On June 4, 2008, the Food and Drug Administration (FDA) said it is investigating a potential link between four rheumatoid arthritis drugs and the increased risk of cancer in children. The investigation was prompted after the agency received 30 reports of cancer in 10 years among children and young adults treated with the drugs.

The rheumatoid arthritis drugs in question are Amgen’s and Wyeth’s Enbrel, Johnson & Johnson’s Remicade, Abbott Laboratories’ Humira and UBC’s Cimzia. The agency has not elaborated on how many children had taken the drugs or whether cancer incidence was higher than expected. The agency also said it believed the potential benefits of the drug outweigh the potential risks.

All of the drugs work by attempting to dampen inflammation by blocking a protein, called tumor necrosis factor, and are used to treat various immune diseases like rheumatoid arthritis, psoriasis and Crohn’s disease. About 70,000 to 100,000 children in the United States suffer from juvenile idiopathic arthritis.

Source: Andrew Pollack, “FDA reviews arthritis drugs for links to cancer,” New York Times, June 5, 2008.

In June 2008, the Journal of Orthopedic Trauma published an article linking Merck’s Fosamax to a rare type of fracture in the femur. The study looked at 70 patients who experienced a femur fracture and found 36 percent (25) of the patients were taking Fosamax for at least four years.

The femur fractures in the Fosamax patients had distinct characteristics, like a simple fracture with a straight line across the bone and a beak-like overhang on one side. Fosamax patients’ bones also looked strong, as apposed to a typical osteoporotic bone. The study may help determine if Fosamax patients are vulnerable to fractures.

Fosamax has previously been linked to other significant side effects; ongoing litigation against Merck alleges the drug caused osteonecrosis of the jaw – also known as “dead jaw.”

Source: Heather Won Tesoriero, “Side effect watch: femur fractures in Fosamax patients,” Wall Street Journal Health Blog, June 4, 2008.

In August 2006, the Food and Drug Administration (FDA) sent a warning letter to Actavis for failing to provide periodic safety reports at its manufacturing plant in New Jersey, and a Digitek class action lawsuit says some of the Digitek included in an April 2008 recall was manufactured at that plant.

The Digitek class action lawsuit mentions Actavis’ previous warning while raising questions about the way the defective pills were made. The lawsuit also says a 2006 FDA inspection uncovered six potentially serious and unexpected adverse drug events for products that include generic Digitek from as far back as 1999.

Actavis recalled Digitek after realizing some tablets contain twice the active ingredient indicated on the label, which could lead to accidental overdose or death. Patients suffering from renal failure who take some of the recalled Digitek face a serious risk of digitalis toxicity. The company received reports of sick Digitek patients, prompting the recall. One patient, who is also a plaintiff in the Digitek lawsuit, said she experienced changed cardiac symptom episodes of nausea and dizziness. Another patient said he took the defective drug and it may have caused kidney damage.

Source: “Digitek recall blamed on shoddy manufacturing,” News Inferno, June 4, 2008.

The United States Food and Drug Administration (FDA) has initiated a second safety review of Pfizer’s smoking cessation drug Chantix. An earlier review by the agency in February linked the drug to serious neuropsychiatric symptoms, at which time the FDA requested Pfizer elevate the prominence of the safety information to Chantix’s prescribing information and label.

The decision for a second review comes less than one month after a report by the Institute for Safe Medication Practices warned Chantix patients could experience a lapse in alertness or motor control, which could lead to massive, serious injury, especially in patients who operate aircraft, trains, buses and other vehicles.

Following the release of this report, the Federal Aviation Administration (FAA) and the Federal Motor Carrier Safety Administration (FMCSA) decided to change their stances on employees’ use of Chantix.

Source: Anna Boys, “FDA to run a safety review on Chantix,” EFluxMedia, June 2, 2008.

On July 15, 2008, a 28-year-old man had been taking Pfizer’s smoking cessation drug Chantix for two days and was driving home with his girlfriend on a country road in Louisiana. On the way home, however, he swerved left, landing in a bayou. His girlfriend would later tell him that his eyes had rolled back into his head, and it seemed as if he was frozen at the wheel.

His girlfriend is still struggling with a neck injury she suffered as a result of the car accident. The man, who had no history of seizures and does not drink alcohol, said his doctor, who has treated him from childhood, made the connection between the car accident and Chantix.

