Drug Injury Watch

Actemra Side Effects: Pulmonary Hypertension, Interstitial Lung Disease, Pulmonary Alveolar Proteinosis

FDA Watch List Includes Actemra: Evaluating Regulatory Action Based On Possible Signs Of Serious Risk, New Safety Information

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In July 2018 the FDA issued this document, "Potential Signals of Serious Risks/New Safety Information Identified from the FDA Adverse Event Reporting System (FAERS): January - March 2018", which is sometimes generally referred to as the "FDA Watch List".

Included on this July 2018 FDA Watch List is the Actemra (tocilizumab) injection.

In particular, the FDA is evaluating the need for Actemra drug safety regulatory action due to adverse event reports involving these three medical conditions:

• pulmonary hypertension;
• interstitial lung disease; and,
• pulmonary alveolar proteinosis.

These pulmonary or lung conditions are listed under the heading "Potential Signal of a Serious Risk/New Safety Information" for Actemra on this FDA Watch List. Put otherwise, these pulmonary or lung conditions may be Actemra side effects.

__________________________________________________________________

Actemra

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

As background, Actemra is approved by the FDA for the treatment of several different medical conditions:

1. Moderately to severely active rheumatoid arthritis in adult patients who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs);
2. Giant Cell Arteritis (GCA) in adult patients;
3. Polyarticular Juvenile Idiopathic Arthritis (PJIA) in patients 2 years of age and older; and,
4. Systemic Juvenile Idiopathic Arthritis (SJIA) in patients 2 years of age and older.

The responsible drug company is Genentech, Inc.

We first wrote about Actemra back in June 2017 as regards another possible Actemra side effect: "Despite The High Number Of Actemra - Pancreatitis Cases Reported To FDA, No Warning Added To Drug Label".

We will continue to monitor the FDA for any regulatory action concerning Actemra regarding pulmonary hypertension, interstitial lung disease, and pulmonary alveolar proteinosis, as well as pancreatitis.

Of course, if you have any experiences or observations relevant to Actemra which you would like to share, you can post a Comment below or you can email me.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)

Viberzi - Pancreatitis Side Effects Can Develop At Any Time While Taking This IBS Drug, According To FDA Safety Warning

Severe Cases Of Pancreatitis And Sphincter Of Oddi Spasm Reported Even After Just The First Dose Of Viberzi, With Some Resulting In Patient Deaths

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In March 2017 this document was issued, "FDA Drug Safety Communication: FDA warns about increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder".

The following month, in April 2017, the drug company Allergan released a new Viberzi drug label, the details of which are set forth in this earlier article, "FDA Warns of Serious Pancreatitis Risk in Some Patients Taking Viberzi", on our Drug Safety Developments blog.

Viberzi (eluxadoline) is approved for use in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D).  Viberzi works by activating opioid receptors in the gut to decrease bowel contractions, which leads to less diarrhea. It can also help to ease stomach-area or abdomen pain and improve stool consistency.

According to the above-mentioned March 2017 FDA document:

• Hospitalizations related to pancreatitis, including deaths, have been reported with Viberzi in patients who do not have a gallbladder.
• Hospitalizations related to pancreatitis have also been reported in patients with a gallbladder.
• Symptoms of pancreatitis can occur after just one or two doses of Viberzi.

__________________________________________________________________

Viberzi

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

In more detail, from the Data Summary part of this Viberzi FDA Drug Safety Communication:

From May 2015, when Viberzi was first approved, through February 2017, FDA received reports of 120 serious cases of pancreatitis or death in the FDA Adverse Event Reporting System (FAERS) database. Seventy-six of these cases resulted in hospitalization, of which two patients died. Some cases of serious pancreatitis or death also reported sphincter of Oddi spasm (n=6) or abdominal pain (n=16).

Among the 84 cases that reported a time to onset of the adverse event, serious cases of pancreatitis or death occurred after one or two doses of Viberzi (n=48). Serious cases of pancreatitis also occurred subsequently with prolonged use (n=36).

Among the 68 cases that reported gallbladder status, 56 cases of pancreatitis or death occurred in patients who do not have a gallbladder. The majority of patients (n=44/56) received the currently recommended dosage of Viberzi (75 mg) for patients who do not have a gallbladder. Of the 56 cases in patients who do not have a gallbladder, 21 reported that the patient did not abuse alcohol and 35 did not report the patient’s alcohol use status.

