Defective Drug News

Axcil and Desirin

10/17/07 - Be Careful How you Control Your Diet

Some people exercise to the point of passing out regularly, eat almost nothing but foods that contain no fat and try just about everything possible to either maintain or lose weight.  Unfortunately, for different reasons, these efforts just don’t always produce the results for some, which is why so many people in the United States turn to pills for help with their diets and weight problems. 

Sometimes, these dietary supplements will help with the overall effort people are making.  However, whenever someone buys something that’s available in any store and that affects the metabolism directly, risk is involved, regardless of the person’s general health situation.  The most daunting aspect of this reality is that the side effects that people can experience with many over-the-counter dietary supplements can be extremely serious.

This general belief was reinforced tangibly in recent weeks by the recall of two products manufactured and sold by TWC Global LLC, Inc. – Axcil and Desirin, dietary supplements that have come under intense scrutiny that led to a voluntary recall that was publicized by both TWC Global and the FDA.

The Problem
These two products have been marketed and sold as dietary aids, and the crux of the danger with them is the presence of what is officially termed as “undeclared ingredients.”  These ingredients, it turns out, can lead to serious problems for those who used these products, especially those who took them and have conditions including diabetes, high blood pressure, high cholesterol and heart problems who often take other medications to control these conditions.

Specifically, Axcil and Desirin have been found to contain sildenafil, the active ingredient in many erectile dysfunction pills, as well as sulfosildenafil and sulfohomosildenafil, both of which are analogs of sildenafil.  These ingredients have been known to interact negatively with the nitrates that are often present in medications that treat the conditions stated above.

Another aspect of this issue is that many men who suffer from conditions such as high blood pressure and diabetes often suffer from erectile dysfunction, but the interaction of sildenafil and nitrates creates a chemical reaction inside the body that can lower the blood pressure to dangerous levels. 

Anyone who has been taking these pills is advised to stop doing so immediately.  These unfortunate consumers should also seek immediate medical attention to make sure that no undiscovered side effects are beginning to take effect.  After you’ve received the medical evaluation you need, contact a defective drugs attorney as soon as possible to schedule an initial consultation.

Ortho Evra

Exclusive: Women Claim Birth Control Patchs' Risks

Undisclosed Women Claim Ortho Evra Patch Gave Them Blood Clots, Pulmonary Embolisms

POSTED: 10:18 pm MST February 8, 2007

AP-DENVER -- More than 4 million women use the birth control patch, but the patch may hold risks for some women who use it, risks they may not be aware of.
A number of women told 7NEWS that the patch ruined their lives. They all made the choice to use the patch because they said they were told it was just as safe as other birth control.

Six Colorado women said they believe they were victims of a corporate secret. Three of the women had pulmonary embolisms and three had blood clots. All six said they never were informed about the greater risks associated with taking the Ortho Evra birth control patch.

"I just remember thinking that I was going to die," said Merlinda Maldonado, who used the Ortho Evra birth control patch.

"I was awakened by what I thought was a heart attack. I was in excruciating pain," said Carrie Grater.

"I had a blood clot that went from my ankle up to my knee," said patch-user Myndee Allen.

All of them thought they were at no greater risk with the patch than with the pill, saying that's what they were told.  But it's what the women said they were not told that raises questions about patchmaker Johnson & Johnson.

When it hit the market in 2002, women were not told the patch contained 60 percent more estrogen than the common 35 microgram oral contraceptive. They were not told that the patch more than doubled their chances of experiencing problems with clotting, heart attacks, stroke and pulmonary embolisms.

"They didn't do enough testing and they ultimately didn't know how much estrogen the patch was going to deliver," said Colorado attorney Michael Burg.  Burg represents some of the more than 4,000 women nationwide claiming they were injured by the Ortho Evra patch.  "Their lives have changed for the rest of their life because Johnson & Johnson and Ortho-McNeil told them, 'Change your contraceptive. It's more convenient,' without telling them, 'Oh, by the way, we're going to double your risk of getting blood clots, pulmonary embolisms, strokes and heart attacks.' It's outrageous," Burg said.

Burg's accusation gets support in a recent legal filing from a doctor who worked for patchmaker Ortho-McNeil and Johnson & Johnson. In a lawsuit over wrongful termination, Dr. Joel Lippman claims he warned the company of serious health concerns connected to the patch -- claims that Johnson & Johnson has denied.

In the lawsuit, Lippman said the patch "released dangerously high levels of estrogen into patients." The complaint also said Lippman advised that the company should "conduct further research to understand the impact of the hormones released by the patch." Lippman said in the legal filing that Ortho disregarded his concerns and launched the product.

