Drug Injury Watch

June 2008 FDA Meeting Will Address Problem Of Look-alike And Sound-alike Drug Names

Confusion Between Similar Drugs Is A Cause Of Medication Errors That Agency Will Focus On In New Pilot Program

(Posted by Tom Lamb at DrugInjuryWatch.com)

To start, we get this background information from "Medication Errors: FDA 101", which was posted March 14, 2008 on the FDA's web site:

A medication error is any preventable event that may cause or lead to inappropriate medication use or harm to a patient. Since 2000, the Food and Drug Administration (FDA) has received more than 95,000 reports of medication errors. FDA reviews reports that come to MedWatch, the agency's adverse event reporting program.

"These reports are voluntary, so the number of actual medication errors is believed to be higher," says Carol Holquist, R.Ph., Director of the Division of Medication Error Prevention in FDA's Center for Drug Evaluation and Research.

FDA works with many partners to track medication errors, including the U.S. Pharmacopeia (USP) and the Institute for Safe Medication Practices (ISMP). "Every report received through the USP/ISMP Voluntary Medication Error Reporting Program (MERP) automatically gets sent to FDA's MedWatch program," says Mike Cohen, R.Ph., Sc.D., President of ISMP. "It takes a cooperative approach to monitor errors, evaluate them, and educate the public about strategies to keep errors from happening again."

Medication errors occur for a variety of reasons. For example, miscommunication of drug orders can involve poor handwriting, confusion between drugs with similar names, poor packaging design, and confusion of metric or other dosing units.

On June 5-6, 2008 the FDA will be convening a public meeting to address the miscommunication problems and confusion the can be caused by look-alike or sound-alike drug names.  In late May the agency released a 29-page draft concept paper that will be used as a guide for discussions during the two-day meeting.

For more about the June 2008 FDA public meeting and this draft concept paper, we look to the May 29, 2008 edition of FDAnews Drug Daily Bulletin, published by Washington Business Information, Inc. / FDAnews:

Reducing medication errors caused by look-alike and sound-alike proprietary names — through a two-year pilot program it expects to begin in 2009 — is the focus of a draft concept paper the FDA has released in advance of a public meeting scheduled for June 5–6.

 The pilot program will be designed to let drug companies volunteer to evaluate proposed proprietary names and submit the data for review to CDER or CBER, as appropriate....

In the pilot program, CDER and CBER will evaluate the safety and promotional implications of submitted drug names. If a name seems prone to cause confusion, the relevant center “will not recommend its approval for use in the market and will request the applicant propose an alternate name for evaluation,” the draft says. “Any preventable risk of error that can be identified prior to drug approval should be addressed.”

Returning to the FDA document we started with for background, it provides these links for those who want more information about medication errors and mistakes:

6 Tips to Avoid Medication Mistakes
www.fda.gov/consumer/updates/medtips062107.html

Medication Errors (FDA)
www.fda.gov/cder/drug/MedErrors/default.htm

Reporting Adverse Experiences to FDA
www.fda.gov/medwatch/how.htm

Institute for Safe Medication Practices
www.ismp.org

U.S. Pharmacopeia
www.usp.org

To assist the FDA with keeping track of adverse drug events, we encourage doctors and patients, both, to submit MedWatch reports to the agency when appropriate.

Digitek Update May 2008: When Old News Is Better Than No News At All

A Month After FDA Class 1 Digitek Recall, We Have Been Told Little About Actavis Manufacturing Problem

(Posted by Tom Lamb at DrugInjuryWatch.com)

More than thirty days have passed since Actavis Totowa first announced the Digitek recall that was issued due to an apparent quality control problem at their manufacturing plant in Little Falls, New Jersey -- not somewhere in China, as numerous patients have presumed during our initial discussion about the situation.

Being that Actavis and the FDA are being relatively closed-mouth about the extent of the manufacturing problems with Digitek that resulted in the production and release of tablets with too much digoxin, we have been looking for information from other sources.

One item that got our attention was a March 1, 2007 article, "Actavis Totowa nets warning for QC, cleaning validation.", written by Joseph Pickett and published by Validation Times.

