Drug Injury Watch

Is This What Medtronic's March 21, 2007 "Dear Doctor" Letter Said About Sprint Fidelis Lead Problems?

One Person Took The Impression That Medtronic Was Trying To Lay Blame For Lead Wire Failures On Those Physicians Who Were Doing The Defibrillator Implants

(Posted by Tom Lamb at DrugInjuryWatch.com)

To start, our thanks to a fellow in Florida who was kind enough to share with us what he found as a result of some investigation into that hard-to-find March 21, 2007 "Dear Doctor" letter about problems with Medtronic's Sprint Fidelis defibrillator leads. Unfortunately, his motivation came from the fact that he has one of the recalled Sprint Fidelis leads implanted currently. 

The following material comes from an April 8, 2007 article posted on a somewhat obscure blog called Random Thoughts on Pacemakers & Personal Finance that this fellow found after some looking-around on the Internet:

... On March 21st, Medtronic issued a "Dear Doctor" letter concerning higher than expected conductor fracture rates with the Sprint Fidelis lead. The Sprint Fidelis is Medtronic's premium defibrillation lead. It is the first sub-7 french ICD to be released (St Jude Medical released the Riata ST lead approximately 18 months after the Sprint Fidelis).

The body of the letter is as follows:

Dear Doctor,

Medtronic has received reports from a limited number of implanting physicians indicating they have experienced higher than expected conductor fracture rates in their centers with Sprint Fidelis leads. While current overall Sprint Fidelis performance is consistent with other leads, Medtronic is actively investigating these reports, has reviewed them with our Independent Physician Quality Panel, and would like to share what we know at this time.

Through detailed assessment of reported fractures, we have identified two primary locations where conductor fractures have occurred: 1) distal portion of the lead and 2) near the anchoring sleeve tie down. The distal conductor fractures affect the anode (ring electrode) and fractures that occur around the anchoring sleeve affect the cathode (helix tip electrode). Fractures at both locations appear to prsenet clinically as over-sensing, increased interval counts and inappropriate shocks. Medtronic has worked closely with physicians who have experienced fractures and conducted significant bench testing in an attempt to reproduce the fractures and identify root cause. At this point, our investigation suggests that variables within the implant procedure may contribute significantly to these fractures.

For distal conductor fractures, our investigation has identified severe bending or kinking of the distal end of the lead over the lead body while passing through tortuous vasculature as a significant contributing factor. If the lead is severely bent or kinked at the distal end, the conductor may be compromised such that the conductor may fracture after implant due to chronic fatigue from natural cardiac motion. The venous structure or pathway, venous access location, length of introducer sheath and lead insertion force are all factors that may contribute to sever bending or kinking of the lead. Medtronic recommends avoiding severe bending or kinking of the lead during implantation. If you encounter excessive resistance resulting in severe bending or kinking while advancing the lead, please remove the lead and return it to Medtronic.

For conductor fractures that occur around the suture sleeve, our preliminary investigation suggests that under certain implant techniques, the lead appears to be exposed to severe bending or kinking in the pectoral area. We are still investigating and actively partnering with physicians to better understand this type of fracture. If excessive kinking or bending is observed during lead suturing and/or pocket formation, Medtronic recommends the lead be re-sutured and/or pocket reassembled per guidelines in the Medtronic lead implant manual. In addition, positioning the anchoring sleeve against or near the vein may be helpful.

Sprint Fidelis lead models 6949, 6948, 6931, and 6930 were market released in the U.S. and internationally in September and October 2004. Performance of model 6949, the Sprint Fidelis lead currently followed in our System Longevity Study, indicated survival is 98.9% at two years. Sprint Fidelis 6949 performance based upon return product analysis shows 99.86% chronic fracture-free survival at two years. Both evaluation methods suggest performance is in line with other Medtronic leads and consistent with lead performance publicly reported by other manufacturers.

The unknown person who posted this April 8 article on the Random Thoughts on Pacemakers & Personal Finance blog then went on to make these comments regarding this March 2007 Dear Doctor letter from Medtronic about its Sprint Fidelis lead failures:

This letter was sent to all implanting U.S. physicians and nowhere was there any request for confidentiality. That is why I posted it.