"He had told them not to put it on the market and his suggestion was just ignored," Burg said.

Last September, the FDA required the maker of the patch to provide better warnings, but for the six former users who talked to 7NEWS, they said the warnings came too late.  They said the change to the label and the addition of a 98-word warning inside a 19,000-word insert are far too subtle, leaving women at risk.

7NEWS Investigator Tony Kovaleski asked the group of women if they believed Ortho Evra is properly informing women today.  They all said "no."

Ortho-McNeil declined 7NEWS' request for an on-camera interview, saying they cannot comment on ongoing litigation.  The company did say the patch is a safe and effective birth control choice when used as directed.

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Wrongful-Death Lawsuit Filed Against Ortho Evra Manufacturer Ortho-McNeil

18 Dec 2006

AP- Tennessee--The mother of a woman who died in June 2003 after using Johnson & Johnson subsidiary Ortho-McNeil's birth control patch Ortho Evra recently filed a wrongful-death lawsuit in San Francisco Superior Court alleging that the company knowingly misinformed the public about the drug's risk of severe side effects, the AP/San Jose Mercury News reports. Celena Devault, a 26-year-old woman from Tennessee, began using Ortho Evra in April 2003 and died of a pulmonary embolism in June 2003. Her mother, Mary Devault, filed the lawsuit alleging Ortho McNeil misled the public about the drug's risk of side effects, including pulmonary embolism, stroke, deep vein thrombosis and blood clots (AP/San Jose Mercury News, 12/12).

The Associated Press in July 2005 reported that, according to FDA records it obtained through a Freedom of Information Act request, women using Ortho Evra in 2004 were three times as likely as women using birth control pills to die or develop nonfatal blood clots.  The FDA in November 2005 updated its warning label for the drug to say that women who use Ortho Evra have a higher risk of experiencing blood clots and other side effects than previously stated (Kaiser Daily Women's Health Policy Report, 11/11/05). The FDA in September announced it had updated the warning label to include information from two conflicting studies on increased risk of blood clots among patch users (Kaiser Daily Women's Health Policy Report, 10/18).

Another pending lawsuit filed by 55 women alleges they experienced blood clots and other serious illnesses that they claim were caused by Ortho Evra. "We believe that Ortho-McNeil knew of the dangers of the Ortho patch sold in the U.S. and choose to ignore them," Brian Kabateck -- whose law firm Kabateck Brown Kellner, along with the Law Offices of Shawn Khorrami, filed both suits -- said, adding, "Patches sold in other countries, including Canada, actually contain a smaller, less dangerous dosage." Ortho-McNeil does not comment on pending litigation, according to Gloria Vanderham, spokesperson for Ortho Women's Health and Urology.

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Zyprexa

Manufacturer Eli Lilly Loses Effort to Censor Zyprexa Documents off the Internet

AP- NEW YORK - February 13 - A U.S. District Court judge today refused Eli Lilly's request to ban a number of websites from publishing leaked documents relating to Zyprexa, Eli Lilly's top-selling drug. Although the judge rejected the First Amendment arguments made by a variety of individuals eager to publish the documents, the court concluded that "it is unlikely that the court can now effectively enforce an injunction against the Internet in its various manifestations, and it would constitute a dubious manifestation of public policy were it to attempt to do so." The order is a victory for the Electronic Frontier Foundation (EFF), which represents an anonymous individual who was previously barred by the court's earlier orders from posting links to the Zyprexa documents on zyprexa.pbwiki.com.

The Zyprexa documents were leaked from an ongoing product liability lawsuit against Eli Lilly. The internal documents allegedly show that Eli Lilly intentionally downplayed the drug's side effects, including weight gain, high blood sugar, and diabetes, and marketed the drug for "off-label" uses not approved by the Food and Drug Administration (FDA). The documents were the basis for a front-page story in the New York Times in December of last year, and electronic copies are readily available from a variety of Internet sources. EFF's client posted links to one set of copies on a wiki devoted to the controversy that were part of extensive, in-depth analysis from a number of citizen journalists.

"This ruling makes it clear that Eli Lilly cannot invoke any court orders in its futile efforts to censor these documents off the Internet," said EFF Staff Attorney Fred von Lohmann. "We are disappointed, however, that the judge failed to appreciate that its previous orders constituted prior restraints in violation of the First Amendment."

The court stayed its ruling for 10 days in order to permit an appeal. Zyprexa is Eli Lilly's best selling drug, used to treat schizophrenia and bipolar disorder. Eli Lilly has paid more than $1.2 billion to resolve lawsuits involving Zyprexa.

