Drug Injury Watch

Is Bayer Warning Or Attacking With Its New YAZ / Yasmin Package Insert, Or Label, In The U.S.

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)

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UPDATE:  "Bayer Affirms Safety Of YAZ / Yasmin And Refutes 2011 BMJ Articles About Risk Of Blood Clots"  

(4/25/11)
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UPDATE:  "Another Rather "Odd" YAZ Label Change By Bayer: March 2011"

(3/21/11)
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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 to use the terms "unreliable" and "may not be reliable" as regards the Lidegaard publication and the Van Hylckama Vlieg publication in Europe, as it apparently intends to do 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.

P.S.  Here are the FDA-approved label changes for YAZ and Yasmin:

April 2010 YAZ Label Change Approved by FDA

April 2010 Yasmin Label Change Approved by FDA

(5/14/10)

Free Case Evaluation:  YAZ / Yasmin / Ocella / Gianvi / Zarah / Loryna / Syeda / Beyaz / Safyral
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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

New Extensively Documented Case Report About Patient With Probable Byetta-Induced Pancreatitis

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.

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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.

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

YAZ, Yasmin, Ocella: 1,100 Lawsuits Filed As Of Mid-February 2010, According To Bayer

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.

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

FDA Wants Studies Done On Byetta Safety, With Focus On Pancreatitis, Pancreatic Cancer, Thyroid Neoplasm, And Acute Renal Failure

FDA Letter About Byetta Sent To Amilyn In October 2009; Drug Company Tries To Downplay, But Investors React When They Learn About It In December 2009

(Posted by Tom Lamb at DrugInjuryWatch.com)

On October 30, 2009 Amylin Pharmaceuticals Inc. issued a press release, "BYETTA Approved for Expanded Use as First-Line Treatment for Type 2 Diabetes Prescribing Information Also Includes Updated Safety Information", in which they announced that the FDA had approved an expanded indication for BYETTA® (exenatide) injection:

BYETTA is now approved for use as a stand-alone medication (monotherapy) along with diet and exercise to improve glycemic control in adults with type 2 diabetes. Previously, it was approved for use only in patients who were also taking other common diabetes medications and had not achieved adequate glycemic control.

It was not until the end of December 2009, however, that we got the rest of the picture.  From a December 23, 2009 Bloomberg article, "Amylin Falls as Analyst Says FDA Wants Byetta Study", by reporter Rob Waters:

San Diego-based Amylin and Indianapolis-based Eli Lilly & Co., which co-market the drug, announced Oct. 30 that the Food and Drug Administration had cleared the drug for use as standalone therapy for Type 2 diabetics and that prescribing information would warn about the risk of pancreatitis, an inflamed pancreas, in patients with severe kidney disease. That statement didn’t say the FDA wanted more studies.

Citigroup analyst Yaron Werber said today in a note to investors that he had obtained a copy of the FDA’s approval letter and that the agency was requiring animal and human studies aimed at clarifying the risk of pancreatitis posed by the drug. A statement e-mailed by Lilly and Amylin today said most of the requested studies are under way and have shown no increased risk of pancreatitis in patients taking Byetta.

“The FDA considers post-marketing reports of acute pancreatitis (fatal and non-fatal hemorrhagic or necrotizing pancreatitis), acute renal failure and thyroid neoplasms as ‘new safety information’ and is requiring Amylin to conduct additional studies,” Werber said in his note.

Amylin dropped $1.48, or 9.6 percent, to $13.97 at 4 p.m. in Nasdaq Stock Market composite trading, the most since April 2. The shares have gained 29 percent this year.

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Byetta / Victoza / Januvia

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From the October 30, 2009 FDA letter to Amilyn sent by Mary Parks, M.D. -- who is the Director of the agency's Division of Metabolism and Endocrinology Products in the Center for Drug Evaluation and Research -- we get these relevant excerpts:

Since Byetta (exenatide) was approved on April 25, 2005, we have become aware of postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, and postmarketing reports of acute renal failure, sometimes leading to death or transplantation, in patients taking Byetta (exenatide). We have also become aware of postmarketing reports of thyroid neoplasms associated with the use of Byetta (exenatide) and of a signal of thyroid neoplasms observed pre-clinically with other GLP-1 analogues. We consider this information to be “new safety information” as defined in section 505-1(b)(3) of the FDCA.

