The FDA issued an early communication last August indicating that they were investigating reports of Xenical and Alli liver damage. In a follow up drug safety communication issued Thursday, the agency indicates that at least 13 cases of severe liver injury from Alli and Xenical have been found, including at least two cases where patients died and three where a liver transplant was needed.

Xenical (orlistat 120mg) is a prescription medication that was approved by the FDA in 1999. The lower dose Alli (orlistat 60mg) is an over-the-counter weight-loss drug that was approved in 2007. Both drugs are marketed by GlaxoSmithKline, PLC, though Xenical is manufactured by Roche.

The medications are intended for use together with a reduced-calorie diet. They work by preventing the absorption of fats, thereby reducing caloric intake. In 2008, Xenical generated sales of $30 million and Alli generated sales of $131 million during its first full year on the market.

The new label changes will warn of rare cases of severe liver injury, and indicate that healthcare professionals and consumers should watch for symptoms of liver injury, including:

• Itching yellow eyes or skin
• Dark urine
• Light-colored stools
• Loss of appetite

Patients should stop using the drugs and contact their healthcare professional if these symptoms develop.

The FDA notes that an estimated 40 million individuals have used the medications, and only one of the reports of liver problems were found in the United States, involving a user of Alli. The remaining 12 cases occurred outside the United States, and involved liver problems with Xenical. There has been no direct causal relationship established between the two orlistat-based drugs and liver injury.

The primary known side effects of Alli and Xenical include oily and loose stools, fecal incontinence, frequent or urgent bowel movements and flatulence, which tend to be most severe when the treatment is started and may decrease with time.

There have been suggestions that orlistat could increase the risk of colon cancer and breast cancer, and the consumer advocacy group Public Citizen has called for an Xenical recall since 2006.

Health Canada issued the Avelox liver injury warning to health care professionals on Monday, following a safety review of Avelox side effects. The reviewers concluded that Avelox can cause rare, but potentially fatal, liver injury and liver failure.

Health Canada is requiring Bayer to update the label warnings of the drug in Canada to include the association with severe liver injury.

Avelox (moxifloxacin) is an antibiotic sold by Bayer, which was approved in the United States by the FDA in 1999. It is currently sold in more than 80 countries. Avelox is a member of a family of drugs known as fluoroquinolones, which includes other antibiotics such as Levaquin, Cipro, Proquin, and Floxin. They are used to prevent infection by stopping the reproduction of bacteria and are a popular class of medications.

All of the drugs of this class have been linked with an increased risk of tendon ruptures, but the risk appears to be greatest with Ortho-McNeil-Janssen Pharmaceuticals, Inc.’s Levaquin (levofloxacin). According to reports received by the FDA, Levaquin tendon ruptures accounted for 61% of all fluoroquinolone-associated ruptures between November 1997 and December 2005. However, the drug only accounted for about 45% of all prescriptions written for fluoroquinolones during that time.

Fluoroquinolones, as a group, were also linked to vision problems by a September 2010 study by researchers from the Casey Eye Institute in Oregon. They found that the drugs could cause double vision, a condition that goes away when patients stop taking the drug.

According to a statement posted Thursday on the FDA MedWatch website, the new label will contain a boxed warning indicating that Exjade may cause renal impairment, including kidney failure, hepatic impairment, including liver failure, and gastrointestinal hemorrhage. Among some reported cases, these problems with Exjade were fatal.

The warnings come approximately five months after the FDA issued an early communication in September 2009 to alert healthcare professionals that they were reviewing the potential side effects of Exjade.

Exjade (deferasirox) is an iron chelating medication manufactured by Novartis for people with chronic anemia and iron overload due to a blood transfusion. It was approved by FDA in November 2005, and generated $531 million in sales in 2008.

In 2007, the FDA warned that the drug could cause kidney failure and had resulted in at least eight deaths. The drug’s warning label was subsequently updated to include risks of kidney failure, blood vessel inflammation, hives, and hypersensitivity.

In the most recent safety review, the FDA looked at adverse event data for Exjade and data from a global safety database. The agency concluded that that older patient suffering from myelodysplastic syndrome (MDS) may face a greater risk when compared to younger patients with other chronic anemias.

