August 2008

Unlike the previous Duragesic and Fentanyl recalls of millions of patches, this one covers only one lot of one size patch:

Watson Pharmaceuticals has recalled one lot of its 75-mcg/hour fentanyl transdermal system in the U.S. because a small number of patches were leaking a gel form of the pain medicine.

The recalled patches are from lot No. 92461850 with an Aug. 31, 2009, expiration date. They were shipped between Jan. 30 and March 19. No other strengths or lots were affected, and the company does not anticipate any product shortages as a result of the recall, according to its statement.

Source: Watson Voluntarily Recalls Pain Patch Lot

At this time, I don’t know what the specific manufacturing defect in this lot was, or how it was discovered.  But as always, if you think you have a defective Fentanyl or Duragesic patch, do not touch it with your bare hands.  And do not wash your hands with soap if you do touch it. 

I have several pictures of Fentanyl patches, but not of the Watson patches.  You can view my existing photos of Fentanyl here.  If you have any pictures of Watson patches, please send them my way. 

I saw that the press have tracked down the name of the person who can answer the important questions about the Digitek recall, but he seems to be ducking the press:

Numerous attempts to reach someone with Actavis Totowa were unsuccessful by press time.

A receptionist, who declined to identify herself, said the only person who could answer questions about Digitek was Ajordis Arnadottir, the company’s media representative. But repeated attempts to reach Arnadottir were unsuccessful as well.

Source: Memphis Daily News – Local Attorney Reviews Digitek Recall Cases

I’ve gleaned the following information from filings with the FDA and documents released by Actavis to pharmacies:

  • The Digitek tablets covered by the recall were distributed between March of 2006 and April of 2008.  We do not know what the manufacture dates of these tablets are.
  • 166 Lots are covered by the recall.  We do not know how many tablets are in each lot.
  • The recall covers all Digitek tablets.

It’s simply unconscionable that Actavis is being so tight-lipped about this recall when one considers that thousands of lives are at stake.  Thankfully, we have a strong civil justice system and one of the Digitek lawsuits will likely reveal the answers to these and other important questions that Actavis won’t answer voluntarily.

Here’s some more information about Digitek / Digoxin to consider.

A Brief History of Digitek

In 1779, the English doctor William Withering discovered that the Foxglove plant could be used to treat congestive heart failure, and in 1785 he published An Account of the Foxglove and some of its Medical Uses.   Foxglove is the common name for the roughly twenty plants in the Digitalis family.

In 1930, a scientist named Sydney Smith at the Wellcome Chemical Works in Dartford, England was working with the plant Digitalis Lanata and extracted a substance he dubbed Digoxin.  Digoxin is the active ingredient in several heart medications, including Digitek.  Wellcome (now GlaxoSmithKline) brought the first Digoxin product to market in the United States in 1934.

While there was an FDA in 1934, it was nothing like the FDA we have today.  The Federal Food, Drug, and Cosmetic Act that granted the FDA many of its powers wasn’t passed until 1938.  And it wasn’t until 1962 that amendments were passed that allowed the FDA to make pharmaceuticals prove drugs were safe and effective before they could be sold to the general public.

After the 1962 amendments were passed, the FDA began the difficult task of ensuring that existing drugs – many of which had been sold for decades – were also safe and effective.  By the late 1960’s, the FDA was convinced that the drug Digoxin was safe and effective if manufactured properly.  Drug manufacturers in the 1960’s had a very hard time ensuring the Digoxin pills they produced were of appropriate strength.  In April of 1970, the FDA began working with pharmaceuticals to test individual lots of Digoxin tablets.  Between April and November of 1970, there were 79 recalls of Digoxin tablets.  Deja vu, anyone?

In 1974, the FDA enacted a series of regulations designed to ensure the safety of Digoxin tablets.  Even with those regulations in place, there were still safety problems with Digoxin; the problems continued into the 1990’s.  By that time, the FDA believed the only solution to the Digoxin safety problem was to treat Digoxin as a new drug, and require pharmaceuticals to submit new applications to the FDA.  Treating Digoxin tablets as a new drug would force pharmaceuticals to run tests and studies that didn’t even exist when Digoxin first came to market in 1934.

