Drug Injury Watch

Tequin Revisited: Health Canada And The FDA Failed To Take Action, At Our Expense

Bristol-Myers Squibb Was Allowed To Withdraw Their Unsafe Drug For "Economic Reasons", And Only After Selling Off Its Inventory

(Posted by Tom Lamb at DrugInjuryWatch.com)

An article by Joel Lexchin, MSc MD, "Information about a discontinued drug", published in the March 11, 2008 edition of the Canadian Medical Association Journal (CMAJ), reminded me about how Health Canada and the FDA failed to order a recall of Tequin (gatifloxacin) a couple of years back.  Instead, Bristol-Myers Squibb (BMS) was allowed to do a gradual withdrawal of Tequin and, in so doing, the drug company largely succeeded in not drawing any additional attention to Tequin's safety problems.

In the spring of 2006, Bristol-Myer said that a continuing decline in Tequin sales was the reason for deciding to stop selling Tequin.  In fact, however, Tequin was an unsafe drug that had been linked to various blood-sugar disorders -- but the FDA as well as Health Canada let the drug company have it their way.

For the following review of developments and events leading up to how BMS ended its Tequin sales in the U.S. and Canada, I draw from two of my earlier reports about this dangerous antibiotic:   

• Bristol-Myers Squibb To Stop Selling Antibiotic Drug Tequin
• Antibiotic Tequin Should Be Banned By FDA, Says Public Citizen Petition

Mid-February 2006: BMS, the FDA, and Health Canada announced that the Tequin label would be changed to include stronger warnings about the threat of life-threatening events from blood-sugar changes.

March 1, 2006: The New England Journal of Medicine (NEJM) published online an early-release version of a study which found that patients using Tequin had four times the risk of hypoglycemia (low blood sugar) and an astounding 17 times the risk of hyperglycemia (high blood sugar) -- collectively referred to as dysglycemia -- when compared to other antibiotics.

April 27, 2006:  A newspaper article is the first announcement that BMS has decided to stop selling Tequin.  According to this Wall Street Journal article, however, Tequin product shipments would not end in most markets until sometime in May or June 2006.

May 1, 2006: Public Citizen asked the FDA to ban Tequin in order to immediately get this unsafe drug off pharmacy shelves in the U.S.  According to the Public Citizen petition, an analysis of adverse event reports submitted to the FDA reveals that during the period January 1, 2000 through June 30, 2005 there were 388 cases of hypoglycemia and hyperglycemia; 20 on those reports involved patient deaths.

To my knowledge, the FDA never banned Tequin in the U.S. as requested by Public Citizen.

The March 2008 CMAJ article which is mentioned at the outset of this piece confirms that Health Canada did nothing:

Health Canada issued a number of alerts about the potential for this product to interfere with glucose metabolism but never bothered to formally inform either the public or health care professionals that oral and intravenous forms of this drug were withdrawn from sale in Canada. The only place where one can find this information is by searching the discontinued products in Health Canada's Drug Product Database (http://cpe0013211b4c6d-cm0014e88ee7a4.cpe.net.cable.rogers.com/dpdonline/searchRequest.do). This failure to communicate important information about a drug raises serious concerns about Health Canada's ability to keep health care professionals and the public informed about safety issues.

I believe the same thing -- "raises serious concerns" -- can be said about how the FDA let the drug company Bristol-Myers Squibb seemingly sell-off its inventory of Tequin instead of the FDA ordering an immediate recall of Tequin. 

In the end, this history of Tequin appears to be a prime example of putting profits over public safety.

More Reports Of Serious Blood Clots In Women Using Birth Control Patch Or Vaginal Ring

January 2008 Health Canada Newsletter Presents These Adverse Reaction Cases, And Announces "Canada Vigilance"

(Posted by Tom Lamb at DrugInjuryWatch.com)

The Canadian Adverse Reaction Newsletter (CARN), in its January 2008 edition (Volume 18, Issue 1), has two articles of interest regarding side effects associated with birth control products that are alternatives to oral contraceptives.  In the index of this January 2008 CARN the short name for these articles are:

Case presentation: NuvaRing and aortic thrombosis

Evra: myocardial infarction and thromboembolic adverse reactions

We start with the article about the birth control patch, which is known as Evra in Canada.  From the start of this article, "Transdermal norelgestromin-ethinyl estradiol (Evra): myocardial infarction and thromboembolic adverse reactions":

Evra is a transdermal hormonal contraceptive system containing 6 mg of norelgestromin and 0.6 mg of ethinyl estradiol per patch. Since its introduction on the Canadian market in early 2004, 16 cases of thromboembolism and 1 of myocardial infarction suspected of being associated with the product have been reported to Health Canada (Table 1). Two of the 17 patients died.

