Drug Injury Watch

Popular Asthma Medicine Singulair Associated With Psychiatric Disorders In Children

New Medical Journal Article Follows June 2009 FDA-Required Warning For Singulair About Neuropsychiatric Events

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 12, 2009 the FDA announced a new warning about an increased risk of neuropsychiatric events for the asthma medicine Singulair (montelukast)-- as well as some other less popular leukotriene inhibitors, Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton).

This announcement was followed closely by a medical journal article, "Montelukast and psychiatric disorders in children.", which was published in the June 23, 2009 edition of Pharmacoepidemiology and Drug Safety.  The Abstract for this new Singulair article starts with a relatively ominous line:  "A signal has been raised concerning montelukast and adverse drug reactions (ADRs) in children."

This June 2009 Singulair medical journal article presents the findings of a study whose purpose was "to evaluate psychiatric ADRs during treatment with [Singulair (montelukast)] in children."  For this purpose, a team of researchers from Department of Clinical Pharmacology and Regional Pharmacovigilance Centre, Sahlgrenska University Hospital, Göteborg, Sweden, analyzed all reports of psychiatric disorders during treatment with Singulair in children under age 18 in the Swedish ADR database SWEDIS for the period 1998 to 2007.

From the Abstract for this Swedish Singulair study concerning adverse reactions in children:

RESULTS: A total of 48 reports of psychiatric disorders in children during treatment with montelukast were found in SWEDIS. Reports appeared every year after registration. Psychiatric disorders reported more than once included nightmares (n = 15), unspecified anxiety (n = 11), aggressiveness (n = 11), sleep disorders (n = 10), insomnia (n = 3), irritability (n = 3), hallucination (n = 3), hyperactivity (n = 3), and personality disorder (n = 2). In 23 reports (48%), the child experiencing psychiatric ADRs was ADR was indicated in 35 reports. In 28 of these (80%), the time from exposure to ADR was less than 1 week. A statistical signal for psychiatric disorders appeared in the fourth quarter of 1998 (three reports, IC-value: 2.34, 95% lower confidence limit: 0.62).

These findings led the researchers to conclude that psychiatric adverse reactions can occur in children during their treatment with Singulair (montelukast), which indicated to them that "[f]urther studies are needed to establish the magnitude of the problem."

We agree that more research should be done, and soon, about the extent of Singulair possibly causing psychiatric disorders in children using this very popular asthma drug from Merck.

Smoking Cessation Drugs Chantix, Wellbutrin, And Zyban Are Getting New "Black-Box" Warning

Will Warn About Risk Of Serious Neuropsychiatric Symptoms Including Agitation, Depression, Suicidal Thoughts, And Attempted Suicide

(Posted by Tom Lamb at DrugInjuryWatch.com)

On July 1, 2009 the FDA issued a Public Health Advisory about Chantix (varenicline) as well as Wellbutrin (bupropion) and Zyban (bupropion) which announced that these smoking cessation drugs will be getting a so-called "black-box" warning:

...highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The added warnings are based on the continued review of postmarketing adverse event reports for varenicline and bupropion received by the FDA. These reports included those with a temporal relationship between the use of varenicline or bupropion and suicidal events and the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease.

Contemporaneous with this July 1 FDA Public Health Advisory the FDA issued a news release -- "FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban" -- and a document intended primarily for relevant medical professionals -- "Information for Healthcare Professionals: Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics)".

This second item had some concise and helpful background information about the history of safety issues concerning Chantix, Wellbutrin, and Zyban:

FDA first informed the public about the possibility of serious neuropsychiatric symptoms with [Chantix] in the November 20, 2007 FDA Early Communication About an Ongoing Safety Review.  A complete history of related communications on [Chantix] and [Wellbutrin / Zyban] can be found at: Varenicline (marketed as Chantix) Information.  Since that time, information about serious neuropsychiatric symptoms in patients taking varenicline has been added to the POST-MARKETING EXPERIENCE section of the prescribing information.

As FDA received additional information the suggestion of a possible association between both varenicline and bupropion (which was evaluated as a comparator to varenicline) and serious neuropsychiatric symptoms, in both patients with and those without previous history of psychiatric illness, became more evident as its review progressed....