As of February 2017, two deaths considered to be associated with Viberzi have been reported to FDA. Both deaths occurred in patients who did not have a gallbladder. One death was associated with pancreatitis and the other death was associated with sphincter of Oddi spasm. The case of death from pancreatitis was characterized by acute, severe abdominal pain, nausea, and vomiting within 60 minutes of taking a single dose of Viberzi. The case of death associated with sphincter of Oddi spasm reported severe abdominal pain and vomiting shortly after taking the first dose of Viberzi. Both patients were hospitalized for treatment. Notably, the patient who experienced pancreatitis died within 3 days of taking the initial Viberzi dose.

We are investigating possible Viberzi lawsuits against Allergan, the responsible drug company.

Of course, we will continue to monitor the medical literature and regulatory actions for developments concerning Viberzi side effects such as pancreatitis and sphincter of Oddi spasm.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb) 

Despite The High Number Of Actemra - Pancreatitis Cases Reported To FDA, No Warning Added To Drug Label

June 2017 Investigative Article Published By STAT Calls Into Question FDA Oversight After Drugs Are Approved By Agency

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Actemra (tocilizumab) is approved by the FDA for the treatment of several different medical conditions:

1.  Moderately to severely active rheumatoid arthritis in adult patients who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs);
2.  Giant Cell Arteritis (GCA) in adult patients;
3.  Polyarticular Juvenile Idiopathic Arthritis (PJIA) in patients 2 years of age and older; and,
4.  Systemic Juvenile Idiopathic Arthritis (SJIA) in patients 2 years of age and older.

An insightful article by reported Charles Piller, "Failure to warn: Hundreds died while taking an arthritis drug, but nobody alerted patients"(subscription required), published June 5, 2017 online by STAT, put the spotlight on some serious but little-known side effects associated with this medicine from Genentech, Inc.

From that recent article we get this rather alarming safety information about Actemra:

... STAT analyzed more than 500,000 side-effect reports on rheumatoid arthritis drugs, and found clear evidence that the risks of heart attacks, strokes, heart failure, and other conditions were as high or higher for Actemra patients than for patients taking some competing drugs.

Most of those medications warn about these risks on their labels. Actemra does not.

Consumers are barraged every day with drug ads accompanied by numbing lists of side effects, but STAT’s investigation shows that the risks to patients might be greater than they are led to believe. The Food and Drug Administration has received reports on 1,128 people who died after taking Actemra, and has reviewed its safety several times since it was approved. But the agency doesn’t have sophisticated tools to determine whether the drug was a culprit or a bystander in those deaths....

Experts who examined the data at STAT’s request said the FDA should immediately consider warnings for heart failure and pancreatitis — an inflammation of the pancreas that in its acute form can kill up to 50 percent of patients. They said the evidence that Actemra might increase the risk of heart attacks, strokes, and interstitial lung disease, a sometimes-fatal scarring of lung tissue, is less convincing but warrants further review.

__________________________________________________________________

Actemra

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

This focus on Actemra side effects and the lack of warnings about these adverse reactions shines the light on the apparent inadequate standards of post-marketing surveillance for drugs approved by the FDA.

On this critical issue, we get this commentary from the June 2017 STAT investigative report:

“We’ve done a very good job of making it easier to approve drugs, often based on very preliminary evidence. But we haven’t ramped up the standards of post-marketing surveillance to make sure that what’s been out there for several years is safe and effective,” said Dr. Vinay Prasad, an oncologist and medical ethicist at the Oregon Health and Science University. “The system is broken, and all the financial incentives are lined up to keep it broken.”...

When this STAT article takes a closer look at how the FDA has handled the apparent safety signal for pancreatitis, which is a potentially life-threatening medical condition, what is reported is rather alarming:

[In 2012], Roche asked the FDA to allow wider use of Actemra, for patients who have failed to get relief from only one other type of rheumatoid arthritis drug, rather than two. In its review, the agency found 258 cases of pancreatitis and 185 of interstitial lung disease among Actemra users in clinical trials, FAERS, and epidemiological data, according to a 2012 report.

An FDA clinical expert said that despite uncertainty in the pancreatitis data, a warning should be included on the drug label “given the potential seriousness of the event.” The expert wrote that interstitial lung disease should be monitored closely.

