FDA warning

FDA seeks tougher labeling for Byetta after deaths

Christe Bruderlin-Nelson — Tue, 19 Aug 2008 03:37:00 -0400

They warned you once and they'll warn you again. FDA is upping the label ante on Byetta, the diabetes drug that Eli Lilly and Amylin Pharmaceuticals developed and market, following reports of deaths in patients taking the drug. Greater than 700,000 patients have used the medication since 2005, bringing the companies nearly $700 million in sales.

Patients taking the twice-daily injectable drug Byetta are at increased risk of acute pancreatitis, a dangerous form of pancreatitis that comes on suddenly and can be rapidly fatal, even with treatment. The FDA is warning patients on Byetta to stop taking the medication immediately if they develop symptoms of acute pancreatitis, including abdominal pain, nausea, vomiting, diarrhea, fever and chills.

The two drug companies say the reports of complicated or fatal pancreatitis are "very rare," and that diabetes patients already have an increased risk of pancreatitis.

The medication already had warnings following about 30 reports of nonfatal pancreas concerns in Byetta patients, but now the FDA has received at least six new reports of patients taking Byetta coming down with an aggressive type of pancreatitis. Of these, two have died.

For their parts, Lilly and Amylin are in the process of developing a once-a-week version of the medication that had piqued some investor interest despite recent lackluster sales, but this news has some analysts raising a red flag about investing, saying that it will likely influence how the FDA will view the new version. Not surprisingly, shares in both companies saw a dip in price on Monday.

--see the release
--read the story in the New York Times
--see more at ABC News
--find the Pharmalot blog post

Are black box warnings inevitable?

Tracy Staton — Mon, 11 Aug 2008 11:22:08 -0400

A sociologist and health policy researcher has some stern language for drugmakers and their regulators. "Drug disasters are literally built into the current system of drug testing and approvals in the United States," Donald Light said in presenting his figures on new drugs to the American Sociological Association.

According to Light's data review, one in seven new drugs is superior to existing ones, but two in every seven end up emblazoned with a black box, an adverse reaction warning--or they're withdrawn.

And all those post-marketing adverse event reports and black box warnings? They're almost inevitable, given the fact that drugmakers test their products on patients that are typically healthier than the entire population actually targeted by the drugs. And trials are long enough only to pick up short-term side effects, Light said.

Some would argue that the uptick in drug warnings is actually a reflection of the FDA's newly cautionary stance rather than an indication that drug safety is slipping overall. Check out Light's data and see what you think.

- read the post at Pharmalot

Anemia meds get tougher warnings

Tracy Staton — Thu, 31 Jul 2008 09:59:41 -0400

The labeling on Amgen and Johnson & Johnson's anemia meds is about to get even more restrictive. Using its new authority to force label changes, the FDA is ordering the drugmakers to say the drugs shouldn't be used in chemotherapy patients whose cancer might be cured. The new label will also say that the drugs shouldn't be given when hemogrlobin levels are 10 grams per deciliter or more.

The label changes follow an FDA advisory panel meeting in March, when experts recommended usage limits--and another not adopted, that any patients with breast or head-and-neck cancers avoid the drugs. According to the Wall Street Journal, Amgen and the FDA had been negotiating new label language, but failed to come to an agreement.

You'll recall that a debate has been raging for months about the safety of these meds, which Amgen markets as Epogen and Aranesp, and J&J sells under the Procrit name. Medicare set up some restrictive guidelines for their use, saying it wouldn't reimburse for the meds outside those parameters. Given that Medicare's hemoglobin threshold was 10 grams per deciliter, it's unlikely that the new warnings will help loosen its purse strings.

- see Amgen's release
- read the WSJ story
- check out the article in the New York Times

FDA: Test before giving GSK med

Tracy Staton — Thu, 24 Jul 2008 10:30:46 -0400

Personalized medicine, here we come--at least that's the message in two genetic-testing developments today. First, the FDA is advising docs to screen HIV patients for a particular genetic variant before prescribing abacavir, a GlaxoSmithKline anti-AIDS med sold under the brand name Ziagen and as part of the combo treatments Trizivir and Epzicom. That's because people with that genetic variation are at a far higher risk of a severe allergic reaction.

Though that risk was first reported several years ago, it was only recently quantified in a clinical trial. The genetic test will be recommended in a "black box" warning on abacavir labeling. With this move, abacavir becomes one of only a handful of meds for which the FDA has recommended genetic screening--but we can expect more to come.