We will watch for corporate press releases from Pfizer (which sells Chantix) as well as GlaxoSmithKline (which sells Wellbutrin and Zyban) which might be issued to present the drug company's reaction to this FDA announcement about adding a black-box warning for neuropsychiatric side effects being added to their respective product's Package Insert, or label.

Brandname Accutane Acne Medicine Is Being Removed From U.S. Market By Roche

Accutane Recall Due To Safety Issues Or Declining Sales Or Lawsuit Losses Or Some Combination Of These Factors?

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 26, 2009 we learned from a Blooomberg news report, "Roche Pulls Accutane Off Market After Jury Verdicts", that Accutane will no longer be available to American patients:

Roche Holding AG, the world’s biggest maker of cancer drugs, is pulling its Accutane acne medicine from the U.S. market after juries awarded at least $33 million in damages to users who blamed the drug for bowel disease.

Roche notified the U.S. Food and Drug Administration today that it was withdrawing Accutane after a “reevaluation” of its product lines showed it faced serious challenges from generic competitors, company officials said in a statement.

“In addition, Roche has been faced with high costs from personal-injury lawsuits that the company continues to defend vigorously,” according to the statement.

About 13 million people have taken Accutane since it went on the market in 1982. The medication was Roche’s second-biggest selling drug before the patent expired in 2002 and rivals started selling generic versions. Roche’s prescription market share of the drug is now below 5 percent, the company said.

From the above information, the apparent reasons for this June 2009 Accutane recall are loss of market share and mounting personal injury lawsuits. 

This brought to mind the Tequin recall by Bristol-Myers Squibb (BMS) in April 2006. 

Here is an article from September 2009 regarding what the FDA had to say about how and (really) why BMS decided to remove its unsafe antibiotic Tequin from the U.S. market -- "FDA: Tequin Was Withdrawn From U.S. Market "For Reasons Of Safety Or Effectiveness" -- Recall That Bristol-Myers Had Said Decline In Sales Was Reason For Its Decision To Stop Selling Tequin" (emphasis added):

On September 2, 2008 the FDA issued a Notice entitled "Determination That TEQUIN (Gatifloxacin) Was Withdrawn From Sale for Reasons of Safety or Effectiveness" which provides (and confirms) the real reason that Bristol-Myers Squibb Co. (BMY) decided to pull Tequin from the U.S. market in the spring of 2006:

SUMMARY: The Food and Drug Administration (FDA) has determined that TEQUIN (gatifloxacin) Tablets, Injection, and Oral Suspension, were withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not accept or approve abbreviated new drug applications (ANDAs) for gatifloxacin oral tablets, injection, or oral suspension that refer to any previously approved dosage forms and strengths of TEQUIN (gatifloxacin).

As you may recall, in April 2006 when the news first broke that Bristol-Myers had decided to stop selling Tequin -- an antibiotic which was increasingly associated with potentially fatal blood-sugar problems -- the drug company said a continuing decline in Tequin sales was its reason for deciding to stop selling Tequin.

Returning to the June 26 Bloomberg article and its headline which implicates the Accutane lawsuit losses as being the primary reason for Roche deciding to pull Accutane, there have been some recent developments in the Accutane litigation. 

In mid-June a New Jersey Superior Court judge ruled that Roche could not name new experts in the retrial of Andrew McCarrell v. Hoffman-La Roche Inc., et al.(No. ATL-L-1951-03-MT, N.J. Super., Atlantic Co.), a personal injury case where the plaintiff had alleged Accutane caused his inflammatory bowel disease (IBD).  I defer to a March 13, 2009 post on the Drug and Device Law blog, "Accutane: McCarrell Remanded For New Trial", concerning the appeal of this Accutane jury verdict for the plaintiff.