The FDA went to GSK (who merged with Wellcome, the original inventor of Digoxin) and asked them to submit a New Drug Application for a Digoxin product.  in 1993, GSK submitted an application for a Digoxin drug it called Lanoxin.  The drug was approved in 1997.  Lanoxin was approved as a new, brand-name drug, which means that other pharmaceuticals could choose to make a generic form of Lanoxin.

One such manufacturer was Amide Pharmaceuticals, who asked the FDA to approve a generic drug it called Digitek.  (Actavis bought Amide Pharmaceuticals in May of 2005.)  The FDA approved Digitek on December 23rd of 1999 and Amide began manufacturing Digitek in Little Falls, New Jersey.  Here’s an overhead shot of the factory, courtesy of Google Maps:


In February of 2001, Amide and Bertek (a distributor of Digitek and the source of the “B” stamped on Digitek tablets) wrote to the FDA urging it to eliminate the 1974 Digitek regulations.  Amide wanted the FDA to require all Digoxin manufacturers to submit the same applications to the FDA that it did to bring Digitek on the market.  In this excerpt of the letter, Amide specifically acknowledges the difficulty in manufacturing Digoxin tablets:


Just seven years later, Actavis would recall every drug made in the Little Falls plant  – including Digitek – because  it couldn’t maintain consistency between product batches.

The FDA finds Serious Problems at the Little Falls Plant in 2006

The FDA inspected the Little Falls plant in January & February of 2006 and issued a warning letter to Actavis on August 15th of 2006.  (Yes, the warning letter was issued six months after the inspection.)  The FDA found several problems which they determined were “serious:”

  • Pharmaceuticals must tell the FDA about any patients who experience an adverse event while taking any drugs the pharmaceutical manufactures.  Actavis (and Amide before it) failed to report at least six  adverse events related to several drugs, including Digitek.
  • Actavis didn’t have a proper system to monitor adverse events, and it wasn’t properly following up on the adverse events it learned about.
  • Actavis never filed the “periodic safety report” it was legally obligated to file with the FDA
  • Actavis was also manufacturing drugs that had not been approved by the FDA.  Amide had a similar violation some years earlier.

The FDA warned Actavis that, “The specific violations noted in this letter are serious and may be symptomatic of underlying problems.”  (Emphasis added.)

The online archive of FDA warning letters only goes back to 11/1996, so a search for Amide leaves out the 13 years it operated prior to 1996.  That said, a search of the archive only turns up one warning letter for Amide: In 2002, they were manufacturing an unapproved extended-release version of an expectorant.  In other words, the Little Falls plant hadn’t failed any inspections since at least 1996.  So what happened between May of 2005 when Actavis bought the plant and the January 2006 inspection?  Did too many people quit or get fired for Actavis to run the plant safely?

Considering the first failed inspection took place just months after Actavis bought Amide, it’s possible that the FDA missed problems in prior inspections and that Actavis merely inherited existing problems.  But even if that’s the case, Actavis knew that there were serious problems at the Little Falls plant but didn’t correct them.

The Problems Had Worsened By July of 2006

The FDA inspected the Little Falls plant again in July and August of 2006, and things had gotten decidedly worse.  Now, Actavis wasn’t just failing to report adverse events, it was failing to follow “Good Manufacturing Practice” regulations.   Here’s what Actavis has to say about Good Manufacturing Practices:  “Good Manufacturing Practice (GMP) is a regulatory gui
deline imposed on all manufa
cturers of pharmaceuticals to ensure that finished products have the identity, strength, quality and purity they are required to have.”

Here are some of the most disturbing parts of the warning letter the FDA sent Actavis in February of 2007:

  • “Significant deficiencies were found in the operations of your firm’s quality control unit, and as a result there is no assurance that many drug products manufactured and released into interstate commerce by your firm have the identity, strength, quality and purity that they purport to possess.”
  • “Our investigators observed numerous instances where your firm’s quality control unit either ignored or failed to recognize that some tablets that did not meet in-process specifications.”
  • “[W]e are concerned about the quality of drug products that have been released from your facility under the serious lack of cGMP controls found during the inspection. Your  response provides no assurance that the records and conditions of manufacture and testing of each such lot of drug products released and marketed by your firm will be evaluated to assure that the released drug products have their appropriate identity, strength, quality, and purity. “

Remember, Amide had previously told the FDA that it’s very difficult to maintain consistency in the manufacture of Digoxin tablets.  Yet the FDA found “significant deficiencies” in the quality control unit and the manufacturing unit.  These violations are never excusable at any facility, but they’re even worse when the facility makes a highly toxic drug like Digitek that is so easy to manufacture incorrectly.

