Author: Tom Lamb

Bayer Says YAZ / Yasmin Safety Profile Is Comparable To Older Birth Control Pills, But European Regulators See Possible Increased Risk Of Blood Clot Side Effects

(Posted by Tom Lamb at DrugInjuryWatch.com)

On April 9, 2010 Bayer HealthCare Pharmaceuticals announced that that it will update the labels for YAZ® (3 mg drospirenone / 0.02 mg ethinyl estradiol) and Yasmin® (3 mg drospirenone / 0.03 mg ethinyl estradiol) in the United States.

We have not seen the actual new YAZ / Yasmin package insert, or label, but the press release by which Bayer made this announcement, “BAYER UPDATES LABELS FOR YAZ and YASMIN — Body of Evidence Affirms VTE Risk/Benefit Profile for YAZ and Yasmin Is Comparable to Other Combination Oral Contraceptives”, makes us wonder whether Bayer is issuing it to warn doctors and patients or to attack medical researchers who have suggested that these unique “fourth generation” pills containing the progestin drospirenone (DRSP) may be unsafe to use.

From this April 2010 press release we get this “preview” of what the new YAZ / Yasmin label will state about this emerging drug-safety issue:

…the new labels now state:

• A prospective cohort study (EURAS), conducted in Europe, showed the risk of thromboembolism (particularly venous thromboembolism) and death in Yasmin users to be comparable to that of oral contraceptive preparations, including those containing levonorgestrel.

• Another prospective cohort study (Ingenix), conducted in the USA, also showed a comparable risk of thromboembolism in Yasmin users compared to users of other COCs, including those containing levonorgestrel. In this study, COC comparator groups were selected based on having similar characteristics to those being prescribed Yasmin.

As part of its evaluation of the risk/benefit of YAZ and Yasmin, the FDA also reviewed data from one case-control study (van Hylckama Vlieg et al.) and one retrospective study (Lidegaard et al.) which suggested that the risk of venous thromboembolism occurring in Yasmin users was between the risk associated with levonorgestrel-containing COCs and desogestrel/gestodene-containing COCs. Based on the FDA’s review, the new labels now state that key conclusions from both studies are unreliable:

• With regard to the case-control study, the label indicates that, “…the number of Yasmin cases was very small (1.2% of all cases) making the risk estimates unreliable.”

• Concerning the retrospective cohort study, the label indicates that, “The relative risk for Yasmin users in the retrospective cohort study was greater than that for users of other COCs when considering women who used the products for less than one year. However, these one-year estimates may not be reliable because the analysis may include women of varying risk levels. Among women who used the product for one to four years, the relative risk was similar for users of Yasmin to that for users of other COCs.”

[Footnotes omitted; emphasis added]

So, essentially, it seems that Bayer is claiming that YAZ and Yasmin are as safe as “second generation”  birth control pills which contain the progestin levonorgestrel and that the following two medical journal articles should be disregarded:

• Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. “Hormonal contraception and risk of venous thromboembolism: national follow-up study.” BMJ. 2009;339:b2890. (hereinafter, “the Lidegaard publication”): and,

• Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. “The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study.” BMJ. 2009;339:b2921. (hereinafter, “the Van Hylckama Vlieg publication”).

Now let us take a look at what has been happening recently in Europe with regard to YAZ and Yasmin.  In March 2010 Bayer said it would update the Yasmin label in Europe to add the results from four medical studies, namely those mentioned in the Bayer press release discussed above.

Again, we have not seen the actual new YAZ / Yasmin package insert, or label, that will be used in Europe.  We do, however, have some indication that this European label change by Bayer may need to be different from their U.S. label change.

The April 2010 edition of Drug Safety Update published by the Medicines and Healthcare products Regulatory Agency (MHRA) includes an article entitled “Yasmin: Update on risk of venous thromboembolism”.  From that MHRA article, in relevant part:

The incidence of VTE in association with the use of levonorgestrel, desogestrel
and gestodene-containing pills has been studied extensively. Overall, these studies have shown that women who use desogestrel or gestodene-containing pills have a slightly higher risk of developing VTE than those who use levonorgestrel-containing pills. Because Yasmin was licensed relatively recently, fewer studies on its associated risk have been carried out.

In 2006, the results from two large prospective cohort studies (EURAS and
Ingenix), suggested that the risk of VTE in Yasmin users is comparable with that
for other contraceptives that contain a similar level of oestrogen, including those
containing levonorgestrel. More recently, the results from a Danish cohort study
and a Dutch case-control study have suggested that this risk may be slightly
higher than previously estimated and somewhere between the risk associated with levonorgestrel-containing pills and with desogestrel or gestodene-containing pills (relative risks for the comparison of Yasmin with levonorgestrel-containing pills: 1·64; 95% CI 1·27–2·10 and 1·7; 0·7–3·9, respectively).

Because of some limitations in the methodology of these recent studies, further
analyses are needed before any firm conclusions can be drawn….

[Footnotes omitted]

It remains to be seen whether Bayer will be allowed in Europe to use the terms “unreliable” and “may not be reliable” as regards the Lidegaard publication and the Van Hylckama Vlieg publication, as it apparently intends to in the U.S.  The April 2010 MHRA Drug Safety Update article above, however, suggest that the drug company will not be permitted to essentially tell doctors and patients that those two medical articles — which are among the most recent additions to the medical literature about the safety of YAZ and Yasmin — should be flat-out disregarded.

Returning to the April 2010 Bayer press release about the YAZ / Yasmin label change in the U.S., we point out this statement:

“At Bayer, our unwavering commitment to our customers’ health and well-being is always our first priority and we will continue to provide information which will support health care providers and their patients in making informed decisions about appropriate treatment choices,” said [Kemal Malik, MD, Chief Medical Officer at Bayer HealthCare].

When the actual new YAZ / Yasmin label is finally available for review, we will let you be the judge about the accuracy or sincerity of that particular statement made on behalf of Bayer.

______________________________________________________________________________

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

New Study Finds Increased Risk Of Developing Ulcerative Colitis; New Jersey Jury Decides Accutane Caused Man’s Inflammatory Bowel Disease

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the first quarter of 2010 there were two significant developments concerning the acme medication Accutane (isotretinoin).

As general background, in June 2009 the drug company Roche Holding AG announced that Accutane will no longer be available to American patients.  The apparent reasons for this June 2009 Accutane recall are loss of market share and mounting personal injury lawsuits. 

As regards what has been happening with Accutane in 2010, we start with the legal realm.

In mid-February 2010 a New Jersey state court jury decided that Roche must pay $25.16 million in damages to Andrew McCarrell, a former user of its Accutane drug who blamed the acne medicine for his inflammatory bowel disease (IBD).  Mr. McCarrell developed his IBD after taking Accutane for acne in 1995; he needed five surgeries, including one to remove his colon.

As some may recall, in May 2007 a New Jersey state court jury handed down a $2.619 million verdict in favor of Mr. McCarrell.  A New Jersey appeals court subsequently overturned that verdict and ordered a retrial.  It was this retrial, or second trial, in February 2010 that resulted in the $25.16 million award to McCarrell.

We move, next, to the medical developments regarding Accutane and its active ingredient, isotretinoin.

By means of an April 6, 2010 article, “More evidence ties acne drug to bowel disease”, we learned about a recent medical journal report about a study which found that patients on Accutane or isotretinoin were four times more likely than non-users to develop ulcerative colitis within a year.  From this April 6 Reuters Health article we get this summary:

Reporting in the American Journal of Gastroenterology, researchers say that the risk of any one isotretinoin user developing ulcerative colitis is “likely quite small.”