After consideration of this new safety information, we have determined that postmarketing requirements are needed to assess the risk of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, and the risk of thyroid neoplasms, and that a REMS is necessary for Byetta (exenatide) to ensure that the benefits of the drug outweigh the risks of acute pancreatitis and acute renal failure....

We have determined that an analysis of spontaneous postmarketing adverse events reported under subsection 505(k)(1) of the FDCA will not be sufficient to assess the signal of a serious risk of acute pancreatitis, including hemorrhagic or necrotizing pancreatitis, and the signal of a serious risk of thyroid neoplasms.

Furthermore, the new pharmacovigilance system that FDA is required to establish under section 505(k)(3) of the FDCA has not yet been established and is not sufficient to assess this serious risk.

Therefore, based on appropriate scientific data, FDA has determined that you are required, to conduct [several studies about these possible Byetta 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.

P.S.  Excerpt from the Abstract for "Benefit-risk assessment of exenatide in the therapy of type 2 diabetes mellitus"  (Drug Saf, January 1, 2010):  "This review gives a benefit-risk assessment of exenatide."

(2/15/10)

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

 

A Review Of Recent Research On Issue Of Whether Januvia Can Cause Pancreatitis

Is Pancreatitis A Januvia Side Effect Or Is There An Increased Risk Of This Medical Condition Among Type 2 Diabetics Across All Treatments

(Posted by Tom Lamb at DrugInjuryWatch.com)

A few weeks back we reported that the FDA wants Merck to change the package insert, or label, for the diabetes drug Januvia (sitagliptin) so as to show an increased warning about the risk of developing pancreatitis.

Since then we have found some reports about relatively recent research about this issue of whether or not there is, in fact, any link between Januvia and pancreatitis.

We start with the early online publication of "Beneficial Endocrine but adverse Exocrine effects of Sitagliptin in the HIP rat model of Type 2 Diabetes, interactions with Metformin" in the medical journal Diabetes back in late April 2009.

From a press release which was issued by UCLA in connection that online publication, "Popular diabetes treatment could trigger pancreatitis, pancreatic cancer", we get these points:

• [R]esearchers from the Larry L. Hillblom Islet Research Center at UCLA found that sitagliptin, sold in pill form as Januvia, caused abnormalities in the pancreas that are recognized as risk factors for pancreatitis and, with time, pancreatic cancer in humans.

• Sitagliptin [i.e., Januvia] is a member of a new class of drugs that enhance the actions of the gut hormone known as glucagon-like peptide 1 (GLP-1), which has been shown to be effective in lowering blood sugar in people with Type 2 diabetes.

• The UCLA study suggests that there may indeed be a link between drugs that enhance the actions of GLP-1 and pancreatitis — by increasing the rate of formation of cells that line the pancreatic ducts.

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Moving on, we turn next to an October 1, 2009 article, "EASD: No Extra Risk of Acute Pancreatitis Seen with Exenatide", published online by MedPage Today.  While this article is principally about a presentation on a large study concerning the diabetes drug Byetta (exenatide), it contains some discussion that is relevant to the Januvia - pancreatitis issue.

To start, the underlying study is "Incidence of acute pancreatitis in exenatide initiators compared to other antidiabetic drug initiators: a retrospective, cohort study", by Gary Bloomgren, of Amylin Pharmaceuticals, et al, which can be found in the medical journal Diabetologia (2009; 52: S9).

From the October 1 MedPage Today article we set these items for thought:

• Two years ago, after reports of 30 cases of acute pancreatitis in patients taking exenatide, the FDA forced Amylin and its marketing partner, Eli Lilly, to add a caution to the drug's prescribing information. [See: "FDA Alerts Doctors About Diabetes Drug Byetta And Acute Pancreatitis Reports"]

• The issue of acute pancreatitis and drugs acting on the glucagon-like peptide-1 pathway gained new prominence last week when the FDA requested a caution on the drug sitagliptin (Januvia), after 88 cases were reported to the agency.