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Puzzle of antipsychotic drug Zyprexa weight gain solved

WASHINGTON, Feb 12 (Reuters) - Researchers said on Monday they have pinpointed the reason some drugs used to treat mental illnesses like schizophrenia cause patients to gain a lot of weight, raising hope for developing drugs without this side effect.

Antipsychotic medications such as Zyprexa, made by Eli Lilly and Co., increase the activity of an enzyme called AMPK in cells in the part of the brain that regulates eating behavior, according to research in mice led by scientists at Johns Hopkins University in Baltimore.

"It's a big increase and it occurs with very little doses of the drug," Dr. Solomon Snyder, professor of neuroscience at Johns Hopkins School of Medicine, said in an interview.

The study was published in the Proceedings of the National Academy of Sciences.

Zyprexa's use has been crimped by concerns over weight gains. Patients using antipsychotic drugs tend to put on so many pounds that they are at heightened risk for serious complications including diabetes and heart disease.

"Their use has been hampered primarily by the fact that for some of them there is this horrible gain, largely due to just eating too much from increased appetite, and others don't do that," Snyder said. 
"Unfortunately, Zyprexa, which everybody agrees is the best therapeutic agent, gives the worst weight gain, along with clozapine, the parent drug in the class. And it was sort of a puzzle," Snyder added.

The researchers also showed that AMPK's increase was because the antipsychotic drugs were interfering with the important protein histamine, which is involved in allergy symptoms and long has been suspected for a role in weight control.

Snyder said the findings point to the possibility of developing a new generation of antipsychotic drugs that are effective but do not cause weight gain.

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Fentanyl Patch

July 17, 2005-FDA Issues Public Health Advisory on the Fentanyl Patch

The FDA today issued a Public Health Advisory regarding the safe use of transdermal fentanyl patches in response to reports of deaths in patients using this potent narcotic medication for pain management. In addition, a patient information sheet and an alert to healthcare professionals were issued identifying several important safety precautions for the use of fentanyl transdermal patches. These safety precautions include but are not limited to patient education regarding signs of overdose, proper patch application, use of other medications while using the patch, safeguards for children, and proper storage and disposal.

The FDA is conducting an investigation into the deaths associated with these patches. The Agency has been examining the circumstances of product use to determine if the reported adverse events may be related to inappropriate use of the patch or factors related to the quality of the product. It is possible that some patients and their health care providers may not be completely aware of the dangers of these potent narcotic drug products and the important recommendations regarding their safe use.

The Agency is working closely with the manufacturers of fentanyl patches to fully evaluate the risks associated with their use and to develop a plan to help patients avoid accidental fentanyl overdose.

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Teenager Overdoses on Fentanyl Patch

ABC News- Dec. 10, 2006

A 17-year-old Washington State high school senior overdosed on a pain patch, causing some people to question the safety of pain treatment that is growing in popularity. Worn on the skin, pain patches release powerful pain killers into the wearer's system.

The 17-year-old boy is still hospitalized and in critical condition after using a fentanyl patch without a prescription. The teen reportedly got the drug from a fellow student at school, and took it while on other medications.

The fentanyl patch must be prescribed by a doctor and can be 80 times more powerful than morphine. It is usually only prescribed to people suffering from chronic pain.

The patch works similarly to the nicotine patch and the birth control patch by delivering medication through the skin on a time release system.

A Beaverton, Ore., man who did not want his name or face broadcast, told ABC affiliate KATU that a fentanyl overdose led to the death of his wife just two months ago. The 65-year-old woman was prescribed the patch for stomach pain and took more than the prescribed amount.

"One patch is supposed to last for three days, and she used all five patches from Thursday to Sunday," the man said. "She was in such pain, she probably didn't really know what she was supposed to do."
He said he hopes others can learn from her story.

"The patch is one of many methods … that are very safe and effective and can be very dangerous when abused or used without the help of a physician," said Dr. Scott Fishman, chief of the pain medicine division at the University of California, Davis, and author of "The War on Pain." "There may be a perception that a patch is safer than a pill and that's certainly not the case."

Instead, Fishman said, patches need to be used with caution and care.

"Typically, an overdose starts with sedation," he said, "and progresses with a loss of consciousness and a loss of breathing."

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Fentanyl Patch Abuse Blamed for Deaths

ST. LOUIS Jun 16, 2006 (AP)

Justin Knox bit down on the bitter-tasting patch, instantly releasing three days' worth of a drug more powerful than morphine. He was dead before he even got to the hospital.

