Worth a read, a case involving Starbucks, a stolen laptop and ID Theft. Hollow win for the Plaintiff.
The Ninth Circuit noted that under Washington law, "actual loss or damage is an essential element" of a negligence claim. The Court noted that plaintiffs waived the argument that "anxiety constitutes actionable injury.
Find the decision here: http://www.scribd.com/doc/45307040/Krottner-v-Starbucks-No-09-35823-9th-Cir-Dec-14-2010-Opinion
"Although we have not previously determined whether an increased risk of identity theft constitutes an injury-in-fact, we have addressed future harm in other contexts, holding that “the possibility of future injury may be sufficient to confer standing on plaintiffs; threatened injury constitutes ‘injury in fact.’ ” Cent. Delta Water Agency, 306 F.3d at 947. More specifically, [a] plaintiff may allege a future injury in order to comply with [the injury-in-fact] requirement, but only if he or she “is immediately in danger of sustaining some direct injury as the result of the challenged . . . conduct and the injury or threat of injury is both real and immediate, not conjectural or hypothetical."
Thursday, December 16, 2010
FDA Says More Scrutiny Over Dietary Supplements
Image via WikipediaThe FDA took new steps aimed at keeping consumers safe from harmful products that are marketed as dietary supplements and that contain undeclared or deceptively labeled ingredients. The FDA has found that these products are often promoted for weight loss, sexual enhancement, and bodybuilding.From the FDA site:
Among the substances found in products that are marketed as dietary supplements and that contain hidden or deceptively labeled ingredients are
- the active ingredients in FDA-approved drugs or their analogs (closely-related drugs).
- other compounds, such as novel synthetic steroids, that do not qualify as dietary ingredients.
FDA has also alerted consumers to hundreds of products with these often deceptively labeled and harmful ingredients, including more than 80 products marketed for sexual enhancement, more than 70 products marketed for weight loss, and more than 80 products marketed for bodybuilding.
Interesting: We've been working on cases involving unsafe supplements for several years, and to me the problem is getting worse, not better. Let's see how the FDA moves on this.
Tuesday, December 14, 2010
Florida Law: Appellate Court Reverses Trial Court Over Discovery Limits
An interesting decision from the Florida 4th DCA. It goes to show what lengths a corporate defendant will go to keep information from being disclosed (in this case, four years of 'protracted' fights). From the appellate opinion:
It is said in this case that a trial judge unreasonably curtailed one party's pretrial discovery of directly relevant, valid and reliable information reasonably calculated to lead to admissible evidence. The argument is that the critical information about the subject matter was lodged solely with the adverse party, but the court's errant discovery restrictions resulted in one-sided evidence before the jury. Hence, there was a verdict based on faulty, defective information. It is contended that the resulting judgment must be reversed and the case returned to the trial court to allow the full measure of discovery in accord with the principles and purposes of the rules governing that process.
The underlying action was based on a personal wreck involving a fatality. The Plaintiff claimed that a tire tread separation caused a wreck, and Cooper Tire was sued. The principal issue for discovery centered on the issue of whether the tire was defective and unreasonably dangerous in ordinary operation. Equally critical to discovery's scope was Cooper Tire's "state-of-the-art" affirmative defense.
When certain documents were sought, the Defendant filed numerous motions to keep the discovery out of the hands of the Plaintiff. Typical, you say. In this case, there was at least one evidentiary hearing that last four days, and there were 'protracted hearing over the span of four years." This fight continued over the course of two judges assigned to the action.
I reversing the lower court, the 4th DCA wrote this critical explanation that discovery should have been permitted on the issue of tire tread separation:
It is difficult to comprehend any valid basis for concluding that it could not possibly have affected the jury's consideration of the claims and defenses. This was evidence from Cooper Tire's own design and manufacturing processes of all its models of passenger-light truck tires. What might be thought by reasonable jurors as merely an anomaly if found in only a single model tire quite reasonably could be seen as strong evidence of design defects if found in tires across the spectrum of the kind of product at issue. Denying plaintiff the discovery of this evidence from Cooper Tire itself is the equivalent of denying Cooper Tire discovery from plaintiff as to the use of seatbelts and maintenance of the tires, as well as of the financial and emotional effects of the death of the decedent on the members of his family.