• However, the agency never determined that [Byetta] actually caused these effects, or that the incidence was any greater than might be expected in a diabetic population.

• Bloomgren cited one recent study that found the risk of acute pancreatitis among type 2 diabetics is about three times that of nondiabetic individuals, across all treatments.

• Exenatide [i.e., Byetta] is a synthetic GLP-1 mimic, while sitagliptin [i.e., Januvia] inhibits the dipeptidyl dipeptidase-4 (DPP-4) enzyme that degrades GLP-1, thereby making the peptide more available.

• Another DPP-4 inhibitor was reported here to have no association with acute pancreatitis in a review of controlled clinical trial data involving nearly 12,000 patients.

• The drug was vildagliptin, marketed in Europe as Galvus but not available in the U.S.

As you can see, the findings from these two recent medical studies about the diabetes drugs Januvia and Byetta are mixed as regards the issue of whether Januvia causes an increased risk of pancreatitis.

We welcome any and all feedback or guidance as regards this emerging drug safety issue concerning Januvia.  Please participate in the conversation by submitting a Comment, below.

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

October 2009: Yasmin And Yaz Multidistrict Litigation (MDL) Transfer Order For Injury And Death Cases Filed In Federal Court

MDL No. 2100 -- IN RE: Yasmin and Yaz (Drospirenone) Marketing and Sales Practices and Products Liability Litigation -- Assigned To Southern District of Illinois

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE: Our Focus Page on YAZ / Yasmin / Ocella has a complete collection of our articles about these birth control pills as well as selected news reports about YAZ, Yasmin, and Ocella.

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UPDATE: Visit the YAZ, Yasmin, and Ocella Information page at our Drug Injury Law web site for more recent developments regarding personal injury and wrongful death lawsuits that involve YAZ, Yasmin, and Ocella. 
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On October 1, 2009 the United States Judicial Panel on Multidistrict Litigation (JPML) filed its Transfer Order which serves to consolidate all Yaz and Yasmin personal injury and wrongful death cases filed in federal court in a U.S. Code Section 1407 Multidistrict Litigation, or MDL. 

MDL No. 2100 was assigned to the Southern District of Illinois according to this October 1 Transfer Order, with U.S. District Court Judge David R. Herndon presiding over these Yaz and Yasmin cases for "coordinated or consolidated pretrial proceedings".

In relevant part, from the JPML Yasmin and Yaz Transfer Order for MDL No. 2100:

On the basis of the papers filed and hearing session held, we find that these 32 actions involve common questions of fact, and that centralization under Section 1407 in the Southern District of Illinois will serve the convenience of the parties and witnesses and promote the just and efficient conduct of this litigation. All actions share factual questions relating to at least one of the drospirenone-containing oral contraceptives Yaz and Yasmin, which are manufactured by Bayer. Plaintiffs in the products liability actions challenge the safety of those oral contraceptives and bring claims for personal injuries or wrongful death stemming from use of the drugs....

Yaz and Yasmin, as well as the generic Ocella, have been associated with various serious side effects, including deep vein thrombosis (DVT), pulmonary embolism (PE), and ischemic stroke (CVA).

The official name given to MDL No. 2100 is IN RE: Yasmin and Yaz (Drospirenone) Marketing and Sales Practices and Products Liability Litigation.

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

FDA Wants Merck To Change Januvia Label With Increased Warning About Pancreatitis Risk

Is Januvia Similar To Byetta In Terms Of The So-Called Class Effect And Drug Injury Lawsuits Being Filed?

(Posted by Tom Lamb at DrugInjuryWatch.com)

On September 25, 2009 the FDA posted on its web site "Information for Healthcare Professionals - Acute pancreatitis and sitagliptin (marketed as Januvia and Janumet)".

