The appeal is being pursued by generic drug makers including Teva Pharmaceuticals, Actavis Elizabeth and UDL Laboratories, who are attempting to be dismissed from lawsuits over generic Reglan (metoclopramide).

In the complaints, users allege that the drug makers failed to adequately warn about the risk of movement problems, such as tardive dyskinesia, from side effects of Reglan. Actavis and the other generic drug makers argue that the claims should be preempted by federal laws governing generic drug labeling, which require generic drugs to carry the same label as the brand name medication.

In an order issued this week, the Supreme Court invited the Solicitor General to file briefs in the cases expressing the views of the United States.

At issue on appeal is whether a generic drug manufacturer can change its label or otherwise warn the public of a health risk before the maker of the brand name drug. FDA regulations require that generics seeking approval have the same label as the brand name manufacturer, and it also stipulates that the generic’s label has to remain consistent with the brand name label. However, the lower appeals court ruled that the regulations do not prevent generics from requesting a label change to warn of a health risk, nor do they prevent the drug company from other methods of warning the public, such as sending out a “Dear Healthcare Professionals” letter to warn of potential risks.

Brand-name Reglan was originally formulated and marketed by Wyeth, but it is currently only available as generic metoclopramide. Although the drug is only approved for short-term use, taking the drug over longer periods of time has been linked to an increased risk of tardive dyskinesia from Reglan, with symptoms that can include uncontrolled lip smacking, grimacing, repetitive chewing, rapid eye movements and blinking, pursuing and puckering of the lips, tongue protrusion, impaired finger movements and involuntary movements of the extremities. The movement disorder can be permanent and irreversible in many cases.

In February 2009, the FDA required that manufacturers of all variations of generic metoclopramide add a black box warning about the Reglan tardive dyskinesia risk, which is the strongest warning that can be placed on a prescription medication. The generic drug makers were also required to develop mitigation and risk evaluation strategies to help ensure patients are aware of the potential metoclopramide side effect.

There are a large number of generic Reglan lawsuits over tardive dyskinesia warnings pending in state and federal courts throughout the United States. Last year, the U.S. Judicial Panel on Multidistrict Litigation denied a request to consolidate the Reglan litigation for pretrial proceedings, finding that centralization in an MDL, or multidistrict litigation, was not appropriate because there is no single common defendant and many of the generic drug makers are only involved in a few cases. Therefore, all lawsuits over Reglan are proceeding as individual claims in various courts throughout the United States.

The lawsuit was brought by Judith Finnicum last August in the U.S. District Court for the Eastern District of Texas, alleging that she developed uncontrollable movements after taking generic metoclopramide to treat gastrointestinal problems.

While the complaint included Wyeth and Schwarz, which originally developed metoclopramide and sold the medication as Reglan, U.S. District Judge Marcia A. Crone granted a summary judgment motion to dismiss the two drug makers from the litigation, indicating that the case will move forward only against Actavis-Elizabeth. According to a scheduling order in the generic metoclopramide lawsuit, the remaining parties are expected to be ready to try the case by early January 2011.

A number of similar lawsuits over generic metoclopramide and Reglan are pending in various courts throughout the United States against Wyeth, Schwarz and a number of generic drug makers. The cases all involve similar allegations that side effects of metoclopramide caused tardive dyskinesia, and that the drug makers failed to adequately warn about the increased risk associated with long-term use of the medication.

In June 2009, the U.S. Judicial Panel on Multidistrict Litigation denied a request to consolidate the federal Reglan litigation. Therefore, all federal cases are proceeding as individual cases in courts across the country.

Reglan was originally introduced by Wyeth in 1989, and the drug company continued to market and distribute the drug through late December 2001, when Schwarz acquired the rights to Reglan. Schwarz continued to manufacture and distribute the drug until 2008, when they ceased production, leaving only generic metoclopramide versions. Since the mid-eighties metoclopramide generic has been manufactured by a number of companies.

While metoclopramide is only approved for short-term treatment of gastrointestinal disorders, like diabetic gastroparesis, gastroesphageal reflux (GERD) and delayed gastric emptying, it is often prescribed for longer periods of time given the chronic persistence of those ailments. Use of metoclopramide for more than 12 weeks has been shown to increase the risk of tardive dyskinesia and other movement disorders, and plaintiffs allege that Wyeth and Schwarz failed to adequately research their medication and attempted to minimize the risk.