The referenced Table 1 is "Summary of reports submitted to Health Canada of myocardial infarction and thromboembolic disorders suspected of being associated with Evra, from date marketed in Canada [January 2004] to Aug. 27, 2007".  This table shows reports of myocardial infarction (heart attack), pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as thrombophlebitis in the leg or arm, in women using the Evra birth control patch in Canada.

The article about NuvaRing, the vaginal ring, is in the form of a Case Presentation: "Etonogestrel-ethinyl estradiol vaginal ring (NuvaRing) and aortic thrombosis".  It provides the fundamental facts of a case report, some of which are set forth below:

• Subject was a 21-year-old obese woman (body mass index 36.3 kg/m2).
• She smoked 10-20 cigarettes per day.
• Was diagnosed with an aortic thrombosis 15 months after she started using the etonogestrel-ethinyl estradiol slow-release vaginal ring (NuvaRing) for contraception.
• Following an aortic thrombectomy, an embolus was also removed from her left leg.
• She had no known history of varicose veins, recent injection or infusion, long-distance travel, prolonged immobilization, surgery or trauma.
• Her personal and family history of venous thrombosis was also negative.

These facts lead to the conclusion that her adverse reactions were most likely caused by her use of the vaginal ring, NuvaRing.

Lastly, this January 2008 edition of The Canadian Adverse Reaction Newsletter informed us that Health Canada is changing the name of its Canadian Adverse Drug Reaction Monitoring Program; going forward it will be called "Canada Vigilance". Furthermore, Health Canada is implementing a new database for its postmarketing surveillance of adverse drug reactions (ADRs), which will be known as "the Canada Vigilance database".

We have previously reported, here, that the the Ortho Evra birth control patch has been linked to serious blood clots and that the vaginal ring NuvaRing can cause pulmonary embolism, deep vein thrombosis, stroke, and heart attack.

We will continue to monitor adverse event reports for these two birth control methods.

Cholesterol Drug Zetia May Cause Serious Liver Injury Including Hepatitis And Liver Failure

Health Canada First Raised This Zetia Safety Issue In February 2005; News Reporter Discovers In December 2007 That Information Known By Merck and Schering-Plough About These Zetia Side Effects May Have Been Withheld

(Posted by Tom Lamb at DrugInjuryWatch.com)

Back on February 1, 2005 Health Canada posted on its web site a so-called "Dear Doctor" letter about Zetia (ezetimibe) -- called Ezetrol in Canada -- from Merck Frosst / Schering Pharmaceuticals that was intended to draw attention to some serious side effects associated with Zetia.  That 2005 Dear Doctor letter included the following:

The Warnings, Precautions, and Adverse Events sections are being updated to reflect the occurrence of the following adverse events in patients taking Ezetrol® (ezetimibe) alone or in combination with a statin:

• myalgia;
• rhabdomyolysis;
• hepatitis;
• acute pancreatitis;
• thrombocytopenia; and
• suspected interaction between Ezetrol® (ezetimibe) and warfarin 

In the U.S., however, Merck and Schering-Plough -- the drug companies responsible for Zetia, here -- chose not to send any corresponding Dear Doctor letter to American health care professionals, nor did the FDA mandate that they do so.

Returning to this 2005 Dear Doctor letter about Zetia, here is what was said about liver injuries to patients using Zetia and a statin drug (such as Zocor, Lipitor, Crestor, Lescol, Mevacor, or Pravachol):

Adverse hepatic events:

Elevations of liver transaminases and cases of hepatitis have been reported in patients treated with [Zetia]. Liver function monitoring is recommended when therapy with [Zetia] is initiated in patients treated or about to begin treatment with a statin.

Health care professionals should be aware that the use of [Zetia] in combination with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations of liver transaminases.

In the two years since this 2005 Dear Doctor letter about Zetia was sent by the Merck and Schering group in Canada there have been some case reports of serious liver injury in patients using Zetia and statins -- but for the most part Zetia-induced liver injury had been off-the-radar for most drug safety observers. 

