In a rush? You can use our Quick Contact Form to tell us the basic information about your case.
A class of diabetes drugs referred to as dipeptidyl peptidase-4 inhibitors may be associated with rhabdomyolysis, a side effect which involves severe muscle damage.
In more detail, rhabdomyolysis is the breakdown of muscle tissue that leads to the release of muscle fiber contents into the blood. These substances are harmful to the kidney and often cause kidney damage.
According to a new FDA quarterly report, “Potential Signals of Serious Risks / New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS): April – June 2017”, the following 13 oral diabetes medicines are being investigated for this possible rhabdomyolysis side effect:
- Glyxambi (empagliflozin and linagliptin) tablets
- Janumet (sitagliptin and metformin hydrochloride) tablets
- Janumet XR (sitagliptin and metformin hydrochloride extended-release) tablets
- Januvia (sitagliptin) tablets
- Jentadueto (linagliptin and metformin hydrochloride) tablets
- Jentadueto XR (linagliptin and metformin hydrochloride extended-release) tablets
- Kazano (alogliptin and metformin hydrochloride) tablets
- Kombiglyze XR (saxagliptin and metformin hydrochloride extended-release) tablets
- Nesina (alogliptin) tablets
- Onglyza (saxagliptin) tablets
- Oseni (alogliptin and pioglitazone) tablets
- Qtern (dapagliflozin and saxagliptin) tablets
- Tradjenta (linagliptin) tablets
We will be watching for reports of rhabdomyolysis in patients using Onglyza, Nesina, Januvia, and the other Type-2 diabetes drugs containing saxagliptin, alogliptin, sitagliptin, or linagliptin.
Thomas J. Moore, of the Institute for Safe Medication Practices, recently wrote a “Perspective” piece about new Pradaxa-versus-warfarin study, which is described below.
Medical researchers reviewed population-wide electronic medical records from the Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority to identify the 30-day readmission rates for patients with nonvalvular atrial fibrillation treated with Pradaxa (dabigatran) or warfarin.
The bottom line for this retrospective cohort study is that the patients treated with Pradaxa appeared to be at higher risk for 30-day hospital readmission due to bleeding.
In his “Perspective” piece, Moore added some contextual information pertinent to the Hong Kong researchers’ findings:
… This new study’s annualized hospitalization rates of 5% and 5.8% for [Pradaxa (dabigatran)] and warfarin for bleeding in patients with atrial fibrillation also are consistent with previously published results. However, had this Hong Kong study been conducted in the United States, one would expect even higher hospital admission rates for [Pradaxa (dabigatran)] because the lower 110-mg dose — taken by 75% in this population — was not available in the United States until recently, and is not recommended for use in atrial fibrillation.
The study also identifies an important new anticoagulant safety issue — high rates of rehospitalization for bleeding within 30 days affecting 13.5% of dabigatran patients compared with 5.1% of warfarin patients. After a bleeding event, the warfarin dose can be adjusted downward, a flexibility not available for [Pradaxa (dabigatran)] except for the untested 75-mg dose….
Given these still-present safety issues when using Pradaxa, we continue to investigate possible drug injury cases against the responsible drug company, Boehringer Ingelheim, for patients who have suffered serious bleeding events.
A liver side effects issue for Ocaliva was presented in this document, “FDA Drug Safety Communication: FDA warns about serious liver injury with Ocaliva (obeticholic acid) for rare chronic chronic liver disease”, issued on September 21, 2017.
From the Safety Announcement part of that document:
The Food and Drug Administration (FDA) is warning that the liver disease medicine Ocaliva (obeticholic acid) is being incorrectly dosed in some patients with moderate to severe decreases in liver function, resulting in an increased risk of serious liver injury and death. These patients are receiving excessive dosing, particularly a higher frequency of dosing than is recommended in the drug label for them. Ocaliva may also be associated with liver injury in some patients with mild disease who are receiving the correct dose…. [emphasis added]
Intercept Pharmaceuticals Inc’s Ocaliva (obeticholic acid) was approved by the FDA in May 2016 for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.