Why Did It Take So Long To Recall Digitek?

On April 25th of 2008, over a year after receiving the February letter, Actavis issued a recall notice for all of its Digitek tablets.  A remarkably tight-lipped recall notice; the notice doesn’t indicate how many tablets are being recalled or a time range for the recalled tablets.  You can read the actual recall notice here.

I dug a little deeper, and found a copy of the recall notice  that was sent to pharmacies at the North Carolina Board of Pharmacy.  According to that notice, the recall applies to Digitek that was distributed between March of 2006 and April of 2008.  Even still, that notice doesn’t give us any idea of how many tablets were distributed.  Normally, a pharmaceutical company tells the FDA the quantity being recalled.  But in the latest Enforcement Report, the FDA only states that there are 166 Lots being recalled.

An even more important question than how many tablets are being recalled is why did Actavis wait so long to recall them?  In August of 2006, the FDA told Actavis that it had serious problems at the plant.  Just six months later, the FDA told Actavis what it likely already knew: Serious deficiencies in its manufacturing and quality control process were putting lives at risk.  Actavis should have been recalling drugs by April of 2007, not April of 2008.

What’s even worse is that despite being thoroughly warned by the FDA in February of 2007, Actavis continued manufacturing defective drugs for another year before initiating the recall.  After receiving that letter, shouldn’t Actavis have stopped manufacturing potentially deadly drugs and fixed the problems?

One has to wonder just how bad the “significant deficiencies” that the FDA found in Actavis’ quality control unit when one considers what the defect was: Some Digitek tablets were twice as thick as they should be.  What kind of quality control program can’t spot pills coming out twice as thick as they should?  The FDA found that the quality control department was ignoring some defects.  Surely they couldn’t have been so incompetent as to ignore a double-thick tablet, could they?

Actavis Recalls “All” Drugs Made at Little Falls

On August 2nd of 2008, Actavis issued a recall of “all drug products manufactured at its Little Falls, New Jersey facility.”  There are two interesting facts about this recall.  First, it was triggered after an FDA inspection that presumably didn’t go well.  Second, the recall notice states that it applies to “all” drugs made at the Little Falls factory, and enumerates them.  One drug is missing from that list: Digitek.  Did Actavis cease manufacturing Digitek?  Did it move production to a safer factory?  Or is Digitek still being produced and distributed at Little Falls?

Four days after the recall, Actavis’ CEO stepped down for purportedly unrelated reasons.

How Could This Have Been Prevented?

It’s too early to put attribute a death toll to the defective Digitek, but I’m aware of several individuals who were taking Digitek pills subject to the recall and died from Digitalis Toxicity.   Countless others have likely been hospitalized and suffered other injuries because of Actavis’ incompetence and a weak FDA.

The warning letters the FDA sounded harsh but amounted to not much more than a dog with a big bark and a little bite.  Where are the multimillion dollar fines?  Where are the criminal prosecutions?  How many strikes does a pharmaceutical get before they’re out?

Thankfully, preemption won’t prevent injured individuals from suing Actavis because their injuries were caused by manufacturing defects, and not design defects.  But the Digitek recall shows us that the FDA either cannot or will not keep us safe from pharmaceuticals who place profits above all else.

Watson Pharmaceuticals has announced a recall of all 75mcg Fentanyl patches from lot number 92461850.  These patches are being recalled for the same reason many of Johnson & Johnson’s Duragesic patches were recalled: Manufacturing defects that could lead to leakage.  Here’s an excerpt from Watson’s press release:

CORONA, CA – August 8, 2008 – Watson Pharmaceuticals, Inc., a leading specialty pharmaceutical company, announced today that one lot of 75 mcg/hr Fentanyl Transdermal System patches sold in the United States is being voluntarily recalled from wholesalers and pharmacies. The recalled patches are from Lot Number 92461850, have expiration dates of August 31, 2009 and were manufactured by Watson Laboratories, Inc. The affected lot of Fentanyl Transdermal System patches was shipped to customers between January 30, 2008 and March 19, 2008. No other strengths or lots were affected and the Company does not anticipate any product shortages as a result of this recall. The Company has notified the U.S. Food and Drug Administration (FDA) of the recall.

