FDA investing potential link between arthritis drugs, cancer in children

Agency received 30 cancer cases in arthritis drug patients

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.

Fosamax study may link the drug to rare femur fracture

36 percent of femur fracture patients in study were taking Fosamax

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.

Digitek class action lawsuit highlights Actavis’ past warning

FDA warned company for failing to provide periodic safety reports

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.

FDA decides to perform second safety review of Pfizer’s Chantix

Agency is reviewing all reported adverse events

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.

Louisiana man thinks Pfizer’s Chantix may have led to dangerous car accident

Two days after taking smoking cessation drug, eyes roll into back of head

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.

FMCSA warns truckers about Pfizer’s smoking cessation drug Chantix

Administration advises against qualifying Chantix patients for commercial motor vehicle licenses

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.

FAA bans Chantix for pilots, air-traffic controllers after study highlights additional side effects

Report suggests smoking cessation drug connected to heart trouble, diabetes

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.

Merck agrees to pay $58 million settlement in Vioxx defective marketing lawsuit

Company must submit all new TV advertisements to FDA for review

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.

Pfizer updates Chantix label to include warnings of severe mood and behavior changes

FDA believes it likely that changes are related to Chantix

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.

Amgen’s experimental cancer drug has minimal effect on brain cancer

AMG-102 may only work in subpopulation of patients with recurring brain cancer

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.