Well, the lead fails and they state, "variables within the implant procedure may contribute significantly to these fractures." It's the implanter's fault. Of course, that makes perfect sense. The same physician who has implanted endocardial defibrillation leads since 1992 now suddenly doesn't know how to operate one of these new-fangled leads. Are they suggesting that for patients with a tortuous anatomy a different lead should be used - possibly a Sprint Quattro Secure? I don't know. What's going to happen if physicians get nervous and every time they try to implant the lead and "excessive kinking" occurs, they abandon the lead a try a different lead? Will returns to Medtronic increase?

Of course, if and when we learn that the (said-to-be) text of this March 21 Dear Doctor Sprint Fidelis letter from Medtronic which was posted on the Random Thoughts on Pacemakers & Personal Finance blog back in April 2007 is not accurate or correct somehow, we will let you know, immediately. 

Until then, this fellow in Florida seems to have found one of the pieces that might help us further fit together an evolving Sprint Fidelis story.

Cephalon Added Warning To Provigil Label About Serious Skin Reactions In August 2007

A "Dear Doctor" Letter About Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated With Provigil Was Sent In September 2007

(Posted by Tom Lamb at DrugInjuryWatch.com)

On October 24, 2007 the FDA sent an email alert to inform doctors and other healthcare providers that the drug company Cephalon issued a revised package insert, or label, for Provigil (modafinil) in August 2007.

According to this October 2007 FDA alert about Provigil:

• Provigil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder....  Healthcare professionals and consumers should also be aware that Provigil is not approved for use in pediatric patients for any indication.
• The revised labeling updates safety information to include warnings regarding serious rash, including Stevens-Johnson Syndrome (SJS) and hypersensitivity reactions, and psychiatric symptoms. Rare cases of serious or life-threatening rash, including Toxic Epidermal Necrolysis, and Drug Rash with Eosinophilia and Systemic Symptoms have been reported in adults and children in worldwide postmarketing experience....  Physicians should instruct their patients to immediately discontinue the use of Provigil and contact them if a rash or other hypersensitivity reaction occurs.

Cephalon sent a so-called "Dear Doctor" letter about Provigil in September 2007 to convey this information about serious skin reactions such as SJS and TEN as well as to bring attention to the revised label for this sleep disorder drug.

As we had reported in September 2007, the Fall 2007 FDA Drug Safety Newsletter (Volume 1, Number 1) included a report that the FDA had been monitoring cases of serious skin rashes associated with Provigil.

Congressman Waxman Sends A Letter To FDA Requesting Medtronic Sprint Fidelis Information

Committee on Oversight and Government Reform Wants To Know What The FDA Knew About Defibrillator Lead Wire Fractures And When They Knew It

(Posted by Tom Lamb at DrugInjuryWatch.com)

On October 22, 2007, as Chairman of the Committee on Oversight and Government Reform, Congressman Henry Waxman (29th District, CA) sent a letter to FDA Commissioner Andrew von Eschenbach about the recently recalled Medtronic Sprint Fidelis defibrillator lead wires.

As characterized on the web site for this Committee, Waxman's letter is "requesting information about the Agency’s approval of Medtronic’s Sprint Fidelis leads, which are components used in implantable cardiac defibrillators."

A reading of the October 22, 2007 Waxman letter to the FDA, however, reveals that the Congressman is equally interested in learning about when and what Medtronic, Inc. reported to the FDA about the failures of its Sprint Fidelis leads.

In Waxman's October 22 letter we find these requests for information:

• Please provide a chronology of agency actions related to approval of the Sprint Fidelis leads, including, but not limited to, the date of approval for the Sprint Fidelis leads, the PMA or supplement number under which the Sprint Fidelis leads were approved, and any subsequent agency actions or approvals related to the Sprint Fidelis lead.
• Please provide information relating to when and how FDA first became aware of the
  potential fracture problem and when FDA first proposed that action be taken on this
  problem to the company. Please also describe the events leading to the voluntary recall, including any communications FDA had with the company regarding the recall and the dates of such communications.
• Please provide the number and types of adverse events that have been reported to FDA since the introduction of these devices, by month. Were all adverse events related to fracture problem submitted in a timely manner?

We look forward to hearing about the responses that Congressman Waxman gets from the FDA about the timing of this recent Sprint Fidelis recall in the context of what Medtronic was telling the agency during the period leading up to the October 14, 2007 FDA recall.