In relevant part, this article describes how quality control at the Actavis facility in New Jersey where Digitek was made had been an issue as far back as the summer of 2006:

A July 10-Aug. 10, 2006 inspection of Actavis Totowa, Little Falls, NJ, a prescription drug manufacturer, found significant deviations from [Good Manufacturing Practices (GMP)] regulations which included the following:

Significant deficiencies in the company's quality control unit;....

Regarding quality control, FDA investigators noted in the Feb. 1 warning letter numerous instances where the quality control unit failed to adequately investigate and resolve laboratory deviations and out-of-specification (OOS) test results involving drug products that ultimately were released for distribution into interstate commerce. Additionally, investigators uncovered out-of-specification test results in laboratory raw data that were not documented in laboratory notebooks, and found that products were released based on retesting without any justification for discarding the initial out-of-specification test results.

Numerous instances were observed where manufacturing process deviations occurred and in-process specifications were not met, yet there was no indication that action was taken promptly to investigate or to correct the deviations and the products were approved for release and distribution by the quality control unit, the agency wrote....

FDA stated that it had reviewed the firm's corrective actions promised in a letter dated Aug. 29, 2006. The agency found that while corrections the firm promised in its correspondence appeared to adequately address many of the GMP violations, FDA reiterated its concern about the quality of drug products that were released from the facility under the serious lack of GMP controls found during the inspection.

Further, the agency stated that the company should promptly initiate an audit program by a third-party having appropriate GMP expertise, to provide assurance that all marketed lots of drug products that remain within expiration have their appropriate identity, strength, quality, and purity.

One wonders whether or not the FDA-suggested "audit program" was ever implemented by Actavis. 

Given that production and release of double-dose Digitek pills were the types of things this audit was intended to prevent, I am skeptical.

Actavis Tells Us More, But Not Much More, About April 2008 Digitek Recall

Actavis, Mylan, Or The FDA Should Tell Public Their Current Estimate Of How Many Defective Digitek Pills Were Distributed To Pharmacies, And During What Time Period

(Posted by Tom Lamb at DrugInjuryWatch.com)

On May 9, 2008 Actavis North America issued this press release "Digitek® recall – customer support and frequently asked questions", which looked like it contained some new information about the Digitek recall.

But on the critical issue of how extensive is the Actavis manufacturing problem which led to the FDA recalling Digitek (digoxin), the company is still vague in terms of quantity and time, saying no more than this is an "all-lot" recall.

From speaking with patients around the country who have taken Digitek the past couple of years, it seems that this Digitek recall is not limited to only those digoxin tablets which were manufactured by Actavis a month or two before the company's April 25, 2008 announcement about the Digitek pill manufacturing problem it had discovered.

What these patients and their families deserve to know is an estimated number of defective Digitek pills that were distributed by Mylan Pharmaceuticals to pharmacies under the "Bertek" and "UDL" labels, as well as the period of time when one might have been taking a Digitek pill that had double the intended dose of digoxin.

As we learned from a "recall notice" posted on the North Carolina Board of Pharmacy (NCBOP) web site, the Bertek Digitek pills might have had the double-dose problem as far back as March of 2006.  But this is all we know.

Is this all that Actavis, Mylan, and the FDA know?

FDA Safety Evaluation Of Antibiotic Maxipime Is Not Completed, Yet

Six Months After It Announced Start Of This Investigation, FDA Gives An Update On Status Of Maxipime Safety Review

(Posted by Tom Lamb at DrugInjuryWatch.com)

In mid-November 2007 the FDA announced the start of its investigation into the safety of Maxipime (cefepime), and said their safety evaluation should take about four months to complete. 

The focus of this FDA investigation was the possible increased risk of death associated with Maxipime, which is an injectable antibiotic that is manufactured by Bristol-Myers Squibb Co. (BMY) and marketed in the U.S. by Elan Corp. PLC (ELN).

In mid-May 2008 the FDA let us know that their Maxipime safety evaluation was taking longer than initially anticipated.  A May 14 MedWatch email from the FDA provided a link for Update of Safety Review: Follow-up to the November 14, 2007, Communication about the Ongoing Safety Review of Cefepime (marketed as Maxipime), which purportedly "reflects FDA’s current analysis of available data concerning this drug."