MDS is a disorder where the patient’s bone marrow does not create enough normal blood cells, resulting in anemia. Those with MDS often need regular blood transfusions, which can cause a buildup of iron in the blood known as iron overload. Iron overload can cause damage to the heart, liver and other organs.

The new warning suggests that doctors closely monitor patients taking Exjade. In particular, they should watch for changes in creatinine levels, as well as changes in the levels of transaminases and bilirubin.

The study, published late last month in the American Journal of Gastroenterology, looked at 17 cases of liver damage where Hydroxycut may have been a factor and found that in many of them, the likelihood that the weight-loss supplement was the cause of the damage was almost a certainty. In addition, the study suggests that the number of people affected by Hydroxycut liver damage could be much larger than the number of cases that prompted a Hydroxycut recall last May.

Hydroxycut is a dietary supplement and weight-loss aid that was recalled on May 1, 2009, after the FDA identified a number of reports where users suffered serious and potentially life-theatening liver damage. The FDA also reported that use of Hydroxycut was linked to reports of seizures, heart problems and a rare muscle damaging condition known as rhabdomyolysis.

Iovate Health Sciences, the manufacturer, faces a number of Hydroxycut lawsuits over liver damage and other injuries in state and federal courts. The federal cases have been consolidated and centralized for pretrial proceedings as part of an MDL, or multidistrict litigation, in the U.S. District Court for the Southern District of California. All of the cases in the litigation over Hydroxycut involve allegations that Iovate Health Sciences failed to adequately research their weight-loss products or warn about potential side effects of Hydroxycut.

In the new study, researchers looked at cases that had not yet appeared in medical literature, and examined the patients’ risk factors for liver disease, and the timing of Hydroxycut usage in connection with liver damage. In eight cases, scientists said there was a greater than 95% chance that the weight-loss supplement caused the patients’ liver damage. In five of the 17 cases, researchers concluded that it was “highly likely” that Hydroxycut caused the patients’ liver damage, meaning there was a 75% to 95% chance. In another two cases, Hydroxycut was ruled probably to blame, with a chance of 50% to 74%.

Researchers were able to eliminate most other likely causes for the liver damage. Subjects were generally healthy, with an average age of 30, and they were able to eliminate autoimmune diseases and exposure to other toxins that may have caused liver problems. In their conclusions, the researchers warned consumers to be cautious about the use of such weight-loss supplements, which are not clinically tested and do not need to be approved by FDA.

The Videx side effects warning was issued on January 29 by the FDA. The agency noted that it has received 42 adverse event reports among users of Videx and Videx EC involving the rare, but serious, liver disorder over the last 18 years. At least four of the patients died from bleeding or liver failure on Videx after developing the condition.

Videx (didanosine) is an antiretroviral drug marketed by Bristol-Myers Squib. It was first approved by FDA in 1991. In 2000, the FDA approved a delayed-release version called Videx EC. The drug belongs to a class of medications known as nucleoside analogues, and reduces the growth of HIV.

Non-cirrhotic portal hypertension is the result of restricted blood flow through a major vein in the liver. The blood backs up to veins in the esophagus, which become enlarge and distended. The enlarged veins can sometimes rupture, leading to serious bleeding and, potentially, death.

Despite the risk of Videx liver damage, the FDA says that the drug should stay on the market, because the benefits for HIV patients still outweigh the risks. The FDA is requiring new label warnings, as well as changes to the medication guide to alert users about the potential risk of the Videx side effects. The drug already has been known to cause liver toxicity when combined with some other antiretroviral medications, such as hydroxyurea and ribavirin.

The FDA recommends that doctors with patients taking Videx regularly monitor for signs of portal hypertension.

The product liability lawsuits were filed on November 17 on behalf of Jesse Woods and Heath Stevison in Galveston County District Court in Texas against Competitive Edge Labs, the manufacturer, and TF Supplements, which distributed the products. According to a report by Iron Magazine, the claims allege that the dietary supplements are defective and unreasonably dangerous, resulting in both men suffering liver damage.

Both plaintiffs say they were hospitalized with signs of liver failure after taking M-Drol for several weeks in an effort to put on muscle mass. Woods also said he took P-Plex, another Competitive Edge Labs supplement, which also allegedly contributed to his injuries. The products were bought online through Galveston-based TF Supplements.