A better result in June 2009 for Roche came from the federal court system's 11th Circuit Court of Appeals, which upheld a summary judgment in favor of the drug company in a case where it was alleged that Accutane caused the son of U.S. Rep. Bart Stupak, D-Mich., to commit suicide.  The essential ruling reportedly there was that the plaintiff failed to produce evidence that Hoffman-La Roche Inc. knew or should have known that Accutane could cause suicide without premonitory symptoms (Laurie A. Stupak v. Hoffman-La Roche Inc., et al., No. 07-15980, 11th Cir.; 2009 U.S. App. LEXIS 12482).

We will watch to see if more information comes out in the future which will explain why Roche decided to remove Accutane from the market in June 2009.

Generic Drug Maker Caraco Fails To Correct Manufacturing Problems First Discovered In May 2008

FDA And U.S. Marshals Seize Drug Products From Caraco’s Three Michigan Facilities Due To Continuing Lack Of Quality Controls

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 25, 2009 the FDA issued a press release, "U.S. Marshals Seize Drug Products Manufactured by Caraco Pharmaceutical Laboratories Ltd. -- FDA acts to prevent repeated drug quality problems", which began as follows:

U.S. Marshals, at the request of the Food and Drug Administration, today seized drug products manufactured by Caraco Pharmaceutical Laboratories Ltd. (Caraco), at the company’s Michigan facilities in Detroit, Farmington Hills, and Wixom. The seizure also includes ingredients held at these same facilities....

This action follows Caraco’s continued failure to meet the FDA’s current Good Manufacturing Practice (cGMP) requirements, which assure the quality of manufactured drugs. Through this seizure, the FDA seeks to immediately stop the firm from further distributing drugs until there is assurance that the firm complies with good manufacturing requirements.

Since January 2009, Caraco has initiated voluntary recalls of drug products to protect the public from potentially defective medications. The recalls involved manufacturing defects, including oversized tablets and possible formulation error.

On March 31, 2009 Caraco recalled its digoxin pills due to the possibility that some of those pills might be oversized and contain too much active ingredient.  Because digoxin is known to have a narrow therapeutic index, it is possible that oversized Caraco digoxin pills caused digitalis toxicity, or digoxin poisoning, in patients using that product.

Earlier, the FDA issued a warning letter to Caraco in October 2008 after FDA inspectors had discovered failures to conform to current Good Manufacturing Practices (cGMP) at some of the companies facilities.

The FDA has provided a list of the 33 Caraco drugs that may be affected by the June 25, 2009 seizure at the company's three Michigan plants.

Merck's Popular Asthma Drug Singulair Associated With Suicide And Depression

FDA Has Gone From "No Link" In January 2009 To Wanting An Increased Warning About These Neuropsychiatric Events In June 2009

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 12, 2009 the FDA announced that Singulair (montelukast) as well as some other less popular leukotriene inhibitors -- Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton) -- must start to include a warning on its package insert, or label, regarding an increased risk of neuropsychiatric events including suicide and depression.

This June 2009 FDA warning about Singulair is seemingly a reversal from an earlier position taken by the FDA in January 2009 when the agency said their review of clinical trials did not suggest Merck's Singulair asthma drug caused suicide or suicidal thoughts.

For some perspective, let's look back in time to see how this Singulair - suicide link has become a very significant emerging drug-safety issue at the FDA. 

We start with a March 27, 2008 ABC News report, "Doctors Not Concerned by US FDA Probing Safety of Merck's Singulair":

The Food and Drug Administration (FDA) announced an investigation Wednesday examining a link between suicide and Merck's popular allergy and asthma drug, Singulair.

Concerns over "behavioral issues" with Singulair developed over the past year. Merck periodically updated the drug's labels to include warnings for tremors, depression and anxiety. FDA spokesperson Susan Cruzan said reports of suicides by "three or four" people who were taking Singulair prompted Merck to clarify suicide warnings on labels and patient information sheets in October 2007.

We get some additional background information from a March 27, 2008 article, "FDA Investigates Possible Suicide Link With Montelukast (Singulair)", published online by MedPage Today:

The FDA said it will probably take at least nine months for it to complete a safety review of the popular asthma and allergy drug montelukast (Singulair).

The ongoing investigation is examining a possible association between use of the drug and behavior/mood changes, suicidality (suicidal thoughts and behavior), and suicide, the agency said....