In their September 2017 Ocaliva Drug Safety Communication the FDA said patient should contact their doctors if they develop any of the following symptoms that may be signs of liver injury:
New or worsening fatigue
Nausea and vomiting
Change in behavior or confusion
Vague symptoms such as anxiety or unease
Yellow eyes or skin
We will continue to monitor the safety profile of Ocaliva and watch for any drug label revisions, such as a black-box warning, which may be mandated by the FDA.
On August 22, 2017 attorneys for Merck filed their Petition For A Writ Of Certiorari, which sets the stage for Merck’s Fosamax appeal to the Supreme Court with the following:
The question presented is: Is a state-law failure-to-warn claim preempted when the FDA rejected the drug manufacturer’s proposal to warn about the risk after being provided with the relevant scientific data; or must such a case go to a jury for conjecture as to why the FDA rejected the proposed warning.
As background, in March 2017 the Third Circuit Court of Appeals decided to reverse a ruling by U.S. District Court Joel Pisano which had dismissed all the federal court Fosamax – femur fracture cases on federal preemption grounds. In turn, hundreds of those Fosamax lawsuits have been reinstated at the trial court level.
From our Drug Injury Watch blog article about that development, “Fosamax – Femur Fracture Lawsuits In Federal Court MDL: March 2017 Appellate Court Ruling Reinstates Lawsuits”:
Essentially, the Third Circuit held that the ultimate question of whether the FDA would have rejected a Fosamax label change by Merck to warn about an increased risk of femur fractures is a question of fact for the jury — rather than for Judge Pisano — to decide….
Certainly the Third Circuit’s ruling on the Fosamax appeals is a positive development for the patients who suffered femur fractures after long-term Fosamax use and filed drug injury lawsuits against Merck.
However, it is just a first step in terms of the Fosamax – femur fracture litigation moving forward. Significantly, at the present time we do not know Merck’s plans regarding any further appeal to the United States Supreme Court.
Now we know, by means of an August 2017 legal filing, Merck wants the U.S. Supreme Court to reverse this appeals court decision reinstating those Fosamax – femur fracture cases.
We will watch to see whether Merck’s request for review of the earlier federal appeals court ruling is granted by the Supreme Court.
In September 2017 Health Canada required Janssen, the drug company responsible for Invokana and Invokamet, to send a Dear Healthcare Professional Letter — commonly referred to as a “Dear Doctor” letter — about the lower limb amputations side effect.
Here are some of the points presented in this September 2017 Janssen letter to Canadian healthcare professionals:
- Carefully monitor patients with risk factors for amputation events, e.g., patients with previous amputations, existing peripheral vascular disease or neuropathy.
- Advise patients to notify their healthcare provider if they develop sores, ulceration, discoloration, infection, new lower extremity pain or tenderness.
- Initiate early treatment for foot problems for, but not limited to, ulceration, infection, new pain or tenderness.
- Discontinue canagliflozin treatment in patients who develop a significant complication, such as a lower-extremity skin ulcer, infection, osteomyelitis or gangrene.
To our knowledge, no such “Dear Doctor” letter has been sent out in the US, yet. If you know otherwise, however, you can let us know by submitting a Comment below or sending an email to me.
Up in Canada, it was back in October 2016 that the Product Monographs for Invokana and Invokamet were updated to include a warning about the risk of toes, foot, and leg amputations. This action was based on interim results of the Canagliflozin Cardiovascular Assessment Study (CANVAS) study.
We will continue to monitor this risk of lower limb amputations for Invokana and Invokamet as well as watch to whether this adverse reaction also involves other diabetes medicines in this SGLT2 class of drugs, such as Farxiga and Jardiance.
In the August 2017 edition of the European Journal of Surgical Oncology (EJSO) we found this article, “Breast implant associated anaplastic large cell lymphoma: The UK experience. Recommendations on its management and implications for informed consent”.
From the Abstract for this August 2017 EJSO article we get this new information about the breast implants associated lymphoma and blood cancer situation as it has developed in the United Kingdom (UK):
Methods: Between 2012 and 2016, 23 cases of BIA-ALCL were diagnosed in 15 regional centres throughout the UK. Data on breast implant surgeries, clinical features, treatment and follow-up were available for 18 patients….
Discussion: BIA-ALCL is a rare neoplasm with a good prognosis. Our data support the recommendation that stage I disease be managed with surgery alone. Adjuvant chemotherapy may be required for more invasive disease and our experience has shown the efficacy of Brentuximab as a second line treatment.
