TWO Drug Alerts: Seroquel and Digoxin

#1 Seroquel
Last year we had articles about a number of veterans treated by the VA in West Virginia who died in their sleep.
They were taking a drug cocktail which included Seroquel.
The families of those dead veterans are still looking for answers.
And now, two of the families testified before an FDA panel looking into allowing expanded use of Seroquel.
More info on Seroquel is here...
Latest story below:
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http://www.philly.com/inquirer/business/20
090409_A_minor_victory_in_Seroquel_battle.html
A minor victory in Seroquel battle

By Miriam Hill
Inquirer Staff Writer


WASHINGTON - A government panel opened the door a crack yesterday toward allowing AstraZeneca P.L.C. to sell its Seroquel XR more widely, after an emotional meeting that included stories from two families who say their loved ones died after taking the powerful antipsychotic.

The Food and Drug Administration advisory committee recommended the agency approve Seroquel XR for use as an additional therapy in patients suffering from depression who do not respond adequately to their current medications.

AstraZeneca, whose U.S. headquarters is in Wilmington, had asked the panel to approve Seroquel much more broadly, to treat depression and anxiety as a single therapy.

Recommending the broader use would have dramatically expanded the market for Seroquel. The drug is currently approved to treat schizophrenia and bipolar disorder, relatively rare diseases, and generates $4.47 billion in yearly sales.

Depression and anxiety, by contrast, affect 10 percent to 20 percent of the population. Wyeth's Effexor XR, one of the world's top-selling antidepressants, generates about $4 billion in sales annually.

"It's certainly going to help their bottom line, but it's not the great victory they had hoped for," said Daniel Carlat, a Tufts University psychiatrist who was not on the advisory panel. He said companies could use such narrow approvals to market a drug more widely.

Bristol-Myers Squibb, for example, has heavily advertised its schizophrenia drug Abilify in TV ads since winning approval for its use as an add-on treatment for depression.

The FDA could still decide to approve Seroquel for even broader uses, but the agency usually follows the recommendations of its advisory panels.

In a statement, Howard Hutchinson, chief medical officer of AstraZeneca, said, "We are pleased that the committee found Seroquel XR to be effective and acceptably safe for use as adjunctive therapy for treatment of [depression]. . . . We look forward to having further discussions with the FDA."

Panel members, including scientists from outside the FDA and consumer advocates, said Seroquel's risks in depression and anxiety outweighed its benefits. The drug leads to weight gain, and some research suggests it can trigger diabetes and heart problems.

Schizophrenia and bipolar disorder are more serious psychiatric illnesses than depression and anxiety, which seemed to change the risk-benefit calculations for several panelists.

"The risks are fairly well-documented, and I don't think they are acceptable for this use," said Richard Malone, a panel member and Drexel University scientist.

Another member, James Neaton, a biostatistics professor at the University of Minnesota, agreed.

"The bar should be higher," Neaton said. "Twenty-five to 30 percent of these patients would be treated chronically, and the longest study was 48 weeks. I accept the fact that the drug is better than placebo, but the effect is modest, and the cardiovascular risk is uncertain."

AstraZeneca scientists presented reams of data asserting that Seroquel was safe and effective for treating depression and anxiety, but several panelists said they would like to see studies that tracked patients for several years, because some cardiovascular diseases take that long to develop.

Allen Jones, a former fraud investigator with the Pennsylvania Inspector General's Office whose work led to the conviction of a state psychiatrist for taking bribes from drug companies, asked the FDA to force AstraZeneca to release every shred of data on Seroquel. He cited documents uncovered by lawyers suing AstraZeneca on behalf of clients who say they were injured by Seroquel.

Those documents, released in a court case earlier this year, include company e-mails in which AstraZeneca employees discussed "buried" studies and congratulated one another for doing "nice smoke-and-mirrors" jobs on Seroquel data.

Janette Layne believes Seroquel may have contributed to the death of her husband, Eric, who was prescribed the drug, along with several others, to treat the post-traumatic stress disorder he developed after serving in Iraq.

Eric Layne died at home in West Virginia in January 2008 while his wife was pregnant with their second child, Jubilee, who accompanied her mother to yesterday's hearing.

"I am the widow of Sgt. Eric Layne. I found my husband dead when our son, Shamus, was 17 months old," Janette Layne told the committee between her tears.

"In summer of 2007, he began taking Klonopin and Seroquel. He ate excessively and would fall asleep with food in his mouth. He had tremors and was extremely lethargic. His speech was slurred to the point I couldn't tell what he was saying. Eric did not have any of these problems before he took these medications."

She showed a short video of her husband slumped over a table in their home and barely able to respond to her questions on Christmas, shortly before he died at age 29.

Stan and Shirley White, also of West Virginia, testified that their 23-year-old son, Andrew, died suddenly after taking the same drugs Layne did. Some researchers suspect that Seroquel can trigger sudden cardiac death, and the Whites have asked Congress to look into the unexpected deaths of about 40 young members of the armed services.

The Veterans Administration determined that White and Layne died "from combined drug intoxication involving prescribed and nonprescribed medications," and said it could not "draw conclusions about the relationship between medication regimens and these deaths."