However, the findings do strengthen the evidence of a cause-and-effect relationship between the acne drug and inflammatory bowel disease (IBD) — a group of digestive disorders that includes ulcerative colitis and Crohn’s disease….

[Roche] has maintained that there is no strong evidence that the acne drug triggers IBD. Between 1997 and 2002, 83 cases of IBD among isotretinoin users were reported to the U.S. Food and Drug Administration, but that does not prove that the drug itself is to blame.

For the new study, Dr. Seth D. Crockett and colleagues at the University of North Carolina Chapel Hill tried to test the cause-and-effect relationship.

Using a database of information from 87 U.S. health insurance plans, the researchers identified 8,189 people — mostly adults — who’d been diagnosed with IBD. They then compared each of those individuals with up to three other health plan members the same age and sex with no history of IBD.

Of the nearly 8,200 IBD patients, Crockett’s team found, 24 had used isotretinoin in the year before diagnosis; and of the nearly 22,000 controls, 36 had used the acne drug over a one-year period.

Overall, the researchers found, isotretinoin users were roughly four times more likely than non-users to have ulcerative colitis. There was no association, however, between isotretinoin use and Crohn’s disease.

The report about this study regarding Accutane-related ulcerative colitis cases, “Isotretinoin Use and the Risk of Inflammatory Bowel Disease: A Case–Control Study”, was published online March 30, 2010 by the American Journal of Gastroenterology.

We will continue to watch for legal and medical developments regarding serious side effects associated with the acne drug Accutane.

______________________________________________________________________________

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

Higher Rate Of Cardiac Failure In Men Taking Avodart (Dutasteride) – 0.7 Percent vs. 0.4 Percent For Those Taking The Placebo

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the April 1, 2010 edition of the New England Journal of Medicine (NEJM) there is an article, “Effect of Dutasteride on the Risk of Prostate Cancer” (free Abstract), which may spell trouble for the efforts of GlaxoSmithKline to get FDA approval for the use of Avodart (dutasteride) to prevent prostate cancer.

From the full-text of this April 2010 NEJM article about Avodart (subscription required), we get this information about its apparent cardiac side effects:

There was an unexpected imbalance in a composite event termed “cardiac failure,” which included conditions such as congestive heart failure, cardiac failure, acute cardiac failure, ventricular failure, cardiopulmonary failure, and congestive cardiomyopathy. Although there was no significant difference between the two groups in the overall incidence of cardiovascular events or deaths from cardiovascular events, there was a higher incidence of the composite event of cardiac failure in the dutasteride group than in the placebo group (0.7% [30 of 4105 men] vs. 0.4% [16 of 4126 men], P=0.03; relative risk estimate, 1.91; 95% CI, 1.04 to 3.50).

From an April 1, 2010 Associated Press (AP) article, “Study finds possible heart risk with prostate drug”, by AP Medical Writer Marilynn Marchione, we get these background and contextual details:

Last year, a panel of health experts recommended that men consider Proscar [(finasteride) — sold in generic form and as Proscar, made by Merck & Co. Inc.] or Avodart if they are regularly getting screened for prostate cancer. But the Avodart study was not available when the advice was developed.

The two drugs work in different ways and may not have the same safety profile, said Dr. Barnett Kramer, a National Institutes of Health scientist who led the expert panel and had no role in the study.

In the full Avodart results, “the important detail is there’s a heart failure signal here that was unanticipated,” Kramer said.

Dr. Otis Brawley, who helped run the study before becoming the American Cancer Society’s chief medical officer in 2007, said the heart failure risk may be a fluke, but men would need to be watched for it. If it develops, “it’s reason to stop the drug,” he said.

One presumes there will further studies about whether this finding of cardiac failure in men taking Avodart is truly a signal of an emerging drug-safety issue or a fluke, as mentioned by Dr. Brawley, above.

______________________________________________________________________________

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

Two Newer Studies Found An Increased Venous Thromboembolism (VTE) Risk in Yasmin Users Compared To Levonorgestrel-Containing Birth Control Pills

(Posted by Tom Lamb at DrugInjuryWatch.com)

In October 2009 we reported that Yasmin and YAZ birth control pills were under scrutiny by drug regulators in Europe.

Now, a March 26, 2010 press release issued by Bayer HealthCare and Bayer Schering Pharma gives us an update on this safety review in the European Union (EU), in particular the part which focused on the risk for venous thromboembolism (VTE) in Yasmin users.

The bulky, and perhaps promotional, title of this March 2010 Bayer press release is: “CHMP’s Pharmacovigilance Working Party completes review: Bayer will update Yasmin® label in the EU — Positive benefit/risk profile of Yasmin® confirmed”.

From it we learn that Bayer will update the prescribing information — also referred to as the package insert, or label — for Yasmin (drospirenone / ethinylestradiol) in the EU to include results of the following four epidemiological studies:

1) Dinger, Jürgen et al.: The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance study on Oral Contraceptives based on 142,475 women-years of observation. In: Contraception, 75, 2007, 344–354. [Publication of EURAS data]

2) Seeger, John et al.: Risk of Thromboembolism in Women Taking Ethinylestradiol/Drospirenone and Other Oral Contraceptives. In: Obstetrics & Gynecology, Vol. 110, No. 3, September 2007, 587–893. [Publication of INGENIX data]

3) Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890. [Lidegaard publication]

4) Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ. 2009;339:b2921. [Van Hylckama Vlieg publication]

Also from this Bayer press release about the Yasmin label change in Europe we get this “interpretation” of those four medical studies:

Bayer sponsored two large observational post authorization safety studies (EURAS and Ingenix) on combined oral contraceptive (COC) use for European and US (Food and Drug Administration) Health Authorities. These prospective cohort studies conducted by independent investigators found that the risk for venous thromboembolism (VTE) in Yasmin users is comparable to the risk found for women who use levonorgestrel-containing COCs. Bayer Schering Pharma will update the European Summary of Product Characteristics for Yasmin with these results.

At the request of the Pharmacovigilance Working Party (PhVWP) of the Committee for Medicinal Products for Human Use (CHMP) two recently published retrospective studies (Lidegaard et al., van Hylckama Vlieg et al.) will also be included in the update. These two studies found the VTE risk in Yasmin users to be between the risk associated with levonorgestrel-containing COCs and desogestrel/gestodene-containing COCs. The results of one of these two studies were not statistically significant. Leading epidemiologists as well as Bayer Schering Pharma,[sic] have identified several methodological issues in these recently published studies that need to be clarified before a final conclusion on Yasmin’s VTE risk can be made. Bayer Schering Pharma is working with the PhVWP on a reanalysis of some of these data.

It is unclear whether the Yasmin label change will be done in the near future or only after this “reanalysis” by Bayer of the two studies (#3 and #4, above) which found an increased VTE risk in Yasmin users compared to levonorgestrel-containing COCs.

We will watch for the revised Yasmin label to come out in the EU, and we ask our European readers for their assistance in that regard.

Of course, one cannot help but wonder if and when a similar change to the package insert for Yasmin (and perhaps YAZ) will be made by Bayer in the U.S.

______________________________________________________________________________

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

Numerous Factors, Including Temporal Relation Of Symptoms To Drug Use Dates And A Naranjo Scale Score Of 7/9, Strongly Suggest Byetta Caused This Case Of Acute Pancreatitis

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 25, 2010 an article from Endocrine Practice — 2010;16(1):80-83. © 2010 American Association of Clinical Endocrinologists — titled “Exenatide-induced Acute Pancreatitis” was posted on the Medscape web site (access requires free registration).  This article provides a thoroughly documented case report concerning a woman with non-insulin-dependent diabetes (NIDDM) receiving Byette (exenatide) who developed acute pancreatitis.