Children And Young Adults Apparently Have A Higher Risk Of Their Sprint Fidelis Heart Wire Fracturing

This Medtronic Defibrillator Lead Line Was Particularly Popular In Younger Patients Due To Its Smaller Size

(Posted by Tom Lamb at DrugInjuryWatch.com)

In an October 19, 2007 article, "Heart Wires May Pose More Risk for the Young", Wall Street Journal (WSJ) reporters Anna Wilde Mathews and Thomas M. Burton continued to develop the evolving story about the Medtronic Sprint Fidelis recall.  This latest news report concerns children and younger adults who have defibrillators with Sprint Fidelis leads.

Here is what we learned from this WSJ article about pediatric patients and why their risk of experiencing a defibrillator malfunction is higher than older patients:

[Medtronic Inc.] said that of the 268,000 Sprint Fidelis leads implanted, 2,085 were in patients under the age of 21....

Preliminary data from physicians at 32 institutions who specialize in treating pediatric patients and adults with congenital heart disease showed a fracture rate of 6.7% among 569 patients with Sprint Fidelis leads over 30 months. The "vast majority" of the patients are likely to be under the age of 21, given the physicians involved, says Wayne H. Franklin, an associate professor at Northwestern University's Feinberg School of Medicine, who gathered the physician reports.

Medtronic has reported a lower failure rate, 2.3% after 30 months, for all patients implanted with one particular Sprint Fidelis model. For that same model, Dr. Franklin saw a fracture rate of 4.9% among 304 patients in his survey. The real difference may be slightly greater, because the failure rate from Medtronic includes more than just fractures.

These WSJ reporters point out in their October 19 article that all defibrillator lead wires, not just the Sprint Fidelis line by Medtronic, have higher fracture rates in children and young adults because the leads are subjected generally to a higher level of stress for two reasons: children's hearts beat more quickly than older adults; and, these younger patients tend to be a more physically active.

Returning to this October 19 WSJ article about Medtronic's Sprint Fidelis defibrillator leads:

Dr. Franklin's data add to those released Monday by Medtronic. The company said that in patients younger than 21, the failure rate of one Sprint Fidelis model after 30 months was higher than that for all patients: 3.8% compared with 0.8%. That finding was based only on data gathered from devices returned to the company and thus likely doesn't paint a full picture. The more-definitive Medtronic data for that same model, in the entire patient population, show a failure rate of 2.3% over the same period.

As has been widely reported in connection with this Sprint Fidelis recall, when a defibrillator lead wire fractures the patient can get either an unnecessary and massive electrical shock to their heart or the defibrillator fails to deliver a life-saving shock after a cardiac arrest.

We will continue to monitor and report developments regarding what is known about defibrillators with Sprint Fidelis; in particular, the rate at which they have fractured and harmed patients implanted with such a heart device.

P.S.  For some background on this October 19 WSJ aricle, visit the Dr. Wes blog post listed below and read the comment submitted by Northwestern University pediatric cardiologist Wayne H. Franklin, M.D.

"Kick 'em When They're Down"
http://drwes.blogspot.com/2007/10/kick-em-when-theyre-down.html

We appreciate the insight from this discussion over at the Dr. Wes blog.  (11/6/07)

FDA Alerts Doctors About Diabetes Drug Byetta And Acute Pancreatitis Reports

Package Insert Will Be Changed To Include Stronger Warning About This Potentially Fatal Side Effect

(Posted by Tom Lamb at DrugInjuryWatch.com)

On October 16, 2007 the FDA issued an alert to doctors informing them that the agency had reviewed 30 postmarketing reports of acute pancreatitis in patients taking Byetta (exenatide), a drug used to treat adults with type 2 diabetes.