Second, a new study tagged a particular variant with statins' most serious side effect. People who have that genetic variation were five to 17 times more likely to develop muscle pain and weakness--which can lead to muscle breakdown, kidney failure and death--when taking the cholesterol-lowering meds. The finding could lead to a predictive genetic test, which could help doctors know which patients can tolerate the higher doses that are increasingly common amongst statin-users.

- read the abacavir news from the New York Times
- check out the Washington Post statin story

No "black box" for epilepsy meds?

Tracy Staton — Fri, 11 Jul 2008 08:53:09 -0400

It was a close shave for 11 epilepsy drugs yesterday. An FDA advisory panel agreed that they may raise the risk of suicide--but not enough to warrant a "black box" warning on their labels. You'll recall that the agency did a meta-analysis of trial data and found higher rates of suicidal behavior and thinking in dozens of studies. FDA staffers have been indicating for weeks that they intended to issue a warning based on that analysis. And that warning would affect products made by almost every big name in pharma: GlaxoSmithKline, Pfizer, Merck, et al.

It wasn't a close vote at the meeting, however; 14 panelists voted against a "black box", with four in favor and three abstaining. The expert panelists did recommend sending a medication guide to doctors that details the risk of suicide possible with these meds. And in a separate vote the panelists affirmed the agency's conclusions about the suicide risks. Despite voting against the "black box," one panelist said, "I do think there's a serious need to communicate this knowledge." The panelists just wanted to make sure that the warning wasn't so strong that it scared patients off drug therapy.

The 11 meds--which bring in a combined $10 billion-plus annually--aren't totally out of the woods yet. The FDA generally follows its panels' advice, but doesn't have to. You can bet the drugmakers who sell those products will be watching closely.

- read the article in the International Herald Tribune
- check out the Wall Street Journal story

FDA finalizing epilepsy black-box warnings

Christe Bruderlin-Nelson — Wed, 09 Jul 2008 10:23:56 -0400

Stringent epilepsy drug black-box labeling is likely to worry consumers and drug manufacturers alike, and will bring the total of drugs with a suicide risk warning up to about 35. The new warnings will be on the labels of 11 epilepsy drugs as soon as tomorrow, as FDA is very near finalization. Sales of the widely used drugs--which physicians also prescribe to treat migraines, certain types of pain and some psychiatric disorders--were over $8 billion last year.

The FDA made the decision to issue the warnings after analyzing data for nearly 200 trials of over 40,000 patients in a medication safety evaluation it initiated in 2005. They found that patients taking the epilepsy medications had almost double the risk of suicidal ideation or behavior compared to patients taking placebos. Additionally, while none of the individuals taking placebo medications committed suicide, four of those taking the epilepsy medications did.

The risk of suicidal thought and behavior increases after only a week of taking one of the medications and can last at least six months into it. The results were consistent regardless of the particular drug.

The medications affected include some neurology dinosaurs and include carbamazepine (Carbatrol, Equetro, Tegretol), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), tiagabine (Lyrica), tiagabine (Gabitril), topiramate (Topamax), valproate (Depakote, Depakene, Depacon) and zonisamide (Zonegran).

Pfizer argued against inclusion on the list, saying that its drug, Lyrica, was different from others in the class. Lyrica is relatively new and might feel the black-box pain more than other drugs.

- here's the Wall Street Journal story
- see eFlux Media's take

FDA orders warning for antibiotic class

Christe Bruderlin-Nelson — Wed, 09 Jul 2008 10:17:16 -0400

The many makers of fluoroquinolone antibiotics--which include well-known and frequently prescribed meds Cipro (Bayer) and Levaquin (J&J)--will have to up the ante on a side-effect warning that apparently doesn't have enough oomph.

The labels of these medications already list warnings about side effects, including the possibility of tendon rupture. Tendons, such as the Achilles tendon, connect muscles to bones--and tendon rupture requires major surgery and is debilitating. The number of people experiencing this particular side effect was continuing to rise, prompting FDA to require that each company put an obvious "black-box" warning on the medication labels.

The ruling applies to all fluoroquinolone drugs, including ciprofloxacin (Cipro and generic ciprofloxacin), ciprofloxacin extended release (Cipro XR and Proquin XR), gatifloxacin (Tequin), gemifloxacin (Factive), levofloxacin (Levaquin), moxifloxacin (Avelox), norfloxacin (Noroxin) and ofloxacin (Floxin and generic ofloxacin).