As background, the active ingredient in Byetta, exenatide, is a 39-amino acid synthetic version of exendin-4, a naturally occurring component of Gila monster saliva.  The FDA approved Byetta in 2005 as adjunctive therapy for non–insulin-dependent diabetes mellitus (NIDDM).

From this 2010 report about a possible case of Byetta-related pancreatitis we get these relevant facts about the subject patient:

A 64-year-old white woman presented with 1 month of epigastric pain aggravated by food and unrelieved by movements, melena, or rectal bleeding. Medical history included NIDDM, hypertension, hyperlipidemia, and cholecystectomy. She did not smoke cigarettes, had no history of recent trauma or endoscopic retrograde cholangiopancreatography, and did not drink alcohol. Her medications included metformin, 1000 mg twice daily; lovastatin, 40 mg daily; glipizide, 20 mg twice daily; lisinopril, 10 mg daily; furosemide, 40 mg daily; sertraline, 50 mg daily; aspirin, 325 mg daily; calcium carbonate, 1250 mg daily; multivitamin tablet, once daily; and pantoprazole, 40 mg daily. One month before hospital admission, she was prescribed exenatide, 5 mcg twice daily, because of poor glycemic control. This was stopped 10 days before admission because of symptoms that began 2 days after initiation of exenatide therapy.

The authors of this Byetta case report then set forth their analysis, which includes these three parts:

1)  The most common cause of acute pancreatitis is gallstone disease (accounting for 30% to 60% of cases), followed by alcohol (5% to 30%), and hypertriglyceridemia (1.3% to 3.8%). The serum triglyceride levels are usually greater than 1000 mg/dL when hypertriglyceridemia is the etiology.[6] Because this patient had a cholecystectomy, had no evidence of intrahepatic or extrahepatic duct obstruction, had no history of trauma or endoscopic retrograde cholangiopancreatography, did not drink alcohol, and had a normal lipid profile, we explored other etiologies. The commencement of exenatide treatment just before the onset of symptoms was striking.  [footnotes omitted]

2)  We believe the patient we describe represents the most thoroughly documented case of probable exenatide-induced pancreatitis and is supported by a Naranjo score of 7/9, signifying a probable association.[10] The Naranjo scale consists of a 10-item, yes or no questionnaire used to estimate the probability of a change in clinical status being due to an adverse drug reaction. A score of 9 or greater indicates that an adverse drug reaction is “highly probable”; 5–8 indicates “probable”; 1–4 indicates “possible”; and 0 or less indicates “doubtful.” For a quarter of a century, the Naranjo scale has been widely accepted in the pharmacologic literature to assess the probability of an adverse drug reaction.  [footnotes omitted]

3)  Obviously, an occult etiology for the patient’s pancreatitis cannot be entirely discounted without rechallenging with exenatide, an unethical intervention in this circumstance. Although pancreatitis has been reported with furosemide, lisinopril, lovastatin, sertraline, and metformin, their protracted use in the described patient without change in dosage militates against their being the etiologic agent.[12] To our knowledge, there has been no report of glipizide causing pancreatitis, although single case reports of the association of pancreatitis and glimepiride and gliclazide do exist.[13,14] Reinstitution of these medications, with the exception of glipizide and exenatide, at the same dosages did not result in recrudescence of symptoms, abnormal serum lipase concentration, or radiographic evidence of pancreatitis in our patient.  [footnotes omitted]

The authors conclude their article with the advice that where there is a diabetic patient with pancreatitis, “exenatide must be ruled out as the cause and its use discontinued.”

As we reported previously, in October 2009 the FDA said in a letter to Amilyn that the agency wants studies done on the safety of Byetta, with a focus on pancreatitis and pancreatic cancer as well as some other possible side effects.

We are currently investigating cases of pancreatitis — acute, hemorrhagic, and, necrotizing pancreatitis — kidney failure, and renal insufficiency involving patients who have used Byetta.

______________________________________________________________________________

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

Will The FDA Be The Last To Insist On Increased Warning; In Fall 2007 Bayer Updated Its Avalox Label In Europe

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 22, 2010 Health Canada issued a press release, “Updated Labelling for Antibiotic Avelox (Moxifloxacin) Regarding Rare Risk of Severe Liver Injury Information Update”, which informed doctors and patients about newly updated labeling information for Avelox in Canada that incorporates important safety information related to the rare risk of severe liver problems when using Avelox.

Symptoms of liver problems include:

• Abdominal pain;
• Loss of appetite;
• Yellowing of the skin and eyes;
• Severe itching;
• Dark urine; and,
• Pale-colored stools.

In its March 2010 press release about Avelox, Health Canada advised: 

Patients who experience any of these symptoms are advised to stop taking Avelox and contact a health care professional immediately.

While this advisory from Health Canada about Avelox is important, it is far from new.

In an article which we posted to this site more than two years ago, “February 2008 ‘Dear Doctor’ Letter About Avelox / Avalox Is Sent By Bayer In Europe”, we reported that this letter from Bayer to doctors in Europe was intended to emphasize the addition of a warning about severe, possibly fatal liver injury to the package insert, or label, for Avalox (slightly different brand name for this antibiotic is used in the European Union) back in the fall of 2007.

We concluded our February 2008 article about this Avalox “Dear Doctor” letter that Bayer sent out only in Europe with this remark:

We will watch for any similar Avelox “Dear Doctor” letter from Bayer here in the U.S.

Two years later, we are still waiting and watching, here.

It is unclear thus far whether Bayer will notify doctors in Canada by letter about the Avelox label change concerning the risk of liver injury for patients using this apparently unsafe antibiotic.

Here’s our “obvious” question to the FDA, now:  Is the FDA looking at Avelox for serious side effects such as drug-induced hepatitis and liver failure, which seem to be unique to this antibiotic among the fluoroquinolones?

We would like to hear about what you know regarding this liver-related Avelox safety issue.  As always, please share by leaving a Comment, below.

______________________________________________________________________________

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

Active Ingredient Simvastatin Is Found In Vytorin, With Zetia, And Simcor, With Niacin, Also

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 19, 2010 the FDA issued a News Release about Zocor (simvastatin) 80 mg pills which starts as follows:

The U.S. Food and Drug Administration today warned patients and healthcare providers about the potential for increased risk of muscle injury from the cholesterol-lowering medication Zocor (simvastatin) 80 mg. Although muscle injury (called myopathy) is a known side effect with all statins, today’s warning highlights the greater risk of developing muscle injury, including rhabdomyolysis, for patients when they are prescribed and use higher doses of this drug. Rhabdomyolysis is the most serious form of myopathy and can lead to severe kidney damage, kidney failure, and sometimes death.

Review of simvastatin is part of an ongoing FDA effort to evaluate the risk of statin-associated muscle injury and to provide that information to the public as it becomes available,” said Eric Colman, M.D., Deputy Director of FDA’s Division of Metabolism and Endocrinology Products (DMEP). “It’s important for patients and healthcare professionals to consider all the potential risks and known benefits of any drug before deciding on any one therapy or dose of therapy.”

For further information, the agency referred us to an FDA Drug Safety Communication, “Ongoing Safety Review of High-dose Zocor (simvastatin) and Increased Risk of Muscle Injury”, also issued on March 19, 2010.  From that document we learn the basis for this new Zocor warning from the FDA as well as more about myopathy and rhabdomyolysis — which is sometimes called “rhabdo” as its short name:

The clinical trial data being reviewed is from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial. The agency is also reviewing data from other clinical trials, observational studies, adverse event reports, and data on prescription use of simvastatin to better understand the relationship between high-dose simvastatin use and muscle injury…

The muscle injury, also called myopathy, is a known side effect with all statin medications. Patients with myopathy generally have muscle pain, tenderness or weakness, and an elevation of a muscle enzyme in the blood (creatine kinase). The higher the dose of statin used, the greater the risk of developing myopathy….