A good read not only for the rules regarding discovery, but for the lengths a party will to to thwart the very purpose of the rules.
Find the case here: http://scholar.google.com/scholar_case?case=16653302306530515981&hl=en&as_sdt=2&as_vis=1&oi=scholarr
It is said in this case that a trial judge unreasonably curtailed one party's pretrial discovery of directly relevant, valid and reliable information reasonably calculated to lead to admissible evidence. The argument is that the critical information about the subject matter was lodged solely with the adverse party, but the court's errant discovery restrictions resulted in one-sided evidence before the jury. Hence, there was a verdict based on faulty, defective information. It is contended that the resulting judgment must be reversed and the case returned to the trial court to allow the full measure of discovery in accord with the principles and purposes of the rules governing that process.
The underlying action was based on a personal wreck involving a fatality. The Plaintiff claimed that a tire tread separation caused a wreck, and Cooper Tire was sued. The principal issue for discovery centered on the issue of whether the tire was defective and unreasonably dangerous in ordinary operation. Equally critical to discovery's scope was Cooper Tire's "state-of-the-art" affirmative defense.
When certain documents were sought, the Defendant filed numerous motions to keep the discovery out of the hands of the Plaintiff. Typical, you say. In this case, there was at least one evidentiary hearing that last four days, and there were 'protracted hearing over the span of four years." This fight continued over the course of two judges assigned to the action.
I reversing the lower court, the 4th DCA wrote this critical explanation that discovery should have been permitted on the issue of tire tread separation:
It is difficult to comprehend any valid basis for concluding that it could not possibly have affected the jury's consideration of the claims and defenses. This was evidence from Cooper Tire's own design and manufacturing processes of all its models of passenger-light truck tires. What might be thought by reasonable jurors as merely an anomaly if found in only a single model tire quite reasonably could be seen as strong evidence of design defects if found in tires across the spectrum of the kind of product at issue. Denying plaintiff the discovery of this evidence from Cooper Tire itself is the equivalent of denying Cooper Tire discovery from plaintiff as to the use of seatbelts and maintenance of the tires, as well as of the financial and emotional effects of the death of the decedent on the members of his family.
A good read not only for the rules regarding discovery, but for the lengths a party will to to thwart the very purpose of the rules.
Find the case here: http://scholar.google.com/scholar_case?case=16653302306530515981&hl=en&as_sdt=2&as_vis=1&oi=scholarr
FDA takes a Look at Mercury in Tooth Fillings
Image via WikipediaFour consumer advocacy organizations have challenged the FDA's March 2009 ruling about mercury fillings or amalgams. From 2009 on the FDA site:The U.S. Food and Drug Administration today issued a final regulation classifying dental amalgam and its component parts – elemental mercury and a powder alloy—used in dental fillings. While elemental mercury has been associated with adverse health effects at high exposures, the levels released by dental amalgam fillings are not high enough to cause harm in patients.
The regulation classifies dental amalgam into Class II (moderate risk). By classifying a device into Class II, the FDA can impose special controls (in addition to general controls such as good manufacturing practices that apply to all medical devices regardless of risk) to provide reasonable assurance of the safety and effectiveness of the device.
The special controls that the FDA is imposing on dental amalgam are contained in a guidance document that contains, among other things, recommendations on performance testing, device composition, and labeling statements.
Specifically, the FDA recommended that the product labeling include:
- A warning against the use of dental amalgam in patients with mercury allergy;
- A warning that dental professionals use adequate ventilation when handling dental amalgam;
- A statement discussing the scientific evidence on the benefits and risk of dental amalgam, including the risks of inhaled mercury vapor. The statement will help dentists and patients make informed decisions about the use of dental amalgam.
The advocacy groups cite new studies pointing to neurological conditions and even Alzheimer's disease as consequences of some people's dental work. The organizations are asking the FDA's dental-products panel to, at the very least, reclassify the amalgam to bar its use in pregnant women and children. According to the news reports, "groups are also accusing the FDA and the American Dental Association of maintaining too cozy a relationship with the dental products industry."