But Genentech convinced the agency not to label for pancreatitis, arguing that the illness, like interstitial lung disease, had occurred at expected rates for rheumatoid arthritis patients. Without providing specifics about the company’s arguments, the FDA report said there wasn’t “sufficient evidence to support causality and include information in the product label at this time.” The agency approved the broader use of Actemra.

We are interested in hearing about patients who were diagnosed with pancreatitis or some other serious side effect while using Actemra. You can do this by submitting a Comment below or contacting us privately by using the "Email Me" link found in the sidebar.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb) 

Iclusig: Leukemia Drug With Many Different Serious Side Effects Had More Warnings Added In November 2016

Black-Box Warning Now Includes Venous Thromboembolism As Well As Various Types Of Arterial Occlusions, And There Are More New Safety Issues

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Iclusig (ponatinib) is a kinase inhibitor approved by the FDA as a treatment for certain types of leukemia in adult patients.

On November 28, 2016 we learned about several alerting and wide-ranging safety labeling changes for Iclusig which were recently approved by the FDA Center for Drug Evaluation and Research (CDER).

The complete set of new side effects warnings can be seen on the FDA's Drug Safety Labeling Changes (SLC) page for Iclusig.

__________________________________________________________________

Iclusig

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

Here is overview of this rather significant and substantial November 2016 Iclusig Prescribing Information revision which was mandated by the FDA.

In the Boxed Warning section of the Iclusig drug label there was some additional safety information put in the pre-existing parts about (1) various types of arterial occlusions and (2) heart failure. Also, there is a new part entitled Venous Thromboembolism which addresses venous occlusive events.

Under the Warnings and Precautions section of the Iclusig drug label there were some additional facts and new information put in the following pre-existing parts, which are presented the order in which they were set forth on the FDA CDER SLC page for Iclusig:

5.1 Arterial Occlusion
5.10 Hemorrhage
5.11 Fluid Retention
5.12 Cardiac Arrhythmias
5.13 Myelosuppression
5.14 Tumor Lysis Syndrome
5.17 Embryo-Fetal Toxicity
5.2 Venous Thromboembolism
5.3 Heart Failure
5.4 Hepatotoxicity
5.5 Hypertension
5.6 Pancreatitis
5.8 Neuropathy
5.9 Ocular Toxicity

Further, under Warnings and Precaution, this new part now appears: 5.15 Reversible Posterior Leukoencephalopathy Syndrome (RPLS).

Finally as regards this limited Iclusig label changes overview, under the Adverse Reactions section of the Iclusig drug label there were some additional facts and new information put in this pre-existing part, 6.1 Clinical Trial Experience.

We point out there were more revisions mandated by the FDA in November 2016, which can be viewed on the FDA CDER SLC page for Iclusig.

We will continue to monitor the safety profile of the leukemia drug Iclusig and to report significant future developments.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb) 

Emerging Drug Safety Issue: Possible Increased Risk Of Pancreatic Cancer With Byetta, Januvia, And Victoza -- Little Is Known About Long-Term Effects

As "Pancreatitis Is On The Pathway Toward Pancreatic Cancer", Medical Studies Needed To Determine If GLP-1 Diabetes Medications Linked To Cancers Or Malignancies Involving Pancreas

(Posted by Tom Lamb at DrugInjuryWatch.com)

______________________________________________________________________________

UPDATE:  "Cancer of The Pancreas: Possible Side Effect For Diabetics Who Use Byetta, Januvia, Or Victoza?"  (Drug Injury Watch, 6/12/13)

(6/12/13)

______________________________________________________________________________

UPDATE: "European Medicines Agency investigates findings on pancreatic risks with GLP-1-based therapies for type 2 diabetes"  (EMA Press Release, 3/26/13)

(3/26/13)

______________________________________________________________________________

We last wrote about the relatively new and increasingly popular diabetes medications Byetta and Januvia back in November 2011: "Byetta And Januvia: More Debate About The Possible Increased Risk Of Pancreatitis, Pancreatic Cancer, And Thyroid Cancer".

And our last report about Victoza was in November 2012: "The Drug-Induced Pancreatitis Safety Problem That Hangs Around Victoza Gets Another Look".

Now, with a couple of developments in the first part of 2013, it seems that the pancreatic cancer risk is becoming the real drug safety issue as regards Byetta, Januvia, Victoza, and the other incretin mimetic drugs for type 2 diabetes.

In the last few weeks there has been an FDA alert about these diabetes drugs as well as a new significant medical journal article about a study concerning Byetta and Januvia which both have to do, in part, with the possible association between pancreatic cancer and the use of Victoza, Januvia, Byetta, etc.