The 22-year-old construction worker and addict was another victim in an apparent surge in U.S. overdoses blamed on abuse of the fentanyl patch, a prescription-only product that is intended for cancer patients and others with chronic pain and is designed to dispense the medicine slowly through the skin.

"I cannot tell you the amount of people I've seen and the creative ways they abuse this drug," said Dr. Scott Teitelbaum, director of the Florida Recovery Center in Gainesville, Fla. "Fentanyl has been abused for years. But recently there has been an increase. I've seen more chewing, squeezing of the drug off the patch and shooting it up."

Fentanyl, a synthetic narcotic, was introduced in the 1960s, but it was not until the early 1990s that it became available in patch form. Last year, the first generic versions of the patch hit the market.

At least seven deaths in Indiana and four in South Carolina since 2005 have been blamed on abuse of the fentanyl patch, along with more than 100 deaths in Florida in 2004. About a week after Knox's death in Farmington, Mo., in March, a second man in the same county was prescribed the patch legally and died after injecting himself with the gel that he had scraped from it.

Emergency-room visits by people misusing fentanyl shot up nearly 14-fold to 8,000 nationwide between 2000 and 2004, according to the U.S. Department of Health and Human Services. The figures do not indicate how many of those ER visits were because of the patch.

(In recent months, more than 100 deaths have been reported from Chicago and Detroit to Philadelphia among drug addicts who overdosed on heroin mixed with fentanyl. And federal drug agents believe fentanyl is being made in clandestine labs in Mexico and elsewhere.)

The first fentanyl patch was Duragesic, made by Johnson & Johnson. Sales more than tripled from 2000 to 2004. Worldwide sales were more than $2 billion in 2004, and half of that was in the U.S., according to the J&J's Web site. More than 5.7 million prescriptions were written in 2003 for the Duragesic patch, according to IMS Health.

Mark Wolfe, spokesman for PriCari, the J&J unit that oversees Duragesic, said the product comes with strong "black box" warnings about the dangers of abusing Duragesic.

One theory is that addicts are turning to the fentanyl patch because of a government crackdown on abuse of another powerful prescription painkiller, OxyContin, or oxycodone.

"The abuse of oxycodone and the fear of litigation is enough to scare doctors from prescribing it. Duragesic is in vogue, as we've seen over the last year and a half and two years," said Dr. John Brandt, a chronic-pain specialist at the University of Florida.

In Missouri, the man accused of illegally selling the fentanyl patch to Knox has been charged with murder.

"The awareness is just not out there. I had never heard of this patch," said Knox's mother, Rose Marler. "There's a new generation of drugs and people just need to be aware."

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Ketek

FDA restricts use of antibiotic Ketek

Feb 12, 2007 | AP

The government on Monday restricted use of an antibiotic linked to rare reports of severe liver problems, including several deaths, saying the drug now should be used only to treat pneumonia but not less serious bacterial infections like bronchitis and sinusitis.

The Food and Drug Administration said the antibiotic, Ketek, would remain on the market but that its label will bear a new, stern warning. The agency said it and manufacturer Sanofi-Aventis SA also created a guide for patients outlining the drug's risks and its safe use.

The changes are in line with the December recommendations of a panel of FDA expert advisers that the agency modify the label of the drug, also called telithromycin. In 17-2 votes, the outside advisers said the drug's benefits don't outweigh its risks in treating bronchitis and sinusitis, which are less serious infections than pneumonia and often spontaneously resolve on their own.

"The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications," the FDA said in a statement.

The FDA announced the changes on the eve of a House subcommittee hearing on drug safety that will examine irregularities in the approval of Ketek. The FDA's handling of the antibiotic remains under investigation by the Senate as well.

A new so-called "black-box" warning on the Ketek label states the drug should not be used in patients with myasthenia gravis, a disease that causes muscle weakness, the FDA said. The label also now warns about cases of visual disturbances and loss of consciousness reported in some patients.

The label already warns of the drug's risk to the liver. An FDA review released in December cited 13 reports of liver failure in patients treated with the drug.

As of late last year, doctors had prescribed the antibiotic more than 5.6 million times in the United States since it won FDA approval in 2004.

"Ketek, when used as directed in its approved indication, continues to be an important option" for fighting infections "helps to satisfy a medical need," Sanofi-Aventis said in a statement.

The antibiotic Ketek was originally approved in 2004 and is manufactured by Sanofi Aventis.