Interesting reading from newsday, where you can find the article: http://www.newsday.com/long-island/fda-revisits-use-of-mercury-in-tooth-fillings-1.2540068
Friday, December 10, 2010
More Good News about Amazing Aspirin
From NPR:I'm one of those guys who takes an aspirin daily. So, I read this news with interest:
A British study claims evidence that aspirin can prevent death from a variety of cancers, if you take the medicine long enough in middle age. Even a baby aspirin might be enough.
Published in The Lancet, the study suggests aspirin could provide protection against a wide variety of tumors. They range from pancreatic cancer to the type of lung cancer that strikes nonsmokers.
For some of these cancers, the reduction in death was noteworthy. Twenty years after people had started taking aspirin regularly (and kept it up for at least five years), their deaths from esophageal cancer were reduced by 60 percent compared to study subjects who got a placebo.
http://www.npr.org/blogs/health/2010/12/07/131873139/study-aspirin-cuts-deaths-from-wide-variety-of-cancers
Read more:
Levaquine: Verdict for Plaintiff in first trial -Jury's Discussion Point? Responsibility
Image by Ricky Romero via FlickrYesterday a jury in Minneapolis today awarded a verdict in the case of John Schedin, who sued J&J and its Ortho-McNeil-Janssen Pharmaceuticals unit in 2008. Schedin said he ruptured both Achilles tendons after taking Levaquin. He claimed the companies failed to warn doctors and patients of the drug’s association with tendon damage.This is the first case of more than 2,600 claims in U.S. courts alleging that Levaquin caused tendon damage in patients and that J&J failed to disclose the risk adequately.
In a report, particularly telling is a juror's statement: “We talked a lot about the responsibility the company had to the general public, as far as safety goes,” Zach Rawson, a juror from Rochester, Minnesota, said after the trial. “ We felt that they didn’t warn adequately, that they didn’t use enough means of warning the public, especially the doctors.”
Source: http://www.bloomberg.com/news/2010-12-08/johnson-johnson-must-pay-1-1-million-in-punitive-damages-jury-says.html
Vanity Fair's Must Read: Deadly Medicine
Image by higlu via FlickrA gripping article in Vanity Fair this month take a look at the outsourcing of clinical trials for proposed prescription drugs.It's an eye opener. "Many of today’s trials still take place in developed countries, such as Britain, Italy, and Japan. But thousands are taking place in countries with large concentrations of poor, often illiterate people, who in some cases sign consent forms with a thumbprint, or scratch an “X.”
Since the first week of posts on this blog, I have been critical of the FDA and many of the rules, regulations, and efforts by this guardian of the citizens to keep big pharma companies working in a safer way. The FDA fails people like you and me. An excerpt:
One big factor in the shift of clinical trials to foreign countries is a loophole in F.D.A. regulations: if studies in the United States suggest that a drug has no benefit, trials from abroad can often be used in their stead to secure F.D.A. approval. There’s even a term for countries that have shown themselves to be especially amenable when drug companies need positive data fast: they’re called “rescue countries.”
This article - a 21st century version, in shorter form, of The Jungle.
Read it here: http://www.vanityfair.com/politics/features/2011/01/deadly-medicine-201101
Tuesday, December 07, 2010
Monday, December 06, 2010
Prempro: Verdict for the Defendant
Wyeth properly warned a Virginia woman’s doctors about the risks of its Prempro menopause drug, a jury ruled today in rejecting her claim for damages. The Plaintiff was Ms. Torkie -Tork.
The verdict was reached in USDCT in Alexandria, Virginia last week. It took just a few hours to reach the result. Wyeth has now successfully defended four lawsuits in a row.
Also last week the Nevada Supreme Court last week affirmed a $57.6 million award to three women who said Prempro was the cause of the cancer each suffered. The verdict included $35 million in punitive damages the panel handed down in 2007 over Wyeth officials’ mishandling of the drug.
Source: http://www.bloomberg.com/news/2010-12-03/pfizer-properly-warned-about-prempro-health-risks-jury-finds.html?cmpid=yhoo
The verdict was reached in USDCT in Alexandria, Virginia last week. It took just a few hours to reach the result. Wyeth has now successfully defended four lawsuits in a row.
