Drug Injury Watch

Levaquin / Cipro / Avelox: Small But Significant Increased Risk Of Acute Kidney Injury Among Men According To Recent Study

In Addition, A Significant Drug-Drug Interaction Between The Concomitant Use Of Fluoroquinolones And Renin–Angiotensin-System Blockers

(Posted by Tom Lamb at DrugInjuryWatch.com)

An article published by the Canadian Medical Association during June 2013 in its medical journal CMAJ, "Risk of acute kidney injury associated with the use of fluoroquinolones", reported on a study that revealed serious renal side effects in some men who used the popular Levaquin, Cipro, or Avelox, i.e., fluoroquinolone class of antibiotics.

From the Abstract for this June 2013 CMAJ article:

Background: Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin–angiotensin-system blockers.

Methods: We formed a nested cohort of men aged 40–85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011.... to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones,... with amoxicillin and azithromycin as controls.

Results: ... Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74–2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66–1.16) or past (RR 0.86, 95% CI 0.66–1.12) use.... The dual use of fluoroquinolones and renin– angiotensin-system blockers had an RR of 4.46 (95% CI 2.84–6.99) for acute kidney injury. Our case-time–control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52–3.18). The use of amoxicillin or azithro mycin was not associated with acute kidney injury.

Interpretation: We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin–angiotensin-system blockers.

We will continue to monitor this emerging drug safety issue involving acute kidney injury -- as well as the association between retinal detachment and fluoroquinolones, e.g., Levaquin, Cipro, Avelox -- and report further developments here.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)

Levaquin / Cipro / Avelox: Retinal Detachments Are Visual Side Effects Of Oral Fluoroquinolones Antibiotics

Health Canada Suggests That Low Level Or Under-Reporting For These Adverse Reactions Involving Eyesight Is Due To The Limited Information Available

(Posted by Tom Lamb at DrugInjuryWatch.com)

Back in April 2012 we posted this article, "Current Use Of Cipro And Levaquin Associated With Increased Risk Of Detached Retina Eye Injury".

Now, the July 2013 edition of the Canadian Adverse Reaction Newsletter brings us up to date on this emerging drug safety issue concerning Levaquin, Cipro, Avelox, and similar antibiotics with this report, "Oral fluoroquinolones and retinal detachment".  From this Health Canada publication we get this information: 

In Canada, there are 5 marketed oral fluoroquinolones... The risk of retinal detachment is not described in any of the oral fluoroquinolone Canadian product monographs.

Retinal detachment is characterized by a separation of the retina from the underlying tissue in the eye. Among the different types of retinal detachment, rhegmatogenous retinal detachment (RRD) is the most common. RRD results from retinal breaks caused by vitreoretinal traction. Risk factors commonly associated with retinal detachment include advancing age, previous cataract surgery, myopia and trauma. Patients generally present with symptoms such as light flashes, floaters, peripheral visual field loss and blurred vision. Retinal detachment is a serious medical emergency that generally requires prompt surgical intervention.

According to a pharmacoepidemiological study, current use of oral fluoroquinolones was associated with an increased risk of developing retinal detachment....

As of Dec. 31, 2012, Health Canada received one report of retinal detachment suspected of being associated with the use of an oral fluoroquinolone. The report described a 52-year-old woman who experienced retinal detachment after a course of ciprofloxacin prescribed to treat a bladder infection.  Limited evidence linking retinal detachment to oral fluoroquinolones may explain the low level of reporting to Health Canada.  [Footnotes omitted]

This Health Canada report notes that further research is needed to confirm whether there is a potential association between retinal detachment and fluoroquinolones, e.g., Levaquin, Cipro, Avelox, as well as to clarify the mechanism of action for this possible side effect drug injury.