Source: Watson Pharmaceuticals, Inc. | Investor Relations | Press Release

If you have any Fentanyl patches from this lot, you can call 888-667-1508, Mon. through Fri. from 8:00 a.m.-5:00 p.m. Eastern Time, for instructions on how to return the patches.  Watson recommends flushing any patches down the toilet that have already begun to leak, and strongly cautions against touching leaking patches with your bare hands.  If you accidentally touch a leaking patch, wash your hands with water onlyDO NOT USE SOAP as this increases the likelihood you will be injured by the patch.

Many people have already died as a result of leaking Fentanyl patches, and I hope no one dies or is injured from these patches.  Better still, I wish all the manufacturers of Fentanyl patches would switch over to what’s called a Matrix design like they sell in Europe.  Those patches cost a little bit more to manufacture, but they don’t leak and kill people like these patches do.

I’m excited to see that a company has a promising treatment for brain tumors, but I’m worried that they’re using Gadolinium since that drug can cause Nephrogenic Systemic Fibrosis  (NSF) in people with renal problems:

"Enrollment in two Phase 2 trials with motexafin gadolinium for adult brain tumors and childhood gliomas also continues under sponsorship of the National Cancer Institute and we are planning to conduct a pivotal Phase 3 trial with motexafin gadolinium in patients with brain metastases from lung cancer. Our strategy is to build value in these multiple products as we progress with their development."

Source: Pharmacyclics, Inc. Reports Fourth Quarter and Fiscal 2008 Financial Results

Let’s hope that this company properly screens test subjects.

Here is some more information about Gadolinium and Nephrogenic Systemic Fibrosis for you to consider.

I came across an interview with a woman whose partner likely died from defective Digitek, and the following passage jumped out at me:

Then I found out that the drug maker knew and did nothing about it. That is beyond words. When I spoke to Jackie’s doctor we both agreed that something should be done about this. This is way worse than Enron; this drug company is taking people’s lives.

Source: Digitek Maker should worry about Consumer, not Shareholders

As bad as it is that the drug maker knew the drugs were defective, the FDA knew the company wasn’t following “good manufacturing practices” and did little more than send a warning letter to the company.  Calling the FDA’s action a slap on the wrist would be an exaggeration.  The entire Digitek debacle just shows that we can’t count on the FDA to protect us from defective drugs.

Thankfully, we can still count on lawyers to file Digitek lawsuits on our behalf.  For now, anyway – pharmaceuticals are asking the Supreme Court to enact a legal policy called preemption that will eliminate the ability of injured citizens to file most lawsuits against drugmakers. 

Here’s some more information about Digitek / Digoxin to consider.

The FDA recently approved the Gadolinium dye EOVIST to be used to help detect liver problems.  This makes EOVIST somewhat unique because it’s approved to target problems with specific organs.  Like all Gadolinium dyes, this one also carries an FDA black box warning:

“Gadolinium-based contrast agents increase the risk of Nephrogenic Systemic Fibrosis in patients with:

— acute or chronic severe renal insufficiency (glomerular filtration) rate <30 mL/min/1.73 m2), or
— acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.

In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle and internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent from the body prior to any readministration.

As with other contrast media, the possibility of serious or life- threatening anaphylactoid/hypersensitivity reactions with cardiovascular, respiratory and/or cutaneous manifestations should always be considered. The most common adverse reactions observed in clinical trials at the recommended dose included feeling hot, nausea and headache.”

EOVIST is made by Bayer, the company that also made the deadly drug Trasylol.  Let’s hope EOVIST is a safer drug. 


