Drug Injury Watch

May 2010: New Safety Information For Xenical And Alli Regarding Cases Of Severe Liver Injury

FDA Had Been Investigating Reports Of Hepatotoxicity Involving Their Active Ingredient, Orlistat, For Past Year 

(Posted by Tom Lamb at DrugInjuryWatch.com)______________________________________________________________________________

UPDATE:  EMA Decides Orlistat Benefits Worth the Risks

The CHMP finalized its review of the risk of liver injury with orlistat drugs, such as Xenical (Roche) and Alli (GlaxoSmithKline), with the conclusion that the weight-loss drug's benefits outweigh the risks in patients with a body mass index of >28 kg/m2....

(2/21/12)______________________________________________________________________________

Xenical and Alli are relatively popular medications used for weight-loss that contain different strengths of the same active ingredient, orlistat. Xenical (orlistat 120 mg) is available by prescription and Alli (orlistat 60 mg) is sold over-the-counter without a prescription.

In late May 2009 we first reported that the FDA was investigating Xenical and Alli for a possible link with liver damage due to the fact that the agency had received case reports of hepatotoxicity involving orlistat.

About three months later, we reported that the FDA issued its "Early Communication about an Ongoing Safety Review Orlistat (marketed as Alli and Xenical)" on August 24, 2009.

Now, by means of a May 26, 2010 announcement by the agency's the Division of Drug Information (DDI), we have learned that (1) the FDA has approved a revised label for Xenical to include new safety information about cases of severe liver injury, and (2) the FDA also wants a new warning about rare reports of severe liver injury added to the OTC Drug Facts label for Alli.

From the "FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury", released on May 26, 2010, we get these details:

This new safety information, originally announced in August 20091, is based on FDA's completed review that identified 13 total reports of severe liver injury with orlistat; 12 foreign reports with Xenical and 1 U.S. report with Alli (see Data Summary).

• One U.S. case with Alli and 12 foreign cases with Xenical reported between April 1999 and August 2009 out of an estimated 40 million people worldwide who have used Xenical or Alli.
• Some patients in the reported cases also used other drugs or had other conditions that may have contributed to the development of severe liver injury.
• Severe liver injury can occur in people not taking drugs and without a distinct cause.

At this time, a cause and effect relationship of severe liver injury with orlistat use has not been established....

In addition, the FDA has posted on its web site "Questions and Answers: Orlistat and Severe Liver Injury", for patients and providers who want to know more about this most recent development concerning Xenical and Alli.

We will continue to monitor the safety profiles of Xenical and Alli, reporting significant developments here at Drug Injury Watch.

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

Zithromax-Induced Liver Injury Case Report Where There Was No History Of Liver Problems

Drug-Induced Liver Injury (DILI), Or Toxicity, Can Cause Both Acute And Chronic Liver Disease

(Posted by Tom Lamb at DrugInjuryWatch.com)

To get our bearings, we start with some points taken from the Abstract for the article "Diagnosis, management and prevention of drug-induced liver injury", which was published in the Gut medical journal last year:

• Drug-induced liver injury (DILI) is increasingly being recognised as a significant cause of both acute and chronic liver disease.

• Drug-induced hepatotoxicity is generally idiosyncratic in nature.

• Diagnosis of drug-induced liver diseases can be difficult, but the key to causality is to diligently exclude other causes of liver injury, and to identify a characteristic clinical drug-related signature.

Next, we consider the recent case report about a 69-year-old woman developed cholestatic hepatitis after four days of therapy with high-dose Zithromax (azithromycin) for the treatment of suspected bronchitis.

From the Abstract for the article "Azithromycin-induced liver injury", published earlier this year in the American Journal of Health-System Pharmacy we get these key facts:

• After receiving four days of high-dose [Zithromax (azithromycin)] for the treatment of suspected bronchitis, a 69-year-old woman arrived at the emergency room with nausea, vomiting, diarrhea, elevated liver enzyme values, and visible signs of pruritus and jaundice.

• Causes of primary liver injury, including metabolic, viral, and autoimmune liver diseases, were excluded.

• After exclusion of other causes of liver disease, drug-induced hepatotoxicity was considered. A careful review of her medications prior to admission was conducted. A temporal relationship between initiation of [Zithromax (azithromycin)] and the onset of clinical signs and symptoms was noted. The Naranjo et al. probability scale indicated a possible relationship between azithromycin and hepatotoxicity; however, two scales specifically used for evaluating drug-induced liver disease indicated a probable adverse drug-associated event.