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Iraq War Veteran Suffers Liver Disease on Ketek

Dec 12, 2006 | AP

Doctors have diagnosed Iraq War Veteran Chuck Gregg with "drug induced hepatitis" after using Ketek. Gregg says he was in the hospital just five days after being prescribed the powerful antibiotic.
Gregg says he had no history of liver problems and was in good health prior to using Ketek. "He survived 13 months in Iraq... to come home for this," says Sherry Gregg, his wife.
More disturbing is what some believe may be an FDA cover up of indications that the drug posed serious dangers to some.
According to Dr. David Ross, a doctor who formerly worked for the FDA and quit "in disgust" when he could not get his superiors to pay more attention to warning signs:
"Based upon the data available to me, I believe this drug is far more dangerous than other drugs that fight the same infections..."
When his boss, Andrew Von Eschenbach, was informed of potential problems, employees were allegedly told to keep their concerns in-house (at the FDA) and out of the press.
Fosamax

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Dentists concerned about cases of decaying jaw bones

Dec 19, 2006 | www.tribstar.com

Dentists in Terre Haute are among those in the profession who are becoming more concerned about increasing cases of decaying jaw bones apparently linked to osteoporosis drugs such as Fosamax.

The technical name for dying jaw bone is Osteonecrosis of the Jaw, known as ONJ. Symptoms, which may take weeks or months to appear, include pain, loose teeth, exposed jaw bone in the mouth and drainage, according to the American Dental Association Web site.

The drugs being linked to the condition are known as bisphosphonates. They include Fosamax, Actonel and Boniva, which come in pill form, as well as other bone-strengthening medications given through IVs. The oral drugs are often prescribed for osteoporosis patients. The IV versions are more commonly prescribed for patients dealing with cancers that may attack their bones.

“This is a big topic with us right now,” said Terre Haute dentist Dr. Aaron Luttrell, president of the Western Indiana Dental Society.

The ADA is warning dentists to avoid “invasive dental procedures” in patients on IV bisphosphonates and is recommending a “conservative” approach to dental procedures for any patients using oral bisphosphonates. The organization also recommends anyone planning to begin taking bisphosphonate therapy have any dental procedures done before taking the drugs.

Some cases of ONJ have appeared after someone using bisphosphonates has had a tooth pulled or some other dental procedure, but other cases have appeared “spontaneously,” according to a recent article in Dental Economics.

“We’ve seen about five or six patients” with ONJ, said Dr. Michael Deady, a Terre Haute-based oral surgeon. All his patients were on oral bisphosphonates, mostly Fosamax, he said. Some of the cases appeared linked to previous dental procedures, others appeared “spontaneously,” he said.

“Experimental data is a little bit lacking,” on how exactly bisphosphonates are linked to ONJ, said Dr. Don-John Summerlin, a professor of oral and maxillofacial pathology at the IU Medical Center in Indianapolis. “There’s a lot we don’t know yet,” he said.

One prominent theory, however, holds that because bisphosphonates impede cells in the body that remove old bone tissue while allowing cells that add new bone tissue to continue to function as usual, a patient’s bones “become denser and denser,” Summerlin said.

And while this makes bones tougher to break, it may also make it more difficult for them to heal or naturally rebuild themselves, especially after a dental procedure such as a tooth extraction, according to James H. Foulkes, a Terre Haute dentist and former president of the Academy of General Dentistry.

Why the problem affects jaw bones and not so much other bones may be because of the “unique” quality of that bone, according to Luttrell. The jaw bone breaks down and rebuilds itself more than other bones, he said.

“As far as the dental profession is concerned, there is a definite link [between ONJ and bisphosphonates] and there is no question about that,” Foulkes said. “Our controversy is how to deal with it.”

Lawyers are seizing on the data linking Fosamax a best selling osteoporosis drug and other bisphosphonates to ONJ and are advertising to represent ONJ patients who have taken bisphosphonate drugs, whether orally or through an IV. Locally, at least one firm is advertising for such clients.

As of May of this year, Merck and Co. Inc., the pharmaceutical company that makes Fosamax, reported 15 ONJ-related lawsuits had been filed against it, according to CNNMoney.com. In one case, “seven figures” are being sought in damages, CNN reported.

Of the more than 20 million Americans using oral bisphosphonates, the number of reported cases of ONJ seems still to be in the hundreds or few thousands. As of May 2005, just 800 cases had been reported to the FDA, according to Medscape Medical News.

ONJ is “extremely rare,” said Merck spokesman Skip Irvine. “Merck estimates the worldwide cumulative reporting rate … is less than one [case] in 100,000 patient treatment years,” he said.