Over the past year, the maker of Singulair, Merck & Co, has updated the prescribing information and patient information for Singulair to include the following post-marketing adverse events: tremor (March 2007), depression (April 2007), suicidality (suicidal thinking and behavior) (October 2007), and anxiousness (February 2008).

From there we move forward to a January 14, 2009 Reuters article, "FDA says Singulair data do not suggest suicide link":

U.S. regulators on Tuesday said their review of clinical trials does not suggest Merck & Co's Singulair asthma drug or similar medicines cause suicide or suicidal thought, although the data were inadequate to draw a firm conclusion....

The agency also studied trials involving two other medicines that work by blocking inflammation-causing proteins called leukotrienes, AstraZeneca Pls's Accolate (zafirlukast) and Zyflo (zileuton) sold by Cornerstone Therapeutics Inc.

"Although these data do not suggest that [Singulair (montelukast), Accolate (zafirlukast) or Zyflo and Zyflo CR (zileuton)] are associated with suicide or suicidal behavior, these clinical trials were not designed specifically to examine neuropsychiatric events," the FDA said. "As a result, some events may not have been reported."

Concerns about a possible suicidal link have arrested sales growth of Singulair, Merck's biggest product with annual sales of almost $4.5 billion.

Then came the June 2009 announcement from FDA that there may be a link between Singulair and suicide.  From a June 12, 2009 MedPage Today article, "FDA: Leukotriene Inhibitors Associated with Suicide, Depression":

Leukotriene inhibitors must include a warning regarding increased risk of neuropsychiatric events including suicide and depression, according to the FDA.

The requirement applies to montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). All are approved to treat asthma, and montelukast is also approved to treat symptoms of allergic rhinitis and to prevent exercise-induced asthma.

Upon completing a review of the agents in April, the FDA found reports of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicide, suicidal ideation, and tremor associated with use of the drugs.

The FDA based its review on postmarket reports and clinical trial data submitted by the manufacturers of the drugs....

The FDA said physicians should consider discontinuing the medications if patients develop neuropsychiatric symptoms.

Now that the association between Singulair and neuropsychiatric events such as suicide and depression has been announced by the FDA, we expect there to be additional case reports about Singulair users experiencing these serious side effects.

As always, we encourage people with personal knowledge about serious side effects from Singulair use to submit a MedWatch report to the FDA.  We also welcome Comments, here, from people who want to share with others their side-effect experiences, or that of a family member, while using Singulair.

P.S.  Merck Statement in Response to the FDA's June 12, 2009 Communication with Updated Information on Leukotriene Inhibitors, Including SINGULAIR® (montelukast sodium) -- June 12, 2009 press release from Merck & Co., Inc.  (6/24/09)

Have Yasmin-Related Blood Clot Side Effect Cases Flown Below Radar In US?

In Europe Reports Of Pulmonary Embolism And Deep Vein Thrombosis Were Made Soon After Yasmin Birth Control Pill Was Approved In 2000

(Posted by Tom Lamb at DrugInjuryWatch.com)

An April 13, 2002 BMJ article, "Dutch GPs warned against new contraceptive pill" (FREE registration required), was published the week before the Yasmin birth control pill was going to become available to women in the United Kingdom.  From that article we learn, now, that Yasmin was the subject of safety concerns right from the start in Europe:

Dutch GPs are being advised by their own professional body not to prescribe a new low dose, monophasic oral contraceptive, marketed under the trade name Yasmin, until studies have established whether it is as safe as other contraceptive pills.

The new contraceptive, which is a combination of drospirenone (a progestogen) and ethinylestradiol, has been available in several European countries since 2000 and was approved by the US Food and Drug Administration last May. It is licensed for use in the United Kingdom, where it is being launched next week.

Last year a 17 year old Dutch girl who had been taking Yasmin died from a venous thrombosis. Although no direct link with Yasmin has ever been shown, 40 cases of venous thrombosis among women taking Yasmin, two of which were fatal, have now been reported in Europe.

The Dutch College of General Practitioners has now reiterated its position that GPs should continue to choose the second generation pill, because of the lack of epidemiological data on the risk of thrombosis from Yasmin.