First, from the March 14, 2013 "FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes":

The U.S. Food and Drug Administration (FDA) is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis, or inflammation of the pancreas, and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics.

Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

This March 2013 drug safety alert points out that "FDA has not previously communicated about the potential risk of pre-cancerous findings of the pancreas with incretin mimetics."

__________________________________________________________________

Diabetes Drugs Pancreatic Cancer 

Byetta / Victoza / Januvia

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

Diabetes drugs in the incretin mimetic class -- and their manufacturers --include:

Byetta, Bydureon  (Exenatide / injection) -- Amylin, which was acquired by Bristol Myers Squibb (BMS), which co-markets with Astra-Zeneca (AZ);

Victoza  (Liraglutide / injection) -- Novo Nordisk;

 

Januvia, Janumet, Janumet XR, Juvisync  (Sitagliptin / tablets) -- Merck;

 

Onglyza, Kombiglyze XR  (Saxagliptin / tablets) -- BMS / AZ;

Nesina, Kazano, Oseni  (Alogliptin / tablets) -- Takeda; and,

Tradjenta, Jentadueto  (Linagliptin / tablets) -- Boehringer Ingelheim

Next we move to the most recent medical article to raise the possible link between pancreatic cancer and these newer diabetes drugs, "Glucagonlike Peptide 1–Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus: A Population-Based Matched Case-Control Study", published online by JAMA Internal Medicine in late February 2013.

From a February 26 Medscape.com report about this JAMA medical journal article, "GLP-1 Mimetics Double Pancreatitis Risk in Diabetics":

But most important, said [Sonal Singh, MD, from Johns Hopkins University School of Medicine, Baltimore, Maryland], the study should raise a red flag because "pancreatitis is on the pathway toward pancreatic cancer." Writing in an accompanying commentary, Belinda Gier, PhD, and Peter Butler, MD, from the Larry L. Hillblom Islet Research Center, University of California, Los Angeles, agree, calling the issue of pancreatic cancer "the real crux of the controversy with regard to the safety of GLP-1–based treatment."

"At present, the GLP-1 class of drugs is heavily promoted (and prescribed) as having purported advantages that outweigh its risks. Singh and colleagues provide a timely reminder that, despite large numbers of underpowered studies claiming the contrary from marketing companies, little is yet known about long-term adverse effects of the GLP-1 class of drugs on the exocrine pancreas," they observe.

We will look for future announcements or drug safety alerts from FDA about the safety of Byetta, Januvia, and Victoza, as well as monitor the leading medical journals for long-term studies examining the development of pancreatic cancer in diabetic patients using these newer diabetes medications.

______________________________________________________________________________

DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)

The Drug-Induced Pancreatitis Safety Problem That Hangs Around Victoza Gets Another Look

The Relatively New Diabetes Medication Victoza From Novo Nordisk Was Only Approved By FDA In 2010

(Posted by Tom Lamb at DrugInjuryWatch.com)

In November 2012 The Annals of Pharmacotherapy published online before print this new medical journal article about Victoza, "Pancreatitis: A Potential Complication of Liraglutide?".

From the Abstract:

OBJECTIVE: To review the evidence surrounding a potential association between [Victoza (liraglutide)] and pancreatitis....

DATA SYNTHESIS: Eleven cases of pancreatitis have been reported in patients taking [Victoza (liraglutide)]. Seven were from the LEAD (Liraglutide Effect and Action in Diabetes) studies, 1 was reported in the extension of a clinical trial, and 1 was in an unpublished obesity trial. Two were published postmarketing case reports. Nine of the cases reported were diagnosed as acute pancreatitis, while 2 were classified as chronic pancreatitis. The mean age of the patients was 57.5 years and mean body mass index was 33.92 kg/m2. Six of the 11 cases occurred in male patients. Nine of the patients were white and 1 was African American. In 7 of the cases, onset occurred at [Victoza (liraglutide)] doses at or above 1.8 mg daily. Common comorbidities included history of pancreatitis, cholelithiasis, and diabetes. One case was fatal.

Victoza is one of only two GLP-1 agonists currently on the market, the other being Byetta (exenatide). Fundamentally, these GLP-1 agonists exert most of their effects by increasing insulin excreted by the pancreas and slowing down the digestion of food. In turn, the increase in insulin is glucose dependent therefore limiting the risk for hypoglycemia compared to other type 2 diabetic medications.