Tardive dyskinesia is a neurological disorder that causes repetitive and involuntary movements of the lower face and limbs. Symptoms can include repeated grimacing, chewing, smacking of lips, rapid eye movements and impaired finger movements. There is no known effective treatment for the problems from metoclopramide, and the involuntary movements often persist even after use of the drug has stopped, contrary to what was suggested on the warning labels for Reglan and generic metoclopramide drugs.

In February 2009, the FDA required that the manufacturers of all metoclopramide-containing drugs add a “black box” warning about the risk of metoclopramide tardive dyskinesia problems. In addition, the manufacturers were required to develop a mitigation and risk evaluation strategy to help ensure that patients are made aware of the potential side effects of metoclopramide.

Approved by the FDA in January 2009, Kapidex (dexlansoprazole) is a proton pump inhibitor approved for treatment of heartburn and acid reduction. It is manufactured by Takeda Pharmaceuticals North America, Inc.

The FDA name change approval was issued on March 4, indicating that Kapidex will become known as Dexilant in late April. The medication will also receive a new National Drug Code number, but no other changes will be made to the drug.

The Kapidex name will be changed to avoid medication errors where it may be confused with AstraZeneca’s Casodex, which is used to treat prostate cancer by reducing male hormones, or Actavis’s Kadian, a morphine-based pain killer.

Although there have been no reports of injuries or deaths associated with mixing up the medications, incorrect use of Kadian (morphine sulfate extended release) in particular could lead to a morphine overdose if it were confused for heart burn pills. Morphine is an opioid which can lead to a fatal overdose if too much medication is taken. A morphine overdose can cause respiratory depression and low blood pressure.

The confusion over medication names was identified as part of the FDA’s Safe Use Initiative, which started in November. The initiative is designed to reduce the number of preventable medication errors.

FDA officials said all drug names are evaluated before they go on the market, and FDA reviewers did not expect Kapidex to be confused with Casodex or Kadian.

According to the Institute of Medicine and FDA, there are 1.5 million preventable medication injuries in the U.S. each year, which add an additional $4 billion to the cost of health care. About 60,000 children are seen in emergency rooms nationwide each year due to accidental drug ingestion.

There are currently more than 200 Digitek lawsuits pending in the federal MDL, which all involve similar allegations that Actavis Totowa and their distributors sold over-sized Digitek pills, which caused users to suffer a variety of serious and potentially life-threatening injuries associated with receiving too much of the heart medication.

According to a pretrial order issued Tuesday by Chief Judge Joseph R. Goodwin, the first “bellwether” Digitek trial is scheduled to begin on January 31, 2011. Five cases were selected last month for early trials in the MDL, but the order does not indicate which of those lawsuits will be the first case presented to a jury.

Digitek is a generic version of the drug digoxin, used to treat congestive heart failure, abnormal heart rhythms, atrial flutter and atrial fibrillation. The medication is extremely dose-specific with a narrow therapeutic index. If too little of drug is prescribed it can be ineffective, and if too much is prescribed it can lead to a Digitek overdose, where the drug builds up in the system. This can result in a serious and potentially life-threatening condition known as digitalis toxicity.

In April 2008, Actavis Totowa issued a Digitek recall for all lots of the heart drug after it was discovered that some tablets may have been commercially released that were twice as thick as they were supposed to be. The error potentially exposed thousands of users to a risk of digoxin overdose or poisoning.

According to a December 2008 report released by the non-profit Center for Public Justice, the FDA received reports of at least 667 Digitek overdose deaths tied to the recalled pills between April 2008 and June 2008.

In addition to the cases pending before Judge Goodwin in federal court, there are also many similar lawsuits pending in various state courts. According to an order issued in December, the judges presiding over those state court cases will join Judge Goodwin for a joint hearing in October 2009 to address the scientific and technical issues presented in the Digitek recall lawsuits. Following the joint hearing, each judge will give a seperate ruling as they relate to the cases they are presiding over.

The appeal involved a product liability lawsuit filed by Julie Demahy against Actavis, Inc., which marketed a generic version of the brand name drug Reglan (metoclopramide) for treatment of gastrointestinal disorders. Demahy claimed that side effects of generic Reglan caused her to develop tardive dyskinesia, which is a neurological condition that causes involuntary movements of the lower face and extremities.