About a year later, in the February 1, 2003 edition of BMJ, there appeared a brief Drug Points piece, "Thromboembolism associated with the new contraceptive Yasmin", which provided some details about several cases of serious blood clot side effects in women using the Yasmin birth control pill.

Our centre, the Dutch spontaneous reporting system for adverse drug reactions, recently received five reports of thromboembolism as a suspected adverse drug reaction to the new oral contraceptive Yasmin (ethinylestradiol and drospirenone).

A 17 year old woman suddenly collapsed and died after taking the contraceptive [pill Yasmin] for six months. Autopsy showed that she had had a massive pulmonary embolism [(PE)]. No obvious risk factors for thromboembolism, such as smoking, a period of long immobilisation, air flights, or concomitant medication, were evident....

A 28 year old woman changed her oral contraceptive from ethinylestradiol with desogestrel (Marvelon) to ethinylestradiol with drospirenone [(Yasmin)]. Four months later she had thrombosis in one leg and was treated with acenocoumarol. Risk factors or concomitant drugs were unknown.

Another patient, a 45 year old woman, had deep vein thrombosis [(DVT)] in one leg after taking ethinylestradiol with drospirenone [(Yasmin)] for two months, as did a 50 year old woman who took the contraceptive for three months.

A 35 year old woman had pulmonary thrombosis 17 days after she started taking the contraceptive [pill Yasmin]. She had given birth four months earlier.

Only recently in the U.S. have there been products liability lawsuits filed on behalf of women who have developed a pulmonary embolism (PE) or deep vein thrombosis (DVT) after they used Yasmin -- or YAZ, a newer but very similar birth control pill that also contains the so-called "fourth generation" progestin drospirenone (DRSP).

We expect, however, to see an increasing number of Yasmin lawsuits -- and YAZ lawsuits -- as more women learn about the blood clot side effect risks associated with these "fourth generation" oral contraceptives only after they suffered a pulmonary embolism (PE) or a deep vein thrombosis (DVT).

FDA Investigating Obesity Drugs Xenical And Alli For Possible Link With Liver Damage

Agency Has Received Case Reports Of Hepatotoxicity For Orlistat, The Active Ingredient For Xenical And Alli

(Posted by Tom Lamb at DrugInjuryWatch.com)

There was only this brief mention in the Memorandum of Meeting Minutes for the FDA's April 16, 2009 Drug Safety Oversight Board Meeting:

The Drug Safety Oversight Board (DSB) discussed two topics: the product orlistat and the potential risk of hepatotoxicity and alcohol-based skin antiseptics and the risk of a fire in the operating room.

Now, about a month later, we have some additional information about the orlistat - hepatotoxicity part of that DSB April 2009 meeting.   

As background, the anti-obesity agent orlistat is the active ingredient in the prescription drug Xenical (Roche) and the over-the-counter drug Alli (GlaxoSmithKline).

Reporter Sue Sutter, in her May 21, 2009 article "US FDA examining reports of liver damage with orlistat", published online by Scrip News (subscription required; free trial available), takes us forward from there:

"Orlistat was discussed in the context of both non-prescription and prescription versions and the potential risk of hepatotoxicity based on several postmarketing reports," the FDA told Scrip.

The agency said it was still reviewing the case reports to determine the extent of orlistat's contribution, if any, to the development of liver damage. The FDA declined to provide the number of postmarketing reports it has received and said any action would depend upon results of its ongoing analysis....

Roche said more than 35 million patients have been exposed to orlistat therapy, and obesity is a high risk factor for hepatic injury. "The available information – postmarketing spontaneous reports, clinical trial data and published literature as well as epidemiology data for drug-induced liver disease – does not suggest that orlistat is causally related to hepatic events."

The current package insert, or label, for Xenical (accessed 5/22/09) mentions rare reports of hepatic, or liver, injury.

Previously, the anti-obesity agent orlistat had been under scrutiny at the FDA for concerns about rectal bleeding.  See: Potential Signals of Serious Risks/New Safety Information Identified from the Adverse Event Reporting System (AERS) between April - June 2008

If you are aware of any cases of drug-induced hepatitis, liver injury, or liver failure involving the use of Xenical or Alli, please let us know by submitting a Comment, below, or you can send me a private email.