You can watch a short medical animation video, "GLP-1 and Type 2 Diabetes" (approx. 1.5 mins. on MedPage Today web site), to view the role of GLP-1 in the body.

The drug safety controversy which surrounds Victoza and Byetta, both, includes the issue of whether it is the diabetes drug or the diabetes which causes pancreas disease.

For more about the adverse reactions associated with Victoza, see "The Victoza - Pancreatitis Issue: Some Related Developments From April 2011 To April 2012".

We will continue to monitor the safety profile of the increasingly-popular diabetes drug Victoza and report future significant developments here.

______________________________________________________________________________

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

Drug Injury Case Evaluation - Free & Confidential

The Victoza - Pancreatitis Issue: Some Related Developments From April 2011 To April 2012

A Drug Safety Controversy Continues: Whether It Is The Diabetes Drug Or The Diabetes Which Causes Pancreas Disease

(Posted by Tom Lamb at DrugInjuryWatch.com)

As regards the possible association between Victoza and pancreatitis as a side effect of this diabetes drug from Novo Nordisk, there have been quite a few assorted developments during the period April 2011 to April 2012. In order to get those all out in front of us, and so as to see how this drug safety issue emerged and where it may be headed going forward, we offer the following time-line of sorts.

 
April 2010

"Acute Pancreatitis Associated with Liraglutide", The Annals of Pharmacotherapy.

"Medical Journal Withdraws Article About Januvia And Byetta After It Gets Letters From Two Drug Companies", Drug Injury Watch.

According to a news item published April 11, 2011 by The British Medical Journal (BMJ), letters written by Merck and Novo Nordisk to Anil Rustgi, the editor-in-chief of Gastroenterology, resulted in that journal withdrawing an article which it had posted on its website about how Januvia (sitagliptin) and Byetta (exenatide) have been associated with an increased risk of pancreatitis as well as several cancers.

From this April 2011 BMJ piece, "Journal withdraws article after complaints from drug manufacturers"....

P.S.  The diabetes drug Januvia is marketed by Merck.

Byetta is marketed by Amylin Pharmaceuticals and Eli Lilly.

Novo Nordisk has a relatively new diabetes drug, Victoza (approved by FDA in 2010), which is in the same class of drugs as Byetta.  Victoza (liraglutide) has been linked to pancreatitis, also.

 

June 2011

"FDA Warns of Serious Risks Associated With [Victoza (Liraglutide)]", Medscape.

Victoza (liraglutide [rDNA origin]) Injection: REMS - Risk of Thyroid C-cell Tumors, Acute Pancreatitis, FDA.

Dear Healthcare Professional Letter, Novo Nordisk.

"Acute Pancreatitis Case Associated With Victoza Use, Similar To Byetta And Januvia Case Reports", Drug Injury Watch.

March 2012

"Liraglutide-associated acute pancreatitis.", American Journal of Health-System Pharmacy.

April 2012

"Public Citizen to FDA: Pull Diabetes Drug Victoza From Market Immediately", Press Release issued by Public Citizen.

Petition to Ban Diabetes Drug Liraglutide (Victoza), Letter to FDA from Public Citizen.

"Novo Nordisk rejects diabetes drug Victoza complaint", Reuters

With Novo Nordisk and Public Citizen engaged in this public battle, now, about a year after the Victoza and pancreatitis link first received some profile, I am sure there is much more to come on all fronts, including the FDA, as we go forward.  Of course, we will be watching....

______________________________________________________________________________

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

Drug Injury Case Evaluation - Free & Confidential

Byetta And Januvia: More Debate About The Possible Increased Risk Of Pancreatitis, Pancreatic Cancer, And Thyroid Cancer

Level Of Concern About These Incretin Therapies For Diabetes Was Raised By Gastroenterology Medical Journal Article

(Posted by Tom Lamb at DrugInjuryWatch.com)

In September 2011, at the 47th European Association for the Study of Diabetes (EASD) Annual Meeting, Diabetes Medical Congress, in Lisbon, Portugal, there was a debate about whether there is an increased risk of pancreatitis, pancreatic cancer, and thyroid cancer for patients who use Januvia (sitagliptin) or Byetta (exenatide), which are incretin therapies for diabetes.