From this October 2007 FDA document, "Information for Healthcare Professionals - Exenatide (marketed as Byetta)", we get some breakdown of those 30 adverse reaction reports:

• FDA said there is evidence that suggests an association between Byetta and acute pancreatitis "in some of these cases."
• In six patients the pancreatitis symptoms began or worsened soon after Byetta dose was increased from 5 mcg twice daily to 10 mcg twice daily.
• 22 of the 30 reports indicated that the patients improved after discontinuing exenatide, i.e., "de-challenge".
• Details in three reports indicated that the symptoms of acute pancreatitis returned when exenatide was restarted, i.e., a "re-challenge".
• 21 of the 30 patients were hospitalized.
• Five patients developed serious complications including dehydration and renal failure, suspected ileus, phlegmon, or ascites.
• 27 of the 30 patients had at least one other risk factor for acute pancreatitis such as gallstones, severe hypertriglyceridemia, and alcohol use.
• The package insert, or label, will be changed to include information about pancreatitis in the "Precautions" section.

___________________________________________________________________

 

Free Byetta Case Evaluation 

Strictly Confidential, No Obligation.

___________________________________________________________________________

According to an October 17, 2007 article, "FDA Says Diabetes Drug May Cause Pancreatitis", by Jennifer Corbett Dooren:

Byetta is co-marketed by Amylin Pharmaceuticals Inc., based in San Diego, and Eli Lilly & Co., of Indianapolis. It was approved in 2005....

Alice Bahner Izzo, an Amylin spokeswoman, said information about pancreatitis is already on Byetta's label, but that it's being updated to give clear advice on what signs and symptoms doctors should look for.

"It's a rare but serious event," Ms. Izzo said of pancreatitis. Byetta has been used by 700,000 patients in the U.S. since the drug was introduced.

The FDA recommends that patients taking Byetta who experience unexplained severe abdominal pain, perhaps accompanied by vomiting, should seek immediate medical care.

Medtronic Sprint Fidelis Wire Leads Fracturing In Defibrillators May Have Caused Five Deaths

Events Leading Up To October 2007 FDA Recall Include A Little Noticed March 2007 "Dear Doctor" Letter And July 2007 Medical Journal Article About Model 6949

(Posted by Tom Lamb at DrugInjuryWatch.com)

An October 16, 2007 article in The Wall Street Journal about the Fidelis Sprint leads recall presented the current situation:

In announcing the recall early yesterday, Medtronic said that its Sprint Fidelis leads have broken at a rate apparently higher than that of competing leads, including another from Medtronic....

When the lead fractures, it can have serious consequences: Some patients can receive unnecessary and massive shocks, sometimes compared to the jolt of sticking a fork in a light socket. Other patients don't get the shock when they do need it to save their lives after cardiac arrest. Overall, five patients so far have died in cases Medtronic says may be related to the flaw.

So far, 2.3% of the implanted leads have malfunctioned over a 30-month period studied by Medtronic since the device's introduction in the fall of 2004. Most of these thousands of malfunctions are fractures.

While this fracturing or breaking problem with the Sprint Fidelis wire lead was the subject of a little noticed (and hard to find, now) March 2007 "Dear Doctor" letter from Medtronic, this emerging medical device safety issue only began to get some real public notice in July 2007.

First, Dr. Robert G. Hauser and some of his colleagues had a paper published in the July 2007 edition of Heart Rhythm about the Sprint Fidelis model 6949 having a higher than expected lead failure at their facility.  From the Abstract for this paper, "Early failure of a small-diameter high-voltage implantable cardioverter-defibrillator lead":

• OBJECTIVE: The aim of this study was to assess the performance of small-diameter Sprint Fidelis high-voltage ICD leads.
• RESULTS: The survival of 583 Sprint Fidelis 6949 leads implanted at our center between September 2004 and February 2007 was significantly less than 285 Sprint Quattro Secure model 6947 leads implanted by us between November 2001 and February 2007 (P = .005). Six patients presented with Sprint Fidelis lead failure 4-23 months after implant. Five of the six patients experienced multiple inappropriate shocks associated with pace-sense conductor and coil fractures; the sixth patient had a fixation mechanism failure. The [United States Food and Drug Administration Manufacturers and User Facility Device Experience (MAUDE) database] search rendered reports for 679 Sprint Fidelis leads. The most frequent complaints or observations were inappropriate shocks (33%), high impedance (33%), and fracture (35%). Of 125 leads analyzed by the manufacturer, 62 involved fracture of the pace-sense conductor or coil and the high-voltage (defibrillation) conductor.