Birth Control Pill YAZ Is Subject Of Ongoing Safety Study Regarding Cardiovascular Side Effects

A Comparison Of This "Fourth Generation" DRSP / EE Pill To Other Established Oral Contraceptives For Incidence Of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), Heart Attack (MI), And Stroke (CVA)

(Posted by Tom Lamb at DrugInjuryWatch.com)

YAZ (3 mg drospirenone/20 mcg ethinyl estradiol) is an oral contraceptive (OC) which is the first pill to combine 20 mcg of ethinyl estradiol (EE) with the so-called "fourth generation" progestin drospirenone (DRSP).  YAZ was approved by the FDA in March 2006.

A company press release, "FDA Approves YAZ(R), The First Oral Contraceptive To Offer Drospirenone In A 24-Day, Active-Pill Regimen", issued at the time of FDA approval, can be read so as to suggest that the list of possible serious side effects of YAZ about which women should be most concerned does not include any cardiovascular side effects:

YAZ contains 3 mg of the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to a 25-mg dose of spironolactone. YAZ should not be used in patients with conditions that predispose to hyperkalemia (i.e., renal insufficiency, hepatic dysfunction, or adrenal insufficiency). Women receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium should have their serum potassium levels checked during the first treatment cycle. Medications that may increase serum potassium include ACE inhibitors, angiotensin-ll receptor antagonists, potassium-sparing diuretics, potassium supplementation medications, aldosterone antagonists and NSAIDs.

In fact, the current YAZ package insert, or label (accessed 5/18/09), includes this same text in bolded font, while the warning about cardiovascular side effects like deep vein thrombosis (DVT), pulmonary embolism (PE), heart attack, and stroke is not bolded for emphasis.

Seemingly, however, the FDA has had some concerns about an association between YAZ and DVT, PE, heart attack, and stroke, as seen below.

A study called the International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC), which was started in August 2005 and continues to date, is intended to evaluate the risk of those cardiovascular side effects for women who use DRSP/EE birth control pills like YAZ.

According to a May 11, 2009 article, "ACOG 2009: Preliminary Findings Favor 24-Day Regimen of Drospirenone and Ethinyl Estradiol for Contraception", published online by Medscape:

[P]reliminary findings from the International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC) study were presented here at the American College of Obstetricians and Gynecologists (ACOG) 57th Annual Clinical Meeting by Jürgen Dinger, MD, PhD, from the Berlin Center for Epidemiology and Health Research in Germany....

"The INAS study is a transatlantic prospective cohort study that was requested by the [US Food and Drug Administration] to investigate the safety of a 24-day regimen of 3 mg DRSP and 20 μg ethinyl estradiol (24/4 regimen)," Dr. Dinger told the audience. To date, the INAS study has enrolled 52,219 women....

The study's objectives are to compare the cardiovascular safety of the 24/4 regimen of DRSP/EE to established oral contraceptives (OCs) during standard clinical practice (eg, deep venous thrombosis, pulmonary embolism, acute myocardial infarction, stroke); to investigate the incidence of rare serious adverse events associated with the use of 24/4 and established OCs; and to investigate contraceptive failure rates associated with the use of the 24-day and 21-day regimens of DRSP/EE and all other OCs.

For women using YAZ, here is some important information about the symptoms of these serious cardiovascular side effects from the WebMD.com web site:

This medication may rarely cause serious (sometimes fatal) problems from blood clots (e.g., pulmonary embolism, stroke, heart attack). Seek immediate medical attention if you experience: sudden shortness of breath, chest/jaw/left arm pain, confusion, coughing up blood, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, tingling/weakness/numbness in the arms/legs, headaches that are different from those you may have experienced in the past (e.g., headaches with other symptoms such as vision changes/lack of coordination, existing migraines becoming worse, sudden/very severe headaches), slurred speech, weakness on one side of the body, vision problems/changes.