He is considering filing a Chantix lawsuit against Pfizer. His lawyer said he is aware of at least one other accident being attributed to Chantix, involving a deliveryman who fell out of a moving truck.

In May 2008, the nonprofit Institute for Safe Medication Practices linked Chantix to at least two dozen highway car accidents reported to the Food and Drug Administration (FDA), claiming the accidents occurred because of the drug’s side effects, like seizures.

Pfizer said it added a warning to Chantix’s labels, advising patients to exercise caution when driving or operating machinery while taking the drug until they know how the drug affects them. But doctors, and even some government transportation agencies, seem to have missed the warning.

Until mid-May 2008, the Federal Aviation Administration (FAA) continued listing Chantix as approved for pilots. Now the FAA has banned the use of it for pilots and air traffic controllers. A similar chain of events occurred with the federal truck safety agency. And the military, which currently bans Chantix for flight and missile crews, is considering whether other precautions are needed.

Approved in 2006, Chantix differs from previous smoking cessation drugs because it acts directly on sites of the brain affected by nicotine, blocking cravings and the pleasure that comes from smoking.

Pfizer said there has been no proven direct link between Chantix and the reported problems, including suicidality, depression, seizures, and cardiac arrhythmia.

Source: Ricardo Alonso-Zaldivar, “Drug taken to stop smoking is linked to traffic mishaps,” Los Angeles Times, May 25, 2008.

On May 22, 2008, the Federal Motor Carrier Safety Administration (FMCSA) warned truckers about Pfizer Inc.’s smoking cessation drug Chantix one day after the Federal Aviation Administration (FAA) banned the use of the drug for pilots and air traffic controllers. The FMCSA also advised medical examiners to deny qualification for commercial motor vehicle licenses to anyone currently taking Chantix.

Earlier in the week, the Institute for Safe Medication Practices announced conclusions drawn from a study of the drug, potentially linking it to side effects such as seizures, diabetes, cardiac arrhythmia, confusion and dizziness. Chantix was connected to psychiatric problems like suicidality and depression in 2007.

The FMCSA is responsible for monitoring the interstate trucking and bus industry. Agencies with the Department of Transportation were directed to the warning, at the request that they keep in mind the Administration’s warnings and recommendations.

Meanwhile, the Food and Drug Administration (FDA) has not announced any new actions it will take in regards to Chantix. The agency is currently focusing on the potential links between Pfizer’s drug and neuropsychiatric side effects after Chantix’s warning label was updated to include depression and suicidality.

Source: Alicia Mundy and Avery Johnson, “Trucking regulators warn on use of Chantix,” Wall Street Journal, May 23, 2008.

On May 21, 2008, The Institute for Safe Medication Practices, an organization seeking to improve drug safety, announced conclusions drawn from its study of adverse-event reports of Pfizer Inc.’s Chantix. The reports, filed with the Food and Drug Administration (FDA), linked 988 serious incidents to Chantix in the United States during 2007’s fourth quarter alone, the most for any medication during that time period.

While Chantix has already been connected to psychiatric problems like suicide and depression, the new report highlights such potential side effects as heart trouble, seizures, and diabetes. The FDA received 224 reports of potential heart-rhythm disturbances (cardiac arrhythmia), 372 reports of possible movement disorders, and 544 reports of what appear to be glycemic problems, including diabetes. Chantix patients also reported falls and traffic incidents, presumably the result of factors like muscle spasms, dizziness and confusion.

Based on information presented in the study, the Federal Aviation Administration (FAA) announced an immediate ban on Chantix use for pilots and air-traffic controllers, saying “it is no longer acceptable” for those individuals to take the drug. The FAA sent letters to pilots instructing them to wait 72 hours before flying if they have been using Chantix.

The lead author of the study, Thomas Moore, has requested Pfizer and the FDA immediately change Chantix’s warning label to include information about the additional side effects and emerging safety issues. Pfizer insists the new report’s conclusions are already consistent with the drug’s warning label.

The data used in the new study was from the FDA, which receives consumer adverse event reports. Both Pfizer and the agency routinely study the same reports that were analyzed in the new study, but an FDA spokeswoman said staffing shortages have led the agency to focus only on Chantix’s psychiatric side effects.