The most serious form of myopathy is called rhabdomyolysis. It occurs when a protein (myoglobin) is released as muscle fibers break down. Myoglobin can damage the kidneys as they filter blood out of the body. Patients with rhabdomyolysis may have dark or red urine and fatigue, in addition to their muscle symptoms. Damage to the kidneys from rhabdomyolysis can be so severe that patients may develop kidney failure, which can be fatal.

Some additional information about the development of myopathy is set forth in an article, “High-Dose Simvastatin Associated With Increased Risk for Myopathy, FDA Warns”, published March 19, 2010 by Medscape Today (free registration):

Risk for myopathy may be linked to genetic heterogeneity in statin users. A study published in the October 20, 2009, issue of the Journal of American College of Cardiology found that carriers of the reduced-function single nucleotide polymorphism of the SLCO1B1 gene were at increased risk of developing mild statin-induced adverse effects, including myopathy and myalgia. The risk for adverse events was greatest among those treated with simvastatin, but minimal in those receiving pravastatin.

This Medscape Today article also points out that the FDA’s “Potential Signals of Serious Risks/New Safety Information Identified by AERS, Second Quarter 2009” list of drugs included an item concerning a drug interaction between Zocor (simvastatin) and Cardizem (diltiazem) causing myopathy, included this statement:

FDA is evaluating this issue to determine if simvastatin labeling, which includes myopathy, is adequate.

Going back to the March 2010 FDA Drug Safety Communication about Zocor, toward the very end, we find their position about the current simvistatin package insert, or label:

Moreover, FDA has requested that the sponsor of simvastatin change the product labeling to instruct healthcare professionals to avoid prescribing simvastatin doses greater than 40 mg daily when patients are taking the medication diltiazem, due to an increased risk for myopathy.

We remind you that the FDA advises one should not stop taking any prescription drug, including Zocor, without first speaking to the doctor who prescribed it.

______________________________________________________________________________

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

Includes A New “Black Box” Warning About Renal Impairment, Liver Failure, And Gastrointestinal Hemorrhage

(Posted by Tom Lamb at DrugInjuryWatch.com)

In mid-February 2010 the FDA and Novartis announced a change to the Prescribing Information (PI) — also referred to as the package insert or label — for Exjade (deferasirox), a drug indicated for the treatment of chronic iron overload due to blood transfusions in patients two years of age and older. 

From this MedWatch 2010 Safety summary, “Exjade (deferasirox): Boxed Warning”, in relevant part:

New language was added to the Contraindications, Warnings and Precautions, and Drug Interactions sections of the PI, including a Boxed Warning, that the product may cause:

• renal impairment, including failure
• hepatic impairment, including failure
• gastrointestinal hemorrhage

In some reported cases, these reactions were fatal. These reactions were more frequently observed in patients with advanced age, high risk myelodysplastic syndromes, underlying renal or hepatic impairment or low platelet counts. Exjade therapy requires close patient monitoring, including measurement of serum creatinine and/or creatinine clearance as specified in the PI and serum transaminases and bilirubin as specified in the PI.

For additional information, this February 2010 FDA MedWatch document referred us to the so-called “Dear Doctor” letter dated February 17 from Novartis and the revised Exjade Prescribing Information (January 2010 version).

As some of you will know, Exjade has been under scrutiny by the FDA and Health Canada over safety concerns for some time, now.  Here is a timeline showing some of this regulatory “attention”:

September 2007:  The FDA states in an FDA Drug Safety Newsletter that the agency had received 115 reports of suspected adverse drug reactions (ADR) in association with Exjade use, including 17 deaths in adults.

September 2009:  The FDA issues its “Early Communication about an Ongoing Safety Review of Deferasirox (marketed as Exjade)”, which includes this information:

FDA is reviewing adverse event information for Exjade from a database that tracks all patients who are prescribed Exjade and a company-sponsored global safety database.  This information suggests there may be a greater risk for adverse events such as kidney failure, gastrointestinal hemorrhage (potentially fatal bleeding) and deaths in patients with myelodysplastic syndrome (MDS) compared to patients without these conditions.

November 2009:  Novartis sends out a “Dear Doctor” letter in Canada about Exjade with this Suject line:  “Use of EXJADE (deferasirox) in Patients Diagnosed with Myelodysplastic Syndrome (MDS) and in Elderly Patients regarding Renal Events and Gastrointestinal Hemorrhage (Fatal in Rare Cases)”)”.

We will continue to monitor and report about the safety profile of Exjade going forward.

______________________________________________________________________________

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

These 241 “New” Documents Show How Drug Company Obscured Potential For Patient Weight Gain And Diabetes

(Posted by Tom Lamb at DrugInjuryWatch.com)

In mid-February 2010 Kim Klausner, the Industry Documents Digital Libraries Manager for Drug Industry Document Archive (DIDA) at the University of California, San Francisco, let us know about some “new” documents concerning the drug Seroquel that are now available on the DIDA web site:

I’m pleased to announce that we’ve added to the Drug Industry Document Archive (http://dida.library.ucsf.edu) 241 documents about the marketing of Seroquel from the files of AstraZeneca.  These documents show how the company obscured the potential for patient weight gain and diabetes from physicians and regulatory bodies and how they balanced the desire for sales with the need for scientific rigor.  You can find these documents by entering “ddu:2010*” without the quotation marks in the query box.

Further, Kim listed some of what she thought were the more “interesting” (my characterization, not hers) Seroquel documents for us:

1)  “[Do] not to discuss details surrounding trial 41 with any external customers” who include investigators.

2)  How to spin and de-emphasize weight gain.

3)  AstraZeneca Director of Clinical Research asks for information about BristolMyersSquibb’s trials in exchange for sexual favors (I’m not kidding).

4)  Suggests data mining of Study 50 focusing on efficacy by measuring psychotic relapse.

5)  Suggests that AZ-supported research has suspect results.

6)  Discusses how much to disclose about Study 15.

7)  Suggests pooling data to achieve certain efficacy claims.

8)  “all off-label slides are financed outside of commercial for obvious legal reasons”

9)  “R&D is no longer responsible for Seroquel research – it is now the responsibility of Sales and Marketing.”

10)  Discusses giving limited data to an investigator on Trial 31 because he is perceived to be a “Lily advocate.”  “I don’t want to irritate him nor give him the impression that we are hiding data.”

11)  Proposal for a study on the diabetogenic and hyperlipidemia side effects of quetiapine; concern about the potential risk and damage if the study had negative results.

12)  Questions why “limited” would remain as a qualifier to weight gain in the Core Data Sheet even though SERM [Safety Evaluation and Review Meeting] had decided otherwise.

13)  Email re the request of Dr. Ghaemi, who was asked to be an author on the Trial 104 manuscript, for the study’s raw data. Suggests dropping Dr. Ghaemi as an author.

14)  Contemplates Study 125 endpoints based on potential adverse effects on US sales.

As some of you may recall, we have written previously about this DIDA project:

• Drug Industry Document Archive Has Over 1500 Documents Regarding Big Pharma Conduct — Includes Previously Secret Documents That Were Released During Lawsuits Against Merck & Co., Parke-Davis, Warner-Lambert, and Pfizer
   
• Drug Industry Document Archive (DIDA) Adds 15 More Pharma-Related Documents To Collection In November 2009 — This Archive Contains Some “Secret” Documents Only Made Public In The Course Of Lawsuits Filed Against Pharmaceutical Companies

We thank Kim for letting us know about these Seroquel-AstraZeneca documents that are now available to the public at the DIDA web site, and look forward to receiving her future notices (which, in turn, we will let you know about).