A quick Internet search for the word "YAZ" will show among the results that there are discussion forums with "threads" like "WARNING ABOUT YAZ BIRTH CONTROL PILLS", at the SteadyHealth.com web site, where numerous women have reported having a DVT or PE while using YAZ pills.

All of this leaves us wondering whether YAZ is a possible unsafe birth control method, like Ortho Evra and NuvaRing....

If you or someone you know has developed a deep vein thrombosis (DVT), pulmonary embolism (PE), heart attack, or stroke while using YAZ -- and you want to share your experience with others -- you can do so by submitting a Comment, below.

Possible Heparin-Related Deaths In Delaware Are Different Than Last Year's Illness Outbreak

These New Cases Involve Premixed IV Bags of Heparin And Initial Tests Did Not Detect Oversulfated Chondroitin Sulfate Contamination

(Posted by Tom Lamb at DrugInjuryWatch.com)

The headline used by the Wall Street Journal (WSJ), "Heparin Stirs New Fears", alluded to last year's heparin-illness outbreak when roughly 80 deaths were linked to contaminated heparin and led to a recall of the medicine from several companies.

According to this May 12, 2009 WSJ article, however, there are some important differences between last year's contaminated heparin problem and two possible heparin-related death cases that were reported by a Delaware hospital this past weekend:

• Baxter spokeswoman Erin Gardiner said that, unlike the earlier cases, the Delaware patients didn't have severe hypotension, or low blood pressure. The current symptoms involve intracranial bleeding, she said.
• Ms. Gardiner said the new complications involve premixed intravenous bags of heparin. Last year's problems involved bulk supplies, vials of the medicine and drug-coated medical devices.
• Baxter tests on the Delaware incidents didn't detect a contaminant found in last year's heparin-illness outbreak, oversulfated chondroitin sulfate.

A Wilmington, Delaware newspaper, The News Journal, first reported this still-developing story in a May 11, 2009 article, "FDA investigating deaths at Beebe", from which we get these details:

Two Delaware residents have died after being administered the anticoagulant drug heparin at Beebe Medical Center in Lewes, the hospital said today, as federal authorities took over an investigation into a possible batch of tainted medication.

The patients – a 71-year-old man and a 64-year-old woman – died over the weekend, said Wallace Hudson, Beebe’s vice president for corporate affairs. Both reportedly suffered intra-cranial bleeding, as did a third patient who now is being treated at Christiana Hospital. That patient’s condition is not known.

Two other patients initially believed to have been sickened by the drug were not actually affected by heparin, based on additional testing, Hudson said.

While the Beebe cases remain under investigation, it apparently is not part of a widespread problem, the FDA said in a statement.

“This appears to be an isolated incident,” agency spokeswoman Karen Riley said.

This News Journal article also provided some earlier comments from Erin Gardiner, the Baxter spokeswoman:

“At this point, it is premature to speculate on the relationship, if any, between the reactions the unfortunate patient events and our products,” Gardiner said.

Baxter has made inquiries to other hospitals that use large quantities of the pre-mixed bags including Heparin to determine if they’ve seen any similar reports. She said the reports in Delaware were the only ones Baxter has heard of thus far.

“In terms of where we’re at, it’s three reports from a single institution,” she said. “There isn’t enough information to conclude that the events are associated with the Heparin IV bag yet, but we’re conducting a proactive, thorough investigation.”

If anyone knows about a patient who recently developed intracranial bleeding or any other serious side effect after being administered premixed intravenous (IV) bags of heparin, they should contact the FDA immediately to assist with this ongoing investigation.

P.S.  News Update:  Baxter, FDA Say Heparin Not Responsible for Delaware Deaths (5/15/09)

Hydroxycut Weight-Loss Products Are Recalled Due To Cases Of Serious Liver Injury

Reports Made To The FDA Have Involved Hepatitis, Liver Failure, Liver Transplant, And Death

(Posted by Tom Lamb at DrugInjuryWatch.com)

On May 1, 2009 the FDA warned people to stop using Hydroxycut products -- made by Iovate Health Sciences Inc., of Oakville, Ontario and distributed by Iovate Health Sciences USA Inc. of Blasdell, N.Y. -- due to the fact that some Hydroxycut products are associated with a number of serious liver injuries. Furthermore, the manufacturer, Iovate, has agreed to immediately recall Hydroxycut products from the U.S. market.