Now we have some idea about why, perhaps, Zetia-induced liver injury side effects were not more widely known.

In a December 21, 2007 article, "Data About Zetia Risks Was Not Fully Revealed", New York Times (NYT) reporter Alex Berenson broke the story that Merck and Schering-Plough had conducted several studies of Zetia which, in fact, raised the possibility that Zetia can cause liver damage when used long-term with other statins -- but these drug companies decided not to publish the results of those Zetia studies.

In preparing for his December 2007 Zetia article, the Times' reporter Alex Berenson spoke to a drug company representative and some medical doctors about this reporter's discovery of unpublished research about Zetia and liver-related side effects. 

We'll start with comments from two doctors who spoke with Mr. Berenson about this emerging drug safety issue:

“You don’t want to have data missing,” said Dr. Bruce Psaty, a professor of medicine and epidemiology at the University of Washington. “When there have been adverse effects, when the benefits don’t look impressive, those are the trials that historically don’t make it to press.”...

“We keep telling people we want to practice evidence-based medicine, and what we keep finding out is that much of the evidence is obscured,” said Dr. Harlan Krumholz, a cardiologist at Yale, when told about the previously undisclosed studies. “There is important evidence, but it’s not in public view. It’s hidden from investigators.”

On the other side of things, the Schering-Plough representative had this to say :

A Schering executive, when asked by a reporter about the unpublished [Zetia] studies, confirmed their existence. But the executive, Dr. Robert J. Spiegel, said the companies had not considered the [Zetia] studies scientifically important enough to publish their findings. Some may eventually be published, he said.

"We’re pretty comfortable that people don’t have trouble tolerating Zetia,” said Dr. Spiegel, the chief medical officer of the Schering-Plough Research Institute, Kenilworth, N.J.  (Emphasis added.)

In his December 2007 NYT article Mr. Berenson provides some reasons, however, why doctors and patients may not want to go along with this "reassurance" from Schering's Dr. Spiegel:

Most of the studies about Zetia in which Merck and Schering have published the results covered periods of only 12 weeks — not enough time for liver problems to develop in most patients....

But the F.D.A.’s documents show that Merck and Schering conducted several other long-term trials of Zetia without releasing their findings.

Together those studies cover several thousand patients who took Zetia along with statins for one to two years. The statins include Lipitor and Crestor, as well as Zocor, which is usually prescribed generically as simvastatin and is the statin used in the Vytorin pill....

The companies’ own published studies have generally played down the risk of liver problems. But Dr. Mark Stolk, a gastroenterologist in the Netherlands, last year reported two cases of patients who had developed hepatitis, a liver disease, after taking Zetia alongside Lipitor. One of the patients has since died, Dr. Stolk said in an interview last month. While Zetia is safe for most patients, doctors should carefully monitor patients for liver damage, he said.

“I think other cases will emerge,” he said.

What does the FDA have to say about this news reporter's discovery of unpublished studies suggesting that Zetia can cause serious liver injury when taken with statins?  Mr. Berenson tells us: "The agency did not respond to requests for comment."

To be sure, we will be reporting further developments as more is learned about the safety of Zetia -- one way or the other.

P.S.  Given how NYT reporter Alex Berenson discovered that Merck and Schering-Plough failed to publish some studies about Zetia and liver damage, Ed Silverman timely posted "How To Find Documents On The FDA Site" on his Pharmalot blog:

This cheat sheet should help you find briefing documents - the reams of supporting paperwork submitted by a drugmaker when seeking FDA approval for its med. It was compiled by a professor and students at the Lake Erie College of Osteopathic Medicine’s School of Pharmacy and recently published in the letters section of The Annals of Pharmacotherapy.

Thanks Ed for this insight about how emerging drug-safety issues (like the NYT Zetia story) can be found and exposed.  (12/21/07)

P.S.   Dr. Aubrey Blumsohn, over at the Scientific Misconduct Blog, gives us his strongly worded opinion about the position asserted by Schering's medical director in the NY Times story about Zetia and Vytorin, which I have bolded above. 

In his post, "More problems with Ezetimibe (Zetia, Vytorin): Let there be light", Dr. Blumsohn writes:

... Dr. Spiegel, it's not your decision. When patients might die it's always "scientifically important".