A number of similar generic Reglan tardive dyskinesia lawsuits have been filed in courts throughout the United States. While the plaintiffs allege that the drug makers failed to adequately warn about the potential risk associated with long-term use of Reglan, Actavis and other generic drug makers have argued that the claims are preempted by federal laws governing generic drug labeling, which require that generic drugs carry the same label as the brand name medication.

In a decision filed on Friday, the U.S. Court of Appeals for the Fifth Circuit rejected Actavis’ argument, affirming the lower court’s finding that Dehamy’s state-law failure to warn claims are not preempted.

At issue on appeal was whether a generic drug manufacturer can change its label or otherwise warn the public of a health risk before the maker of the brand name drug. FDA regulations require that generics seeking approval have the same label as the brand name manufacturer, and it also stipulates that the generic’s label has to remain consistent with the brand name label. However, the Fifth Circuit ruled the regulations do not prevent generics from requesting a label change to warn of a health risk, nor do they prevent the drug company from other methods of warning the public, such as sending out a “Dear Healthcare Professionals” letter to warn of potential risks.

Brand-name Reglan was originally formulated and marketed by Wyeth, but it is currently only available as generic metoclopramide. Although the drug is only approved for short-term use, extended use has been linked to an increased risk of tardive dyskinesia, with symptoms that can include uncontrolled lip smacking, grimacing, repetitive chewing, rapid eye movements and blinking, pursuing and puckering of the lips, tongue protrusion, impaired finger movements and involuntary movements of the extremities. In some cases, the movement disorder disappears when the user stops taking the drug, but in other cases has been irreversible and permanent.

In February 2009, the FDA required that manufacturers of all variations of generic metoclopramide add a black box warning about the Reglan tardive dyskinesia risk, which is the strongest warning that can be placed on a prescription medication. The drug makers were also required to develop mitigation and risk evaluation strategies to help ensure patients are aware of the potential metoclopramide side effect.

Last year, the U.S. Judicial Panel on Multidistrict Litigation denied a request to consolidate the Reglan litigation for pretrial proceedings, finding that centralization in an MDL, or multidistrict litigation, was not appropriate because there is no single common defendant and many of the generic drug makers are only involved in a few cases. Therefore, all lawsuits over Reglan are proceeding as individual claims in various courts throughout the United States.

An order identifying the bellwether cases was issued on November 24 by Chief Judge Joseph R. Goodwin, of the U.S. District Court for the Southern District of West Virginia, where all federal Digitek recall lawsuits are consolidated for pretrial litigation.

The lawsuits selected for early trials are commonly referred to as bellwether cases, as they are selected by the parties and the court to help gauge how jurors will respond to evidence presented throughout cases in the litigation.

The five cases selected for the first Digitek trial dates include:

• David Kelch et al., v. Actavis Totowa, LLC et al., 2:08-cv-01282
• William J. Young et al., v. Actavis Totowa, LLC et al., 2:09-cv-00498
• Jacquelyn K. Fox et al., v. Actavis Totowa, LLC et al., 2:09-cv-00389
• Karen Sheahan, et al., v. Actavis Group, et al., 2:08-cv-01051
• Scottie Vega et al., v. Actavis Group hf., et al., 2:09-cv-00768

No trial dates were set, but it is expected that the trials will not begin until at least late 2010, since attorneys have until at least August 31, 2010 to take depositions from various experts and witnesses.

Digitek, which is a generic version of digoxin, is used to treat congestive heart failure, abnormal heart rhythms, atrial flutter and atrial fibrillation. The medication is extremely dose-specific with a narrow therapeutic index. If too little of drug is prescribed it can be ineffective, and if too much is prescribed it can lead to a Digitek overdose, where the drug builds up in the system. This can result in a serious and potentially life-threatening condition known as digoxin toxicity.

In April 2008, Actavis Totowa issued a Digitek recall for all lots of their heart drug, after it was discovered that some tablets may have been commercially released that were twice as thick as they were supposed to be. This could expose thousands of users to a risk of digoxin overdose or poisoning.

Symptoms of a Digitek overdose could include vomiting, nausea, dizziness, confusion, vision problems, palpitations, low blood pressure, bradycardia and cardiac instability.

According to a December 2008 report released by the non-profit Center for Public Justice, at least 667 Digitek overdose deaths throughout the United States were reported to the FDA between April 2008 and June 2008.

Hundreds of lawsuits have been filed in federal court following the Digitek recall. Those lawsuits have been consolidated in a multidistrict litigation (MDL) before Judge Goodwin to be coordinated for pretrial litigation.