The list of Hydroxycut products being recalled by Iovate currently includes:

Hydroxycut Regular Rapid Release Caplets
Hydroxycut Caffeine-Free Rapid Release Caplets
Hydroxycut Hardcore Liquid Caplets
Hydroxycut Max Liquid Caplets
Hydroxycut Regular Drink Packets
Hydroxycut Caffeine-Free Drink Packets
Hydroxycut Hardcore Drink Packets (Ignition Stix)
Hydroxycut Max Drink Packets
Hydroxycut Liquid Shots
Hydroxycut Hardcore RTDs (Ready-to-Drink)
Hydroxycut Max Aqua Shed
Hydroxycut 24
Hydroxycut Carb Control
Hydroxycut Natural

The FDA's reasoning for this May 2009 recall of Hydroxycut products can be found in a Health Hazard Evaluation Board document entitled "The Problem: Liver toxicity following consumption of dietary supplement, Hydroxycut".  From the Conclusion section of this Health Hazard Evaluation document:

Three lines of evidence derived from multiple disparate sources suggest it is very likely that exposure to Hydroxycut can cause idiosyncratic hepatotoxicity. First, many of the subjects described in the adverse event reports to CAERS, in the peer-reviewed literature, and in the case series described by hepatologists reported no history of liver disease or risk factors for liver disease (e.g., alcohol consumption, previous viral infection, hereditary factors, etc.) prior to experiencing liver injury following the ingestion of Hydroxycut. Second, in many subjects, thorough diagnostic evaluations performed in multiple settings ruled out a number of known causes of liver disease, including viral hepatitis, autoimmune diseases, and metabolic/inherited disorders. Third, prompt resolution of liver disease occurred in a number of patients following cessation of Hydroxycut ingestion.

In a Consumer Advisory, "FDA Warns Consumers Not to Use Dietary Supplements Labeled Hydroxycut because of the Potential Risk of Severe Liver Injury", the FDA provides the following medical information:

Consumers who use a Hydroxycut dietary supplement and who experience signs of illness associated with liver disease should immediately consult their health care provider. Symptoms of serious liver disease include jaundice (yellowing of the skin or whites of the eyes) and brown urine. Non-specific symptoms of liver disease can include nausea, vomiting, light-colored stools, unusual tiredness, weakness, stomach or abdominal pain, itching, and loss of appetite.  FDA has also identified several other serious adverse events associated with Hydroxycut, including cases of seizures, rhabdomyolysis (a type of muscle damage that can lead to other dangerous problems, such as kidney failure), and cardiovascular problems, ranging in severity from irregular heart beat to a heart attack.  [bold in original]

The FDA -- as opposed to Iovate, the manufacturer of Hydroxycut products --has issued a "Dear Doctor" letter to healthcare providers in the U.S.

In addition, the FDA has put on its web site a Consumer Questions and Answers document regarding this Hydroxycut recall.

In closing, the FDA has stated that it will continue to investigate the relationship between the use of Hydroxycut dietary supplements and liver injury.

If you are aware of any case of liver damage caused by the use of Hydroxycut products, please consider sharing that information with us by submitting a Comment, below.

P.S.  North of FDA-land, Health Canada says it will continue to monitor adverse reaction reports associated with Hydroxycut products, and will provide Canadians with any new safety information. 

From "Health Canada Reviewing Hydroxycut Products in light of U.S. Advisory":

Health Canada has received 17 domestic adverse reaction (AR) reports associated with Hydroxycut products in Canada. These adverse reactions relate to the cardiovascular, respiratory, gastrointestinal, and neurological systems. None of the adverse reactions reported in Canada relate to liver injury.

It will be interesting to see if Health Canada follows the lead of our FDA and issue a Hydroxycut recall in Canada.  (5/4/09)

P.S.  On May 7, 2009 the FDA announced that Iovate Health Sciences USA, Inc. has provided Universal Product Codes (UPCs) for its products that were part of the May 1 Hydroxycut recall.  (5/8/09)