We will continue to monitor this situation and report significant developments here.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)

Depacon / Depakene / Depakote: 400% Increased Risk Of Birth Defects Compared To Other Anti-Seizure Medications Used By Mothers With Epilepsy

May 2013 Revised Depakote Drug Label Includes "Black-Box" And Warnings About These Congenital Malformations As Well As Decreased IQ Scores In Children

(Posted by Tom Lamb at DrugInjuryWatch.com)

As indicated below, in May 2013 there was a so-called "Black-Box" warning and several other significant label revisions about serious risks for children whose mother used the following anti-seizure medications during pregnancy which were added to the Prescribing Information by FDA and the drug company AbbVie Inc. (formerly Abbott), specifically:

• Depakote (divalproex sodium) Delayed Release
• Depakote ER (Extended Release) Tablets
• Depakote Sprinkle Capsules (divalproex sodium coated particles in capsules)
• Depacon (valproate sodium) Injection
• Depakene (valproic acid) Capsules and Oral Solution

Here is a list of these recent major changes, or revisions, to the label as set forth on the DailyMed web page for Depakote:

Boxed Warning, Hepatotoxicity 05/2013

Boxed Warning, Fetal Risk 05/2013

Indications and Usage, Important Limitations (1.4) 05/2013

Contraindications, Known or Suspected Mitochondrial Disorders (4) 05/2013

Contraindications, Prophylaxis of Migraines in Pregnancy (4) 05/2013

Warnings and Precautions, Hepatotoxicity (5.1) 05/2013

Warnings and Precautions, Birth Defects (5.2) 05/2013

Warnings and Precautions, Decreased IQ (5.3) 05/2013

Warnings and Precautions, Use in Women of Childbearing Potential (5.4) 05/2013

Warnings and Precautions, Brain Atrophy (5.7) 05/2013

As regards the serious risks for children whose mother used the one of those Abbott anti-seizure medications during pregnancy, from the Boxed Warning, titled "WARNING: LIFE THREATENING ADVERSE REACTIONS":

Fetal Risk

Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores following in utero exposure....

Valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition. This is especially important when valproate use is considered for a condition not usually associated with permanent injury or death (e.g., migraine). Women should use effective contraception while using valproate [see Warnings and Precautions (5.2,5.3, 5.4)].

What is most remarkable to me about this May 2013 label revision by AbbVie / Abbott was this new warning: there is a 400% (i.e., four times) increased risk of birth defects, or congenital malformations, associated with the use of Depakote, Depacon, or Depakene during pregnancy.

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In more detail, from the Prescribing Information, also referred to as the package insert or drug label, for Depakote, Depacon, and Depakene:

Warnings And Precautions

5.2 Birth Defects

Valproate can cause fetal harm when administered to a pregnant woman. Pregnancy registry data show that maternal valproate use can cause neural tube defects and other structural abnormalities (e.g., craniofacial defects, cardiovascular malformations and malformations involving various body systems). The rate of congenital malformations among babies born to mothers using valproate is about four times higher than the rate among babies born to epileptic mothers using other anti-seizure monotherapies. Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population.  [Emphasis added]

Of course the other added warnings about potential harm to the fetus which may occur very early in pregnancy where there is the use of Depakote, Depacon, or Depakene are very serious in nature, also:

5.3 Decreased IQ Following in utero Exposure

Valproate can cause decreased IQ scores following in utero exposure. Published epidemiological studies have indicated that children exposed to valproate in utero have lower cognitive test scores than children exposed in utero to either another antiepileptic drug or to no antiepileptic drugs....

5.7 Brain Atrophy

... Reports of cerebral atrophy have also been reported in children who were exposed in utero to valproate products....

For some of the more recent developments leading up to this May 2013 label revision for Depakote, Depacon, or Depakene see our earlier article, Depakote Or Depakene Taken During Pregnancy May Cause Congenital Malformations Or Birth Defects Such As Neural Tube Defects Like Spina Bifida.

Of course, we will continue to monitor this emerging drug safety issue and report new medical findings as well as any further FDA regulatory action concerning these relatively popular Abbott / Abbvie medications for seizures, epilepsy, bipolar disorder, and (until now) migraine headaches.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb) 

July 2013 Update: New FDA Action To Be Taken In Or About September On Issue Of Drug Label Revisions By Generic Manufacturers

Allowing Supplemental Applications For Proposed Labeling Changes Might End Federal Preemption Shield From Legal Liability That Came With Mensing Ruling

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE: The FDA’s long-awaited proposed rule on generic drug labeling is now public.  You can access it using this link. 