For a different perspective on this medical issue, you can take a look at this article, “What’s Your Micromort? A Patient-Oriented Analysis of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)”, which was published in the September 2017 edition of the Aesthetic Surgery Journal (ASJ).
From an August 23, 2017 press release from the ASJ, which is the official publication of the American Society for Aesthetic Plastic Surgery, we take this snippet:
William P. Adams, Jr. MD, one of the study’s authors explains, “Unfortunately, patients are getting the wrong information, and this study is critical to correcting that….”
For what is worth, here is that press release: “ASJ Study Puts The Risk Of Death From Breast Implant-Associated Anaplastic Large Cell Lymphoma Into Plain Perspective for Patients”.
Our law firm is investigating breast implants associated lymphoma and blood cancer cases.
In August 2017 there is some additional information about the increased risk of developing the eye or vision side effect NAION which is included in a recent drug label change for Viagra, Cialis, and Levitra.
As reported previously, the erectile dysfunction (ED) drugs Cialis (tadalafil), Levitra (vardenafil hydrochloride), and Viagra (sildenafil citrate) have been associated with a type of sudden vision loss called Nonarteritic Anterior Ischemic Optic Neuropathy (NAION).
In July 2005 the FDA ordered warnings be put on the package insert labels of these ED drugs, or impotence drugs, to the effect that some users of Cialis, Levitra, and Viagra have developed NAION, a form of blindness. At the same time, however, the FDA stated that it is impossible at present to know if NAION is a side effect of these ED drugs, or an unrelated medical condition.
In June 2006 Health Canada issued a Public Communication alerting Canadians that the drug companies Eli Lilly (Cialis), Bayer (Levitra), and Pfizer (Viagra) were in the process of sending a so-called “Dear Doctor” letter to inform healthcare providers in Canada about changes to the respective package insert, or label, for these drugs regarding this vision loss, or NAION, side effect.
We will continue to monitor the safety profile of Viagra, Cialis, and Levitra as regard the vision-loss condition NAION as well as other possible ED drugs side effects.
In August 2017 the United States Judicial Panel on Multidistrict Litigation (JPML) granted a second motion for centralization or consolidation of federal court lawsuits brought by plaintiffs in proton-pump inhibitors (PPIs) cases alleging kidney injury.
In more detail, the JPML established IN RE: PROTON-PUMP INHIBITOR PRODUCTS LIABILITY LITIGATION (NO. II) – MDL No. 2789. From the JPML’s Transfer Order filed on August 2, 2017 we get these details:
In the complaints in these 161 personal injury and wrongful death actions, plaintiffs allege that as a result of taking one or more proton-pump inhibitors (PPIs), they or their decedents suffered kidney injury (e.g., chronic kidney disease (CKD), acute interstitial nephritis, end stage renal disease, or kidney failure). Plaintiffs allege that defendants failed to adequately warn of the negative effects and risks associated with PPIs….
Notably, during this second time around only one drug company, Takeda. was still opposed to the creation of any PPIs federal court MDL. But the JPML was not convinced by Takeda’s various arguments in opposition, as seen from this excerpt from the Transfer Order:
And, although it is true that AstraZeneca is sued in far more actions than Takeda, a significant number of actions are “mixed use” cases in which the plaintiffs allege use of more than one PPI, and sue Takeda and one or more other PPI manufacturers, including AstraZeneca. The prospect of additional cases against Takeda does not seem far-fetched . Given these circumstances, including the seemingly indivisible nature of plaintiffs’ alleged injuries in the “mixed use” cases, we decline to carve out from the MDL cases or claims against Takeda. [footnotes omitted]
Lastly, this point – which may have been a factor for the JPML when ruling this time on the Prilosec / Prevacid / Nexium federal court MDL consolidation – was mentioned in a footnote for the August 2017 Transfer Order: “The variety of alleged kidney injuries arguably has diminished, as most plaintiffs allege that they suffer from [chronic kidney disease (CKD)]….”
We continue to monitor legal and medical developments regarding the drug injury aspects of Nexium, Prevacid, and Prilosec.
A British medical journal, The Lancet Diabetes & Endocrinology, published this Correspondence item on July 18, 2017, “SGTL2 inhibitors and amputations in the US FDA Adverse Event Reporting System”.