Merck did a 10-year clinical trial of Fosamax before winning FDA approval in 1995. In that trial, involving 17,000 patients, no cases of ONJ were reported, Irvine said. But this does not have area dentists sleeping any easier.

“I don’t know how many people really know what’s going on,” Deady said when asked about the low number of reported cases. “If I’ve seen six cases. It’s pretty scary,” he said.

“We’re afraid it may be the tip of the iceberg,” Foulkes said. The fact that the population is aging and more and more people are using bisphosphonates to not only treat but sometimes to try and prevent osteoporosis, means it’s possible more cases may be just over the horizon, he said.

“Intuitively,” IU’s Summerlin said, he believes the risk of ONJ is increasing, but, he adds, he has no data to say that “factually.”

“I would say ‘don’t panic,’” Summerlin said. And, in the case of cancer patients using IV bisphosphonates, he believes the risk of some bone loss is probably greatly outweighed by the benefits of the drugs.

“I don’t think anyone can produce absolute data saying how significant the problem is. I think it is a minority of the patients that have this problem,” but even a small percentage of the millions using bisphosphonates “could be a large number of people,” he said.

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Another Merck Drug Is Under Legal Attack

Jul 5, 2006 | Los Angeles Times

As Merck & Co. defends itself against a deluge of litigation involving its pain reliever Vioxx, the pharmaceutical giant also is fielding the first of what could be another wave of lawsuits involving Fosamax, its second-biggest seller.

The emerging litigation targeting the osteoporosis drug, still in its early stages, illustrates how quickly lawyers can organize themselves and assemble prospective plaintiffs after reports of adverse drug effects even when those problems appear to be relatively rare.

Reports in the last few years have linked Fosamax and similar drugs, known as bisphosphonates, to a serious side effect in which the jawbone partially crumbles and dies. Researchers agree that the incidence of this problem, called Osteonecrosis, is quite small.

But trial lawyers are advertising on the Internet and in newspapers for patients who have taken Fosamax or the other drugs, and they are finding potential clients.

"We're getting people calling every day," said a lawyer in Minneapolis.

This attorney said his firm had enlisted medical and dental experts to thoroughly review the records of potential plaintiffs who have taken one of the drugs, adding that he would probably file about 20 cases in the coming months.

"It's too early to tell whether these cases will be successful," said a San Francisco defense lawyer who represents drug makers. "But as soon as there is publicity about any kind of possible problems with a medication, the plaintiffs get geared up."

Merck spokesman Skip Irvine says that Fosamax is safe and effective in treating osteoporosis and that the company "will vigorously defend ourselves against these suits."

"Osteonecrosis is very rare and not well understood," Irvine said, noting that in controlled clinical trials involving more than 17,000 patients, there had been no reports of the malady.

Ethel Siris, a professor of medicine at Columbia University College of Physicians and Surgeons who has also consulted for Merck, said new research studies were underway to understand what triggers the onset of this jaw problem.

In the meantime, she said, she tells her osteoporosis patients that the benefits of the bisphosphonate drugs greatly outweigh their risks.

Fosamax is probably the best-known brand-name drug for preventing hip fractures and deteriorating bones that often destroy the quality of life for older women.

Millions of women have taken the drug since it was first marketed in 1995. Fosamax generated $3.2 billion in sales last year, outstripping the other major oral osteoporosis remedies, Actonel, produced by Procter & Gamble Co. and Sanofi-Aventis, and Boniva, made by Roche Laboratories.

Scientific reports of jaw problems have generated a wave of newspaper articles that in turn have sown panic among users of the drugs.

Many have turned to their doctors or dentists for advice on how to prevent jaw decay and the best treatment options. Last month, the American Dental Assn. released a set of treatment guidelines.

Some users have turned to lawyers as well.

One Florida attorney, has filed 30 damage suits involving Fosamax and expects to file at least 300 more over the next few months involving that drug as well as Actonel.

One of his clients is Rochelle Kenig, who took Fosamax for nine years until she woke up one morning in 2004 with "excruciating, excruciating" pain in her jaw.

"This has been a living nightmare, and nobody knew anything about it," the Boynton Beach, Fla., resident recalled.

Kenig, 67, said she underwent multiple courses of potent antibiotics, repeated surgeries, treatment in a hyperbaric chamber and acupuncture. Yet the pain and bone deterioration continued, she said.

She finally got some relief in April after a new group of surgeons replaced part of her jaw with a titanium plate secured with metal hinges. But, Kenig said, the decay and infections had caused a permanent loss of sensation on the right side of her lip and face, as well as the loss of several teeth.