From a November 7, 2013 FDA email "announcement":

A proposed U.S. Food and Drug Administration rule would speed the dissemination of new safety information about generic drugs to health professionals and patients by allowing generic drug makers to use the same process as brand drug manufacturers to update safety information in the product labeling.
 
Under the proposal, generic drug manufacturers would be able to independently update product labeling (also called prescribing information or package inserts) with newly-acquired safety information before the FDA’s review of the change, in the same way brand drug manufacturers do today. Generic manufacturers would also be required to inform the brand name manufacturer about the change.
 
The FDA would then evaluate whether the proposed change is justified and make an approval decision on the generic drug labeling change and the corresponding brand drug labeling change at the same time, so that brand and generic drug products would ultimately have the same FDA-approved prescribing information.

(11/7/13)

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This July 3, 2013 headline from a New York Times (NYT) article by Katie Thomas, "F.D.A. Rule Could Open Generic Drug Makers to Suits", was much welcomed news to many patients who have been harmed by serious side effects from generic drugs yet prevented from filing any drug injury products liability lawsuit for legal compensation.

Here is just one example. At the present time Bayer is settling YAZ, Yasmin, and Ocella lawsuits, as well as certain Gianvi cases. YAZ and Yasmin are brand-name drugs made and sold by Bayer. Ocella and Gianvi are generic drugs but were made by Bayer -- which is why Bayer is paying settlements on those cases -- and sold by Teva / Barr.

As background, like all of the drospirenone (DRSP) containing birth control pills, the YAZ, Yasmin, Ocella, and Gianvi types have been associated with an increased risk of blood clots that can cause serious side effects such as a deep vein thrombosis (DVT) and/or pulmonary embolism (PE).

If at the time of her DVT and/or PE event a woman was taking one of the "true" generic DRSP birth control pills like Zarah, Loryna, Syeda, or Vestura, i.e., made by a generic (not brand-name) manufacturer, however, there is a completely different legal outcome for her. This is because no such drug injury cases are being filed for those women, much less settled, because at the present time one cannot successfully sue a generic drug manufacturer due the Pliva, Inc., et al. v. Mensing case decided by the Supreme Court of the United States in 2011 (the so-called "Mensing ruling"), which is explained in these earlier posts:

March 2012 Update: Generic Drug Manufacturers Immunity By Means Of Mensing Preemption Ruling

Public Citizen Group Files FDA Petition To Fix Problems Exposed By Mensing Case Ruling

Generic Drug Company Should Not Be Allowed To Use Federal Preemption To Defeat Lawsuits

Returning to that July 3 New York Times article mentioned at the outset:

The Food and Drug Administration on Wednesday signaled its intention to permit generic drug makers to make changes to their safety labels, a move that could open the door to lawsuits against generic drug companies for the first time since a Supreme Court decision barred such suits two years ago.

Consumer advocates applauded the development, calling it a necessary fix for a system that they say is unfair to patients who take generic medicines.

“It’s common sense,” said Dr. Sidney M. Wolfe, a senior adviser to the Health Research Group at Public Citizen, which in 2011 petitioned the F.D.A. to pass just such a rule. “It will obviously end this situation where people are being harmed physically and yet, although they are harmed, they have no right to go into court and get redress for serious damages.”...

The F.D.A.’s intentions came in the form of a bureaucratic step in which the agency must notify the Office of Management and Budget [(OMB)] of its plans to publish a proposed new rule. In a summary posted Wednesday on the budget office’s Web site, the F.D.A. said the proposed rule would “create parity” between generic and brand-name drug makers with respect to how they update their labels — the lengthy list of a drug’s uses, dosages and risks.

Under the current system, brand-name manufacturers can change the label if they receive important new information about their drug. If the F.D.A. agrees that the label change is necessary, the generic manufacturers of the drug must also change their labels. The rule change could also allow generic manufacturers to change their labels if they became aware of safety concerns, which could make them liable if a court were to find they failed to warn patients about potential harms.

The required notice which was posted by FDA July 3 on the OMB website -- "Title: Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products" -- indicates the FDA’s intent to publish such a proposed rule by September 2013, when the public would be asked to comment.

We certainly look forward to learning more about what these changes in the FDA regulations might be as regards prescription drug label revisions by generic manufacturers.