Chantix is a smoking cessation pill that works by acting on brain receptors that affect a patient’s desire to smoke. Although the drug was approved for U.S. use by the FDA in 2006, it was not until November of 2007 that the agency first made public the number of adverse event reports of suicidality and depression it had received.

There were almost 1,000 serious-injury reports related to Chantix reported to the FDA in the fourth quarter of 2007 alone, topping the Institute for Safe Medication Practices’ list of nearly 800 drugs studied for serious side effects. Most medications on the list with similar adverse event data already contain a “black box” label warning, the FDA’s most serious. To put the Chantix numbers in perspective, the median number of serious-injury reports during the fourth quarter of 2007 for other medications is five.

Adverse-event reports, however, do not establish a definitive connection between a drug and a side effect. The FDA has said it will continue to review neuropsychiatric events associated with Chantix, but it has not begun an investigation into the new reported side effects.

Source: Avery Johnson and Alicia Mundy, “Report links Pfizer drug to accidents, heart trouble,” Wall Street Journal, May 22, 2008.

On May 20, 2008, Merck & Co. announced an agreement to pay $58 million to settle a multistate Vioxx defective marketing lawsuit. The lawsuit alleged Merck deceptively downplayed the health risks associated with its arthritis medication.

As part of the Vioxx settlement, Merck must also submit all new television commercial advertisements for its products to the Food and Drug Administration (FDA) for review before they can be aired. Additionally, Merck is barred from “ghostwriting,” in which academic scientists receive compensation for attaching their names to positive research articles written by company-hired medical writers.

Vioxx was withdrawn from the market in 2004 after it was found to double the risk of heart attacks and strokes, triggering thousands of product liability lawsuits against Merck. The company’s direct-to-consumer television advertising provoked patients to request Vioxx prescriptions before understanding the effects.

The Vioxx settlement will be divided among the following states:

• Arkansas,
• Arizona,
• California,
• Connecticut,
• Florida,
• Hawaii,
• Idaho,
• Illinois,
• Iowa,
• Kansas,
• Maine,
• Maryland,
• Massachusetts,
• Michigan,
• Nebraska,
• Nevada,
• New Jersey,
• North Carolina,
• North Dakota,
• Ohio,
• Oregon,
• South Carolina,
• South Dakota,
• Tennessee,
• Texas,
• Vermont,
• Washington, and
• Wisconsin.

Merck’s settlement comes three months after it agreed to pay $671 million to settle allegations the pharmaceutical giant overcharged the government for Vioxx and three other drugs, and bribed doctors to prescribe its drugs.

Source: Martha Raffaele, “Merck agrees to $58M settlement over Vioxx ad claims,” My Fox Raleigh, May 21, 2008.

On May 16, 2008, the United States Food and Drug Administration (FDA) issued a public health advisory concerning Pfizer’s smoking cessation drug Chantix. Pfizer has, at the request of the FDA, added warnings about the possibility of severe changes in mood and behavior in Chantix patients.

In November of 2007, the FDA first notified the public about the possibility of severe changes in mood and behavior in Chantix patients, but at that time, the connection between Chantix and the symptoms was unclear. However, as the FDA continued to review the data, the agency determined it was increasingly likely that these severe behavioral changes may be related to Chantix.

It is estimated that 44 percent of all cigarettes in the United States are smoked by people with diagnosed mental disorders, including schizophrenics and alcoholics. Smokers with psychiatric illnesses were not included in Pfizer’s premarketing trials for Chantix, however, leading to one possible explanation for the flood of adverse event reports. Chantix is marketed and sold to all adult smokers, regardless of mental health status.

In early February of this year, the FDA reported receipt of 420 reports of suicidal thoughts and 34 suicides among the 4.5 million Americans using Chantix.

As a result, the FDA has provided the following safety information on Chantix:

• Patients who are taking Chantix should tell their doctor about any history of psychiatric illness before they begin to take Chantix because the drug may cause worsening of a psychiatric illness or may cause an old psychiatric illness to reoccur.
• Patients treated with Chantix should be monitored for changes in mood and behavior, including anxiety, nervousness, tension, depression, unusual behaviors and suicidality. Patients who stop taking Chantix should also be monitored for these symptoms.
• A patient who experiences changes in mood and behavior while taking Chantix should immediately report the changes to the doctor.
• Chantix patients may experience vivid, unusual or strange dreams.
• Impairment of the ability to drive or operate heavy machinery may occur in Chantix patients.