"He was told, and I as his mother was told, 'These medications will not harm you,' " Shirley White told the panel. "I trusted the doctors to do what was best for my son, and he died in his sleep."
2. Drug Alert Digoxin

A veteran sent me the above photo of a VA prescription vial. The vet told me he had found out, on his own, that the drug had been recalled, but he hadn't heard word one from his VA pharmacy.

The drug listed, Digoxin 0.25mg with NDC# 57664-0441-18, has been recalled by the manufacturer. (see below)

But, to our knowledge, it has not yet been recalled by the VA. It is not listed on the VA's Medication Safety News page, here...
http://www.pbm.va.gov/VACenterFo
rMedicationSafety-Index.aspx

To double-check on this, I called my VA pharmacy (West Coast). They knew nothing about it. When I gave them the NDC#, they checked and said no vets were given that lot number.

I wondered about that.

So, I called the VA pharmacy where the prescription was filled (East Coast). The VA pharmacist told me the same thing... they knew nothing about a recall... and they did not fill any Digoxin prescriptions with that NDC#. How can that be? I'm not sure.

I talked with Veterans' Advocate Jim Strickland who told me that this is a Class 1 recall, defined this way: Class I recalls go all the way down to the consumer level and are for dangerous or defective products that predictably could cause serious health problems or death.

And, this is from a former FDA investigator:

VA departments like VA hospitals and VA District Offices tend to operate as independent fiefdoms. When you contact the VA people you know, they may know nothing of the recall and you will have to explain it to them.

You may probably find the recall notice was sent to the department that purchases the drugs and they never sent it to any pharmacy. The main VA supply depot may not have forwarded this to the pharmacy's or notified VA Administrators so the medical staff was alerted. Or the VA is unaware that this alert is down to the patient-consumer lever and can injure heart patients.

The doctors may only become aware of the problem when they read it in medical journals two months after the fact.

Well, we don't want you to find out two months after the fact.

If you are a veteran taking Digoxin with the NDC codes (lot numbers) listed below, here is what you should do.


1. CONTINUE TAKING THIS MEDICATION. Discontinuing Digoxin could cause very serious problems.

2. Contact your VA physician immediately and seek guidance regarding your supply of Digoxin.


And, another complication. There is a Digoxin shortage right now because of a number of recalls. In fact, one manufacturer has stopped production.

Recall information is below:



The FDA recall page for this drug is here...
http://www.fda.gov/oc/po/firmrecalls/caraco03_09.html
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Recall -- Firm Press Release

FDA posts press releases and other notices of recalls and market withdrawals from the firms involved as a service to consumers, the media, and other interested parties. FDA does not endorse either the product or the company.
Caraco Pharmaceutical Laboratories, Ltd. Announces a Nationwide Voluntary Recall of All Lots of Digoxin Tablets Due to Size Variability

Contact:
Daniel Movens: (313) 871-8400
Thomas Versosky: (313) 556-4150

FOR IMMEDIATE RELEASE -- DETROIT, March 31, 2009 -- Caraco Pharmaceutical Laboratories, Ltd. (NYSE AMEX: CPD), a generic pharmaceutical company, announced today that all tablets of Caraco brand Digoxin, USP, 0.125 mg, and Digoxin, USP, 0.25 mg, distributed prior to March 31, 2009, which are not expired and are within the expiration date of September, 2011, are being voluntarily recalled to the consumer level. The tablets are being recalled because they may differ in size and therefore could have more or less of the active ingredient, digoxin. The recalled tablets were manufactured by Caraco Pharmaceutical Laboratories, Ltd. This recall is being conducted with the knowledge of the Food and Drug Administration.

Digoxin is a drug product used to treat heart failure and abnormal heart rhythms. It has a narrow therapeutic index and the existence of higher than labeled dose may pose a risk of digoxin toxicity in patients with renal failure. Digoxin toxicity can cause nausea, vomiting, dizziness, low blood pressure, cardiac instability, and bradycardia. Death can also result from excessive digoxin intake. A lower than labeled dose may pose a risk of lack of efficacy potentially resulting in cardiac instability. Consequently, as a precautionary measure, Caraco is recalling these tablets to the consumer level to minimize any potential risk to patients.

Consumers with the products with the following NDC codes that are within expiration should return these products to their pharmacy or place of purchase.

Product Identification

Caraco Digoxin 0.125 mg is a scored round biconvex yellow tablet imprinted with “437”

Caraco Digoxin 0.25 mg is a scored round biconvex white tablet imprinted with “441”

NDC Numbers:

Digoxin Tablets, USP, 0.125 mg
57664-437-88 (100-count)
57664-437-18 (1000-count)

Digoxin Tablets, USP, 0.25 mg
57664-441-88 (100-count)
57664-441-18 (1000-count)

Patients using Caraco's Digoxin tablets, USP, 0.125 mg or 0.25 mg, who have medical questions should contact their healthcare provider for additional instructions or guidance.

Retailers who have this product should return the product to their place of purchase. Retailers can call Caraco customer service at (800) 818-4555, Monday through Friday, 8:00 a.m. – 5:00 p.m. EST, for instructions on how to return the affected product or for any other inquiries related to this action.

Any adverse reactions experienced with the use of all affected product, and/or quality problems should also be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088, by Fax at 1-800-FDA-0178, by mail at Med Watch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.

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