We know already that these changes are long overdue and, unfortunately, most likely too late for many patients whose statute of limitations for filing their respective drug injury lawsuit expired during the time when the Mensing ruling was the law of the land -- with its federal preemption shield from legal liability that it afforded generic drug companies and, in turn, prevented those patients from receiving any legal compensation for their serious side effects.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)

 

Infuse Bone Graft Lawsuits Filed Against Medtronic Before And After June 2013 Yale Study Results

Legal Cases Involve Injured Infuse Patients With Serious Side Effects Such As Ectopic, Excessive, Or Unwanted Bone Growth And Neurological Impairment

(Posted by Tom Lamb at DrugInjuryWatch.com)

As part of our series of articles about the Medtronic Infuse Bone Graft spinal product, this article focuses on lawsuits being filed on behalf of patients who have developed ectopic, excessive, or unwanted bone growth and neurological impairment.

By way of background, in August 2011 Medtronic gave a $2.5 million grant to Yale University for the purpose of conducting an independent review of all clinical study data that examined the effectiveness and safety of the Infuse Bone Graft product -- also known as Medtronic’s recombinant bone morphogenetic protein-2 (rhBMP-2) product -- as well as post-marketing and safety data.

The results of the much anticipated Yale Medtronic Infuse study were released in June 2013 and are summarized in these two news reports:

• "Medtronic bone graft has limited benefit, may cause harm: reviews"  (6/17/13, Reuters)
• "Reviewers: Medtronic's controversial Infuse offers little to no benefit"  (6/17/13, Minnesota Public Radio)

Even before these somewhat damning study results became public, Infuse Bone Graft lawsuits were being filed by patients allegedly injured by this Medtronic product, and more legal claims against Medtronic involving Infuse have been filed since then.  But as noted below, these new Infuse Bone cases face some legal obstacles.

From a June 15, Reuters article "Plaintiff lawyers seek a new lifeline in medical device cases"  (accessed 6/18/13; paid subscription required now):

Plaintiff lawyers are trying a new strategy to get around a 2008 Supreme Court ruling [Riegel v. Medtronic] that protects many types of medical device makers from personal injury lawsuits....

Now, in a new wave of litigation, hundreds of plaintiffs allegedly injured by Medtronic Inc's Infuse Bone Graft device are claiming that the company illegally promoted the device for uses not approved by the FDA. That alleged off-label promotion, they argue, constitutes a parallel claim, which means that their lawsuits are not barred by federal law....

Around 300 lawsuits have been served on Medtronic, alleging off-label promotion of its Infuse device, with 900 more cases in the investigation stage....

The litigation over off-label promotion as a parallel claim is still in its early stages and has already divided some courts, said Louis Bograd of the Center for Constitutional Litigation....

"It's a really undeveloped area of post-Riegel pre-emption jurisprudence," said Bograd....

Bograd said he knows of seven trial court rulings over Infuse so far, with four finding that the plaintiffs' claims were pre-empted, and three rejecting that defense.

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For an example of an Infuse lawsuit against Medtronic filed after the Yale study was released in mid-June 2013, we get this information from a June 21, 2013 news report, "Medtronic profited from improper bone graft sales, California suit claims":

In a jointly filed California state court suit, 37 plaintiffs say they were injured by undergoing spinal fusion procedures in which Medtronic’s Infuse bone graft product was used in a way unapproved by the federal government....

The plaintiffs say Medtronic paid false consulting fees and kickbacks to influential medical community members, leading to an 80 percent increase in “off-label” use of Infuse bone growth stimulant since its 2002 debut....

The suit says Medtronic encouraged sales representatives to promote Infuse for unapproved procedures, including posterior lumbar interfusions, posterolateral fusions and transforaminal lumbar interbody fusions, all involving surgery done from the back.

Medtronic is also accused in the complaint of suggesting the use of Infuse in the cervical spine, or neck, despite FDA warnings that such use risks life-threatening throat and neck swelling, according to the suit.

The plaintiffs allege the Infuse bone graft material caused them to develop “heterotopic,” or unwanted bone growth, resulting in pain and nerve damage.

We are monitoring legal developments in the Infuse Bone Graft litigation and investigating possible Infuse cases against Medtronic.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)