Also last week the Nevada Supreme Court last week affirmed a $57.6 million award to three women who said Prempro was the cause of the cancer each suffered. The verdict included $35 million in punitive damages the panel handed down in 2007 over Wyeth officials’ mishandling of the drug.
Source: http://www.bloomberg.com/news/2010-12-03/pfizer-properly-warned-about-prempro-health-risks-jury-finds.html?cmpid=yhoo
Sunday, December 05, 2010
Google Earth: Using it as Demonstrative Evidence
Found this from another lawyer on the web:State ex rel J.B., Case No. A-2228-08T4 (N.J. Ct. App.; Sept. 27, 2010)
Some key language in the opinion:
The [c]ourt finds that other than very recently what would have happened is . . . that the State would have brought in an atlas map and ask[ed] somebody familiar with the area to point on the map where different locations are and how you would get there. And this is just an updated manner of getting the same information. If the [d]efense wants to show that the information is incorrect, they can certainly do it by either cross examination or they can do exactly what I just suggested and bring in an atlas map and show where the exhibit that the State is offering is incorrect.
Pretty sound reasoning in my view.
Saturday, December 04, 2010
Keeping an Eye on Lupron News
Lupron As Hormone Therapy
Abbott Labs is the marker of Lupron, more commonly referred to as leuprolide. Lupron is supposed to help both men and women's sexual health, ailing in the treatment of prostate cancer for men and helping to combat endometriosis in women. The medication may also be used for early puberty.There are five types of Lupron that can be injected under a patients skin to help with his or her hormone therapy. The kinds of Lupron are:
- Lupron Depot 30
- Lupron Depot 22.5
- Lupron Depot 7.5
- Lupron Depot 11.25
- Lupron Depot 3.75
There is a long list of potential side effects linked to Lupron. Some apply only to men and others affect just women, but others, such as chronic muscle pain, have been reported in both sexes.
Lupron side effects that have been documented are:
- Chronic muscle pain and weakness
- Back pain
- Joint pain
- Limb pain
- Urine with blood in it
- Diarrhea
- Severe headaches
- Vomiting
- Muscle atrophy
- Depression
- Decreasing of hemoglobin
- Decreasing of hematocrit
- Bone density changes
- Loss of the sense of smell
- Loss of the sense of taste
- Enlargement and sensitivity to breasts (women)
- Decrease in size of testicles (men)
- Erectile dysfunction (men)
- Decreased sexual desire (both men and women)
- Thyroid problems
The U.S. Food and Drug Administration (FDA) has notified the manufacturers of the Gonadotropin-Releasing Hormone (GnRH) agonists of the need to add new safety information to the Warnings and Precautions section of the drug labels. This new information warns about increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men receiving these medications for the treatment of prostate cancer. FDA’s notification to manufacturers of GnRH agonists to add this safety information is based on the Agency’s review of several published studies1-7, described in the Agency’s Ongoing Safety Review of GnRH Agonists and possible increased risk of diabetes and certain cardiovascular diseases, issued in May 2010.
GnRH agonists are approved to treat the symptoms (palliative treatment) of advanced prostate cancer. The benefits of GnRH agonist use for earlier stages of prostate cancer that have not spread (non-metastatic prostate cancer) have not been established.
Although the risk for diabetes and cardiovascular diseases appears to be low in men receiving GnRH agonists for prostate cancer, it is important for healthcare professionals to evaluate patients for risk factors for these diseases. Healthcare professionals should always carefully weigh the benefits and risks of using GnRH agonists before determining appropriate treatment for prostate cancer.
Patients who are receiving treatment with GnRH agonists should undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin (HbA1c). Increased blood glucose levels may represent development of diabetes or worsening of blood glucose control in patients with diabetes. Healthcare professionals should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage according to current clinical practice.
Additional Information for Patients
- GnRH agonists are sold as the brand names – Lupron, Zoladex, Trelstar, Viadur, and Eligard.
- Before receiving GnRH agonists, tell your healthcare professional if you have diabetes, heart disease, a previous heart attack or stroke, or any cardiovascular risk factors like high blood pressure, high cholesterol, or cigarette smoking.
- If you have any concerns about receiving these medicines, talk to your healthcare professional.