From the Background and Data Summary part of that document:

FDA has completed a review of 88 cases of acute pancreatitis in patients using sitagliptin or sitagliptin/metformin. The cases were reported to FDA’s Adverse Event Reporting System (AERS) between October 2006 and February 2009. Hospitalization was reported in 58/88 (66%) of the patients, 4 of whom were admitted to the intensive care unit (ICU). Two cases of hemorrhagic or necrotizing pancreatitis were identified in the review and both required an extended stay in the hospital with medical management in the ICU. The most common adverse events reported in the 88 cases were abdominal pain, nausea and vomiting.

Additionally, the analysis found that 19 of the 88 reported cases (21%) of pancreatitis occurred within 30 days of starting sitagliptin or sitagliptin/metformin.  Furthermore, 47 of the 88 cases (53%) resolved once sitagliptin was discontinued. It is important to note that 45 cases (51%) were associated with at least one other risk factor for developing pancreatitis, such as diabetes, obesity, high cholesterol and/or high triglycerides.

Based on the temporal relationship of initiating sitagliptin or sitagliptin/metformin and development of acute pancreatitis in the reviewed cases, FDA believes there may be an association between these events....

Also on September 25 Merck & Co., Inc. issued a statement saying its own analysis of the post-marketing adverse experience reports data did not confirm an excess risk for developing acute pancreatitis.  From this "Merck Statement About JANUVIA™ (sitagliptin) and JANUMET™ (sitagliptin/metformin)" document:

The safety profile of JANUVIA and JANUMET has been established through an extensive clinical development program.  In addition, in the nearly three years of marketed use, more than 18 million total prescriptions have been dispensed for sitagliptin worldwide.

In the September 25 edition of MedPage Today there appears an article, "Sitagliptin Label to Reflect Pancreatitis Risk", which suggests that the increased risk of developing acute pancreatitis may be a so-called "class effect" for some of the newer diabetes drugs such as Januvia and Byetta:

Acute pancreatitis is beginning to look like a class effect for the newer drugs against diabetes that act through the glucagon-like peptide-1 pathway.

Two years ago, the FDA demanded a similar label change for the incretin mimetic exenatide (Byetta), after 30 pancreatitis cases were reported. (See FDA Wants Pancreatitis Caution Added to Exenatide (Byetta) Label)

Both exenatide and sitagliptin act through receptors for GLP-1 -- exenatide is a synthetic mimic of the peptide, while sitagliptin inhibits the dipeptidyl peptidase-4 enzyme that degrades GLP-1 in vivo.

According to a September 25, 2009 Wall Street Journal Health Blog post, "Another Diabetes Drug is Linked to Pancreas Inflammation", by Jacob Goldstein:

This is the second time in just over a year that a popular, new-ish diabetes drug has been linked to pancreatitis — the previous case was Byetta, which is co-marketed by Amylin and Eli Lilly. In that instance, several deaths were reported....

Amylin and Lilly have been named as defendants in Byetta cases brought by 110 plaintiffs in cases primarily related to pancreatitis, Amylin said in its most recent quarterly report. Byetta sales fell slightly in the first half of this year, to $332.8 million from $336 million in the year-earlier period.

As we reported two years ago, the FDA first issued an alert to doctors informing them reports of acute pancreatitis in patients taking Byetta back in October 2007.

We will have to wait to see whether this increased warning about pancreatitis for Januvia results in any drug injury lawsuits being filed against Merck.

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

Amylin And Lilly Hope A New Byetta Study Eases Concern Over Drug-Safety Issues

Nonetheless, Pending Byetta Label Change Will Probably Add Stronger Warnings About Severe Pancreatitis Side Effect

(Posted by Tom Lamb at DrugInjuryWatch.com)

As some may recall, in August 2008 the FDA issued a MedWatch alert about six cases of hemorrhagic pancreatitis and necrotizing pancreatitis associated with the diabetes medicine Byetta.

Just last week we reported the March 2009 Drug Safety Newsletter (UK) had an article that addressed the European reports of Byetta-induced pancreatitis and brought some attention to a different, emerging drug-safety issue for Byetta users, this one being kidney, or renal, failure.