The generic drug recall was issued on August 14 for one lot of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate (mixed amphetamine salts) 20 mg tablets, which were sold in 100 count bottles. Some of the tablets from lot 311756 could contain tablets exceed weight requirements, which may result in super-potent pills.

The generic Adderall tablets are approved to treat Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy, and are also often used off-label for weight loss. The 20mg pills are oval and peach in color, with “b/973″ stamped on one side and “2/0” stamped on the other. The recalled Barr ADHD pills were distributed between June 11, 2009 and June 16, 2009, but could have been filled by a pharmacy after that.

Taking an oversized pill could lead to an overdose, with symptoms like palpitations, tachycardia, hypertension, headache, tremor, tic, dyskinesia, dizziness, blurred vision, sweating, insomnia, agitation, euphoria, mania, anxiety, restlessness, nausea, diarrhea, constipation, dry mouth and decreased appetite.

No injuries have been reported in connection with the oversized tablets, according to Barr Laboratories. Consumers who have any of the recalled dextroamphetamine/amphetamine tablets have been advised to stop using the drug and contact their doctor or pharmacist. Any adverse reactions should be reported to the FDA’s MedWatch program.

The recall is the latest in a string of recalls involving generic drugs that were distributed with too much of the active medication in each tablet.

In late June 2009, U.S. Marshals raided generic drug manufacturer Caraco Pharmaceutical Laboratories, Ltd., shutting down production due to unsafe manufacturing processes that allowed similar problems to occur. In March, Caraco issued a generic digoxin recall for tablets of their heart medication due to irregular sized pills.

In April 2008, a Digitek recall was issued by Actavis Totowa for their brand of digoxin which were distributed with up to twice the appropriate amount of the active pharmaceutical ingredient. At least 667 deaths from digoxin overdose were linked to the recalled Digitek tablets in FDA adverse event reports following the announcement of the manufacturing problems.

Last year, generic drug maker Ethex Corp suspended manufacturing and shipments for all products after issuing several generic drug recalls due to oversized tablets. Among tablets that were distributed with too much of the active medication were generic versions of morphine, which could cause a potentially fatal morphine overdose. Also included in the recall were dextroamphetamine tablets that were generic versions of Dexedrine and Dextrostate.

Consumers in Canada have been urged to return any 60 mg pms-Phenobarbital to their pharmacist for replacement. However, Health Canada indicates that they should not stop taking the medication without first consulting with their doctor, as it could cause symptoms of withdrawal or an increase in seizures.

Phenobarbital is a barbiturate typically used to treat anxiety and sleep disorders that has been on the market since 1912. It is also widely used as an anticonvulsant to control seizures.

The Canadian recall of Phenobarbital was issued on June 26, 2009, after some oversized tablets were found on the market that contain more Phenobarbital than they were supposed to have. Pharmascience is the distributor of the drug in Canada and indicates that all lots of the 60mg format of the drug are being recalled.

Although no injuries or reactions have been reported to date, a Phenobarbital overdose could cause symptoms like decreased breathing and heart rate, lack of muscle coordination, impaired speech, extreme drowsiness and uncontrolled eye movements. Symptoms generally begin to appear within one to two hours, and could be life-threatening.

There is no indication at this time that the Phenobarbital recall will affect any products distributed in the United States, where it is manufactured by several companies. However, a number of U.S. generic drug makers have experienced manufacturing problems over the past two years involving oversized or undersized pills.

In April 2008, a Digitek recall was issued for all lots of the generic heart drug digoxin manufactured by Actavis Totowa at their New Jersey facility. At least 667 digoxin deaths among users of the drug were reportedly linked to the oversized tablets, according to FDA adverse event reports.

Earlier this year, Caraco Pharmaceutical Laboratories issued a generic digoxin recall for their version of the heart drug, due to manufacturing problems at their Michigan facilities which allowed some pills to contain too much or too little of the active drug. Last week, after the FDA identified continued problems with the drug maker adhering to the current Good Manufacturing Practice requirements, U.S. Marshalls shutdown Caraco’s production facilities and seized their inventory.

Late last year, all generic drugs manufactured by Ethex Corp. were recalled due to manufacturing problems which led to oversized tablets of morphine and other drugs being distributed. A lawsuit was filed last month in Illinois on behalf of three consumers who suffered a morphine overdose allegedly caused by the oversized tablets.