A consumer group called Public Citizen first petitioned FDA to increase warnings on the drugs almost two years ago and resorted to a lawsuit about six months ago. While the warning was already on the medications, it was along with a laundry list of other possible side effects, and the number of individuals suffering tendon rupture was continuing to rise. FDA said the number was in the hundreds, but refused to be specific; however, a Public Citizen spokesperson said there were 407 tendon ruptures 341 reports of tendonitis in 2007 alone.

The benefit to increased information is that informed patients can take action if they experience pain or swelling in a tendon after starting the medication. Calling one's physician for an alternative antibiotic and stopping the drug at that point could help prevent a serious rupture. Most at risk are transplant patients, individuals older than 60 and people who are also taking steroids. The black-box warning will not apply to eye drop versions of the antibiotics.

Read the Washington Post story
See more at the Boston Herald
Find out what the LA Times blog says

FDA: Warning imminent for epilepsy meds

Tracy Staton — Thu, 12 Jun 2008 10:51:05 -0400

Apparently drugmakers' fears of new labeling for epilepsy drugs were well founded. The agency says it's very close to a deal with the companies on the labeling changes. And FDA has posted its written review of the data on suicidal thoughts and behavior among patients using the meds. The upshot: Twice the risk of suicidal thoughts or behavior among patients using one of the meds versus those using placebo (0.43 percent versus 0.22 percent). And, the agency said, the risk was consistent across all 11 drugs it studied.

An FDA advisory panel will meet next month to mull over the data themselves. But sources told USA Today that the labeling could be changed even in advance of that meeting.

- read the report
- check out the Pharmalot item

Shift in enforcement halves FDA warnings

Tracy Staton — Mon, 09 Jun 2008 10:58:16 -0400

Think the FDA has been falling all over itself to issue warning letters lately? Think again. A look at agency statistics showed that the number of warning letters actually dropped by half--yes, half--in the last 10 years. Apparently, when FDA changed its rules in 2002, requiring all warning letters to go through its chief counsel's office, the number of missives immediately dropped. In fiscal 2001, the agency sent 1,032; in 2002, it dispatched 538, and and in 2003, 471.

Agency chief Andrew von Eschenbach says that the difference lies only in the seriousness of the letters sent. In the past warning letters were sent out for minor as well as major problems; now they're reserved for serious concerns, he said. And David Elder, enforcement guru at the agency, said counting letters is at best a simplistic measure of its performance. But ex-FDA head David Kessler told the Wall Street Journal that the number of warning letters has "always been one of the surrogate measures of FDA's enforcement performance...[A]ny significant drop raises significant questions."

- see the NYT piece

FDA checks arthritis meds for child-cancer link

Tracy Staton — Thu, 05 Jun 2008 09:30:02 -0400

In a development sure to spawn headlines across the country, the FDA is looking into a possible link between autoimmune drugs such as Remicade and Humira--known as TNF blockers for their action against tumor necrosis factor--and childhood cancers. The meds are already labeled with potential cancer risks for adults, but this is the first time the FDA has analyzed the risk in patients up to 18 years old. Why now? We're not sure, given that 30 reports of cancer in children and adolescents trickled into the FDA over the 10 years since the first TNF blocker was approved.

It's not a huge cognitive leap: TNF blockers do their job by suppressing the TNF protein, an immune-system component that causes inflammation. It also is potentially helpful against tumor cells. But these meds aren't for lightweight diseases, either. Thousands of kids take Amgen and Wyeth's Enbrel and Abbott Laboratories' Humira for rheumatoid arthritis, a serious and painful disorder that erodes joints. Johnson & Johnson and Schering-Plough's Remicade is approved for kids with Crohn's disease, which, left untreated, can destroy the intestines' ability to absorb nutrients. The FDA said in a statement that it believes the benefits of the drugs outweigh the risks--but also recommended that doctors consider the potential cancer link when prescribing.

FDA says the review will take about six months. Analysts are already hand-wringing over a possible black-box warning; Humira was Abbott's best-seller last year, with $3 billion in sales, and Remicade delivered $1.65 million to Schering-Plough. (The number of adults using these meds far outweighs the juvenile use, though.) Expect to hear more discussion of the possible cancer link June 18, when an agency advisory panel hashes over Amgen's application to market Enbrel for kids with psoriasis.

- see the FDA release
- read the story in the New York Times
- check out the Washington Post article
- get the Chicago Tribune's focus on Abbott
- find Amgen and Wyeth's response