In addition, Dr. Blumsohn provides links to some other articles about this emerging Zetia study data controversy.  (12/23/07)

Will New Black Box Warning About Heart Attacks Lead GlaxoSmithKline To Withdraw Avandia From Market?

One Wonders Whether GSK Might Do A "Soft" Recall Of Its Embattled Diabetes Drug, As Was Done By BMS With Serzone And Tequin In Recent Years

(Posted by Tom Lamb at DrugInjuryWatch.com)

Avandia (rosiglitazone) is a prescription drug from GlaxoSmithKline (GSK) approved by the FDA in 1999 to treat Type 2 diabetes.  As many people are aware now, while Avandia might have helped diabetic patients in some regards, it seems that this benefit comes at an increased risk of developing serious heart-related side effects including heart attacks and strokes.

The Avandia safety story started for most of us in May 2007, as follows:

On May 21, 2007 the Los Angeles Times published an Associated Press (AP) article entitled "Diabetes drug linked to heart attack risk" which broke the story about a new analysis of Avandia data that was published online earlier this same day by the New England Journal of Medicine (NEJM).  The new Avandia article, "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death", by Steven E. Nissen, M.D., and Kathy Wolski, M.P.H., will appear in the June 14, 2007 print edition of the NEJM.

More recently, on November 6, 2007 Health Canada issued a MedEffect email alert about Avandia -- as well as the related Avandamet and Avandaryl -- to inform us that GlaxoSmithKline is informing Canadian doctors and patients about new restrictions on the use of its rosiglitazone products (Avandia, Avandamet and Avandaryl) due to "cardiac safety concerns".

More detail was provided in the November 2007 Public Communication document about Avandia posted by Health Canada:

• Rosiglitazone (Avandia®) is no longer approved for use alone to treat type 2 diabetes, except when metformin* use is contraindicated or not tolerated.
• Rosiglitazone is no longer approved for use with a sulfonylurea drug** (such as glyburide), except when metformin is contraindicated or not tolerated.
• Rosiglitazone should not be used if you have heart failure, or have experienced heart failure in the past.
• Patients who are taking rosiglitazone, especially those with underlying heart disease, or those who are at high risk of heart attack or heart failure, should talk to their doctor about the benefits and risks of continuing rosiglitazone therapy.

There was also a November 2007 "Dear Doctor" letter about Avandia posted on the Health Canada web site.

Two weeks before this news from Health Canada, in the U.S. the FDA had announced that it wanted Glaxo to add a "black box" warning about the increased heart attack associated with Avandia, according to an October 24, 2007 article in The Wall Street Journal, "Tougher Avandia Warning Is Urged":

Agency officials are pushing for a "black box" warning, [according to people with knowledge of the matter]. The new label is still being discussed with the company and its final form isn't yet clear. In high-profile safety matters, the agency tends to have strong leverage....

An FDA spokeswoman said the agency "is still involved in internal discussions on this matter" and that when there is a final decision it will become public. A GlaxoSmithKline spokeswoman said the company is "working diligently with the FDA to finalize the label, but it would be inappropriate for us to discuss the ongoing conversations with the agency."...

If it goes into effect, the new warning would focus on Avandia's potential for increased ischemic risk: a risk of events in which blood is choked off from the heart. An FDA analysis that crunched together multiple Avandia studies found that the drug appeared to be linked to a 38% higher risk of ischemic events....

When Avandia gets its new "black box" warning about increased heart attack risks, Avandia sales may be even further diminished going forward.  In turn, GlaxoSmithKline could follow the lead of Bristol-Myers Squibb (BMS) when that drug company experienced increasing scrutiny about the safety of its antibiotic Tequin in 2006.  Rather than do a Tequin safety recall, Bristol-Myers announced that it would stop marketing Tequin in the U.S. for "business" reasons -- which was very similar to what they did with their besieged anti-depressant drug Serzone back in 2004.

This new Big Pharma practice of withdrawing an alleged unsafe prescription drug for said-to-be business reasons (rather than safety reasons) could be called a "soft" recall.

We'll wait to see what Glaxo decides to do about its embattled diabetes drug as more is learned about Avandia side effects going forward.