Now, a March 13, 2009 Dow Jones news report, "Study Downplays Risk Of Amylin's Byetta, But Concerns Remain", brings us the latest developments concerning the issue of whether Byetta increases the risk of pancreatitis.  According to this report, the professional journal Current Medical Research and Opinion, recently published the findings of an analysis that used an insurance company database to show that neither Byetta nor Januvia -- a diabetes drug from Merck & Co. -- increased the risk for pancreatitis, which is an inflammation of the pancreas.  The report points out that this new analysis was funded by Amylin Pharmaceuticals Inc., the drug company that makes Byetta, and Eli Lilly & Co., which is Amylin's marketing partner for Byetta sales in the U.S.

This March 13 Dow Jones report then addresses the pending Byetta label change:

In August, news about the deaths led the FDA to start working with the companies to add stronger warnings about severe pancreatitis to the drug's label. The label revision is expected soon, but its delay also has put off FDA approval for Byetta's use as a monotherapy.

Because diabetes patients have a higher incidence of pancreatitis than the general population, Amylin has stressed that Byetta's use doesn't statistically increase the likelihood of pancreatitis complications or death.

The pending label changes show that FDA seems to differ in that opinion.

There was no word in this March 13 report regarding when the stronger warnings about pancreatitis side effects will be added to the Byetta label -- also known as the package insert -- nor whether the new warnings will be in the form of a bolded warning or, even, a so-called "black-box" warning.

We will be watching for an announcement from Amylin and the FDA -- seemingly in the not too distant future -- about the revised Byetta label.

Warnings About Byetta Associated With Risk Of Severe Pancreatitis And Renal Failure

March 2009 Drug Safety Update Newsletter (UK) Raises Emerging Safety Issue Of Kidney-Related Side Effects From Byetta Use

(Posted by Tom Lamb at DrugInjuryWatch.com)

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

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

(11/03/09)

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We last reported on Byetta (exenatide) in August 2008, when the FDA issued a MedWatch email alert about six new cases of hemorrhagic pancreatitis and necrotizing pancreatitis that had been reported to FDA since an October 2007 "Dear Doctor" letter about Byetta and acute pancreatitis was sent to doctors in the U.S.

The March 2009 Drug Safety Update newsletter -- from drug regulators in the United Kingdom (UK) -- included this article, "Exenatide (Byetta): risk of severe pancreatitis and renal failure".  Therein, we get some new information about two types of serious side effects associated with Byetta, pancreatitis and renal, or kidney, impairment.

We start with the discussion about pancreatitis from this March 2009 Drug Safety Update article about Byetta:

Up to February 2009, we have received six case reports of pancreatitis and a further three cases of acute pancreatitis in the UK.... 396 case reports of pancreatitis have been received worldwide in association with [Byetta (exenatide)] up to September 2008 (mostly from the USA). 80% of these reports were considered to be possibly related to exenatide, and in several cases there was evidence of positive rechallenge. Nine reports of necrotising or haemorrhagic pancreatitis have been received worldwide, two of which had a fatal outcome. After a Europe-wide review, product information for exenatide is being updated to contain further information about this risk.

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We move next to what this article has to say about renal impairment, which may be regarded as an emerging drug-safety issue with Byetta:

Case reports of renal impairment, including several UK reports of renal failure, have
been received in association with exenatide. Up to Jan 30, 2009 we have received seven case reports of acute renal failure in the UK. This medicine is not recommended for use in patients with end-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min). Clinical experience in patients with
moderate renal impairment is very limited.

Byetta is a diabetes drug co-marketed in the U.S. by Amylin Pharmaceuticals Inc., based in San Diego, and Eli Lilly & Co., of Indianapolis.

We will continue to watch for information about serious adverse reactions in patients using Byetta, especially reports about acute renal failure, or kidney failure, as well as reports of renal impairment causing worsened chronic renal failure.

If you have knowledge about these Byetta side effects that you would like to share, you can do so by submitting a Comment below or contacting me directly.