.

P.S. On November 2, 2009 Amylin Pharmaceuticals, Inc., and Eli Lilly and Company issued their joint statement in response to the FDA on BYETTA® (exenatide) injection.  (11/4/09)

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects