Drug Injury Watch

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

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

(Posted by Tom Lamb at DrugInjuryWatch.com)

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

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

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

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

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

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

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

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about how and (really) why BMS decided to remove its unsafe antibiotic Tequin from the U.S. market -- "FDA: Tequin Was Withdrawn From U.S. Market "For Reasons Of Safety Or Effectiveness" -- Recall That Bristol-Myers Had Said Decline In Sales Was Reason For Its Decision To Stop Selling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

On September 2, 2008 the FDA issued a Notice entitled "Determination That TEQUIN (Gatifloxacin) Was Withdrawn From Sale for Reasons of Safety or Effectiveness" which provides (and confirms) the real reason that Bristol-Myers Squibb Co. (BMY) decided to pull Tequin from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

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and Drug Administration (FDA) has determined that TEQUIN (gatifloxacin) Tablets, Injection, and Oral Suspension, were withdrawn from sale for reasons of safety or effectiveness.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

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

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

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

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

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

May 2009 Digoxin Recall By AS Medication Solutions Seems To Be About Six-Weeks Late

This Company Repackaged Caraco Digoxin Tablets That Were Recalled March 31, 2009; Why Did They Delay Their Recall Notice?

(Posted by Tom Lamb at DrugInjuryWatch.com)

On May 11, 2009 AS Medication Solutions, LLC -- which is a drug repackage company --announced that it has recalled all tablets of Caraco digoxin tablets because those pills may differ in size and therefore could have more or less of the active ingredient, digoxin.

If this sounds vaguely familiar, it should.  On March 31, 2009 Caraco Pharmaceutical Laboratories issued a recall notice for all of its digoxin tablets due to pill-size problems.

Why did it take AS Medical Solutions until mid-May to issue its recall notice for the Caraco digoxin tablets that it simply repackaged and distributed when Caraco recalled its digoxin pills at the end of March 2009?

From the company's May 11 press release, "AS Medications Solution LLC. Announces a Nationwide Recall of All Lots of Digoxin Tablets 0.25mg Due to Size Variability":

Digoxin is a drug product used to treat heart failure and abnormal heart rhythms. It has a narrow therapeutic index and the existence of higher than labeled dose may pose a risk of digoxin toxicity in patients with renal failure. Digoxin toxicity can cause nausea, vomiting, dizziness, low blood pressure, cardiac instability, and slow heart rate. Death can also result from excessive digoxin intake. A lower than labeled dose may pose a risk of heart failure and abnormal heart rhythms.. Consequently, as a precautionary measure, A S Medication Solutions, LLC is recalling these tablets to the consumer level to minimize any potential risk to patients.

Consumers with the products with the following NDC codes that are within expiration should return these products to the place of purchase.

Product Identification

Caraco Digoxin
A-S Medication Solutions, Digoxin 0.25 mg is a scored round biconvex white tablet imprinted with “441”

NDC Numbers:
Digoxin Tablets, USP, 0.25 mg
54569-5758-0 (30-count)

As seen above, the company's press release suggests that patients who have any remaining A-S Medication Solutions digoxin 0.25 mg tablets should return those pills to the pharmacy where they were purchased.

If, however, a patient suffered from digitalis toxicity, low blood pressure, cardiac instability, or bradycardia (slow heart rate) while using A-S Medication Solutions digoxin pills, I urge you not to return those pills because they may be important evidence in any possible personal injury or wrongful death case.

In closing, I will ask once again:  What took this drug repackaging company so long to issue its digoxin recall knowing that the A-S Medication Solutions digoxin 0.25 mg tablets it was distributing were the Caraco digoxin pills that had been recalled at the end of March 2009?

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

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

(Posted by Tom Lamb at DrugInjuryWatch.com)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A Timeline For The Psoriasis Drug Raptiva, From Product Launch In U.S. To Market Withdrawal

Raptiva Recalled in U.S. Due To Link With Fatal Brain Infection, Progressive Multifocal Leukoencephalopathy (PML)

(Posted by Tom Lamb at DrugInjuryWatch.com)

On April 8, 2009 Genentech Inc. -- which was just acquired by Roche Holding AG in March 2009 -- issued a press release announcing "a phased voluntary withdrawal of psoriasis drug Raptiva® (efalizumab) from the U.S. market" due to its link to a brain infection, progressive multifocal leukoencephalopathy (PML).

Here is a basic timeline for Raptiva, from product launch to drug recall.

2003:  Raptiva was approved by the FDA as a once-weekly injection for adults with moderate to severe plaque psoriasis.

October 2008:  FDA announced updated labeling for Raptiva to warn of the risk of life-threatening infections, including progressive multifocal leukoencephalopathy (PML).

December 2008:  U.S. sales of Raptiva were approximately $108 million in its last full year on market.

February 2009:  FDA issued a Public Health Advisory for Raptiva informing patients and doctors about the risk of PML in patients taking Raptiva, after receiving reports of four patients with PML, three of whom died.

February 2009:  The same day (February 19) that the FDA issued its Public Health Advisory, the European Medicines Agency announced the benefits of Raptiva do not outweigh its risks.  Accordingly, this regulatory body recommended that the use of Raptiva should be suspended in the European Union.

February 2009:  Two days later (February 21), at the recommendation of Health Canada, the marketing of Raptiva in Canada was suspended due to safety concerns, including the increased risk of developing PML.

March 2009:  FDA approved a Medication Guide for Raptiva and included additional information in Raptiva's labeling regarding PML.

April 2009:  Genentech announces "phased voluntary withdrawal" of Raptiva and sends out a Dear Healthcare Professional Letter, or "Dear Doctor" letter, about Raptiva as well as a Dear Patient Letter about Raptiva.

June 2009:  Raptiva will no longer be available to patients in the U.S.

To put this Raptiva recall into context, here is some information about progressive multifocal leukoencephalopathy (PML) from the April 8, 2009 Genentech press release about Raptiva:

PML is a rare, progressive, demyelinating disease of the central nervous system that leads to death or severe disability. PML is caused by activation of the John Cunningham, (JC) virus. The JC virus resides in latent form in up to 80 percent of healthy adults, typically only causing PML in immunocompromised patients. The factors leading to activation of the latent infection are not fully understood, though abnormalities in T-cells may be important for reactivation and PML. PML has been reported in the published literature in HIV-positive patients, as well as immunosuppressed cancer patients (including patients with hematologic malignancies), organ transplant recipients, and patients with autoimmune diseases. There are no known interventions that can reliably prevent or adequately treat PML.

Since FDA approval in 2003, approximately 46,000 patients worldwide have been treated with Raptiva, with approximately 2,000 patients in the U.S. currently receiving Raptiva at time this drug recall was announced in early April 2009 by Genentech.

Caraco Digoxin Recall Issued March 31, 2009 Is Due To Pill-Size Problems

Digitek Brand Of Generic Digoxin Tablets Had Been Recalled In April 2008 For Same Reason

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 31, 2009 the FDA announced another generic digoxin pill recall by posting this company press release on the agency's web site: "Caraco Pharmaceutical Laboratories, Ltd. Announces a Nationwide Voluntary Recall of All Lots of Digoxin Tablets Due to Size Variability".

This March 31 press release from Caraco, a generic pharmaceutical company, states that:

[A]ll tablets of Caraco brand Digoxin, USP, 0.125 mg, and Digoxin, USP, 0.25 mg, distributed prior to March 31, 2009, which are not expired and are within the expiration date of September, 2011, are being voluntarily recalled to the consumer level. The tablets are being recalled because they may differ in size and therefore could have more or less of the active ingredient, digoxin."

Almost a year ago, in late April 2008, all digoxin pills manufactured by Actavis Totowa -- marketed under the Digitek brand name -- were recalled due to this so-called "double-dose" manufacturing problem.  Those Digitek pills were distributed by Mylan Pharmaceuticals under the Bertek and UDL labels.

The Digitek recall has resulted in personal injury and wrongful death lawsuits being filed on behalf of patients who used Digitek digoxin tablets.

It is too early to tell whether there will be any product liability litigation involving the possible "double-dose" digoxin pills that are now being by Caraco Pharmaceutical.

P.S.  Read about a "new" May 11, 2009 digoxin recall by a company that repackaged Caraco digoxin tablets -- which were originally recalled in late March 2009. 

Why did AS Medication Solutions delay their digoxin recall notice for six weeks?  (5/13/09)

January 2009: ETHEX Corp. Issues Voluntary Recall Of All Pills Due To Suspected Manufacturing Problems

ETHEX Recall Goes To Retail Pharmacy Level For Hydromorphone HCl Tablets And Metoprolol Succinate ER Tablets, Only; All Other ETHEX Generics Recalled To Wholesale Level

(Posted by Tom Lamb at DrugInjuryWatch.com)

In late December 2008 KV Pharmaceutical announced another drug recall involving its subsidiary ETHEX Corporation, which covered "a single production lot of Hydromorphone HCl 2 mg tablets (Lot 90219, Exp: 3/2010; NDC 58177-0620-04), a pain management drug, following the report of an oversized tablet."

In that same December 23, 2008 press release, we learned that KV Pharmaceutical was voluntarily suspending all shipments of its approved tablet-form drugs" to all the drug company an opportunity to improve its "manufacturing and quality systems".

We ended our article about that 2008 ETHEX one-lot Hydromorphone recall in this manner:  "Now we will wait to see if this Hydromorphone recall is expanded beyond the single lot identified initially by ETHEX."

About a month later we got our answer, which came in the form of a January 28, 2008 press release, "ETHEX Corporation Issues Nationwide Voluntary Recall of [All Its] Products".

This January 2008 press release from KV Pharmaceutical, the parent company of ETHEX, includes a list of the more than 60 generic drugs being recalled by ETHEX.  Only two of these generic drug products, Hydromorphone HCl tablets and Metoprolol Succinate ER tablets, were recalled to the pharmacy, or retail, level.  The recall of all other ETHEX drugs was limited to the wholesale level.

From a January 28 FDA MedWatch Email Alert about this all-pills, all-lots ETHEX recall:

These generic products may have been manufactured under conditions that did not sufficiently comply with current Good Manufacturing Practices. Some of these products have had specific lots recalled earlier due to defects found, including oversized tablets delivering higher than labeled doses. These additional products are being removed to assure that no other defective products remain in the marketplace. Patients who may have these medicines in their possession should continue to take them in accordance with their prescriptions, as the risk of suddenly stopping needed medication may place patients at risk. Patients should contact their physician or healthcare provider if they have experienced any problems that may be related to taking or using these products, or to obtain replacement medications or prescriptions.

As some of you know, there were several recalls of ETHEX drugs in 2008:

• Another "Double-Dose" Pill Problem Demonstrates How And Why The Digitek Recall Is So Unusual

• ETHEX Corporation Expands Its Voluntary June 2008 Recall Of Morphine Sulfate Extended Release Tablets

• A New "Double-Dose" Pill Drug Recall Is Issued By ETHEX Corp.

Related to the Metoprolol Succinate ER tablets aspect of this latest ETHEX recall, on January 30 the FDA issued this "Drug shortage" notice, "Metoprolol succinate extended release tablets".

We have heard from many patients affected by this shortage of Metoprolol ER pills -- the generic of Toprol-XL -- in the numerous Comments that have been submitted to these two articles we did previously concerning the earlier Metoprolol recall issued by Sandoz, a subsidiary of Novartis:

Sandoz Metoprolol Succinate ER Tablets Recall Has Been Done Rather Quietly

FDA Warns Sandoz About Possible Quality-Control Problems At Its North Carolina Generic Drug Manufacturing Facility

We would like to hear how your doctor and/or pharmacist is handling this latest recall by ETHEX, and the current Metoprolol pill shortage in particular.

P.S.  For an update, see this February 3, 2009 drug company Press Release which has been posted on the FDA's web site:

ETHEX Corporation Issues Voluntary Nationwide Recall: Previously Issued Recall to Wholesale Level On Certain Products Expanded to Retail Level

We will continue to monitor this ETHEX 2009 drug recall and report significant developments.  (2/4/09) 

ETHEX Recalls One Lot Of Hydromorphone HCl (2mg) After Finding Oversized Tablet

At Same Time, KV Pharmaceutical Suspends Shipments of All ETHEX Tablet-Form Drugs For An Indefinite Period

(Posted by Tom Lamb at DrugInjuryWatch.com)

On December 23, 2008 KV Pharmaceutical announced another drug recall involving its subsidiary ETHEX Corporation.  This latest recall involves "a single production lot of Hydromorphone HCl 2 mg tablets (Lot 90219, Exp: 3/2010; NDC 58177-0620-04), a pain management drug, following the report of an oversized tablet."

In the same December 23 press release, "KV Pharmaceutical Voluntarily Suspends All Shipments of Its Approved Tablet-Form Drugs", we learned that there is an effort underway to improve the "manufacturing and quality systems" as well as "to implement efficiency improvements" at the production facilities where ETHEX tablet-form drugs are manufactured:

KV Pharmaceutical (NYSE: KV-A) has advised the U.S. Food and Drug Administration (FDA) that, effective midnight Dec. 19, 2008, the company voluntarily suspended all shipments of all FDA approved drug products in tablet form. This action is being taken as a precautionary measure to allow KV to expeditiously review and enhance comprehensively the company's manufacturing and quality systems, and to implement efficiency improvements in its production facilities. KV is keeping the FDA informed about the company's plans.

The list of ETHEX drugs covered by this December 2008 suspension of shipments follows:

• Benazepril HCl Tablets
• Buspirone HCl Tablets
• Dextroaphetamine Sulfate Tablets CII
• Doxazosin Mesylate Tablets
• Hydromorphone HCl Immediate Release Tablets, CII
• Isosorbide Mononitrate Extended-Release Tablets
• Metoprolol Succinate Extended Release Tablets, USP
• Morphine Sulfate Extended Release Tablets, CII'
• Ondansetron Orally Disintegrating Tablets
• Oxycodone HCl Tablets, CII
• Potassium Chloride 20 mEq Extended-Release Tablets
• Propafenone HCl Tablets

As we have reported previously, there have been several earlier recalls of ETHEX drugs in 2008:

Another "Double-Dose" Pill Problem Demonstrates How And Why The Digitek Recall Is So Unusual

ETHEX Corporation Expands Its Voluntary June 2008 Recall Of Morphine Sulfate Extended Release Tablets

A New "Double-Dose" Pill Drug Recall Is Issued By ETHEX Corp.

We will watch for further news from KV Pharmaceutical about the new single-lot recall of Hydromorphone HCl 2 mg tablets as well as the shipment suspension of all ETHEX tablet-form drugs.

P.S.  Sometime after the above article was posted yesterday, this press release, "ETHEX Corporation Initiated Nationwide Voluntary Recall of a Single Lot of Hydromorphone HCl 2 mg Tablets Due to Potential for Oversized Tablet", was published on the FDA web site.

From the December 23 ETHEX press release we get some additional information from this generic drug company about its December 2008 recall of a single lot of Hydromorphone tablets:

If someone were to take a higher than expected dose of Hydromorphone, the risk of adverse effects known to be associated with the drug may be increased, including respiratory depression (difficulty or lack of breathing), low blood pressure, and sedation.

There are other companies in the United States producing and marketing versions of Hydromorphone HCl tablets and consumers and their caregivers are encouraged to check their prescriptions to determine the source of their tablets. Hydromorphone HCl 2 mg tablets marketed by ETHEX are a blue, round tablet with a script "E" on one side and a "2" on the other side.

Now we will wait to see if this Hydromorphone recall is expanded beyond the single lot identified initially by ETHEX.

Prescription Oral Sodium Phosphate (OSP) Products Visicol And OsmoPrep Get Black-Box Warning

Related Recall Of Over-The-Counter OSP Fleet Phospho-Soda, Which Is Subject Of Product Liability Lawsuits

(Posted by Tom Lamb at DrugInjuryWatch.com)

On December 11, 2008 the FDA issued by email a MedWatch Safety Alert which was titled "Oral Sodium Phosphate (OSP) Products for Bowel Cleansing: reports of acute phosphate nephropathy, Boxed Warning to be added to labeling".

According to this December 2008 Alert, the FDA was taking action because it had become aware of reports of a type of serious kidney injury, acute phosphate nephropathy, that was associated with the use of oral sodium phosphate products (OSP) for bowel cleansing prior to colonoscopy or other procedures.  Further, some of these cases acute phosphate nephropathy cases occurred in patients who had not have any pre-existing, identifiable factors that would have put them at risk for developing this acute kidney injury.

For more information, the FDA directed patients and doctors to the MedWatch 2008 safety summary about this new Boxed Warning (also known as a black-box warning) for Visicol And OsmoPrep -- the only two prescription OSP products available in the U.S.

From there, for those who wanted more details, the MedWatch summary directed one to this FDA Drug Information Page, "Oral Sodium Phosphate (OSP) Products for Bowel Cleansing (marketed as Visicol and OsmoPrep, and oral sodium phosphate products available without a prescription)".

Taken from that page is what seems to be the FDA's current understanding of this OSP adverse reaction:

Acute phosphate nephropathy is a form of acute kidney injury that is associated with deposits of calcium-phosphate crystals in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy is a rare, serious adverse event that has been associated with the use of OSPs. The occurrence of these events was previously described in an Information for Healthcare Professionals sheet and an FDA Science Paper issued in May 2006. Additional cases of acute phosphate nephropathy have been reported to FDA and described in the literature since these were issued.

Individuals who appear to have an increased risk of acute phosphate nephropathy following the use of OSPs include persons: who are over age 55; who are hypovolemic or have decreased intravascular volume; who have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).

All of this was followed closely by a drug company announcement about some similar over-the-counter (OTC) products; from their press release, "C.B. Fleet Voluntarily Recalls its Fleet Phospho-soda Product after FDA Safety Alert":

Following the issuance of FDA's Safety Alert on Thursday stating that oral sodium phosphates bowel cleansing solutions should be available by prescription only, C.B. Fleet Company immediately announced a voluntary recall of their over-the-counter products Fleet® Phospho-soda® and Fleet® Phospho-soda® EZ-Prep® BowelCleansing System. The voluntary recall is directed to retailers and wholesalers.

Interestingly, one of these two products, Fleet Phospho-soda, is the subject of several ongoing product liability lawsuits that have been filed on behalf of patients with kidney damage who used this now-recalled C.B. Fleet OSP product.

These lawsuits filed against Fleet allege that the drug company marketed Phospho-soda at dosages higher than the FDA permitted for OTC oral laxatives containing sodium phosphate -- up to twice the permitted daily amount according to these lawsuits. 

In turn, use of the higher dosage of Fleet Phospo-soda can leads to deposits of calcium and phosphate in the kidneys, a condition known as nephrocalcinosis. This damage to the kidneys is often permanent, and requires dialysis or even a kidney transplant.

Returning to the FDA's information, above, it seems that the risk of developing an OSP-induced kidney injury is increased in certain patients, such as those taking certain blood pressure medications or diuretics, and that the risk of this adverse reaction kidney damage increases with a patient's age.

We will continue to monitor this emerging drug safety issue, and we welcome any insight you may have about these several different OSP products causing kidney problems like acute phosphate nephropathy or nephrocalcinosis.

Sandoz Metoprolol Succinate ER Tablets Recall Has Been Done Rather Quietly

Many Patients Are Dissatisfied With Lack Of Information From Sandoz, FDA, Or Their Pharmacy About Why This Generic Toprol Pill Was Pulled

(Posted by Tom Lamb at DrugInjuryWatch.com)

In an August 26, 2008 Drug Injury Watch post, "FDA Warns Sandoz About Possible Quality-Control Problems At Its North Carolina Generic Drug Manufacturing Facility", I reported FDA inspectors found that Sandoz had failed to properly validate its manufacturing process for Metoprolol Succinate ER Tablets (Generic Form Of Toprol XL).

Here is the August 12, 2008 FDA Warning Letter (08-ATL-13) sent to Sandoz concerning the"Good Manufacturing Practices" (GMP) problems found at its generic drugs facility located in Wilson, North Carolina.

Returning to my earlier post, there I noted:

It is unclear as of August 26 whether Sandoz will cease distribution of its metoprolol succinate ER tablets (generic Toprol XL) and/or issue a recall of this medication.  We will be watching for these possible related developments.

Well, in the few months that followed we never saw any Metoprolol Succinate ER Tablets recall notice from the FDA nor Sandoz. 

Starting in November 2008, however, we started to get some Comments submitted to the August 26 post which indicated that, in fact, some type of recall was underway.  And elsewhere on the web, such as this Topix forum, "recall at Rite-aid -- Posted in the Metoprolol (generic), Toprol XL Forum", there were various reports coming in to this effect.

Thankfully, one of the participants in that Topix forum posted a link to this November 12, 2008 notice, "Recall: Metoprolol ER Tablets by Sandoz" published online by Pharmacy Industry News:

Sandoz is voluntarily extending the September 17, 2008, recall of Metoprolol Succinate Extended Release Tablets 25mg and 50mg, to include all strengths of distributed lots with expiration dates through August 2010. This voluntary action by Sandoz is due to deficiencies in documentation practices and in-process controls for this product. This voluntary recall is being conducted down to the retail level with the knowledge of the FDA. The affected lots were shipped approximately between November 2006 and October 2008. (Sandoz Press Release 11/3/08)

Unfortunately (but not surprisingly) I could not find the above-referenced November 3, 2008 press release on the Sandoz web site when I checked today, nor could I find there any press release about this Metoprolol Succinate ER Tablets recall from back in September 2008.

Likewise, there is nothing to be found readily on the FDA's web site about this Sandoz Metoprolol Succinate ER Tablets recall.

If you have more information about how Sandoz is carrying out this relatively "quiet" recall of its Metoprolol Succinate ER Tablets, please let us know by submitting a Comment, below, or sending me a private email.

P.S.  AstraZeneca issued a May 18, 2009 press release to announce that all wholesale ordering restrictions in place for its Toprol-XL (metoprolol succinate) extended release tablets have been removed and that supply levels of Toprol-XL are approaching near usual levels at all points in the distribution chain.  (5/21/09)

A New "Double-Dose" Pill Drug Recall Is Issued By ETHEX Corp.

First It Was Their Morphine Tablets; Now ETHEX Dextroamphetamine 5mg Pills May Be Oversized And Contain Two Times The Active Ingredient

(Posted by Tom Lamb at DrugInjuryWatch.com)

By means of an October 16, 2008 MedWatch Email Alert the FDA announced that ETHEX Corporation has recalled three lots of Dextroamphetamine Sulfate 5mg tablets because of the potential presence of oversized tablets that may contain as much as twice the labeled amount of the active ingredient. From the October 16 FDA Alert:

Taking a higher than expected dose of Dextroamphetamine Sulfate may be associated with an increased risk of adverse effects such as tachycardia, hypertension, tremors, decreased appetite, headache, insomnia, dizziness, blurred vision, stomach upset, and drug mouth. Consumers and their caregivers should not use any Dextroamphetamine Sulfate tablets that appear to be oversized and should consult their healthcare professional with any questions.

An October 15 drug company press release, "ETHEX Corporation Voluntarily Recalls Three Lots of Dextroamphetamine Sulfate 5mg Tablets Due to the Potential for Oversized Tablets -- Lot Number 77946, 81141 and 81142 NDC #58177-311-04", provides these details:

ETHEX Corporation announced today that it has voluntarily recalled three specific lots (77946, 81141 and 81142) of Dextroamphetamine Sulfate 5 mg tablets, as a precaution, due to the possible presence of oversized tablets. Oversized tablets may contain as much as about twice the labeled amount of the active ingredient. The recalled lots were distributed by ETHEX Corporation under an "ETHEX" label between January 2007 and May 2008. The 5 mg product is an orange round tablet debossed with "ETHEX" and "311" on one side.

... ETHEX Corporation is conducting this precautionary, voluntary recall because it found a small number of oversized tablets in lots which had not yet been distributed. These oversized tablets were removed before the lots were distributed.

Previously, in June 2008 ETHEX Corp. announced that it was recalling Morphine Sulfate 60 mg Extended Release Tablets.  With this earlier situation, initially there was the recall of a single lot due to a report of a tablet with twice the appropriate thickness.  Soon thereafter, however, that first ETHEX recall was expanded to all 30 mg and 60 mg Morphine Sulfate Extended Release Tablets made during a two-year period, June 2006 To May 2008.

As you may know already, in April 2008 Actavis Totowa LLC recalled all strengths of Digitek due to the possibility that tablets with double the appropriate thickness may contain twice the approved level of active ingredient.  These "double-dose" Digitek pills created a risk of ditigalis toxicity, especially in patients with renal failure.  Since then, numerous personal injury and wrongful death Digitek lawsuits have been filed against Actavis.

As I have asked rhetorically in the recent past:

Where is the FDA on taking steps to ascertain that Good Manufacturing Practices (GMP) are being adhered to so that our nation's supply of FDA-approved generic drugs is safe?

What do you think about this series of double-dose pill recalls involving ETHEX and Actavis?