The M-Drol lawsuits say Woods and Stevison suffered permanent liver damage from taking the supplement, and have accused the defendants of negligence, product liability and breach of warranty. TF Galveston has stopped selling M-Drol.

Competitive Edge Labs’ website has a notice that it has ceased to sell M-Drol and P-Plex.

Dietary supplements have come under increased scrutiny in recent months by federal regulators in the wake of a Hydroxycut recall issued in May, after FDA identified a number of reports where users suffered serious and potentially life-threatening liver damage. In July, the FDA warned consumers not to take dietary supplements which contained ingredients identified as steroids. The agency recommended that anyone taking dietary supplements containing steroids should immediately see a doctor if they showed signs of liver problems.

A number of Hydroxycut lawsuits have been filed throughout the country against the maker of that supplement, Iovate Health Sciences. In October, all federal lawsuits were consolidated as part of a multidistrict litigation (MDL) for pretrial proceedings in the U.S. District Court for the Southern District of California. All of the cases in the Hydroxycut litigation involve allegations that Iovate Health Sciences failed to adequately research their weight-loss products or warn about potential side effects prior to issuing the Hydroxycut recall.

Intelence (etravirine) was approved by the FDA in January 2008 for use in combination with other drugs to treat HIV or AIDS. It is manufactured by Tibotec Therapeutics, a subsidiary of Johnson & Johnson.

Although the drug’s label already included information about potential skin reactions as a side effect of Intelence, the severity of reactions found in post-marketing reports, including at least one death, has resulted in a strengthening of the warnings.

According to a letter sent by Tibotec this month to healthcare professionals, one patient has died from toxic epidermal necrolysis (TEN), which is a more severe version of Stevens-Johnson syndrome (SJS), and one other has been seriously injured. A third patient reportedly developed SJS and suffered liver failure after beginning Intelence treatment. As a result, doctors have been cautioned to stop treatment immediately if patients show signs of skin hypersensitivity or severe skin reactions.

“Discontinue Intelence immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia).” the letter to healthcare professionals states. “Clinical status including liver transaminases should be monitored and appropriate therapy initiated. Delay in stopping Intelence treatment after the onset of severe rash may result in a life-threatening reaction.”

Stevens-Johnson syndrome is a severe skin reaction that is known to occur as a side effect of several medications. It is highly debilitating and causes the skin to burn from the inside out, producing blisters, severe rashes and the skin may begin to fall the body. When the skin lesions affects more than 30% of the body, the condition is referred to as Toxic Epidermal Necrolysis (TEN). Treatment in a hospital Intensive Care Unit (ICU) or Burn Unit is often required, and the conditions are fatal in many cases.

Alli (orlistat 60mg) is an over-the-counter product that was approved by the FDA in 2007 to help promote weight loss when used together with a low-calorie, low-fat diet. During its first full year on the market in the United States, Alli generated $131 million in sales for GlaxoSmithKline and has been viewed as a very important product for phamaceutical company.

On August 24, the FDA issued an Early Communication to notify the public that they are reviewing a potential liver damage risk with Alli and Xenical, a prescription version of the weight loss drug that contains 120 mg of orlistat. The FDA has received 32 reports of liver injury among users of orlistat weight loss drugs, including 27 cases that resulted in hospitalization and six that involved liver failure. The most common symptoms reported were jaundice, weakness or fatigue and stomach pain.

In a press release issued on August 25, GlaxoSmithKline refuted the potential Alli liver damage risk, pointing out that orlistat has been well-studied and no evidence has been found to indicate that it causes liver damage. The drug maker also pointed out that there can be many causes of liver damage, and people who are overweight and obese are predisposed to such disorders.

“alli is a ‘non-systemically’ acting medicine – it is minimally absorbed in the blood and works locally in the gastro-intestinal tract,” said GlaxoSmithKline in the statement responding to the FDA’s Early Communication. “There is therefore no obvious biological mechanism to suggest liver damage can occur with alli.”

An Early Communication by the FDA does not mean that any conclusions have been made that there is a causal relationship between Alli and liver damage. The communication is designed to keep the public informed of ongoing safety reviews involving drugs, and the agency indicated that they will communicate their findings as soon as the review of orlistat liver side effects is complete.