On one side was Peter Butler, MD, of the University of California Los Angeles (UCLA), who found higher rates of pancreatitis and pancreatic cancer in patients.  Those findings are the subject of a paper by Dr. Butler and his colleagues, "Byetta and Januvia: Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies" which was published by the medical journal Gastroenterology-- initially online back in February 2011 and later in the July 2011 print edition.

On the other side of this drug safety debate was Michael Nauck, MD, of the Diabetes Center Bad Lauterberg in Harz, Germany.  Dr. Nauck pointed out that those findings set forth in the Gastroenterology article were based on an analysis of data from the FDA's Adverse Event Reporting System (AERS).

A September 18, 2011 MedPage Today article, "EASD: Debate Brings Incretin Risks to Forefront", did a good job of presenting the main points made by Dr. Butler and Dr. Nauck:

(1)  In their paper, Butler and colleagues reviewed AERS data between 2004 and 2009, and found a six-fold increased likelihood of reported pancreatitis with [Byetta] or [Januvia] compared with control reports.

They also found a significant threefold greater likelihood of reported pancreatic cancer with either drug, as well as a four-fold greater likelihood of reported thyroid cancer with [Byetta].

(2)  "There will be a lot of reporting bias," Nauck said during an interview with MedPage Today. "If there is public awareness for certain things, then physicians and others will feel more inclined to report such events to the database."...

But given the limitations of the FDA data set, researchers said data from other sources still need to be analyzed before drawing any conclusions about the potential side effects of the drug class.

Nauck said randomized controlled trials would be a near-impossibility because the number of patients needed in each arm would have to be exceedingly large in order to have the power to detect true risk, since pancreatitis and pancreatic cancers are so rare.

Instead, researchers will need to assess large databases, potentially individual registries or combined ones, Nauck said.

(3)  Butler echoed those sentiments. "It is important from these studies that we look carefully at the possibility," of the link between the incretin therapies and these side effects.

"This does not establish that pancreatitis is caused by GLP-1's," he said. "It simply raises the level of concern, and appropriate prospective studies are needed."

__________________________________________________________________

Diabetes Drugs Pancreatic Cancer 

Byetta / Victoza / Januvia

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

Back in June 2010 a different observational study of medical claims data done by the pharmacy benefit manager Medco Health Solutions in association with the University of Texas Southwestern Medical School found that Januvia and Byetta did not increase the risk of developing pancreatitis compared with other diabetes drugs.

From a June 27, 2010 Reuters report by Lewis Krauskopf about that earlier study, "No pancreatitis risk seen in Byetta, Januvia drugs-study":

Dr. Merri Pendergrass, who conducted the study, acknowledged that it was an observational study of data, as opposed to the gold standard of a randomized clinical trial.

But the results were reassuring about use of Byetta and Januvia, said Pendergrass, national practice leader of Medco’s therapeutic resource center for diabetes.

“There does not seem to be a signal of increased risk,” Pendergrass said from Orlando, Florida, where the study was being presented at the American Diabetes Association scientific sessions in Orlando. “There’s no smoke here, so that’s reassuring.”...

For the group taking various diabetic medicines, there were 5.72 cases of acute pancreatitis for every 1,000 patient years. It was 5.69 for Byetta, and 5.54 for Januvia.

Furthermore, according to this June 2010 Reuters report:

The study also found that diabetics generally are at increased risk of acute pancreatitis, compared with non-diabetics, which the study’s author said confirmed previous research, although the risk remains very low.

In the end, one thing that can be said with certainty is that the safety profiles of Byetta and Januvia remain a subject deserving of more medical research.  We will continue to monitor the situation and report significant developments here.

______________________________________________________________________________

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

Drug Injury Case Evaluation - Free & Confidential

Acute Pancreatitis Case Associated With Victoza Use, Similar To Byetta And Januvia Case Reports

Drug Safety Issue Controversy Continues: True Serious Side Effect, Or Attributable To Type 2 Diabetes Condition

(Posted by Tom Lamb at DrugInjuryWatch.com)

______________________________________________________________________________

UPDATE:  Victoza (liraglutide [rDNA origin]) Injection: REMS - Risk of Thyroid C-cell Tumors, Acute Pancreatitis   [Posted 06/13/2011]

AUDIENCE: Endocrinology, Family Practice

ISSUE: Novo Nordisk reminded healthcare professionals of important safety information about Victoza (liraglutide [rDNA origin]) injection required in a Risk Evaluation and Mitigation Strategy (REMS). The letter is being sent because a recent assessment of healthcare providers showed that some primary care providers are not fully aware of the serious risks associated with the use of Victoza.   (Read more)

______________________________________________________________________________

Novo Nordisk has a relatively new diabetes drug, Victoza (liraglutide), approved by FDA in 2010, which has been linked to pancreatitis recently.  From the Abstract for this medical journal article, "Acute Pancreatitis Associated with Liraglutide", The Annals of Pharmacotherapy, April 2011, we get these basic facts:

OBJECTIVE: To report what is, to our knowledge, the first postmarketing case of acute pancreatitis associated with [Victoza (liraglutide)].