In March 2009, Caraco recalled digoxin, a heart medication that requires exact dosage, after it was discovered that some tablets distributed were thicker or thinner than they were supposed to be. This created a serious risk for consumers, as receiving too much of the drug could cause a potentially life-threatening condition known as digoxin toxicity, and receiving too little of the medication could result in injury from the underlying heart condition.

A similar manufacturing problem with Actavis Totowa in April 2008, which led to a recall of Digitek brand digoxin, was linked to 667 deaths according to FDA adverse event reports during the months following the discovery that some oversized tablets were commercially released.

Caraco received an FDA warning letter in October 2008, but the FDA identified continuing failure to meet the current Good Manufactring Practice (cGMP) requirements during a follow up inspection completed in May 2009.

“Today’s seizure is intended to lead to major changes at Caraco’s facilities,” said the FDA in a statement issued June 25, 2009. “If the FDA identifies further significant problems, which pose risks to patient safety with any Caraco drug products on the market, the agency will take appropriate regulatory action and immediately notify the public.”

The Caraco raid will affect the company’s production of 33 different drugs, including pain, heart, high blood pressure and psychotropic medications. The FDA has said the company will not be allowed to ship any more medication until its facilities meet cGMP requirements. The raids were conducted by federal marshals on the company’s plants throughout Michigan, including facilities in Detroit, Farmington Hills, and Wixom.

Although other companies also manufacture most of the drugs seized, the FDA said the raid might cause a shortage of choline magnesium trisalicylate, a pain killer. Consumers and health care providers should seek alternatives or contact the FDA’s drug shortage program.

Despite the seizure, the FDA said consumers should continue to use any Caraco medications they have already had filled. Agency officials say that they believe that any defective medications have already been recalled, but they find any other problems with Caraco medications currently on the market, they will notify consumers immediately.

A motion to form an MDL, or Multidistrict Litigation, was filed on behalf of plaintiffs in 15 Reglan lawsuits pending in 11 different district courts throughout the United States, asking the Panel to consolidate all cases before one judge for pretrial proceedings to eliminate duplicative discovery, avoid conflicting rulings and serve the convenience of the parties, witnesses, attorneys and the courts.

Reglan is the brand name for metoclopramide, which is prescribed to treat gastrointestinal disorders like diabetic gastroparesis, GERD (gastroesphageal reflux and delayed gastrict emptying. Although the medication is only approved for short term use of up to 12 weeks, it is often prescribed for longer periods and at higher doses, which substantially increases the risk of Reglan tardive dyskinesia side effects.

Tardive dyskinesia is a neurological disorder that causes involuntary and repetitive movements of the lower face and limbs, such as lip smacking and pursing, chewing, grimacing, rapid eye movements and impaired finger movements. The condition is often permanent and there is no known effective treatment available.

The plaintiffs’ request for Reglan lawsuit consolidation is being opposed by the various pharmaceutical companies involved in the litigation, including Wyeth, who manufactured the brand name Reglan products, and several manufacturers of generic versions, such as Baxter, Pliva, Barr, Duramed, Actavis, Teva and Scwarz Pharma.

The drug makers have indicated that consolidation is not necessary, pointing to more than 20 years of Reglan litigation since the first case was filed in 1998. More than 70 metoclopramide lawsuits have been filed in federal and state courts, of which 80% have been resolved.

In oppositions filed before the hearing, the defendants pointed out that of the 15 Reglan lawsuits referenced in the motion filed by the plaintiffs, only 11 are at issue at this time, as four have been resolved. In addition, of the remaining cases, three are already “trial ready” with 2009 trial dates and another 5 cases have 2010 trial dates.

Transfer of the remaining cases would hinder the continued efficient resolution of the remaining cases, according to the defendants. In addition, with most of the generic discovery from the pharmaceutical defendants already complete, the drug makers point out that an MDL is not necessary.

In February 2009, the FDA announced that they are requiring that a new “black box” warning be added to all metoclopramide drugs about the tardive dyskinesia risks with Reglan, which some have speculated will lead to an increase in the number of lawsuits filed. However, the drug makers indicate that they believe the impact of the new warning will be minimal since the content was already on the label elsewhere.

Following today’s hearing, the Judical Panel on Multidistrict Litigation will determine whether consolidation is warranted and, if so, determine which jurisdiction the cases should be transferred to. The plaintiffs have suggested that the District of Nevada would be the best location. However, the defendants have proposed various other districts if the Panel establishes the MDL.