- Report any side effects from the use of GnRH agonists to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.
Thursday, December 02, 2010
Drug Induced Liver Injuries from Anti-microbial Medications
This month there will be a report released in Hepatology journal that suggest that anti-microbial medications are a common cause of drug-induced liver injury (DILI) leading to acute liver failure or ALF. Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease (such as jaundice), and indicates that the liver has sustained severe damage (loss of function of 80-90% of liver cells). The complications are hepatic encephalopathy and impaired protein synthesis (as measured by the levels of serum albumin and the prothrombin time in the blood). Source.
What could be the cause? More than 1100 drugs, herbal remedies, natural products, vitamins, minerals, and dietary supplements are known to cause liver injury.
(You may find the abstract here: http://onlinelibrary.wiley.com/doi/10.1002/hep.23937/abstract)
Detailed case reports were collected from 1,198 subjects with ALF enrolled at 23 sites participating in the National Institutes of Health-funded Acute Liver Failure Study Group. The findings included evidence that showed high female predominance in DILI ALF, suggesting that women may be more susceptible to liver injury or use more prescription drugs than men.
What were the types of drugs and products? More than sixty, alone or in combination, could cause liver injury and failure in the study population. Anti-microbial agents were found to be the most common cause of DILI ALF cases and included anti-tuberculosis drugs (25), sulphur-containing drugs (12), nitrofurantoin (12), other antibiotics (7), antifungal agents (6), and anti-retroviral drugs (4).
So, what type of drugs/brand names might make this sub group of 60? Examples of drugs that can cause acute liver hepatitis include acetaminophen (Tylenol), phenytoin (Dilantin), aspirin, isoniazid (Nydrazid, Laniazid), diclofenac (Voltaren), and amoxicillin/clavulanic acid (Augmentin). Examples of drugs that can cause chronic hepatitis include minocycline (Minocin), nitrofurantoin (Furadantin, Macrodantin), phenytoin (Dilantin), propylthiouracil, and fenofibrate (Tricor). The Merck Manual has a comprehensive list as well: http://www.merckmanuals.com/professional/sec03/ch024/ch024c.html
.
Patients who develop ALF after taking these typically did not experience a spontaneous recovery—the transplant-free survival rate in this study was 27%.
Stay tuned for the full article.
What could be the cause? More than 1100 drugs, herbal remedies, natural products, vitamins, minerals, and dietary supplements are known to cause liver injury.
(You may find the abstract here: http://onlinelibrary.wiley.com/doi/10.1002/hep.23937/abstract)
Detailed case reports were collected from 1,198 subjects with ALF enrolled at 23 sites participating in the National Institutes of Health-funded Acute Liver Failure Study Group. The findings included evidence that showed high female predominance in DILI ALF, suggesting that women may be more susceptible to liver injury or use more prescription drugs than men.
What were the types of drugs and products? More than sixty, alone or in combination, could cause liver injury and failure in the study population. Anti-microbial agents were found to be the most common cause of DILI ALF cases and included anti-tuberculosis drugs (25), sulphur-containing drugs (12), nitrofurantoin (12), other antibiotics (7), antifungal agents (6), and anti-retroviral drugs (4).
So, what type of drugs/brand names might make this sub group of 60? Examples of drugs that can cause acute liver hepatitis include acetaminophen (Tylenol), phenytoin (Dilantin), aspirin, isoniazid (Nydrazid, Laniazid), diclofenac (Voltaren), and amoxicillin/clavulanic acid (Augmentin). Examples of drugs that can cause chronic hepatitis include minocycline (Minocin), nitrofurantoin (Furadantin, Macrodantin), phenytoin (Dilantin), propylthiouracil, and fenofibrate (Tricor). The Merck Manual has a comprehensive list as well: http://www.merckmanuals.com/professional/sec03/ch024/ch024c.html
.
Patients who develop ALF after taking these typically did not experience a spontaneous recovery—the transplant-free survival rate in this study was 27%.
Stay tuned for the full article.