CASE SUMMARY: A 60-year-old female with type 2 diabetes presented with a 16-hour history of mid-epigastric pain 3 weeks after treatment was changed from exenatide 10 μg twice daily, which she had taken for 4 years, to liraglutide 1.8 mg daily. Her serum lipase level was elevated (478 units/L) at admission, and other laboratory values were within normal limits. Liraglutide was discontinued at admission. Standard therapy for pancreatitis resulted in symptom resolution and a significant decrease in serum lipase (131 units/L) by hospital day 4; she was discharged on hospital day 5.

DISCUSSION: Based on the Naranjo scale, this case represents a probable adverse drug reaction. Eight cases of pancreatitis were observed in liraglutide-treated patients in premarketing clinical trials. Extensive literature describing exenatide-related pancreatitis and premarketing reports of liraglutide-related pancreatitis, along with the temporal relationship between the initiation of liraglutide and the onset of this patient's symptoms, suggest that the episode of pancreatitis was induced by liraglutide.

CONCLUSIONS: Liraglutide should be used cautiously in patients with a history of pancreatitis, and clinicians should have a high index of suspicion for this rare, but potentially serious, adverse effect.

Victoza is in the same class of drugs as Byetta (marketed by Amylin Pharmaceuticals and Eli Lilly) and Januvia (marketed by Merck).

As regards the possible link between Byetta and pancreatitis, our first articles were written back in 2008:

• More Information About Reports Of Byetta Use Being Linked To Acute Pancreatitis
• August 2008: Byetta Associated With Hemorrhagic Pancreatitis And Necrotizing Pancreatitis

___________________________________________________________________

 

Free Byetta Case Evaluation 

Strictly Confidential, No Obligation.

___________________________________________________________________________

We have been monitoring the pancreatitis drug safety issue for Januvia since 2009, when we wrote these two articles:

• FDA Wants Merck To Change Januvia Label With Increased Warning About Pancreatitis Risk
• A Review Of Recent Research On Issue Of Whether Januvia Can Cause Pancreatitis

This June 1, 2011 news report headline, "Diabetics show higher risk of pancreas disease", states succinctly why the apparent association between pancreatitis and Victoza -- as well as Byetta and Januvia -- has been questioned by some.  From that Reuters Health report:

People with type 2 diabetes may have a heightened risk of a painful condition known as acute pancreatitis, but those odds are curbed in people on diabetes drugs, a new study suggests....

The findings back up earlier studies that have linked type 2 diabetes to acute pancreatitis, according to senior researcher Dr. Pei-Chun Chen, of China Medical University College of Public Health in Taiwan.

But they also add something new, Chen told Reuters Health in an email.

Among people with diabetes, the study found, those on diabetes medications had a lower risk of acute pancreatitis. And the more medications they were using, the lower the risk.

The potential benefit was seen with a range of diabetes drugs -- including metformin (Glucophage); sulfonylureas, which include drugs like glimepiride (Amaryl) and glipizide (Glucotrol); thiazolidinediones, including rosiglitazone (Avandia) and pioglitazone (Actos); and alpha-glucosidase inhibitors, like miglitol (Glyset) and acarbose (Precose).

In recent years, certain other diabetes drugs -- including the brand names Januvia and Byetta -- have been linked to cases of pancreatitis, and warnings are included in the drugs' prescribing information.

However, it has not been clear whether the drugs themselves cause the pancreas inflammation. The medications were not specifically analyzed in the current study.

Chen said that these latest findings cannot prove that any diabetes medication protects against acute pancreatitis. Nor do they prove that diabetes, itself, causes pancreatitis in some people, the researcher said.