At this time, the FDA has urged consumers to report any Xenical or Alli side effects to their MedWatch Adverse Event Reporting program and to contact their doctors if they are experiencing symptoms possibly associated with the development of liver damage.

The FDA indicates that consumers currently taking Alli should continue to use the product as directed, and users of Xenical have been advised keep taking the drug as prescribed, pending any final conclusions.

GlaxoSmithKline PLC’s Avandia (rosiglitazone) and Takeda’s Actos (pioglitazone) are type 2 diabetes drugs, which are both part of the same class of medications known as thiazolidinediones (TZDs).

In August 2007, the FDA added a black box heart failure warning to both drugs, which is the strongest warning that can be placed on a prescription medication. However, a Canadian study published in the August 19 online issue of the British Medical Journal provides further evidence that the risk of heart failure and death among patients 66 years and older is greater for Avandia.

The retrospective cohort study looked at data from 39,736 patients who used Avandia or Actos over a six-year period. For every 93 patients treated with Avandia instead of Actos, researchers found that there would be one additional case of Avandia heart failure, which is a condition where the heart can not pump a sufficient amount of blood to other organs.

“Among older patients with diabetes, pioglitazone is associated with a significantly lower risk of heart failure and death than is rosiglitazone,” researchers said in the study’s conclusion. “Given that rosiglitazone lacks a distinct clinical advantage over pioglitazone, continued use of rosiglitazone may not be justified.”

The conclusion matches concerns expressed by both the American Diabetes Association (ADA) and the consumer advocacy group Public Citizen. In 2008, the ADA recommended against the use of Avandia, and Public Citizen has petitioned the FDA for an Avandia recall.

In addition to the risk of heart failure, other reports have suggested that Avandia side effects may also increase the risk of heart attacks, liver failure, bone fractures, vision loss known as macular edema and death, leading many to conclude that the risks outweigh any potential benefits provided by Avandia.

GlaxoSmithKline PLC currently faces hundreds of lawsuits over Avandia filed by users who allege that the drug maker failed to adequately warn about the health risks associated with the drug. All federal Avandia lawsuits have been consolidated in an MDL, or Multidistrict Litigation, centralized in the Eastern District of Pennsylvania, where the first trial is scheduled to begin early next summer.

Concerns over Actos and Avandia fractures have existed for some time, but recent studies, including the most recent study published in the Archives of Internal Medicine, have begun to quantify and confirm those suspicions. The newest report, which is the largest to date, studied the fracture rates of diabetics using thiazolidinediones, which includes Avandia (rosiglitazone) and Actos (pioglitazone).

The study looked at 84,339 patients from British Columbia, Canada, and compared the bone fracture rates of patients on thiazolidinedione with those taking another class of antidiabetic drugs known as sulfonylureas. Both classes of drugs are prescribed for the treatment of type 2 diabetes, and researchers found users of Actos and Avandia faced a 28% increased risk of fractures.

Avandia is manufactured by GlaxoSmithKine PLC, and Actos is manufactured by Takeda Pharmaceuticals North America, Inc.

The Avandia fracture risk is one of several safety concerns associated with GlaxoSmithKline’s drug, which have caused many to call for it to be removed from the market. Other studies have indicated Avandia side effects could also increase the risk of heart attacks, congestive heart failure, liver failure and a type of vision loss known as macular edema.

The FDA added a “black box” warning in 2007 regarding the Avandia heart attack risk, which some experts say could be responsible for as many as 100,000 heart attacks since the drug was first introduced.

The consumer group Public Citizen filed a petition with the FDA last year calling for an Avandia recall, indicating that the risks associated with the medication outweigh any potential benefit provided over other available medications. The American Diabetes Association, European Association for the Study of Diabetes and other experts have also questioned the continued use of Avandia.

GlaxoSmithKline PLC currently faces thousands of Avandia lawsuits filed by individuals who allege that the drug maker failed to adequately research their medication or warn about the serious side effects. In federal court, the Avandia litigation is consolidated in an MDL, or Multidistrict Litigation, in the U.S. District Court for the Eastern District of Pennsylvania for pretrial litigation.