Zithromax, sometimes called "Z-Pak", is a popular antibiotic manufactured by Pfizer that is used to treat a variety of bacterial infections.  In recent years Zithromax has been associated with not only hepatitis (as in the case report, above) but also more serious types of liver damage such as liver failure and necrosis of the liver, medical conditions which may require a liver transplant or result in death.

The possibility of liver damage from Zithromax arises because Zithromax, like the other antibiotics in the macrolide class of drugs, is primarily eliminated from the body through the liver.

P.S.  As of February 2011 the FDA is continuing to evaluate liver failure as a potential drug safety issue for Zithromax to determine the need for any regulatory action.

• "Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS) between January – March 2010" (Quarterly Report issued by FDA on or about 2/1/11)

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

Serevent, Advair, and Foradil: Despite The Increased Risk of Severe Asthma Episodes and Death, Monotherapy Use Continues

Numerous Safety Warnings From FDA About These LABA Asthma Drugs Have Seemingly Been Ignored By Patients, According To New Medco Study

(Posted by Tom Lamb at DrugInjuryWatch.com)

As some of you may recall, back in November 2005 the FDA issued a Public Health Advisory regarding Serevent, Advair, and Foradil to inform doctors and patients that the use of asthma medication inhalation powders containing long-acting beta 2-adrenergic agonists ("LABA") may increase one's risk of severe asthma episodes and death.

The asthma inhalation powders addressed in the November 2005 FDA warning are:

• Serevent Diskus (salmeterol xinafoate inhalation powder), made by GlaxoSmithKline;
• Advair Diskus (fluticasone propionate & salmeterol inhalation powder), made by GlaxoSmithKline; and,
• Foradil Aerolizer (formoterol fumarate inhalation powder), made by Novartis Pharmaceuticals Corp.

Almost four-and-a-half years later, on February 18, 2010, that November 2005 Public Health Advisory about these LABA asthma drugs was updated.  From this more recent safety warning, "FDA Drug Safety Communication: New safety requirements for long-acting inhaled asthma medications called Long-Acting Beta-Agonists (LABAs)": 

Safety Announcement

[02-18-2010] Due to safety concerns, the U.S. Food and Drug Administration (FDA) is requiring changes to how long-acting inhaled medications called Long-Acting Beta-Agonists (LABAs) are used in the treatment of asthma. These changes are based on FDA's analyses of studies showing an increased risk of severe exacerbation of asthma symptoms, leading to hospitalizations in pediatric and adult patients as well as death in some patients using LABAs for the treatment of asthma (see Data Summary below).

LABAs are approved as single-ingredient products (Serevent and Foradil) and as an ingredient in combination products containing inhaled corticosteroids (Advair and Symbicort) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). They work by relaxing muscles in the airway and lungs. This helps patients breathe easier, and lessens symptoms such as wheezing and shortness of breath. The new recommendations only apply to the use of LABAs in the treatment of asthma.

To ensure the safe use of these products:

• The use of LABAs is contraindicated without the use of an asthma controller medication such as an inhaled corticosteroid. Single-ingredient LABAs should only be used in combination with an asthma controller medication; they should not be used alone.
  
• LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications. 
  
• LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patients should then be maintained on an asthma controller medication.

• Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA, to ensure compliance with both medications.

During the several years between those two FDA warnings, we reported on some of the developments concerning this still-emerging drug safety issue, as seen by this list of articles posted previously on this Drug Injury Watch blog:

1.  GlaxoSmithKline Will Revise "Black-box" Warning On Its Asthma Drugs Advair And Serevent --Novartis, However, Continues To Disagree With FDA About The Need To Change Label On Foradil   (3/9/06)

2.  Is Advair Use Causing Asthma-related Deaths? -- Glaxo's Best-selling Asthma Drug May Be Unsafe For Some Users   (4/6/06)

3.  Should The Popular Asthma Drug Advair Be Pulled From The Market? -- Study Finds Increased Risk Of Serious Side Effects For A Broad Range Of Users   (6/6/06)

4.  FDA Report Says Popular Asthma Drugs Serevent And Advair May Have Deadly Side Effects For Some Children-- November 2007 Advisory Panel Meeting To Consider Safety of These Glaxo Drugs As Well As Novartis' Foradil   (11/26/07)

5.  November 2007 FDA Advisory Panel Recommends That Serevent And Advair Get Stronger Warnings About Use By Children-- Some Panel Members Want Serevent Withdrawn From Market; FDA And GSK Say Asthma Drug Recall Is Not Appropriate   (11/29/07)

Accordingly, we were surprised earlier today when we saw this May 11, 2010 Medco press release, "Medco Study: Despite FDA Warnings, Nearly One-Third of Asthma Patients Still Treated with Long-Acting Beta Agonists Without Controller Medications, Increasing Their Risk for Complications and Hospitalizations".