Both the FDA and Pfizer are working to finalize a Medication Guide for Chantix patients. The FDA will notify the public about any new information arising from its review of Chantix data. The agency may also consider additional changes to Chantix prescribing information.

Source: “Public Health Advisory: Important Information on Chantix (varenicline),” United States Food and Drug Administration Public Health Advisory, May 16, 2008; Melinda Beck, “Puff Power: Drug Warnings Speak to Nicotine’s Sad Grip,” Wall Street Journal, February 19, 2008.

On May 15, 2008, Amgen Inc. released initial results in the Phase II trial of its experimental drug AMG 102. The trial found the drug may only be effective in a subpopulation of patients who have recurring brain cancer. AMG 102 is meant to target a specific growth factor that may play a significant role in many different forms of cancer.

The trial studied 20 patients with a type of brain cancer who were treated every two weeks with infusions of AMG 102 until either their disease progressed or they withdrew from the trial.

Out of the 18 trial participants with available data, one had a confirmed partial response, one had a minor response but withdrew due to tissue swelling, and in two patients the cancer stabilized, however one of these two withdrew because of swelling and the other withdrew because of deep vein thrombosis. Five of the patients reported side effects like swelling, nausea, and fatigue. 14 patients had their cancer worsen.

The results of the study suggest that for a subpopulation of brain cancer patients with a particular form of the recurrent cancer, the disease may be dependent on what AMG 102 targets.

Source: Deena Beasley, “Amgen drug has little impact on brain cancer,” Reuters, May 15, 2008.

On May 14, 2008, the Committee on Oversight and Government Reform held a hearing addressing whether Food and Drug Administration (FDA) drug and medical device regulation should bar injured patients from filing product liability lawsuits.

Patients can file damage lawsuits against drug and medical device manufacturers under state law, but the current administration is arguing that a company cannot be held liable for selling a drug or device that has been approved by a federal regulator.

The committee heard several testimonies, including one from actor Dennis Quaid and his wife Kimberly Quaid. In November 2007, the couples’ newborn twins were given a nearly fatal overdose of the blood-thinner Heparin to treat a staph infection. The Quaids testified that Baxter Healthcare’s labeling of its Heparin product was not sufficient to protect against mistakes – the bottle of 10-units of the Heparin product and the bottle of the 10,000-unit bottle were similar in labeling and size, and when stored were virtually indistinguishable.

Upon further research, the couple found that infant Heparin overdose had occurred one year prior, resulting in the deaths of three infants, with three additional infants suffering serious injuries.

After the incident, Quaid filed a negligence lawsuit against Baxter, alleging the company was negligent in packaging different doses of Heparin in similar vials, with similar labels. The actor cited a relabeling of the drug by Baxter before the birth of his twins, but said the company did not recall the drug vials that had already been shipped with similar labels.

After the Quaids filed the negligence lawsuit against Baxter, the company filed a motion to dismiss, citing that the FDA’s approval of the Heparin product label exempted the company from product liability lawsuits. Thus, the Quaids’ lawsuit may not be heard.

Concluding their testimony, Mr. and Mrs. Quaid said a federal ban on product liability lawsuits against drug companies would deny victims the compensation they may deserve, in addition to relieving drug companies of their responsibility to ensure their products are as safe as possible.

Sources: “Committee Holds Hearing on Whether FDA Regulation Should Bar Liability Claims,” Committee on Oversight and Government Reform Press Release, May 13, 2008; “Dennis Quaid Tells Lawmakers How Drug Mix Up Nearly Killed His Newborn Twins,” Medical News Today, May 14, 2008.

On May 14, 2008, the New England Journal of Medicine published a report that concluded patients receiving Trasylol (aprotinin) during cardiac surgery have an increased risk of death when compared to patients receiving one of two other drugs in the same class: Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid).

The 2,331-patient BART study found that the 30-day all-cause death rate for Trasylol patients was 6 percent, versus 3.9 percent for Cyklokapron patients and 4 percent for Amicar patients. In addition, researchers determined that Trasylol was not significantly more effective in preventing excessive bleeding than other drugs. Trasylol also costs about $1,400 per patient, compared to less than $4 for Amicar.