From this May 2008 Maxipime Update, we learn where the FDA is in their investigation:

FDA is continuing to review safety data for the drug [Maxipime].  There are a large number of studies to be reviewed and some, but not all, of the requested study data have been received by the FDA.  As a result, FDA has not reached a definitive conclusion as to whether or not the increased mortality seen with cefepime compared to other β-lactam antibiotics observed in the meta-analysis is due to cefepime.

Maxipime is a broad-spectrum antibiotic approved by the FDA in 1996 for the treatment of infections due to susceptible strains of microorganisms.

We will continue to monitor the FDA's progress with this ongoing safety evaluation of Maxipime.

May 2008 Update: Sprint Fidelis Lead Wire Failures Due To Design Flaw, Not Doctors

Medtronic Had Initially Suggested That It Was Implant Technique That Caused The Sprint Fidelis Malfunctions

(Posted by Tom Lamb at DrugInjuryWatch.com)

For today's post we have to thank Westby G. Fisher, MD, FACC, who is a board-certified internist, cardiologist, and cardiac electrophysiologist, as well as an associate professor of medicine, in Evanston, Illinois.

Dr. Fisher is better known to some of us as "Dr. Wes", the name of a blog that he began publishing in November 2005.

In his May 13, 2005 article, "Medtronic's Sprint Fidelis Defibrillator Lead Performance Update", Dr. Wes provides us with a summary of and link to the May 7, 2008 Medtronic update on the recalled Sprint Fidelis Model 6949 defibrillator lead.  Thereafter, he expresses this opinion:

The implications of these recommendations are far-reaching, for it now seems that the fault with the lead was not a physician implant technique problem as originally surmised, but rather a design flaw.

You should read this brief but informative May 13 post by Dr. Wes to see how he arrives at this opinion.

If, however, you want to do your own analysis of what caused the Sprint Fidelis defibrillator leads to malfunction or fail altogether, here's some material for you to start with:

• October 15, 2007 Medtronic Letter: "Urgent Medical Device Information Sprint Fidelis® Lead Patient Management Recommendations"
• May 7, 2008 Medtronic Letter: "Sprint Fidelis® Lead Performance Update (Models 6949, 6948, 6931, 6930)" 

Switching gears a bit -- for those of you who have not heard the bad news, yet -- on February 20, 2008 in the Riegel v. Medtronic case, the U.S. Supreme Court granted legal immunity to manufacturers of medical devices which had been approved by the FDA based on the legal doctrine of federal preemption.

But as Dr. Robert Hauser, of the Minneapolis Heart Institute, told a news reporter who was preparing a story about the Sprint Fidelis recall:  "Just because a device is FDA-approved does not necessarily mean it is safe."

It is my opinion that Congress should move quickly to pass legislation that would correct the Riegel decision by the Supreme Court.   

This legislation is needed because, in my experience, the possibility of becoming involved in product liability litigation is a significant incentive for the medical device manufactures to ensure that their products are safe for use by American patients.

I would like to hear what you think about this issue as well as my opinion about use of the federal preemption doctrine in this context.  You can do so by submitting a Comment, below, or by taking part in a poll on this issue -- "What if you were hurt by a drug and couldn't sue?" -- over on the HeyMonkeyBrain! part of Squidoo.

May 2008 Congressional Hearing On Federal Preemption Of Drug And Medical Device Lawsuits

Committee Will Hear From A Diverse Set Of Witnesses On The Various Aspects Of This Controversial Legal Doctrine

(Posted by Tom Lamb at DrugInjuryWatch.com)

On May 14, 2008 the House of Representative's Committee on Oversight and Government Reform will convene a hearing to explore the legal doctrine of federal preemption in the context of product liability lawsuits involving FDA-approved drugs and medical devices.