Wednesday, December 01, 2010
12/1/10 Darvocet Legal: FDA Drug Safety Podcast for Healthcare Professionals: FDA recommends against the continued use of propoxyphen
Good stuff in this transcript from the FDA's podcast:
Welcome, my name is Mary Kremzner, a pharmacist in the Division of Drug Information. On November 19, 2010, the Food and Drug Administration issued a Drug Safety Communication recommending against continued prescribing and use of the pain reliever propoxyphene because new data show that the drug can cause serious toxicity to the heart, even when used at therapeutic doses. FDA has requested that companies voluntarily withdraw propoxyphene from the United States market.
Propoxyphene is an opioid pain reliever used to treat mild to moderate pain. It is sold under various names as a single-ingredient product, for example Darvon, and as part of a combination product with acetaminophen, named Darvocet.
FDA's recommendation is based on all available data including data from a new study that evaluated the effects that increasing doses of propoxyphene have on the heart. The results of the new study showed that when propoxyphene was taken at therapeutic doses, there were significant changes to the electrical activity of the heart: prolonged PR interval, widened QRS complex and prolonged QT interval. These changes, which can be seen on an electrocardiogram, or EKG, can increase the risk for serious abnormal heart rhythms. FDA has concluded that the safety risks of propoxyphene outweigh its benefits for pain relief at recommended doses.
In July 2009, FDA announced an ongoing safety review of propoxyphene, which included evaluating its potential effects on the heart.
Following receipt of a Citizen Petition requesting the withdrawal of propoxyphene-containing products from the United States market, FDA convened an Advisory Committee meeting on January 30, 2009. After presentations by FDA, the petitioner, and the company reviewing the efficacy and safety data from the propoxyphene drug applications, the literature and postmarketing safety databases, the committee voted by a narrow margin of 14-to-12 against the continued marketing of propoxyphene products. Those who voted for propoxyphene to remain on the market advised requiring improved labeling, particularly with warnings about use in elderly patients and about use with concomitant opioids or alcohol. Finally, there was general agreement that additional information about the cardiac effects of propoxyphene would be relevant in further weighing the risk and benefit. As a result, under new authorities given to FDA by the Food and Drug Administration Amendments Act, the agency required the drug manufacturer to conduct a thorough QT study to formally evaluate the effects of propoxyphene on cardiac electrophysiology. In order to determine a safe supratherapeutic dose to incorporate into the Thorough QT study, FDA required the drug manufacturer to first conduct a multiple-ascending dose study or MAD.
The MAD study was a randomized, double-blind, placebo-controlled sequential multiple-ascending dose study of propoxyphene for 11 days. The study was conducted in healthy volunteers. The first cohort of study subjects was dosed with a total daily dose of 600 mg of propoxyphene (the maximum labeled dose) and the second cohort was dosed with a total daily dose of 900 mg. Additional doses were planned, however the study was placed on clinical hold due to safety concerns. Study subjects were monitored with telemetry and intermittent EKG recordings, comparable to the monitoring that would occur during a Thorough QT study.
The drug manufacturer has submitted to FDA the results from the 600 mg and 900 mg cohorts.
Significant QTc interval prolongations were observed with the propoxyphene 600 mg and 900 mg dose levels. With the 600 mg daily dose, at steady state on Treatment Day 11, the largest mean change of QTc was 29.8 milliseconds, which occurred 7 hours after the last dose; with the 900 mg dose the largest mean change was 38.2 milliseconds, which occurred 2 hours after the last dose. It is recognized in the International Conference on Harmonisation, or ICH, E14 Guideline1 that drugs that prolong the mean QT/QTc interval by >20 milliseconds have a substantially increased likelihood of being proarrhythmic. In addition, a dose-dependent prolongation of PR and QRS intervals was observed in the study.
Because the elderly and patients with renal insufficiency have a reduction in the clearance of propoxyphene and its cardioactive metabolite, norpropoxyphene, through the kidneys, these populations can be especially susceptible to proarrhythmic effects of the drug.
At this time, FDA recommends that Healthcare Professionals:
Welcome, my name is Mary Kremzner, a pharmacist in the Division of Drug Information. On November 19, 2010, the Food and Drug Administration issued a Drug Safety Communication recommending against continued prescribing and use of the pain reliever propoxyphene because new data show that the drug can cause serious toxicity to the heart, even when used at therapeutic doses. FDA has requested that companies voluntarily withdraw propoxyphene from the United States market.