Researchers who conducted the study believe Trasylol probably does not have a future in cardiac surgery. They have not identified a definite cause of the excess mortality rates seen in Trasylol patients.

“In all likelihood, this is the end of the aprotinin story,” they wrote.

Source: John Gevern, “Medical News: Other shoe drops on aprotinin (Trasylol), MedPage Today, May 14, 2008.

Actavis Totowa LLC, the maker of Digitek, is recalling all lots of the drug because some of the tablets might contain twice the approved level of the active ingredient. Actavis Totowa LLC initiated the Digitek recall after receiving reports that some people were getting sick after taking the drug.

The recalled Actavis drug is used to treat heart failure and abnormal heart rhythms. The company has received 11 reports concerning the recalled Digitek, but no reports of death. For more information, consumers may contact the company at 1-888-276-6166 or visit actavis.us.

Source: The Chicago Tribune, “Digitek heart drug recall,” April 25, 2008.

On May 2, 2008, Pfizer Inc. tentatively settled more than 200 personal injury lawsuits over its painkillers Celebrex and Bextra, days before the first trial was scheduled to begin over allegations the painkillers caused heart attacks and strokes.

While the total amount of the settlement was not disclosed, one of the plaintiffs’ attorneys was quoted as saying each Celebrex suit received between $40,000 and $50,000, and each Bextra suit received around $200,000. Reportedly, Pfizer plans to resolve its Celebrex and Bextra lawsuits on a case-by-case basis, and is prepared to pay out as much as $500 million to resolve all claims.

Bextra is a painkiller withdrawn from the market after it was linked to unpredictable and life-threatening skin reactions. Celebrex is still available and marketed to arthritis patients, though one study linked the drug to an increased risk of heart attack and stroke. The United States Food and Drug Administration (FDA) allowed Celebrex to stay on the market after deciding the benefits outweighed its potential risks.

Source: Lee Howard, “Pfizer settles lawsuits over two top drugs,” Theday.com, May 3, 2008.

On May 1, 2008, Merck & Co. announced it was extending the deadline for eligible United States claimants to participate in its proposed $4.85 billion Vioxx product liability lawsuit settlement. The new deadline for registration is June 30, 2008.

When the settlement proposal was first announced, Merck said it would not commit to the plan until at least 85 percent of eligible former Vioxx users signed up. That benchmark has already been reached, as about 94 percent signed up before the deadline was extended.

To be eligible for the proposed Vioxx settlement, patients or their survivors must have either filed a Vioxx product liability lawsuit or signaled their intent to file such a suit by November 9, 2007.

Thousands of Vioxx product liability lawsuits were filed on the heels of a 2004 study finding long-term users of the drug faced twice the “normal” risk of heart attack and stroke. Vioxx was recalled in September 2004.

Source: Ransdell Piersen, “Merck extends deadline for Vioxx settlement,” YahooNews, May 1, 2008.

On April 30, 2008, the United States Food and Drug Administration (FDA) released a warning letter sent to Merck & Co., ordering the company to correct manufacturing deficiencies at its main vaccine plant in West Point, Pennsylvania.

The Merck plant cited by the FDA produced two vaccines that were recalled in December 2007 due to sterility problems.

The warning letter said the FDA found “significant objectionable conditions” in the manufacture of vaccines and drug ingredients. The plant was inspected repeatedly from November 26, 2007, through January 17, 2008. In addition, the FDA said Merck’s response to the agency after a report of the inspections was inadequate.

Among the problems at that plant was a lack of written procedures, tests, or laboratory controls to ensure “identity, strength, quality and purity” of the products being produced. The FDA said it does not believe the manufacturing errors will affect the safety of Merck’s vaccines.

Merck has 15 days from the date of the FDA’s letter to tell the agency how it will correction the violations.

Source: Linda A. Johnson, “FDA warns Merck to fix vaccine plant problems,” Associated Press, April 30, 2008.

In April 2008, officials at the United States Food and Drug Administration (FDA) said they believe the chemical contamination of Baxter International’s blood thinner heparin was intentional. The contaminant was linked to hundreds of severe allergic reactions and dozens of deaths in the US.

The Director of the FDA’s Center for Drug Evaluation and Research told a congressional hearing the agency believes it was an intentional contamination, though their claim has not yet been proven.