Trasylol Sales In U.S. And Canada Suspended Temporarily By Bayer In Early November 2007

Market Withdrawal Or Recall Of Trasylol Seems Possible As Bayer Waits For Final Data From Halted BART Study

(Posted by Tom Lamb at DrugInjuryWatch.com)

On November 5, 2007 the FDA announced and Health Canada announced that sales of Bayer AG' s anti-bleeding drug Trasylol (aprotinin) would be suspended temporarily in the U.S. and Canada while investigations continued about whether Trayslol is linked to a higher risk of death than competing heart surgery drugs.

As we had reported previously, the FDA has been reviewing the safety of Trasylol since early 2006:

In mid-February 2006 the FDA issued a Public Health Advisory informing doctors and patients that the agency was evaluating the safety of Bayer AG's heart surgery drug Trasylol (aprotinin injection) after new studies had linked it to higher risks of kidney problems, heart attacks, and strokes.  At the end of February 2006, a "Dear Doctor" letter from Bayer regarding Trasylol was posted on Health Canada's MedEffect web site.

Later, in September 2006, an FDA advisory panel reviewed data from medical journals that suggested that Trasylol might increase the chance of kidney damage, heart attacks, and strokes.

A second Trayslol advisory panel meeting was scheduled for September 2007.  Two days before, FDA staff released 235 pages of briefing documents they had prepared for that Trasylol advisory panel meeting which seemingly foreshadowed this most recent development in the Trasylol saga.

From a September 10, 2007 Reuters article, "Bayer's Trasylol may boost death risk: FDA staff", by reporter Kim Dixon:

FDA staff, in briefing documents ahead of Wednesday's advisory panel, said the totality of three recent studies support the risk of renal failure and dysfunction, and noted a "mortality disadvantage detected" in the Bayer study.

A Bayer spokeswoman said the company looks forward to discussing the drug's merits at the advisory panel meeting....

"There is still no new clinical data, so the question is whether (Bayer's) observational study is enough of an alarm," said Ira Loss, an analyst at the investor research firm Washington Analysis.

"My assumption is this drug is being put into the dead-end of drug land," he added.

While the September 2007 Trasylol advisory panel decided this heart surgery drug should remain on the market despite its increased renal and cardiovascular risks, it urged Bayer to conduct a randomly controlled clinical trial on Trayslol.

Bad news for Bayer, however, soon followed when a Canadian study -- the BART study, an independent randomized, controlled trial that was being conducted in high-risk cardiac surgery patients -- was suddenly stopped in mid-October 2007 due to emerging serious safety concerns regarding Trayslol.

On October 25, 2007 the FDA posted on its web site an "Early Communication about an Ongoing Safety Review Aprotinin Injection (marketed as Trasylol)" which said, in part, stated that the 30-day mortality risk in the Trasylol group of the BART trial was nearing statistical significance, compared with other treatments Trasylol was being tested against.

A November 5, 2007 Reuters article about the suspension of Trayslol sales brings us up-to-date with this information:

• On [November 5, 2007] Bayer said it had been informed that BART trial data were now being collected from centers throughout Canada and final data analysis would emerge in around eight weeks.
• "Once the complete BART dataset is available, Bayer will work with health authorities to evaluate whether these data have any impact on the positive benefit-risk assessment for Trasylol," Bayer said [November 5, 2007].
• "Bayer believes that the totality of the available data continue to support a favorable risk-benefit profile for Trasylol when used according to labeling," the company said.

We will wait to see whether or not the final analysis of this BART study data and any other relevant information leads to Bayer withdrawing Trasylol from the market altogether in the months to come.  Of course, it is possible that based on their findings the FDA or Health Canada may make that choice for the drug company.

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.

Health Canada Issues Ketek MedEffect Alert In Early September 2007

Antibiotic Ketek Restricted To Certain Types Of Pneumonia; No Longer Used For Sinusitis, Bronchitis, Tonsillitis, Pharyngitis

(Posted by Tom Lamb at DrugInjuryWatch.com)

On September 5, 2007 Health Canada issued by email a MedEffect alert about Ketek which included this summary:

Sanofi-aventis Canada, Inc. is informing Canadians that the antibiotic Ketek (telithromycin), should no longer be used to treat sinusitis, bronchitis, tonsillitis or pharyngitis. Ketek can still be used to treat certain types of pneumonia.

More information about these restrictions imposed on Ketek in Canada are set forth in the accompanying "PUBLIC COMMUNICATION Health Canada Endorsed Important Safety Information on KETEK (telithromycin)" and the the so-called "Dear Doctor" letter sent to health care professionals by Sanofi-aventis Canada Inc. on August 30, 2007.