The announcement for this May 14 federal preemption hearing is currently on the Committee on Oversight and Government Reform web site (accessed 5/12/08):

Should FDA Drug and Medical Device Regulation Bar State Liability Claims?
Committee on Oversight and Government Reform
Wednesday, May 14, 2008, 10:00 AM at 2154 Rayburn House Office Building

It is expected that the Committee should offer live streaming video of this hearing on their website: http://www.oversight.house.gov

At this May 2008 hearing, members of Congress and those in attendance will likely hear from each of these scheduled witnesses:

• Actor Dennis Quaid and his wife Kimberly, parents of newborn twins, Thomas Boone Quaid and Zoe Grace Quaid, who were victims of a heparin overdose;
• William Maisel, director of the Medical Device Safety Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Boston;
• Aaron Kesselheim of the Harvard Medical School's Division of Pharmacoepidemiology; David Kessler, professor of pediatrics and epidemiology and biostatistics at the School of Medicine, University of California, San Francisco;
• David Vladeck, professor of law at the Georgetown University Law Center;
• Gregory Curfman, editor of the New England Journal of Medicine;
• Christine Ruther, president and chief engineer for C&R Engineering, Inc.; and,
• Utah State Representative David Clark (R) of the National Conference of State Legislatures.

As you may know, the U.S. Supreme Court’s ruling in Riegel v. Medtronic this past February dealt American patients a serious set-back in terms of holding medical device companies legally liable for their unsafe products when, in an 8-to-1 vote, the Supreme Court held that state tort claims regarding medical devices were preempted if the FDA had granted premarket approval for a medical device. 

Looking forward, in October 2008 (what will likely still be) the same Supreme Court hears oral arguments in the case Wyeth v. Levine, relating to the issue of whether the federal preemption doctrine ought to prohibit drug injury cases.

For reasons I have written about previously, I believe that patients should not be pre-empted, or prohibited, from filing lawsuits against medical device and pharmaceutical companies.

Let us know what you think about this federal preemption doctrine in the context of medical device and drug injury cases by submitting a Comment to this article, below, or by taking part in a poll on this issue -- "What if you were hurt by a drug and couldn't sue?" -- over on the HeyMonkeyBrain! part of Squidoo.

P.S.  You can read the transcripts from this May 2008 Congressional hearing on FDA federal preemption being applied so as to prohibit legal liability claims involving prescription drugs and medical devices, including Chairman Henry Waxman's opening statement and the testimony of Dennis Quaid as well as all other witnesses.  (5/19/08)

Recall Notice For Digitek Marketed Under Bertek Label Goes Back To March 2006

North Carolina Board Of Pharmacy Has Posted A Copy Of The Bertek Digitek Drug Recall Notice On Its Web Site

(Posted by Tom Lamb at DrugInjuryWatch.com)

The home page of the North Carolina Board of Pharmacy (NCBOP) currently shows a May 5, 2008 news item about the Digitek recall which includes a link to this document, which they describe as the "recall notice" (7/30/08 update: this Digitek recall notice is still on NCBOP site but off the home page, now):

Urgent: Drug Recall -- Digitek® (digoxin tablets, USP)

• Recall initiated by the manufacturer: Actavis Totowa LLC (formerly known as Amide Pharmaceuticals, Inc.)
• Product Distributed by: Mylan Pharmaceuticals, Inc. under a "Bertek" Label

Therein, we are told that this Digitek recall, at least for Bertek tablets, goes back all the way to March 2006, more than two years before the April 2008 announcements by Actavis and the FDA:

Mylan Pharmaceuticals Inc. is continuing a voluntary recall of the Actavis Totowa recall of Digitek® (digoxin tablets, USP).  This product is being recalled due to the possibility that tablets with double the appropriate thickness may have been commercially released. These tablets may contain twice the approved level of active ingredient than is appropriate. Product was distributed nationwide between March 2006 and April 2008.

(Emphasis added.)

The NCBOP May 5 news item also reminds North Carolina pharmacists that because digoxin is a so-called "Narrow Therapeutic Index" drug, they have special obligations under North Carolina law:

A prescription for a narrow therapeutic index drug shall be refilled using only the same drug product by the same manufacturer that the pharmacist last dispensed under the prescription, unless the prescriber is notified by the pharmacist prior to the dispensing of another manufacturer's product, and the prescriber and the patient give documented consent to the dispensing of the other manufacturer's product. For purposes of this subsection, the term "refilled" shall include a new prescription written at the expiration of a prescription which continues the patient's therapy on a narrow therapeutic index drug.

N.C.G.S. Section 90-85.28(b1).