Merck's Irvine declined to comment on Kenig's claim, adding, "We don't want to argue cases in the newspapers."

The attorney in Florida has asked a Florida federal court to certify a class action for the Fosamax suits. He estimated that he and other lawyers had filed a total of 50 lawsuits with possibly hundreds more to come.

Two bisphosphonates produced by Novartis Pharmaceuticals Corp., Aredia and Zometa, are given intravenously in treating some forms of bone cancer. The drugs have also been targeted in lawsuits from about 100 claimants to date.

Some experts see the relatively slow pace of lawsuit filings against Fosamax and its related drugs compared with the flood of Vioxx suits that followed Merck's decision to pull the drug in 2004 as evidence that plaintiffs' lawyers have become more cautious in recent years.

Litigation involving silicone gel breast implants and Bayer's cholesterol-lowering drug Baycol proved less successful than lawyers initially expected, said Francis McGovern, a Duke University law professor.

"Now, you might take a particularly good case and see how good it is before you take lots of others and invest a lot of money," McGovern said.

Drug makers are also taking more precautions. Merck added language about the potential problem to Fosamax's label in July after a request from the Food and Drug Administration, which had reviewed reports of Osteonecrosis, Irvine said.

The revised label "communicates the issue clearly to physicians," Irvine said.

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Bone-building drugs linked to bone-rotting side effect

Jun 13, 2006 | Star Ledger

Michael Erlichman walked into his dental office last week and encountered a patient with an unusual but growing problem.

An elderly woman was complaining about soreness caused by her dentures, but there was nothing Erlichman could do to relieve her pain. That's because she suffers from a rare jawbone disease that is increasingly being linked to a group of drugs for osteoporosis and cancer. And he noted she'd been taking one of those drugs for several years.

"There's more concern about this all the time now," said Erlichman, an oral surgeon in Little Falls. "The drugs are known to truly help people, but they can also cause the jawbone to become inert to the point where you can't drill a cavity or perform an implant.

"You can't do anything with these patients. And I worry about others developing the problem."

Each year, millions of Americans seeking to ward off brittle bones take pills that belong to a class of medicines called bisphosphonates. By far, the most popular pill is Merck's osteoporosis drug, Fosamax, which has been available for a decade. A much smaller number of patients receive an intravenous version of the medication as part of their chemotherapy.

To date, the incidence of drug-induced jawbone disease remains rare. Researchers report fewer than 400 cases of the disease, known as Osteonecrosis, a painful and debilitating condition that essentially rots the jawbone. And the vast majority of these cases 94 percent are associated with a pair of intravenous medicines sold by Novartis, according to an article last month in the Annals of Internal Medicine.

Nonetheless, oral surgeons and dentists are increasingly worried the number of cases will multiply, and warnings have been posted on Web sites run by their professional groups. The problem, they say, is that bisphosphonates remain in the bones for years. Given that more prescriptions are written each year for the pills, which include Actonel and Boniva, experts suggest the rate at which Osteonecrosis will be diagnosed is likely to increase.

"The concentration in the bones begins to build up by the third year. So it's not surprising that we're starting to see more cases among people who take the pills," said Robert Marx, who chairs the oral and maxillofacial surgery department at the University of Miami medical school, and who first sounded the alarm about the problem three years ago.

Although Fosamax has been prescribed since 1995, usage grew dramatically about five years ago, which Marx said would explain why cases linked to that pill are only now being diagnosed. Actonel has been available since 2000, and Boniva was launched last year. Marx said he doesn't expect to see as many cases associated with those pills right now.

Marx believes Merck researchers didn't anticipate the extent to which bisphosphonates can effect the jaw compared with other bones. In his view, the Fosamax clinical trials should have looked for the problem. If they had, Marx said, "they could've predicted this might have occurred."

A Merck spokesman responded that Fosamax is linked to a very small number of cases compared with the millions of people who have taken the pill. In 1997, for instance, 1.5 million new prescriptions were written for Fosamax; that figure jumped to 4.5 million by 2002, but slid to 4.2 million last year, according to Verispan, a market-research firm.

The idea that greater use will result in an increased risk of Osteonecrosis "isn't substantiated by the current data," Merck spokesman Chris Loder wrote in an e-mail. "To suggest so would be misleading and incorrect." But at the request of regulators, Merck last year changed Fosamax labeling to mention Osteonecrosis has been reported among patients taking bisphosphonates.