The main point of that article is set forth in this excerpt:
In summary, this pharmacovigilance analysis confirms that use of canagliflozin, but not dapagliflozin or empagliflozin, might be associated with an increased risk of amputations. However, [the US Food and Drug Administration (FDA) adverse event Reporting System (FAERS)] data analysis has important limitations because there is no definite causal link between drug exposure and adverse event…. [footnote omitted]
In early August 2017 an article with some additional contextual information, “FDA Reports Further Support for Canagliflozin-Amputation Link”, was published on the Medscape website (free registration required). From that article we get the following points:
Among 66 reports of SGLT2-inhibitor–associated amputations, 57 (86%) involved canagliflozin. Moreover, two-thirds of those reports were among people with no discernible risk factors for amputation, “which, worryingly, points to an unpredictable effect of the drug,” [Gian Paolo Fadini, MD, PhD, of the division of metabolic diseases, department of medicine, University of Padova, Italy] told Medscape Medical News….
Thus far, the FDA has not extended the label warning about amputations to other drugs in the class [e.g., Jardiance (empagliflozin) and Farxiga (dapagliflozin)], although the European Medicines Agency (EMA) has, pending further investigation.
“Our data are the first to confirm the warning originated from CANVAS and tends to suggest this is not a class effect,” Dr Fadini told Medscape Medical News.
We are currently investigating possible drug injury cases against the responsible drug company, Janssen Pharmaceuticals, where a patient who used Invokana or Invokamet had to have a lower limb amputation.
The European Medicines Agency (EMA) recently announced it is taking regulatory action on certain magnetic resonance imaging (MRI) contrast drugs containing gadolinium a couple of months after the U.S. Food and Drug Administration (FDA) decided otherwise.
We start with the timeline of events giving rise to the EMA’s suspension of the MRI drugs Magnevist, Omniscan, and OptiMARK in July 2017.
In this July 7, 2017 EMA document, “PRAC confirms restrictions on the use of linear gadolinium agents”, which included this statement: “No specific conditions linked to gadolinium deposition in the brain have been identified, but the clinical consequences are unknown.”
And in its July 21, 2017 document, “EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans”, we get this further elaboration on that statement:
There is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions for some intravenous linear agents in order to prevent any risks that could potentially be associated with gadolinium brain deposition….
We turn now to the FDA’s treatment of this drug-safety assessment of Magnevist, Omniscan, and OptiMARK, as well as the several other gadolinium-based contrast agents (GBCAs).
From its “FDA Drug Safety Communication: FDA identifies no harmful effects to date with brain retention of gadolinium-based contrast agents for MRIs; review to continue” we get this explanation of why no regulatory action is necessary — at least not yet:
All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because we identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future….
We will be watching for the “public meeting to discuss this issue in the future” mentioned by the FDA — which, perhaps, will be a so-called Advisory Committee Meeting.
In addition, we will monitor the medical literature for “any risks that could potentially be associated with gadolinium brain deposition” mentioned by the EMA.
In the final week of July 2017, the FDA issued a notification that it had approved a revised drug label for Invokana and Invokamet, as well as a revised Medication Guide for these two diabetes drugs from Janssen Pharmaceuticals.
From the most recent drug label, or Full Prescribing Information, for Invokana (accessed 7/27/17), here is the text of the so-called Black-Box Warning:
WARNING: LOWER LIMB AMPUTATION
• An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
• Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur [see Warnings and Precautions (5.1)].
And from the Invokana Medication Guide revised in July 2017, in the “Amputations” section, we get this information directed to patients who are taking this drug, or Invokamet:
You may be at a higher risk of lower limb amputation if you:
o have a history of amputation
o have heart disease or are at risk for heart disease
o have had blocked or narrowed blood vessels, usually in your leg
o have damage to the nerves (neuropathy) in your leg
o have had diabetic foot ulcers or sores
We are currently investigating possible drug injury cases against the drug company, Janssen Pharmaceuticals, where a patient who used Invokana or Invokamet had to have a lower limb amputation. If you or someone in your family has had a toe, foot, or leg amputation, you can get Free Case Evaluation for such a case.
All content by attorney Tom Lamb