From the May 2010 press release from Medco, we get this introduction to what appears to be a continuing, and potentially fatal, problem:

Nearly one-third of asthma patients are taking long-acting beta agonists (LABAs) alone, and not in combination with other asthma control medications, despite years of warnings from the Food and Drug Administration (FDA) on the risk of worsening asthma symptoms and death associated with this practice. This according to a new study from the Medco Research Institute™ and the Medco Pulmonary Therapeutic Resource Center ® (TRC), presented at the 2010 Eastern Allergy Conference and coinciding with National Asthma and Allergy Awareness Month.

For more details, see this clinical research brief from Medco about the new LABA monotherapy-use study: "Prescription patterns of long-acting beta agonist (LABA) monotherapy for patients with asthma".

Our law firm is beginning to investigate death cases involving the use of Advair, Serevent, and Foradil, as well as other LABA asthma drugs.  If you or someone you know has a potential case which you would like us to consider, please send an email to Tom Lamb.

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

Fosamax MDL Litigation Update - May 2010: Maley Case Trial Verdict Goes In Favor Of Merck

Boles Case Retrial Starts On June 2, 2010 And Third Bellwether Trial Is Set For September 2010

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE:  Boles v. Merck Fosamax Trial Jury Verdict Is $8 Million For Plaintiff In June 2010

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The first Fosamax verdict was handed down on May 5, 2010 and, because the jury found that plaintiff Louise Maley had not developed bisphosphonate-related osteonecrosis of the jaw (also known as BRONJ or ONJ), Merck won this lawsuit. 

The case is Maley v. Merck & Co., 06-cv-4110, which is one of the hundreds of federal court lawsuits that are combined in In Re Fosamax Products Liability Litigation, MDL 1789, U.S. District Court, Southern District of New York (Manhattan).

We get these details about the Maley case result from this May 5, 2010 Bloomberg news report, "Merck Wins Second Fosamax Trial on Jaw Death Claims":

Louise Maley of Muncie, Indiana, said she developed osteonecrosis of the jaw, or ONJ, by taking Fosamax, in a complaint filed in May 2006. A federal jury in Manhattan ruled today that Maley didn’t have ONJ....

The trial, overseen by U.S. District Judge John Keenan, began April 19. In September, Keenan declared a mistrial in the first Fosamax case to go to a jury over claims that the drug might hamper blood flow to the jaw, causing jawbone-tissue death. That jury couldn’t reach a unanimous verdict. The case is to be retried in June....

Maley took Fosamax from at least January 1998 to March 2006 to prevent osteoporosis, according to court papers. She stopped taking it due to a throat irritation, according to Merck.

The drugmaker argued in court papers that Maley didn’t offer any evidence Fosamax causes ONJ or that it caused her jaw condition. She was never diagnosed with ONJ, it said.

Instead, she was diagnosed in 2005 with a different condition, neuralgia-inducing cavitational osteonecrosis, or Nico, the company said. That condition doesn’t necessarily imply dead bone, Merck said. It’s characterized by diminished blood flow in the jaw’s bone marrow, causing spaces of marrow to dry out and become hollow, it said.

Maley said in court papers that at least three experts put in reports or pretrial testimony stating that Fosamax causes ONJ. She also said she has ONJ, not Nico, and it was caused by Fosamax.

As alluded to above, the Boles v. Merck trial started in September 2009 and ended in a so-called "mistrial".  The Boles case will be retried, starting on June 2, 2010.

The next case scheduled for trial in the federal court Fosamax MDL was Fleming v. Merck, which was set to begin on January 5, 2010.  In late November 2009, however, Judge Keenan granted Merck's request for summary judgment and dismissed the Fleming case.  In turn, a new bellwether, or test, case was selected; it is scheduled to start in September 2010.

For a current "snap-shot" of the Fosamax litigation, we get this information from Merck's May 5, 2010 press release about this Maley lawsuit verdict, "Merck Wins Second Federal FOSAMAX® (alendronate sodium) Bellwether Trial Jury Rejects Plaintiff's Claims":

This is the second FOSAMAX case to go to trial. The first case, Boles v. Merck, resulted in a mistrial after the eight person jury could not reach a unanimous verdict. The Boles case is set to be retried on June 2, 2010. As of December 31, 2009, approximately 978 cases, which include approximately 1,356 plaintiff groups, had been filed and were pending against Merck in either federal or state court.

Of course, we will be following the Boles case retrial in June and will report the outcome of this next Fosamax MDL trial as soon as possible after the jury verdict for that lawsuit is announced.

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