Two studies about to be published are expected to substantiate that view, according to the lead author, Marjorie Jeffcoat of the University of Pennsylvania dental school. One study traced 320 Fosamax patients for two years and the other tracked 80 Fosamax and Actonel patients for five years.

"The data didn't show a cause and effect," said Jeffcoat. However, she noted the data didn't provide a definitive answer about whether a bisphosphonate pill could cause Osteonecrosis if taken for a lengthy period of time.

The Merck spokesman added that no cases of Osteonecrosis were found among 17,000 patients in its clinical trials, although he acknowledged the company has received side-effect reports. However, he argued these reports "do not necessarily indicate causality," declined to provide the number of side-effect reports received.

An FDA spokeswoman, Laura Alvey, said she could not immediately provide the number of side-effect reports the agency has received involving bisphosphonates and Osteonecrosis.

Paula Koenigs, a spokeswoman for Procter & Gamble, which markets Actonel with Sanofi-Aventis, said there is no scientific study that concludes bisphosphonates cause Osteonecrosis, and the jawbone disease wasn't seen in clinical trials.

Maureen Byrne, a spokeswoman for Roche, which jointly markets Boniva with Glaxo, said Osteonecrosis wasn't seen in trials.

Nonetheless, the growing concerns about Osteonecrosis are prompting lawsuits against the drug makers. So far, Merck faces at least 15 lawsuits over Fosamax, while two have been filed against Procter & Gamble and Sanofi-Aventis.

One Florida lawyer, who is in the process of filing additional lawsuits against Merck, argued the company has failed to properly warn patients. He maintained that despite a 2004 report by the FDA's Office of Drug Safety, Merck hasn't added meaningful language in the Fosamax label to specifically indicate the risk of Osteonecrosis.

"They never come out and say it's a risk factor," said Tim O'Brien, who noted that Novartis is so far the only company to have sent letters to doctors about the risk. "You have to read between the lines (of the product labeling) and read the medical literature to understand what they actually are saying. It's very misleading."

He added the FDA has cited Merck for being too aggressive in promoting Fosamax. The agency sent four letters between 1997 and 2001 for making unbalanced or misleading claims in promotional brochures or consumer advertising.

Lawsuits alleging damaging side effects caused by prescription drugs are increasingly common. The Vioxx scandal has generated more than 11,500 lawsuits against Merck. By comparison, the number of Fosamax lawsuits is minuscule, but the specter of more bad publicity doesn't thrill Wall Street.

"This is definitely a headache that the big drug makers, especially Merck, don't need," said David Moskowitz, an industry analyst at Friedman Billings Ramsey, who noted Fosamax generated $3.2 billion in sales last year. "Merck has few growth drivers, and they can't afford for Fosamax to sustain too much damage."

One solution might crimp Fosamax sales. Hillel Ephros, who chairs the dentistry department at St. Joseph's Regional Medical Center in Paterson, wants doctors to consider alternatives before writing prescriptions for the pills.

"Everyone needs to know that Osteonecrosis can't be fixed," said Ephros, who has seen seven cases of the disease. "The problem makes me feel shackled and frustrated. We have to defer and postpone procedures for patients on oral bisphosphonates, and the day may come when I will decline altogether. Maybe that can be prevented."

The drug makers are advertising their pills widely. Last year, they spent $174.3 million, up from $54.8 million in 2003, according to TNS Media Intelligence, a market-research firm. That's because Boniva was launched last year with a big promotional effort, prompting Procter & Gamble and Sanofi-Aventis to spend more on Actonel.

One doctor suggests ads should explicitly and prominently mention the possibility the pills can cause Osteonecrosis. Salvatore Ruggiero, chief of oral and maxillofacial surgery at Long Island Jewish Medical Center in New Hyde Park, N.Y., believes the risk of developing Osteonecrosis is "very small," but few know it exists.

"The problem has taken a long time to manifest itself, and so I think it'd be unfair to say these drug companies expected this to happen. That'd be a real stretch. The lawyers are creating a perception that it's a big problem," he said. "But we need to realize that there is this side effect. And it needs to be better known."

For Mary Kyle, the debate is taking place too late.

A retired elementary school teacher who lives in Mount Laurel, Kyle said she was prescribed Fosamax four years ago to prevent osteoporosis, but recently was diagnosed with Osteonecrosis after complaining of jaw pain. Last week, she filed a lawsuit against Merck.

"I was told I'll have this problem for the rest of my life," said Kyle, 58. "My oral surgeon couldn't give me much hope there's anything he can do. Now, I want to educate others. There are a lot of people on this drug and this problem may happen to them, but they may not know the drug is causing the problem."

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