Then, seemingly prompted by this medical journal article by Dr. Hauser, reporter Janet Moore of the Star-Tribune newspaper in Minnesota -- where Medtronic Inc. is headquartered -- picked up the Sprint Fidelis story in a July 30, 2007 article, "Medtronic device under scrutiny":

In late March [2007], Medtronic Inc. sent a letter to doctors advising them that the wire leads in a line of widely used heart defibrillators could tear at a "higher than expected" rate.

The "Dear Doctor" letter assured physicians that the performance of the Sprint Fidelis line of leads is consistent with similar products, and it offered suggestions about how to best implant it.

Four months later, several physicians in the Twin Cities have stopped using the leads, and Medtronic is investigating a patient's death in which a model of the Sprint Fidelis lead is "in question."

And it was Janet Moore at the Star-Tribune who apparently first reported on the Sprint Fidelis recall in her October 14, 2007 article, "Medtronic stops selling heart device":

Medtronic Inc. said today it has stopped selling a popular wire lead used with heart defibrillators because the lead may tear inside the body.

About 235,000 patients worldwide may be affected by the [Minnesota]-based company's action. Patients who believe they may have the device implanted in their chest should contact their doctor, but Medtronic does not recommend replacing it.

The Food and Drug Administration (FDA) said it has classified Medtronic's action as a recall, which means Medtronic must stop selling the devices.

For those interested in learning more about what is known at present about the problems associated with Sprint Fidelis leads, we provide these resources:

October 15, 2007 Statement from FDA

October 15, 2007 Consumer Q&As from FDA

October 15, 2007 "Dear Doctor" Letter from Medtronic

October 15, 2007 News Release from Medtronic

We will continue to monitor and report what is learned about the relatively high rate of breaks or fractures in Sprint Fidelis leads used with defibrillators -- even though it is a bit off-topic for us -- because of its importance and because it seems to be closely / coincidentally related to our October 15, 2007 post: "How Should Drug Companies And Their Ad Agencies Respond To Safety Signals?"

P.S.  Insofar that the March 2007 "Dear Doctor" letter reported the five deaths possibly related to faulty Sprint Fidelis leads one must wonder did the FDA wait to long to issue its October 2007 recall?  (10/18/07)

P.S.   Now U.S. Representative Henry Waxman wants to know what the FDA knew about the Sprint Fidelis defibrillator lead wire fractures and when they knew it.  On October 22, 2007, as Chairman of Committee on Oversight and Government Reform, this California Congressman sent a letter to FDA Commissioner Andrew von Eschenbach requesting the Medtronic information which the FDA had access to before its October 2007 Sprint Fidelis recall.  (10/23/07)

How Should Drug Companies And Their Ad Agencies Respond To Safety Signals?

Two Perspectives On How Emerging Drug Safety Situations Should Be Handled Going Forward

(Posted by Tom Lamb at DrugInjuryWatch.com)

The September 1, 2007 edition of Pharmaceutical Executive starts with the piece "From the Editor: What Do You Say?" which carried this intriguing sub-title: "The first safety signal is detected. Proof or disproof is literally years away. What has to happen so no patient will say, 'You hid the risk'?"

For a lead-in on this piece, however, we draw from an October 15, 2007 post by Ed Feather "The Vioxx Moment" over at the ART + science: the PARTNERS+simons Blog:

Patrick Clinton, Editor-in-Chief of Pharmaceutical Executive magazine, uses the terms "the Vioxx moment" and "the Avandia moment" in his September 2007 "From the Editor" column. He describes these as "the moment when a safety signal has been detected on a drug, and no one yet knows for certain whether it is real or not – the moment when pharma companies and FDA alike set themselves up for a kick in the teeth."  In other words, do we tell people that someone died while taking our drug, or should we wait to see if anyone else dies?

Returning to this September 2007 Pharmaceutical Executive piece, Mr. Clinton is a bit (not surprisingly) biased toward Merck and Big Pharma when using the Vioxx experience to consider how one should properly handle an emerging drug safety issue, but his depiction serves its purpose:

The drug was approved in May 1999. In March 2000, the drugmaker announced preliminary results of the VIGOR trial, which was designed to test the gastric effects of Vioxx, but instead suggested that the drug was causing cardiovascular problems. The trial wasn't set up to test for CV side effects, so the results were ambiguous: Maybe it was just showing that naproxen, the drug Vioxx was tested against, was cardioprotective.