This latest study about the development of pancreatitis in patients with type 2 diabetes -- which seems to raise more questions than it does to provide answers -- is "Risk of Acute Pancreatitis in Type 2 Diabetes and Risk Reduction on Anti-Diabetic Drugs: A Population-Based Cohort Study in Taiwan", published online May 17, 2011 by The American Journal of Gastroenterology.

We will continue to monitor this (still) emerging safety issue concerning pancreatitis and Victoza (as well as Byetta and Januvia).

If you have any knowledge about a case of pancreatitis in a patient using Victoza, Byetta, or Januvia, you may want to share what you know with others by leaving a Comment, below.

______________________________________________________________________________

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

Drug Injury Case Evaluation - Free & Confidential

Medical Journal Withdraws Article About Januvia And Byetta After It Gets Letters From Two Drug Companies

April 2011 Edition Of BMJ Breaks News And Provides Insight From One Who Saw An Increased Risk Of Pancreatitis 

(Posted by Tom Lamb at DrugInjuryWatch.com)

According to a news item published April 11, 2011 by The British Medical Journal (BMJ), letters written by Merck and Novo Nordisk to Anil Rustgi, the editor-in-chief of Gastroenterology, resulted in that journal withdrawing an article which it had posted on its website about how Januvia (sitagliptin) and Byetta (exenatide) have been associated with an increased risk of pancreatitis as well as several cancers.

From this April 2011 BMJ piece, "Journal withdraws article after complaints from drug manufacturers":

In the disputed paper the team responsible... used the FDA database of adverse events from 2004 to 2009 to compare the number of cases of disease reported by users of the two drugs with the number reported by users of four other antidiabetes drugs.

They concluded that the risk of pancreatitis was increased by 6.8 times in users of sitagliptin (95% confidence interval 4.7 to 10.2) and by 11.8 times (8.5 to 16.6) in users of exenatide. For pancreatic cancer the risk ratios were 2.4 and 2.0, respectively, and for thyroid cancer 3.4 and 7.6....

___________________________________________________________________

 

Free Byetta Case Evaluation 

Strictly Confidential, No Obligation.

___________________________________________________________________________

The "disputed paper" was put on the Gastroenterlogy journal's web site on or about February 21, 2011.  About two weeks later, the two drug companies took their actions which resulted in getting this article removed:

The companies wrote letters to Anil Rustgi, the journal’s editor in chief, after the paper appeared online. They expressed concern that the analysis, which used data derived from the US Food and Drug Administration’s adverse event reporting system, reached conclusions that could not be justified. Merck warned that the paper could have a negative effect on the care of patients, while Novo Nordisk claimed that it could spark an unnecessary health scare.

One of the authors of the paper, Peter Butler, of the David Geffen School of Medicine at the University of California at Los Angeles (UCLA), said that the drug companies wanted the paper deleted. Gastroenterology’s website initially recorded the paper as “retracted,” which might imply that the authors themselves had chosen to remove it. This was not the case, Dr Butler said: the decision had been taken by the editors. The journal has since changed the paper’s status from “retracted” to “withdrawn.”... 

Dr Butler said he was pleased that the two drug companies had not achieved “complete deletion” of the paper.

We have been monitoring developments concerning the pancreatitis issue for Januvia since 2009, when we wrote these two articles:

• FDA Wants Merck To Change Januvia Label With Increased Warning About Pancreatitis Risk
• A Review Of Recent Research On Issue Of Whether Januvia Can Cause Pancreatitis
  

As for the link between Byetta and pancreatitis, our first articles were written back in 2008:

• More Information About Reports Of Byetta Use Being Linked To Acute Pancreatitis
• August 2008: Byetta Associated With Hemorrhagic Pancreatitis And Necrotizing Pancreatitis

We will continue to watch for reports of pancreatitis that may have been caused by Januvia or Byetta.

If you are aware of such a case, you may want to share your information by leaving a Comment below or, if interested in a possible legal case, by you can submit a Byetta Case Evalution form.

 

P.S.  The diabetes drug Januvia is marketed by Merck.

Byetta is marketed by Amylin Pharmaceuticals and Eli Lilly.

Novo Nordisk has a relatively new diabetes drug, Victoza (approved by FDA in 2010), which is in the same class of drugs as Byetta.  Victoza (liraglutide) has been linked to pancreatitis, also.  See "Acute Pancreatitis Associated with Liraglutide", The Annals of Pharmacotherapy, April 2011.

(5/3/11)

______________________________________________________________________________

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

Drug Injury Case Evaluation - Free & Confidential