Baxter International recalled the tainted heparin and blocked imports from the Chinese supplier that is believed to be responsible for the contamination. The FDA said a chemical called oversulphated chondroitin sulphate was found in supplies in 13 countries.

Source: “Heparin contaminated ‘on purpose’,” BBC News, April 30, 2008.

Dilantin, an epilepsy drug manufactured by Pfizer, could put young women who use the drug for at least a year at a higher risk for osteoporosis, according to researchers publishing in the latest issue of Neurology. The affected rate of bone loss reported in the study was eight times higher than what premenopausal women not taking epilepsy drugs experience.

“That suggests that if these women remain on this medication and have ongoing significant or accelerated bone loss that over time, they will be entering the peri-menopausal period with lower bone density and therefore a greater risk for low bone mineral density over time and therefore a higher risk of fractures,” said study lead author Dr. Alison M. Pack, assistant professor of clinical neurology at Columbia University in New York City.

Dr. R. Eugene Ramsay, director of the International Center for Epilepsy at the University of Miami Miller School of Medicine, said 90 percent of older people who have seizures are put on Dilantin, largely because the drug is less expensive than others.

“It’s particularly important, because the older population has the highest incidence of epilepsy. There are more new-onset seizures occurring there, and yet they are getting the cheapest and worst treatment,” he said.

“We’re just beginning to recognize that we need to look at the long-term health care issues of anti-convulsants,” Ramsay said.

Source: Amanda Gardner, The Washington Post, “Epilepsy Drug Linked to Bone Loss,” April 28, 2008.

An article published in a leading medical journal accuses drug maker Merck of internally drafting a number of research studies for its drug Vioxx, and then looking for big-name doctors to put their names on the studies prior to publication.

“It almost calls into question all legitimate research that’s been conducted by the pharmaceutical industry with the academic physician,” said Dr. Joseph S. Ross of the Mount Sinai School of Medicine, whose article, written with colleagues, was published recently in The Journal of the American Medical Association (JAMA).

In 2004, Vioxx was a best-selling drug before the company took it off the market over claims linking it to heart problems. Late last year, Merck agreed to a $4.85 billion settlement to quiet tens of thousands of personal injury lawsuits filed by former Vioxx patients and their families.

Dr. Catherine D. DeAngelis said it was dishonest for a doctor to put his or her name on a study he or she did not author without disclosing the role of ghostwriter. “I consider that being scammed,” said DeAngelis.

Merck asserts that while the company may hire professional writers to pen early drafts of scientific articles, any outside authors named in its studies were involved in the research, and the final work is the product of the doctor.

Source: Stephanie Saul, The New York Times, “Ghostwriters Used in Vioxx Studies, Article Says,” April 15, 2008.

Rituxan, a cancer drug by Genentech and Biogen Idec, did not slow the disabling effects of the most difficult form of multiple sclerosis in clinical trials conducted over a period of almost two years, according to the two companies.

If the drug had succeeded, it would have been the first to work against the primary progressive form of multiple sclerosis.

”While the primary results are not what we had hoped, we continue to believe in the potential of B cell therapy for patients living with MS,” said Michael Panzara, Biogen’s vice president and chief medical officer of its neurology strategic business unit.

The Rituxan approach of killing inflammatory B cells is different than that of currently approved MS drugs.

The drug makers indicate they will continue to analyze the results of these trials.

Source: Bloomberg News, “Drug Fails to Slow Nerve Damage,” April 15, 2008.

On April 21, 2008, the Food and Drug Administration (FDA) reported it identified hypersulfated chondroitin sulfate, a molecule also identified as a contaminant in Baxter International’s recalled heparin, as the cause of patient fatalities. The FDA also announced that the number of deaths linked to the recalled heparin increased by 19, and now stands at 81.

FDA spokeswoman Janet Woodcock likened a patient’s reaction to the molecule to the extreme hypotension seen in some patients after being injected with contrast agents.

The contaminant was linked to China, but Chinese officials said they disagree with the FDA’s latest conclusions, and do not think the contaminant is the cause of the patient reactions. Chinese officials also question the FDA’s contention that the contaminant came from China.

Source: Peggy Peck, “FDA confirms Heparin contaminant as cause of death,” MedPage Today, April 21, 2008.