______________________________________________________________________________

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

Third Boston Collaborative Drug Surveillance Program Study Analysis Concerning Ortho Evra And Blood Clot Side Effect Risk Causes Confusion

(Posted by Tom Lamb at DrugInjuryWatch.com)

Let us start with this relatively recent medical journal article, “Postmarketing study of ORTHO EVRA and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 mcg of ethinyl estradiol in relation to nonfatal venous thromboembolism”, published in the January 1, 2010 edition of Contraception, which reports the findings from a Boston Collaborative Drug Surveillance Program study about the Ortho Evra birth control patch. 

From the Abstract for this January 2010 article:

BACKGROUND: Concern has been raised that the risk of venous thromboembolism (VTE) in users of the ORTHO EVRA patch is higher compared to users of oral contraceptives (OCs). STUDY DESIGN: We identified idiopathic cases of VTE and controls, matched on age and index date, from among women in the United States PharMetrics/IMS and MarketScan databases who were current users of the patch or levonorgestrel-containing OCs with 30 mcg of ethinyl estradiol….  CONCLUSION: These results provide evidence that the risk of idiopathic VTE in users of the patch is not materially different than that of users of levonorgestrel-containing OCs in women aged 39 years or younger. We cannot rule out some increase in the risk in women aged 40 years or older.

It seems that the findings presented in this January 2010 article come from a Phase IV Ortho Evra clinical trial known as “Relative Risks for Non-Fatal Venous Thromboembolism, Ischemic Stroke and Myocardial Infarction in Users of ORTHO EVRA(Norelgestromin and Ethinyl Estradiol Contraceptive Patch) Compared to Levonorgestrel-Containing Oral Contraceptives.”

From the ClinicalTrials.gov record for this Ortho Evra safety study (last processed on March 5, 2010 according to site; accessed March 8, 2010):

Purpose

This study uses the PharMetrics insurance claims database to estimate relative risks for non-fatal venous thromboembolism (including cerebral venous sinus thrombosis), ischemic stroke, and acute myocardial infarction (heart attack), in current users of ORTHO EVRA (norelgestromin and ethinyl estradiol contraceptive patch) compared to current users of oral levonorgestrel-containing oral contraceptives with 30 micrograms ethinyl estradiol, with special attention to duration of use….

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511784

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Boston Collaborative Drug Surveillance Program

To recap, the bottom line from this January 2010 report about the latest study analysis done by Boston Collaborative Drug Surveillance Program (BCDSP) is that Ortho Evra does not increase the risk of blood clot-related side effects, or venous thromboembolism, any more than birth control pills that contain levonorgestrel and 30 micrograms ethinyl estradiol, with the possible exception of women over 40 years of age.

Now let us go back in time to see what J&J and BCDPS have said previously about a woman’s risk of developing blood clot-related side effects such as pulmonary embolism (PE) and deep vein thrombosis (DVT) as well as heart attack and stroke while using the Ortho Evra patch.

In September 2006 J&J revised the Package Insert for Ortho Evra to include for the first time a warning about the increased risk of venous thromboembolism.  This new label, however, included conflicting information about that risk by mentioning two different study results concerning clotting risk.

According to this new September 2006 label, one study showed that patch users were twice as likely as birth control pill users to develop venous thromboembolism.  The other study showed that patch users and pill users were equally likely to develop venous thromboembolism.

The results from a later study that was done for J&J by the Boston Collaborative Drug Surveillance Program (BCDSP) regarding the safety of Ortho Evra — the second such study done for J&J by BCDSP, to be precise — became available in or about August 2007.  In relevant part, this particular BCDSP study showed that the odds of developing venous thromboembolism were, in fact, higher for women aged 15 – 44 who use the Ortho Evra patch than women using birth control pills.  In January 2008 the FDA ordered J&J to put the results of this second BCDSP study on the Ortho Evra patch label.

So does this January 2010 medical journal report about the latest Ortho Evra study done by BCDSP for J&J — seemingly their third study — serve to refute the key finding from the second study, namely that the odds of developing venous thromboembolism were higher for women who are 15 to 44 year old?

Any guidance or insight would be most appreciated.

______________________________________________________________________________

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

Company Annual Report 2009: “Bayer believes that it has meritorious defenses and intends to defend itself vigorously.”

(Posted by Tom Lamb at DrugInjuryWatch.com)

The Bayer Annual Report for 2009, at page 243, provides some updated information about the number of YAZ, Yasmin, and Ocella lawsuits that have been filed thus far:

As of February 15, 2010, there were about 1,100 lawsuits pending in the United States served upon Bayer on behalf of persons alleged to have suffered personal injuries, some of them fatal, from the use of Bayer’s oral contraceptive products Yasmin®, YAZ® and / or Ocella, a generic version of Yasmin® distributed by Barr Laboratories, Inc. in the U.S. market. Plaintiffs seek compensatory and punitive damages, claiming, in particular, that Bayer knew or should have known the alleged risks and should be held liable for having failed to disclose them or adequately warn users of Yasmin® and YAZ®…. Additional lawsuits are anticipated. Bayer believes that it has meritorious defenses and intends to defend itself vigorously. Bayer is also taking over Barr´s defense in certain cases according to the parties´ supply and licensing agreement….

Previously, in mid-October 2009, Bayer said that there were only 129 Yaz and Yasmin lawsuits filed in the U.S.

YAZ, Yasmin, and Ocella birth control pills are made with ethinyl estradiol (EE) and drospirenone (DRSP). In fact, YAZ, Yasmin, and Ocella are the only birth control pills to contain drospirenone.

These popular oral contraceptives have been associated with several serious side effects such as:

• deep vein thrombosis (DVT);
• pulmonary embolism (PE);
• strokes, or cerebrovascular accident (CVA);
• heart attacks, or myocardial infarction (MI);
• gallbladder problems and gallbladder removal (cholecystectomy);
• kidney failure or renal failure; and,
• pancreatitis.

All YAZ, Yasmin, and Ocella personal injury or wrongful death lawsuits filed in the federal court system have been consolidated in the Southern District of Illinois as part of MDL No. 2100 — IN RE: Yasmin and Yaz (Drospirenone) Marketing and Sales Practices and Products Liability Litigation.  U.S. District Court Judge David R. Herndon is presiding over these Yaz and Yasmin cases for “coordinated or consolidated pretrial proceedings”.

More recently, in mid-February 2010, the New Jersey Supreme Court consolidated all state court lawsuits against Bayer and Barr Phamaceuticals for injuries and damages allegedly arising from the use of the oral contraceptives Yaz, Yasmin, and the generic drug Ocella.  Those cases are now part of In Re YAZ®, Yasmin® and Ocella® Litigation, Case No. 287 (Bergen County), and have been assigned to the New Jersey state court Judge Brian R. Martinotti, who has already issued his Initial Case Management Order for this litigation.

Earlier, in mid-September 2009, Judge Sandra Mazer Moss, who runs the mass tort program for the Philadelphia Court of Common Pleas, consolidated all lawsuits filed in Pennsylvania state court that involve YAZ or Yasmin for case management and discovery purposes.

We will continue to monitor and report about the YAZ, Yasmin, and Ocella lawsuits that have been filed in the federal court MDL as well as the New Jersey and Pennsylvania state court consolidations.

______________________________________________________________________________

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

Six Plaintiffs Selected From Among The 300 Levaquin Lawsuits Filed To Date In Federal Court System

(Posted by Tom Lamb at DrugInjuryWatch.com)

At a February 12, 2010 Status Conference, U.S. District Judge John R. Tunheim received an update about the number of lawsuits in the federal court multi-district litigation, or MDL — known as In re: LEVAQUIN PRODUCTS LIABILITY LITIGATION, MDL No. 08-1943 (JRT) — and in certain state courts around the country.