In their May 2008 news item, the NCBOP acknowledged that the Digitek recall is "unusual" as concerns pharmacist-compliance with this NC statute:

Board staff understands that the Digitek recall will require switching some patients to a different manufacturer’s digoxin product. Compliance with the letter of N.C.G.S. Section 90-85.28(b1) may prove difficult in certain circumstances. In the unusual circumstances of this recall, it is critical to ensure that patients continue to receive their medication. Accordingly, where switching a patient to a different manufacturer’s digoxin product is necessary because of the recall, pharmacists must counsel affected patients on the switch, the reason for it, and possible side effects/therapeutic changes that could be associated with the change. Moreover, pharmacists must contact the patient’s prescriber to alert of the change so that monitoring of digoxin levels and therapeutic effect can, if necessary, begin.

Interestingly, the Digitek recall notice posted on the North Carolina Board of Pharmacy (NCBOP) web site makes no mention of the Digitek pills marketed under the "UDL" label and distributed by UDL Laboratories, Inc. -- part of Mylan Laboratories, Inc. which also includes Mylan Pharmaceuticals, Inc.

One reason may be that UDL apparently provided Digitek in pharmaceutical unit dose packaging for hospitals, nursing homes, and other healthcare institutions, only.  As such, perhaps that aspect of the Digitek recall is not a matter of concern for the NCBOP.

Let us know if you have any news or information about the Digitek recall that we can share.

Ortho Evra Recall Requested By Public Citizen Due To Blood Clot Risks

Women Have Developed Serious Side Effects Like Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) After Using This Birth Control Patch

(Posted by Tom Lamb at DrugInjuryWatch.com)

On May 8, 2008 Public Citizen's Health Research Group (HRG) sent its "Petition to the FDA to Ban Ortho-Evra" to Commissioner Andrew von Eschenbach.  In this 11-page letter, Sidney Wolfe, M.D., the Director of HRG, discusses the increased risk of blood clots and serious side effects associated with Johnson & Johnson's Ortho Evra birth control patch, sometimes referred to simply as "the Patch".  In summary, Dr. Wolfe points out:

Compared to standard 35 microgram estrogen/progestin oral contraceptives, Ortho-Evra results in:

• 60% more estrogen on average exposure;
• greater variability in estrogen levels;
• a possible two-fold increased risk of venous thrombosis (typically, painful blood clots of the leg which can travel to the lungs and cause death)....

This May 2008 Petition concludes with a request for a "gradual recall" of the Patch:

Public Citizen therefore requests a six-month transition period in which  Ortho-Evra will be available for refill prescriptions to allow women time to meet with their healthcare provider and seek an alternative contraceptive method.

A May 8, 2008 Reuters article, "US Group wants FDA to pull J&J birth control patch", summarily presents the long-standing FDA and drug company positions as regards this allegation by Public Citizen that Ortho Evra is unsafe and, therefore, the Patch should be removed from the market:

The FDA has said the chance of developing a clot is low. For every 10,000 women who use hormonal contraceptives for one year, some three to five of them will develop a clot, the agency has said.

Ortho Women's Health & Urology, the J&J division that makes the contraceptive patch, has said its patch has risks and benefits like all hormonal contraceptives.

We will look for what the FDA and J&J have to say, if anything, about this May 2008 Ortho Evra Petition from Public Citizen in the days to come.

Extent Of Digitek Recall Remains A Mystery Ten Days Later; Patients Are Left In The Dark

Heart Medication Sold By Mylan Was Made In Actavis Plant That Received FDA Letter About Manufacturing Problems Over A Year Ago

(Posted by Tom Lamb at DrugInjuryWatch.com)

News about the April 2008 Digitek recall came first in the form of a brief company press release dated April 25, which was followed by an FDA MedWatch Safety Alert posted April 28 on the agency's web site.

As of May 5, ten days later, there had been little additional information from Actavis Totowa, the drug manufacturer, and none from the FDA, about the possible extent of the Digitek recall. 

Meanwhile, patients are being contacted by their pharmacists who, admittedly, know nothing more about the situation than what was set forth in the April 25 half-page press release about this "Class 1 nationwide recall of Digitek (digoxin pills, USP, all strengths)".