Roughly a year later, an FDA advisory committee meets to discuss the results, and roughly another year later, Vioxx's label is changed. And two and a half years after that, the APPROVe trial testing Vioxx for its effect on colon polyps is halted because it's finally clear that Vioxx is causing heart attacks and strokes.

You remember what came next: an endless litany of "Why are we only hearing this now?" That perception—that the period between first discovery of a safety signal and scientific confirmation of a safety problem is basically a cover-up—has had a shocking effect on the credibility of the industry and of FDA. And as things stand, we can expect something similar to happen over and over. As researchers develop more powerful tools, we'll see more safety issues with more drugs emerging in the postmarket phase. And most issues will be sufficiently ambiguous that they'll require further research. They'll trigger a Vioxx moment.

In closing his editorial, Mr. Clinton proposes one possible approach for drug companies and doctors to address this drug safety signal predicament:

I suspect the answer will include both a standard format for reporting safety signals to the public—one that assesses the validity of the evidence and provides a realistic estimate of how long it will take to get more—and perhaps even some sort of informed-consent procedure. That would be a burden to physicians, patients, and pharma alike. It would certainly frighten some patients out of taking their drugs and some doctors out of prescribing them. But that may turn out to be the price of trust.

The execution may prove difficult, but the goal is simplicity itself. No patient should ever be able to say of a risky drug, "You knew, and you didn't tell me." For everyone's sake, that must be utterly nonnegotiable.

And returning to "The Vioxx Moment", Ed Feather -- who says therein that he worked for GlaxoSmithKline in the past and was involved with the marketing of Avandia -- provides some parallel good advice for those advertising agencies that work for Big Pharma:

As marketers, it is our responsibility to ensure we do everything we can to be truthful. While the goal is to sell more product, it should not be at the cost of public faith in medicine, nor at the cost of lives.  We must ensure that we include ALL of the safety information in a clear format that everyone can understand.

Print and online media generally afford the space for longer disclosures of safety information.  But with TV we may find ourselves foolishly searching for ways to shorten the fair balance while staying within FDA regulations.  In the end, if the safety information is not clear, and someone misses an important, life-changing piece of information, you have failed.

My advice: stick with integrity.  Do it right the first time.  Continue to elevate a positive profile for the pharmaceutical industry.  And help healthcare providers, and their patients, make the right medical decisions based on ALL of the necessary information.

Consistent with these two thoughtful pieces, let's hope that the lessons of Vioxx do not go unheeded and that drug safety will continue to improve here in the U.S. and around the world.

Health Canada Provides 2007 Update On Reports Of Suspected Meridia Adverse Reactions

Meridia Can Increase Blood Pressure And Heart Rate Leading To Possible Serious Cardiovascular Problems

(Posted by Tom Lamb at DrugInjuryWatch.com)

The Canadian Adverse Reaction Newsletter (CARN) released in October 2007 (Volume 17, Issue 4) includes an article about the anti-obesity drug Meridia (sibutramine), "Contraindicated use of sibutramine and cardiovascular adverse reactions".  This article updates us on the safety profile of Meridia, which is made for the Canadian market by Abbott Laboratories Ltd.

As background, in March 2002 Meridia was the subject of a Health Canada investigation which resulted in this February 2003 report on the safety of Meridia.

This October 2007 Canadian Adverse Reaction Newsletter article updates that Meridia safety profile report with this information:

Health Canada continues to receive reports of ARs in patients using sibutramine who have contraindications. From Jan. 1, 2001, to May 31, 2007, Health Canada received 65 reports of cardiovascular ARs suspected of being associated with sibutramine. Thirteen of these reports involved patients with at least 1 contraindicated condition....

Contraindications for sibutramine therapy include:

• History of coronary artery disease, congestive heart failure, arrhythmias or cerebrovascular disease (stroke or transient ischemic attack)
• Inadequately controlled (> 145/90 mm Hg) or unstable hypertension
• Psychiatric illness
• Concomitant use of centrally acting drugs (e.g., antidepressants and antipsychotics) or herbal remedies (e.g., St John's Wort) for the treatment of psychiatric disorders; monoamine oxidase inhibitors; or other centrally acting weight-reducing agents
• History of, or presence of, a major eating disorder such as anorexia nervosa or bulimia nervosa
• Hypersensitivity to sibutramine or to any ingredient in the formulation or component of the container

This Health Canada Meridia article goes on to provide a brief description of the 13 cardiovascular adverse reaction cases that involved one or more of these contradicted conditions. 