When a patient undergoes an MRI or an MRA scan, a contrast dye is often used to make the patient’s blood vessels more visible to the doctors.  A commonly used contrast agent is Gadolinium.  Gadolinium is a rare-earth element that has proven to be very useful as a contrast agent.  Unfortunately, it has also proven to cause a rare and sometimes-fatal disease in a number of patients.  The disease is called Nephrogenic Systemic Fibrosis, or NSF.  NSF can be a side-effect of Gadolinium contrast dyes.  Patients most at risk of contracting NSF after the use of Gadolinium are those patients with weakened kidneys.  Patients with weakened kidneys cannot always process the Gadolinium fast enough, so the Gadolinium stays in the body too long.

The first case of NSF wasn’t reported until 1997, and it wasn’t until several years later that scientists linked NSF with Gadolinium.  In fact, it wasn’t until 2007 that the FDA made manufacturers of Gadolinium dyes add a black box warning to the product.  Because of this, it wasn’t until 2007 that most doctors became aware of how dangerous it can be to give Gadolinium to a patient who may have kidney problems.  Thanks to the black box warning, doctors now are more likely to verify that a patient’s kidneys are functioning properly before injecting them with Gadolinium.  What’s so troubling is that thousands of patients who didn’t (and may still not) know their kidneys aren’t functioning properly received injections of Gadolinium. 

How do I know if I’ve been injured by a Gadolinium dye?

There are several symptoms of NSF that are visible to the naked eye.  The first and most obvious is very dry, very hard skin.  Everyone gets dry patches of skin – that’s not what NSF looks like.  Skin affected by NSF has been called “alligator skin” because it is so rough, so leathery, and so hard.  People with advanced stages of NSF report that their skin is literally rock-hard.  The affected skin sometimes changes color, often to a reddish or yellowish color.  NSF can make it very difficult to fully extend your arms and legs.  In advanced stages of NSF, patients will start to curl into a fetal position because they cannot extend their arms and legs anymore.  People with NSF also experience breathing difficulties and pain that seems to come from deep within their bones.  If you have some or all of these symptoms after having an MRI or MRA done, it may be possible you’ve contracted NSF.  Even if you don’t think you have kidney problems, it’s important that you don’t ignore these symptoms.

Do I need a Gadolinium Lawyer?  Should I file a Gadolinium lawsuit?

The decision to file a lawsuit is not one to be made lightly.  It’s a decision you should make only after consulting with a Gadolinium attorney that you trust.  If you contact me and tell me about what happened to you, I will try and put you in touch with a lawyer experienced with Gadolinium lawsuits.  I can’t promise that he or she will be able to win your case.  But I can promise that he or she will listen to your story, will try and help you find medical treatment, and will treat you with dignity and respect.  Most importantly, the attorneys I know aren’t paying me for leads.  I don’t get paid anything for introducing injured people to the Gadolinium attorneys that I know.  Instead, if I help you find a lawyer, I simply ask that you write your elected representatives and let them know you oppose FDA preemption because it prevents injured people like you from suing the manufacturer of a defective drug. 

I’d also like to remind you that I’m a law student, and not an attorney.  So if you email me, you’re not creating an attorney-client relationship.  Nor will you receive legal advice from me.  All I can do for you is listen to your story and introduce you to an attorney I think might be able to help you file and win a Gadolinium lawsuit. 

Why do they use Gadolinium if it causes NSF?

In patients with normally-functioning kidneys, there is very little risk of contracting NSF from a Gadolinium dye.  Only those patients with weakened kidneys seem to be at risk.  And not everyone with kidney problems who is injected with Gadolinium will contract NSF.  That’s why the FDA still allows Gadolinium to be used on some patients with kidney problems.


On February 12th of 2008, Pricara announced a recall of 38 million Duragesic and generic Fentanyl patches because they "may have a cut along one side of the drug reservoir within the patch."  (Duragesic is the brand name of a patch that contains the drug Fentanyl.)  Because of this cut, the Fenantyl inside the patch can leak out and cause an overdose to anyone who handles the patch.  The recalled patches are the 25mcg patches and will have an expiration date on or before December of 2009.  There are two types of patches being recalled: The brand-name Duragesic patches, and the generic Fentanyl batches.  The Duragesic patches will likely have a "Duragesic" label on them, while the generic patches will likely just say "Fentanyl."  The Duragesic patches are sold by Pricara, which is owned by Ortho-McNeil-Jannssen Pharmaceuticals, Inc.  The generic Fentanyl patches are sold by Sandoz, Inc.  All of the patches are made by ALZA corporation, which is why they have the same defect.