The Minutes from this February 12, 2010 Status Conference for the Levaquin MDL provide this summary of that information:

The parties indicated that there are currently 300 MDL cases, with 11 additional cases awaiting transfer and approximately 4 or 5 that the parties anticipate will be removed and transferred soon. There are also 124 New Jersey state court cases, one state court case in Iowa that will be removed, four state court cases in Illinois, and one state court case in New York.

As reported previously, the growing number of Levaquin lawsuits filed in New Jersey have been given a “mass tort” designation which, in effect, operates as a state court MDL for the Levaquin litigation there.

Also on February 12, 2010, Judge Tunheim issued Pretrial Order #6, in which he identified the six so-called “bellwether”, or test, cases which will be the subject of the first Levaquin lawsuits to go to trial in the federal court MDL.  In particular, the following cases were listed therein:

• Sharon Johnson v. Johnson and Johnson, No. 06-3728
• Calvin Christensen v. Johnson and Johnson, No. 07-3690
• Richard Kirkes v. Johnson and Johnson, No.07-1862
• John Schedin v. Johnson and Johnson, No.085734
• Edward Karkoska v. Johnson and Johnson, No. 07-3690
• Eugene Martinka v. Johnson and Johnson, No. 08-5754

This Pretrial Order #6 stated that these six Levaquin bellwether case should be “trial ready” by October 30, 2010.  Judge Tunheim, however, left unanswered some important questions about these first federal court Levaquin trials, namely:

Which cases shall be tried, in what sequence, and whether they shall be tried individually or on a consolidated basis shall be decided at a later date.

Of course, we will continue to monitor this federal court Levaquin MDL for further developments regarding these six bellwether cases.

______________________________________________________________________________

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

Troubled Company Pleads Guilty To Criminal Charges, Pays $27.6 Million In Fines And Restitution For Its Conduct Related To Quality-Control Issues

(Posted by Tom Lamb at DrugInjuryWatch.com)

We last wrote about the troubled generic drug manufacturer ETHEX Corp. a little more than a year ago, when we posted this article: “January 2009: ETHEX Corp. Issues Voluntary Recall Of All Pills Due To Suspected Manufacturing Problems”.

Now, in February 2010, we know how the story ends for ETHEX — for the most part, at least.

From a February 25, 2010 article, “KV Pharmaceutical to plead guilty, pay $27.6M, close generics business”, published by the St. Louis Business Journal:

KV Pharmaceutical Co. must pay $27.6 million in fines and restitution, and plans to cease its generic drugs business after pleading guilty to criminal charges for not disclosing problems with two of its drugs…..

Bridgeton, Mo.-based KV said Thursday its subsidiary, Ethex Corp., plans to plead guilty to two felony counts of failure in 2008 to file field alerts for the generic drugs Dextroamphetamine, a stimulant used to treat ADHD, and Propafenone, which treats rapid heart beats. The company then plans to cease operations of Ethex. The U.S. Food and Drug Administration requires that companies file field alerts to quickly identify drugs that pose potential safety threats from problems such as contamination or mislabeling.

KV’s interim Chief Executive David Van Vliet declined to disclose the specifics of what the problems with the drugs exactly were.

Van Vliet said the company will now focus on regaining FDA compliance so it can return to making both branded and generic drugs under Ethex’s parent company, KV, which retains all related intellectual property, including drug applications and the ability to conduct marketing and distribution of all of its previously approved products.  [Emphasis added]

It remains to be seen whether the U.S. Attorney for the Eastern District of Missouri, the U.S. Department of Justice (DOJ), or the U.S. Food and Drug Administration (FDA) will release details about the extent of the quality control problems at ETHEX and whether those problems resulted in any known-cases of harm to patients using any of the sub-standard generic drugs made by ETHEX.

If you are aware of a drug injury case involving an ETHEX generic drug, we would be interested in hearing about it.  You can do so by posting a Comment below or sending me a private email.

For more articles about quality-control issues at various generic drug companies, view our collection of stories at the Generic Drug Safety part of our blog Archives.

______________________________________________________________________________

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

Heart Risk Is Current Focus Due To GlaxoSmithKline Past Conduct; But Public Citizen Has Pointed The Liver Failure Case Reports Linked To Avandia, Also

(Posted by Tom Lamb at DrugInjuryWatch.com)

As some of you may recall, in October 2008 Public Citizen petitioned the FDA to ban the sale of the diabetes drug Avandia (rosiglitazone) in the U.S. because its risks, which include heart attack and heart failure in addition to liver toxicity, far outweigh its benefits and because much safer alternatives exist for treating Type 2 diabetes.

To our knowledge, there is still no word from the FDA about how long the agency will need to make a determination on the Avandia recall requested by Public Citizen.

More recently, in late July 2009, a new medical journal article about Avandia and liver failure was published in Pharmacoepidemiology and Drug Safety.  This article, “Case series of liver failure associated with rosiglitazone and pioglitazone.” — by James S. Floyd, MD, Elizabeth Barbehenn, PhD, Peter Lurie, MD, MPH, and Sidney M. Wolfe, MD, of Public Citizen’s Health Research Group — seemingly adds further support to the contention that Avandia can cause liver failure and should be recalled by the FDA.

Soon thereafter a July 22, 2009 press release, “Rigorous Study Adds to Case That FDA Should Ban the Diabetes Drug”, was issued by Public Citizen in connection with this new Avandia medical journal article.

Those few items, above, suggest that the serious liver injury risk associated with Avandia could (and should) be a factor in the FDA’s determination about whether to order an Avandia recall, or not.

As far as when any Avandia recall determination will be made by the FDA, currently it seems this issue will have to wait until a joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees in July 2010. At that FDA meeting, the Advisory Committee will provide an updated assessment of the risks and benefits of Avandia.

Returning to the present, during this past week almost all (if not all) of the Avandia safety debate has had to do with the cardiac risks linked to Avandia, namely heart attacks and heart failure.

First, there was a February 19, 2010 New York Times (NYT) article, “Research Ties Diabetes Drug to Heart Woes”, by Gardiner Harris, which was based on “internal FDA reports” and a January 2010 Senate Committee on Finance staff report about Avandia which concludes: “The totality of evidence suggests that [GlaxoSmithKline] was aware of the possible cardiac risks associated with Avandia years before such evidence became public.”

Immediately afterward, in two separate press releases, GlaxoSmithKline (GSK) disputed the reports set forth in the February 19 NYT article and took issue with the conclusions of the Senate Committee’s Avandia report.  Essentially, the party line for GSK is that “the scientific evidence simply does not establish that Avandia increases ischemic cardiovascular risk or causes myocardial ischemic events.”

And then there is renowned cardiologist Steven Nissen, of the Cleveland Clinic, who has been vocal critic of Avandia due to safety reasons.  To learn more about Dr. Nissen’s position on Avandia, we refer you to these two items:

1)  A February 23, 2010 New York Times (NYT) story, “A Face-Off on the Safety of a Drug for Diabetes”, by Gardiner Harris, again; and,

2)  This recent medical journal article from European Heart Journal, “The rise and fall of rosiglitazone”, by Steven E. Nissen — Advance Access published February 12, 2010 (includes a 1999-2009 timeline).

Our law firm is continuing to investigate Avandia injury and death cases involving liver failure as well as heart attack or heart failure.

______________________________________________________________________________

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

 

Reports About Sudden Breaking Of Thigh Bone In Patients Using Fosamax For Five Years Or More

(Posted by Tom Lamb at DrugInjuryWatch.com)

The side effects of Fosamax include osteonecrosis of the jaw (ONJ), esophageal irritation, and musculoskeletal pain. In addition, cases of femur fractures associated with prolonged Fosamax (alendronate) use have been reported.