From this Canadian Ketek Dear Doctor letter we get this more in-depth information about this change in indications for Ketek in Canada:

Upon review of the available safety information, including reported cases of severe liver injury, Health Canada has determined that the benefit-risk profile for KETEK® no longer supports its use for the treatment of acute exacerbation of chronic bronchitis (AECB), acute bacterial sinusitis (ABS) or tonsillitis/pharyngitis. These indications will be removed from the label.

KETEK® continues to be indicated only for the treatment of community-acquired pneumonia (CAP) of mild to moderate severity due to Streptococcus pneumoniae, (including multi-drug resistant isolates [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila (Chlamydia) pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Staphylococcus aureus for patients 18 years old and older.

In view of the following developments regarding Ketek in the U.S., however, this action by Health Canada and Sanofi-aventis Canada seems relatively late:

• In December 2006 an FDA advisory panel recommended the use of Ketek should be restricted to treatment of community-acquired pneumonia, only, and should no longer be used as treatment for acute bacterial exacerbation of chronic bronchitis nor acute bacterial sinusitis;
• In February 2007 we learned that the FDA was going to heed this recommendation by its advisory panel when the agency issued a bulletin entitled "FDA Announces Label and Indication Changes for the Antibiotic Ketek"; and,
• In March 2007 Sanofi-Aventis sent a "Dear Doctor" letter in the U.S regarding these prescribing and treatment changes that were being made for Ketek due to its association with severe liver injury.

Meanwhile, several product liability lawsuits regarding cases of serious liver injury allegedly caused by Ketek have been filed in various courts, here, during 2007.  We are not aware of any Ketek lawsuits filed in Canada but that is not to say that there are not any, there.

Parkinson's Disease Drug Permax Ordered Off The Market By Health Canada

Permax Was Voluntarily Withdrawn From the U.S. Market Earlier This Year At The Insistence of FDA

(Posted by Tom Lamb at DrugInjuryWatch.com)

As you may recall, the Parkinson disease drug Permax was voluntarily withdrawn from the U.S. market in late March 2007 after studies in the New England Journal of Medicine underscored the increased risk of serious heart valve damage associated with Permax.

In Canada, however, Eli Lilly Canada Inc. had continued to sell Permax (pergolide). 

On August 16, 2007, however, Health Canada announced the sales of Permax must cease in their country as of August 30, 2007

In more detail, from a MedEffect Public Communication about Permax issued on August 16, 2007, we get this information about why Health Canada has taken this action:

• Two studies published in the New England Journal of Medicine (NEJM) in January 2007 showed that patients with Parkinson's disease who were treated with Permax had an increased chance of serious heart valve damage when compared to patients who did not receive the drug. [footnotes omitted] In light of this recent information, Health Canada has determined that there is not enough evidence to support the continued safe use of Permax as currently recommended in the prescribing information.
• Eli Lilly Canada Inc., in co-operation with Health Canada, will stop sales of Permax (pergolide mesylate) in Canada as of August 30, 2007 due to the potential for cardiac valvulopathy, a condition involving inflammation or stiffening of the heart valves. Pharmacies may continue to sell Permax after that date to allow patients sufficient time to consult with their healthcare providers and to transition to an alternative medication.

Eli Lilly Canada Inc. has sent a so-called "Dear Doctor" letter to Canadian healthcare providers about Permax informing them that sales of this Parkinson's disease drug will stop in Canada as of August 30.  This Permax Dear Doctor letter also gives advice for discontinuation and transition to alternative medications for Canadian patients currently taking Permax.

FDA / Health Canada: Long Term Use Of Nexium And Prilosec May Cause Heart Attacks Or Cardiac Death

AstraZeneca Study Information Provided To Regulatory Agencies In May 2007 Currently The Subject of Their Ongoing Safety Reviews

(Posted by Tom Lamb at DrugInjuryWatch.com)

On August 9, 2007 the FDA and Health Canada issued email alerts about possible serious cardiac events in patients using the prescription heartburn drugs Nexium (esomeprazole) and Prilosec (omeprazole), made by AstraZeneca (AZN).  These two drugs are prescribed for the treatment of gastroesophageal reflux disease (GERD), esophageal erosions, and for maintenance of healing erosions of the esophagus.