Understandably, patients are asking how far back in time they have been getting and taking Digitek pills that may have contained double the intended dose of active ingredient.

The latest news about the extent of the Digitek recall comes from a May 6, 2008 article, "Double-strength digoxin recalled in US", by Phil Taylor, which is posted online at In-PharmaTechnologist.com ("Breaking News on Pharmaceutical Technology"), of London, UK.

Because we do not want to misconstrue in any manner the intriguing information developed by Mr. Taylor in his May 6 article, we provide this extended excerpt:

A spokesperson for the company told in-PharmaTechnologist.com that the investigation into the problem was still ongoing, but at the moment there was no further information on what caused it and how many tablets were involved.

This is not the first time that there have been manufacturing problems at the Actavis Totowa facility in New Jersey, which was acquired as part of the takeover of Amide Pharmaceuticals by Actavis in May 2005, although the spokesperson said these earlier issues were entirely unrelated to the current incident.

Just over a year ago Actavis Totowa was sent a warning letter by the FDA after an agency inspection revealed that drugs products manufactured in the facility were 'adulterated'.

The quality control unit at the site came under criticism from the agency, which said it failed to reliably establish the identity, strength, quality and purity of drug products manufactured and released onto the market. The FDA inspectors also noticed a general lack of investigation of out-of-specification test results, as well as a lack of sufficient documentation of the results.

It is understood, however, that all these 'Form 483' issues have since been resolved to the agency's satisfaction.

Hopefully Actavis and/or the FDA will be making an official announcement, soon, about how far back in time the Digitek pills sold under the "Bertek" and "UDL" labels may have been double-strength tablets.  Until then, many patients and their families are left wondering if possibly related symptoms were caused by the use of these double-strength Digitek tablets.

FDA Says It Doesn't Know How Long Defective Digitek / Digoxin Pills Were Sold

Actavis Says They Have Received 11 Complaints About Digitek Side Effects That Date Back To 2006

(Posted by Tom Lamb at DrugInjuryWatch.com)

The facts surrounding a late April 2008 recall of Digitek (digoxin) pills that may have twice the usual active ingredient are becoming less clear as we learn more in the days following the FDA's April 28 announcement.

In a May 1, 2008 Newsday.com article, "Pharmacists will call you: Digitek recalled", by reporter Kathleen Kerr, we learn that the defective Digitek tablets may have been sold for more than a year:

"We had some concerns about the process," [Actavis Totowa spokesman John] LaRocca said. He said the company knew of no deaths linked to Digitek use but Actavis and the FDA had received 11 complaints about side effects since 2006.

As reported previously, this improperly manufactured generic digoxin medication could lead to digitalis toxicity; patients with renal insufficiency are especially at risk.

According to Californian staff writer Emily Hagedorn, in her May 1, 2008 article "Recall of heart drug worries Bakersfield family", the FDA is still trying to get a handle on the magnitude and ramifications of this Digitek recall:

Considering it was voluntarily recalled Friday afternoon, it’s too soon to tell how many people have suffered adverse reactions, said Sandy Walsh, spokeswoman for the Food and Drug Administration. She didn’t know how long the defective pills were sold....  The FDA has inspected the manufacturer’s facility since the error was discovered, she said....  While Actavis has 50 percent of the digoxin market, the FDA does not foresee a shortage from other manufacturers, Walsh said.

Going back to the Newsday.com May 1 article, we get some pharmacy perspective on the Digitek recall:

Joel Bassuk, pharmacist at Raindew Pharmacy in Manhasset, said he received the recall notice yesterday....  "They said to immediately examine your inventory and discontinue all lots," Bassuk said....  CVS spokesman Mike DeAngelis said the chain had removed all Digitek from its stores. "We went back to see which patients had prescriptions over the past 12 months and contacted them," DeAngelis said.

As always, we welcome information about emerging drug safety issues:  [email protected].  This situation, in particular, calls for such assistance from anyone who may know more about the extent of this apparent manufacturing problem whereby some digoxin pills may be too potent.  At this juncture, at least, it seems we are not getting much in terms of "specifics" from Actavis, the drug manufacturer, nor the FDA about this Digitek recall.