In the December 18, 2009 edition of the medical journal Clinical Orthopaedics and Related Research (CORR), there is an article about the Fosamax-related femur fractures, “Case Reports: Subtrochanteric Femoral Stress Fractures after Prolonged Alendronate Therapy”. 

From this December 2009 CORR article about Fosamax:

CASE DESCRIPTION: We report the cases of four women who sustained low-energy subtrochanteric or femoral shaft stress fractures while being on alendronate therapy for more than 5 years. All radiographs showed typical patterns consisting of a transverse fracture line with external cortical bone reaction and medial cortical spike. Alendronate discontinuation along with nonoperative treatment was sufficient for one patient, whereas surgical stabilization was required in three patients.

A February 18, 2010 TV news report, “Sudden bone breaks reported in patients taking Fosamax”, provides us with some insight about these femur fractures which might be caused by Fosamax.  For this report, WCBD elicited the following comments and observations from rheumatologist Dr. Robert Bunnin, of the National Rehabilitation Hospital in Washington, DC:

“The drugs are supposed to work by shutting down the cells that re-absorb the bone, the osteoclasts. The ones that make the bone, the osteoblasts, are supposed to keep working. However in biopsies of patients who have had the fracture, it shows that both are shut down.”

Bunning calls it “frozen bone,” which is brittle and more susceptible to these types of clean fractures. He says in the U.S. There have been 50 to 60 reported cases of this.

“Even thought [sic] it’s rare, I think we’re going to be seeing quite a few more cases.”

Dr. Bunning says that in all of the reported cases, most patients had been taking Fosamax or another type of bisphosphonate for more than 5 years.

“The drugs clearly were designed to make the bones stronger and I think they do for the first few years. They make them denser.”…

Dr. Bunning says typically, patients with that condition will suffer breaks in the hip area—and that usually occurs after a fall.

With all of these patients, the breaks are occurring in the thigh and without any sort of trauma.

Dr. Bunning says that in many of these patients they had experienced vague thigh pain before their femur broke.

So Dr. Bunning says if you or someone you know is taking one of these drugs, make sure to see your doctor right away if something doesn’t feel right.

Our law firm is currently handling Fosamax injury cases involving osteonecrosis of the jaw (ONJ), or jaw bone death, as well as low-stress leg fractures of the femur, or thigh.

______________________________________________________________________________

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

Study Says Using Such Data Would Have Resulted In Faster Safety Signal Detection For Increased Risk Of Heart Attacks With Avandia Use

(Posted by Tom Lamb at DrugInjuryWatch.com)

A recent medical journal article suggests that a systematic review of electronic medical records may have allowed the FDA and others to identify the increased risk for heart attack, or myocardial infarction (MI), with Avandia use as early as 18 months after Avandia came on the market in the U.S.

The December 15, 2009 edition of Diabetes Care included the article “Rapid identification of myocardial infarction risk associated with diabetic medications using electronic medical records”.  From the Abstract for that article:

Objective: To assess the ability to identify potential association(s) of diabetic medications with myocardial infarction (MI) using usual care clinical data obtained from the electronic medical record.

Results: … After adjustment for potential MI risk factors, relative risk for MI with rosiglitazone was 1.3 (95% CI, 1.1-1.6) compared to sulfonylurea, 2.2 (95% CI, 1.6-3.1) compared to metformin, and 2.2 (95% CI 1.5-3.4) compared to pioglitazone. Prospective surveillance using these data would have identified increased risk for MI with rosiglitazone compared to metformin within 18 months of its introduction with a risk ratio of 2.1 (95% CI 1.2-3.8).

Conclusions: … Our use of usual care electronic data sources from a large hospital network represents an innovative approach to rapid safety signal detection that may enable more effective post-marketing drug surveillance.

We have reported over time about the FDA’s Sentinel Initiative project for monitoring medical product safety, the goal of which is to develop an active electronic safety monitoring system to strengthen FDA’s ability to track the postmarket performance of medical products.

This recent study about identifying the heart attack risk associated with Avandia by use of electronic medical records seemingly indicates that the Sentinel Initiative will be a good means by which to augment existing drug safety monitoring systems.

______________________________________________________________________________

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

Two Medical Journal Articles Review The Published Research And Suggest Ways To Avoid Cardiac Valve Side Effects

(Posted by Tom Lamb at DrugInjuryWatch.com)

In March 2007 the FDA announced that Permax (pergolide) would be voluntarily removed from the U. S. market because it had been linked to serious heart valve damage.

In August 2007 Health Canada followed suit and announced the sales of Permax must cease in their country, also.

Pfizer’s Dostinex (cabergoline), however, remains on the market despite the January 2007 reports in the New England Journal of Medicine that Dostinex, like Permax, was linked to valvular heart disease.

In September 2008 a so-called “Dear Doctor” letter about Dostinex was sent by Pfizer Ltd., but apparently only to doctors in the U.K.

More recently, there have been two medical journal articles which reviewed and summarized the published research regarding the cardiac valve side effects that have been associated with Permax and Dostinex.

The first article, “Dopamine agonists and valvular heart disease”, published in June 2009, we get this information:

RECENT FINDINGS: Off-target action of dopamine agonists at 5-hydroxytryptamine 2B receptors is now recognized to cause cardiac valve disease in several studies in Parkinson’s disease patients who received high daily dopamine agonist doses, including [Dostinex (cabergoline)] and [Permax (pergolide)]. Generally, dopamine agonist doses in prolactinoma therapy are 10-fold lower than those employed in Parkinson’s disease, although occasionally dopamine agonist-resistant patients require higher doses. Most studies of dopamine agonist use in prolactinoma have not observed valvular abnormalities.

SUMMARY: Dopamine agonists are effective in treating prolactinomas. At typical doses, the risk for valvulopathy appears low. Increased risk of cardiac valvulopathy should be considered in patients requiring higher doses or long duration of therapy. Echocardiography should be performed in these high-risk patients, drug holidays implemented and patients withdrawn from these agents if possible.

The second article, “Potential Cardiac Valve Effects of Dopamine Agonists in Hyperprolactinemia”, first published online in February 2010, reinforces the findings and guidance of the earlier article:

Evidence Synthesis: The majority of studies showed no risk of valvular regurgitation associated with [Dostinex (cabergoline)]. However, an increased risk of mild to moderate regurgitation, usually at the tricuspid valve, was reported in a few studies. Only one study suggested a relationship with the mean cumulative dose of [Dostinex (cabergoline)].

Conclusions: Although most reports do not show an association between use of dopamine agonists and valvulopathy, caution must be exercised, especially in patients requiring long-term, high-dose medication regimens. Clinicians should recommend the lowest possible doses of dopamine agonists and address the question of echocardiographic monitoring on an individual basis.

We continue to investigate possible drug injury cases involving Permax and Dostinex.

P.S.  Excerpt from the Abstract for Cabergoline therapy for prolactinomas: is valvular heart disease a real safety concern?  (Expert Rev Cardiovasc Ther, January 1, 2010):

The clinical significance of the present findings has yet to be confirmed by future larger prospective studies with rigorous echocardiographic protocols and prolonged duration of follow-up.

(2/15/10)

______________________________________________________________________________

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

Authors Suggest That Certain Patients Starting Januvia Should Have Their Liver Function Monitored

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the recent past we considered whether Januvia (sitagliptin) can cause pancreatitis in patients using this relatively new diabetes medication.

Now, a new medical journal “To The Editor” letter suggests that Januvia may have a negative effect on the liver for certain patients, specifically “individuals with a history of nonalcoholic steatohepatitis or elevated hepatic enzymes”.