Propoxyphene is an opioid pain reliever used to treat mild to moderate pain. It is sold under various names as a single-ingredient product, for example Darvon, and as part of a combination product with acetaminophen, named Darvocet.
FDA's recommendation is based on all available data including data from a new study that evaluated the effects that increasing doses of propoxyphene have on the heart. The results of the new study showed that when propoxyphene was taken at therapeutic doses, there were significant changes to the electrical activity of the heart: prolonged PR interval, widened QRS complex and prolonged QT interval. These changes, which can be seen on an electrocardiogram, or EKG, can increase the risk for serious abnormal heart rhythms. FDA has concluded that the safety risks of propoxyphene outweigh its benefits for pain relief at recommended doses.
In July 2009, FDA announced an ongoing safety review of propoxyphene, which included evaluating its potential effects on the heart.
Following receipt of a Citizen Petition requesting the withdrawal of propoxyphene-containing products from the United States market, FDA convened an Advisory Committee meeting on January 30, 2009. After presentations by FDA, the petitioner, and the company reviewing the efficacy and safety data from the propoxyphene drug applications, the literature and postmarketing safety databases, the committee voted by a narrow margin of 14-to-12 against the continued marketing of propoxyphene products. Those who voted for propoxyphene to remain on the market advised requiring improved labeling, particularly with warnings about use in elderly patients and about use with concomitant opioids or alcohol. Finally, there was general agreement that additional information about the cardiac effects of propoxyphene would be relevant in further weighing the risk and benefit. As a result, under new authorities given to FDA by the Food and Drug Administration Amendments Act, the agency required the drug manufacturer to conduct a thorough QT study to formally evaluate the effects of propoxyphene on cardiac electrophysiology. In order to determine a safe supratherapeutic dose to incorporate into the Thorough QT study, FDA required the drug manufacturer to first conduct a multiple-ascending dose study or MAD.
The MAD study was a randomized, double-blind, placebo-controlled sequential multiple-ascending dose study of propoxyphene for 11 days. The study was conducted in healthy volunteers. The first cohort of study subjects was dosed with a total daily dose of 600 mg of propoxyphene (the maximum labeled dose) and the second cohort was dosed with a total daily dose of 900 mg. Additional doses were planned, however the study was placed on clinical hold due to safety concerns. Study subjects were monitored with telemetry and intermittent EKG recordings, comparable to the monitoring that would occur during a Thorough QT study.
The drug manufacturer has submitted to FDA the results from the 600 mg and 900 mg cohorts.
Significant QTc interval prolongations were observed with the propoxyphene 600 mg and 900 mg dose levels. With the 600 mg daily dose, at steady state on Treatment Day 11, the largest mean change of QTc was 29.8 milliseconds, which occurred 7 hours after the last dose; with the 900 mg dose the largest mean change was 38.2 milliseconds, which occurred 2 hours after the last dose. It is recognized in the International Conference on Harmonisation, or ICH, E14 Guideline1 that drugs that prolong the mean QT/QTc interval by >20 milliseconds have a substantially increased likelihood of being proarrhythmic. In addition, a dose-dependent prolongation of PR and QRS intervals was observed in the study.
Because the elderly and patients with renal insufficiency have a reduction in the clearance of propoxyphene and its cardioactive metabolite, norpropoxyphene, through the kidneys, these populations can be especially susceptible to proarrhythmic effects of the drug.
At this time, FDA recommends that Healthcare Professionals:
- Stop prescribing and dispensing propoxyphene-containing products to patients.
- Contact patients currently taking propoxyphene-containing products and ask them to discontinue the drug.
- Inform patients of the risks associated with propoxyphene.
- Discuss alternative pain management strategies other than propoxyphene with your patients.
- Be aware of the possible risk of cardiac conduction abnormalities, for example prolonged QT, PR, and QRS intervals, in patients taking propoxyphene and assess patients for these events if they present with any signs or symptoms of arrhythmia.
- Report any side effects with propoxyphene to FDA's MedWatch program at www.fda.gov/medwatch.
Align Technologies and Invisalign get FDA Warning Letter
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