Furthermore, in this article Health Canada advises doctors and patients, both, to check the Meridia package insert, or label, before starting Meridia so as to be aware of the contraindications and avoid a possible serious adverse reaction.

Bisphosphonate Safety Update: FDA Is Investigating Link With Atrial Fibrillation In October 2007

Merck Addresses Cases Of Fosamax-induced Osteonecrosis Of The Jaw, And Three Reports Of ONJ Are Subject Of A Medical Journal Article

(Posted by Tom Lamb at DrugInjuryWatch.com)

This article is a review of recent reports about the safety of bisphosphonates, with an emphasis on Merck's Fosamax and its association with osteonecrosis of the jaw (ONJ).

We start however with the emerging issue of a possible link between bisphosphonates and the heart condition atrial fibrillation.

In October 2007 the FDA issued an Early Communication of an Ongoing Safety Review entitled "Bisphosphonates: Alendronate (Fosamax, Fosamax Plus D), Etidronate (Didronel), Ibandronate (Boniva), Pamidronate (Aredia), Risedronate (Actonel, Actonel W/Calcium), Tiludronate (Skelid), and Zoledronic acid (Reclast, Zometa)" which is largely based on the following:

An article and an accompanying letter to the editor in the May 3, 2007, issue of The New England Journal of Medicine describe increased rates of serious atrial fibrillation (defined by the authors as life-threatening or resulting in hospitalization or disability) in two different studies of older women with osteoporosis treated with the bisphosphonates, Reclast and Fosamax.  In both studies, more women who received one of the bisphosphonates (Reclast-1.3% or Fosamax-1.5%) reportedly developed serious atrial fibrillation as compared to women who received placebo (Reclast study-0.5%, Fosamax study-1.0%).  In both studies, the rates of all atrial fibrillation (serious plus nonserious) were not significantly different between groups treated with bisphosphonate versus placebo.

This October 2007 FDA item states that the agency has requested additional information, presumably from the drug companies, in order to evaluate the extent of any association between these bisphosphonates and atrial fibrillation, which is a heart rhythm disorder.  Further, the FDA said this bisphosphonate safety evaluation would take up to twelve months for the agency to complete. 

In September 2007 Merck released its latest proclamation about the safety of Fosamax entitled "Fosamax: Statement by Merck & Co., Inc. Regarding FOSAMAX® (alendronate sodium) and Rare Cases of Osteonecrosis of the Jaw".  The online version of this document (accessed 9/18/07) included the following:

Addendum:  Several independent organizations have published statements related to osteonecrosis of the jaw (ONJ).  Merck & Co, Inc., does not necessarily endorse the perspectives or opinions expressed within these statements.  Also, the prescribing information of currently available intravenous and oral bisphosphonates may provide information about ONJ. To help healthcare professionals in their efforts to understand ONJ, a non-exhaustive list of online addresses associated with independent organizations and available intravenous and oral bisphosphonates is provided as follows.

Information from the National Institutes of Health
http://www.niams.nih.gov/bone/hi/oralhealth_bone.htm

Background from the American Dental Association
http://www.ada.org/prof/resources/topics/osteonecrosis.asp

Statement from the National Osteoporosis Foundation
http://www.nof.org/news/pressreleases/osteonecrosis.htm

Statement from the American Association of Oral and Maxillofacial Surgeons
http://www.aaoms.org/docs/position_papers/osteonecrosis.pdf

Statement from the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis
http://www.ecceo8.org/images/mail/osteonecrosis_jaw.pdf

Statement from the American Society for Bone and Mineral Research
http://www.jbmronline.org/doi/pdf/10.1359/jbmr.0707ONJ

Lastly, in July 2007 there was a new medical journal article about bisphosphonate associated osteonecrosis of the jaw (BONJ), "Oral bisphosphonate associated osteonecrosis of the jaws: three case reports", which appeared in the British Dental Journal.

Be assured that we will continue to follow and report developments concerning the safety of Fosamax and the other bisphosphonate drugs going forward.