In more detail, the August 9 FDA alert about Nexium and Prilosec directed one to an online document entitled "Early Communication About an Ongoing Safety Review", which includes this introduction to a possible new drug safety issue:

FDA has received and is reviewing new safety data about Prilosec (omeprazole) and Nexium (esomeprazole).  On May 29, 2007, AstraZeneca, the manufacturer of Prilosec (omeprazole) and Nexium (esomeprazole), sent FDA and other regulatory authorities world-wide their preliminary review of new data from two small long-term clinical studies in patients with severe gastroesophageal reflux disease (GERD).  In both studies, patients were to be randomly assigned to receive treatment with a drug (either omeprazole or esomeprazole) or to have surgery to control their GERD.  The results from the study of Prilosec and analyses from an ongoing study of Nexium raised concerns that long-term use of Prilosec or Nexium may have increased the risk of heart attacks, heart failure, and heart-related sudden death in those patients taking either one of the drugs compared to patients who received surgery.

This August 9 FDA document, however, went on to make this very important point:

At this time, FDA’s preliminary conclusion is that collectively, these data do not suggest an increased risk of heart problems for patients treated with [Prilosec] or [Nexium].

The August 9 Health Canada alert about Nexium and Prilosec directed one to an online document entitled "Health Canada reviewing new safety information on cardiac events in patients taking Losec (omeprazole) or Nexium (esomeprazole)".

As did the FDA, Health Canada made clear that it had not concluded there is a causal relationship between Nexium and Prilosec / Losec and this possible emerging drug safety issue:

At this point in time, Health Canada’s preliminary review suggests that the evidence provided does not confirm the existence of a possible cardiovascular risk. Health Canada will complete its analysis of the new information by the end of the year and will advise Canadians of its conclusions and any resulting recommendations at that time.

In Canada, omeprazole is also sold under the labels of Apo-omeprazole and Ratio-omeprazole.

If there proves to be an increased risk of heart attacks, heart failure, and heart-related sudden death associated with the use of Nexium, the ramifications would be significant due to this fact provided in an August 9, 2007 article, "FDA to Review Heartburn Drugs", published online by The Wall Street Journal:

AstraZeneca recorded $5.2 billion in Nexium sales last year. It was the second best-selling drug in the world behind Pfizer Inc.'s (PFE) Lipitor anti-cholesterol pill, according to IMS Health, a drug-data firm.

Last but not least, as advised by the August 9 Health Canada document, patients taking Nexium or Prilosec "should consult with their doctor before making any change to their medication, as GERD can lead to other complications, if left untreated."

Levaquin Associated With Blood Sugar Problems And Liver Disorders

January 2007 Article Sets Forth Reports Made To Health Canada In Past Ten Years

(Posted by Tom Lamb at DrugInjuryWatch.com)

The January 2, 2007 edition of the Canadian Adverse Reaction Newsletter (Volume 17, Issue 1) includes an article concerning reports of blood sugar problems and liver disorders associated with Levaquin (levofloxacin) made to Health Canada during the past ten years

According to this article, entitled "Levofloxacin: dysglycemia and liver disorders":

• "[Levaquin] is a broad-spectrum fluoroquinolone antibiotic that is indicated for the treatment of certain respiratory tract, skin and urinary tract bacterial infections in adults."
• "From Jan. 1, 1997, to June 30, 2006, Health Canada received 22 domestic reports of dysglycemia suspected of being associated with levofloxacin. Described dysglycemic adverse reactions (ARs) included 1 report of diabetes mellitus, 2 reports of hyperglycemia alone, 16 of hypoglycemia alone and 3 of hyperglycemia and hypoglycemia combined."
• "With regards to liver disorders, from Jan. 1, 1997, to June 30, 2006, Health Canada received 44 domestic reports of liver and biliary disorders suspected of being associated with levofloxacin. Of these 44 cases, there were 5 cases of hepatic failure, 9 of hepatitis and 1 of hepatorenal syndrome. Five of these 15 cases of liver disorders were fatal. The remaining 29 reports included ARs of increased liver enzyme levels, cholestatic hepatitis and jaundice."

This January 2007 article concludes by stating that Health Canada will continue to monitor adverse drug reactions that may be associated with Levaquin, and urges doctors as well as other health care providers to report any new cases of blood sugar problems or liver disorders possibly involving the use of Levaquin.