From this letter titled “Elevated Hepatic Enzymes Potentially Associated with Sitagliptin”— published online January 26, 2010 by The Annals of Pharmacotherapy — we get the following case report concerning a patient who developed elevated hepatic enzyme levels after starting Januvia:

A 58-year-old male with a history of type 2 diabetes and nonalcoholic steatohepatitis (diagnosed in 2006) presented to the clinic for diabetes management. At the time, the patient’s aspartate aminotransferase (AST) was 53 U/L (normal <40 U/L) and alanine aminotransferase (ALT) was 102 U/L (normal <40 U/L). The patient was started on rosuvastatin 10 mg once daily….  One month following therapy, AST and ALT had declined to 35 U/L and 64 U/L, respectively.

Two months after the initiation of rosuvastatin, the patient was started on sitagliptin 100 mg once daily due to elevated hemoglobin A1C of 8.2%. The patient’s other medications included amlodipine 5 mg once daily, benazepril 20 mg once daily, aspirin 81 mg once daily, glucosamine 500 mg once daily, chondroitin 400 mg once daily, and indomethacin 25 mg once daily as needed. One month after initiation of sitagliptin, liver enzymes were monitored and revealed an AST and ALT of 71 U/L and 127 U/L, respectively. Four days later the AST and ALT levels were 70 U/L and 137 U/L, respectively. All other corresponding hepatic function results were within normal range for the patient. A full medication review was performed. Sitagliptin was discussed as a possible cause of increased liver enzyme levels and promptly discontinued. Reexamination of liver enzymes a month after discontinuing sitagliptin revealed a significant decrease in AST and ALT (48 U/L and 90 U/L, respectively). Most recently, 6 months after discontinuation, AST and ALT were 35 U/L and 62 U/L, respectively.

The authors of this letter about Januvia acknowledge that prior studies have not found any liver-related side effects associated with Januvia, and they list several articles concerning those earlier safety studies.  They go on, however, to make this important point:

Although no significant elevation of hepatic enzymes has been reported in the literature, most of the trials involving the safety of sitagliptin were small and short in duration.

As such, in conclusion, they offer that certain patients starting Januvia should perhaps be monitored for possible liver side effects.

We will continue to monitor the safety profile of Januvia, and we welcome any information or insight you may have about this drug safety issue.

______________________________________________________________________________

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

 

Medtronic Says 4.6 Percent Of Leads Failed, While Reports From Some Hospitals Indicate 9.2 Percent Of Sprint Fidelis Wires Failed

(Posted by Tom Lamb at DrugInjuryWatch.com)

In our December 30, 2009 article, “Sprint Fidelis Lead Wire Failure Rate Could Rise To 30 Percent By Four Years”, we provided the little bit of information we could find, then, about the future failure rates for the Medtronic Sprint Fidelis lead wires that were removed from the market back in 2007:

A report by UBS Investment Research Monday said lead failures could accelerate over time, citing independent studies that predict failure rates could hit 30 percent by four years. Medtronic’s own data suggests a 3 percent failure rate at three years.

Now we have some additional data regarding the three-year failure rate, or survival rate, of these Sprint Fidelis leads thanks to a February 4, 2010 article, “Hospitals Dispute Medtronic Data on Wires”, by Wall Street Journal (WSJ) reporter Thomas M. Burton.

From this February 2010 WSJ article we get the following numbers:

Medtronic says its own research shows the Sprint Fidelis leads survive for three years at least 95.4% of the time, for a failure rate of 4.6%. Reports from hospitals including the University of Rochester in New York state, the Minneapolis Heart Institute, the Mayo Clinic and the University of Ottawa, say the overall failure rate for Sprint Fidelis leads is as much as two times as great as the company’s own data indicate. Some of the hospitals also report that the rate of fracture accelerates as the leads age.

“The hazard of [Sprint] Fidelis lead fracture is increasing exponentially with time and, based on our data, occurring at a higher rate than the latest manufacturer’s performance update,” doctors at the University of Rochester concluded in findings published in January’s American Journal of Cardiology. The report said the three-year survival rate of 426 Medtronic leads inserted in the hospital’s patients was 90.8%, meaning 9.2% failed.

Mr. Burton also looked back at a number of other studies that have been performed since the 2007 Sprint Fidelis recall, and he reports:

Last February, a joint report from the Minneapolis Heart Institute and the Mayo Clinic, published in the journal HeartRhythm, said the estimated rate of failure among 848 leads at three years of use was 12.1%. An October 2008 study by the University of Ottawa Heart Institute, also published in HeartRhythm, found that the fracture rate of Sprint Fidelis leads “increased significantly with time.”

In November, a separate Mayo Clinic study showed the failure rate for Sprint Fidelis leads after two years was higher in patients younger than 50, at 20.4%, than in older patients, with a rate of 3.5%. There were 89 patients under 50 who received the leads, and 362 patients who were 50 or above.

Our law firm continues to review possible Sprint Fidelis lawsuits involving incidents of harmful unnecessary shocks in anticipation that the Medical Device Safety Act (MDSA; HR 1346 / S 540) will become law in 2010 and, thereafter, lawsuits can be filed against Medtronic on behalf of those injured patients.

______________________________________________________________________________

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

 

Merck Lost Its Attempt To Have Louise Maley’s Fosamax Lawsuit Dismissed Before Her April 19, 2010 Trial Date

(Posted by Tom Lamb at DrugInjuryWatch.com)

We have been reporting about the three bellwether trial cases for the federal court Fosamax MDL and, in this article, we continue to do so.

To start, Louise H. Maley v. Merck & Co. Inc. is the next Fosamax case set for trial in the federal court MDL, and this trial will start as scheduled on April 19, 2010.

Recent efforts by Defendant Merck to avoid this Maley Fosamax trial were summarized in a January 28, 2010 news article, “Merck Loses Dismissal Bid in Third Fosamax Case”, by Bloomberg reporter Thom Weidlich:

Merck & Co. lost its bid to dismiss the third case scheduled for trial over claims its osteoporosis drug Fosamax caused so-called jaw death.

The claim of the plaintiff, Louise Maley, “does not fail as a matter of law from a lack of evidence of exposed necrotic bone,” U.S. District Judge John Keenan in Manhattan wrote in a ruling entered into the case docket today. “Specific causation remains a material issue of fact for the jury.”

A trial is scheduled for April 19. Maley, of Muncie, Indiana, said she developed osteonecrosis of the jaw, or ONJ, by taking Fosamax, according to her complaint filed in May 2006….

Keenan declined to grant Merck’s request for a so-called summary judgment on Maley’s claim that the drugmaker failed to warn about Fosamax’s dangers. [Maley] didn’t contest Merck’s dismissal request on her strict-liability and warranty claims, and the judge tossed those.

This January 28 Bloomberg article also provides an overview of the Fosamax litigation in terms of the number of Fosamax lawsuits filed and the money Merck has reserved for the defense of those Fosamax cases:

Merck, based in Whitehouse Station, New Jersey, as of Sept. 30 faced about 953 Fosamax cases, including suits with multiple patients, the company said in a Nov. 2 regulatory filing. About 700 lawsuits have been consolidated before Keenan for evidence gathering….

As of Sept. 30, Merck set aside $48 million for defending the litigation, according to the regulatory filing. It hasn’t earmarked any money for damages.

In closing, the next scheduled Fosamax trial is Maley v. Merck & Co., 06-cv-4110, which is one of the hundreds of pending Fosamax lawsuits in In Re Fosamax Products Liability Litigation, MDL 1789, U.S. District Court, Southern District of New York (Manhattan).

______________________________________________________________________________

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