If you think you have a defective 25mcg Duragesic patch, call 1-800-547-6646.  If you think you have a defective 25mcg generic Fentanyl patch, call 1-800-901-7236.

On February 2nd and March 3rd of 2008, Actavis announced two recalls of all of their generic Fentanyl patches, which is estimated to be over 21 million patches.  Like the Johnson & Johnson Duragesic Fenatyl patch, the Actavis generic Fentanyl patch suffers from a manufacturing defect that can kill individuals who handle the patch. 

Actavis recalled all of their 25mcg, 50mcg, 75mcg, and 100mcg doses with expiration dates between May and December of 2009.  If you think you have a defective Actavis Fentanyl patch, call 1-877-422-7452.

If you accidentally touch one of these patches, wash your hands with water onlyDO NOT USE SOAP as this increases the likelihood you will be injured by the patch.

How do I know if I've been injured by a Duragesic or Fentanyl patch?

The most serious injury that can occur with a defective Duragesic or Fentanyl patch is death.  If an autopsy was performed, "Fentanyl overdose" or "Fentanyl toxicity" may be listed as one of the causes of death.

Other symptoms of Fentanyl Toxicity include: agitation, circulatory failure, coma, confusion, convulsions, hallucination, hypotension, myoclonic jerks, nightmares, pinpoint pupils, renal failure, respiratory depression, rhabdomyolysis, and vivid dreams.  If you think you’ve experienced an overdose of Fentanyl, get medical help immediately. 

Do I need a Duragesic or Fentanyl Lawyer?  Should I file a lawsuit?

If you or a family member were injured by a defective Duragesic or Fentanyl patch, you may want to consult with an attorney to see what your legal rights are.  I personally know several attorneys involved in Duragesic & Fentanyl litigation, and can put you in touch with one of them to see if you have a case.  The lawyers I know aren't paying me to refer them cases.  And I'm not getting a "cut" of any recovery you may receive.  All I ask from you is that you consider writing a letter to your elected representatives to tell them you oppose FDA preemption, which will prevent many injured citizens from filing lawsuits against manufacturers of defective drugs.

I'm not an attorney – I'm a law student.  So contacting me does not and can not create an attorney-client relationship.  And I will not give you any legal advice, either.  What I will do is listen to your story and put you in touch with an attorney I believe may be able to help you.  I can't promise that the attorney will win your case, if you have one.  All I can promise is that the attorney I put you in contact with will treat you and your family with dignity and respect, and that he or she will vigorously fight for your rights.

Over 60 million defective patches?  What happened?

Several problems contributed to all of these defective patches.  For one thing, it's only recently that the manufacturers implemented an electronic inspection program to verify the patches weren't defective.  Before then, they were relying on purely visual inspection.  This is a problem because the machine that makes the patches was spitting them out at a rate of 240 per minute.  That's four patches every second. No one can look at four patches every second.

Another problem is that the way the patches are made makes it impossible for there not to be leaking patches.  One of the manufacturers even stated that leaking patches are an inherent part of the manufacturing process.  The internal goal was for only 1/10th of 1% of patches each year to leak.    1/10th of 1% is still 8,000 defective patches per year, meaning that if everything went according to plan 8,000 people per year could be injured or die from defective patches.  Does that sound acceptable to you? Unfortunately, the defective lots had a rate closer to 20% of all patches being defective.

The recalled patches were defectively manufactured.  But there's also plenty of evidence that the design of the patch is defective, too.  If the manufacturers switched over to what's called a "Matrix" design, or to a "drug in adhesive" design, there would be little to no risk of leaky patches.  In fact, ALZA corporation even acknowledged to the FDA that a "Matrix" design would eliminate the risk of gel leakage.  In fact, Fentanyl patches sold in Europe do use the Matrix design.  You're probably wondering why we don't use the Matrix design here.  If you've been injured by a Duragesic or Fentanyl patch, perhaps the manufacturer will have to tell a jury why it doesn't use a safer design.