Drug Injury Watch

Invokana / Jardiance / Farxiga: Increased Risks Of Lower-Limb Amputations Compared To Another Class Of Diabetes Drugs

Today Only The Invokana Drug Label Includes Warnings About Amputations Of Legs, Feet, And Toes; Will There Be Label Changes For Farxiga And Jardiance?

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Another new medical study indicates that lower extremity amputations is a drug class side effects of SGLT-2 inhibitor diabetes drugs such as Invokana, Jardiance, and Farxiga.

Earlier this month we reported that a medical study found that SGLT-2 inhibitors have a higher risk of leg, feet, and toe amputations when compared to older diabetes drugs such as sulfonylureas, metformin, and thiazolidinediones. An article setting forth the findings of this study was published online August 13, 2018 by the medical journal JAMA Internal Medicine

More recently, within the past week, a presentation at the 2018 European Society of Cardiology Congress in Munich, Germany included evidence that the SGLT-2 inhibitors Invokana, Jardiance, and Farxiga all are associated with twofold increases for lower-limb amputations when compared to GLP-1 receptor agonists diabetes drugs.

____________________________________________

Invokana / Farxiga / Jardiance

Free Case Evaluation

Strictly Confidential, No Obligation.

____________________________________________

 

From an August 25, 2018 Healio.com article, "SGLT2 inhibitor therapies may raise risk for amputation, diabetic ketoacidosis in diabetes with CVD", we get the following details:

In an observational study, [Peter Ueda, MD, PhD, from the department of medicine at the Karolinska Institute in Solna, Sweden,] and colleagues analyzed data from 17,213 patients without severe comorbidities who were prescribed any SGLT2 inhibitor, identified via nationwide registries in Sweden and Denmark. To reduce the risk for confounding by indication,  Ueda said, researchers employed an active-comparator design with GLP-1 receptor agonist therapies, due to important shared features between the two drug classes in reducing CV risk and no known association for GLP-1 receptor agonists with the studied outcomes....

Within the SGLT2 inhibitor arm, 61% of patients were prescribed [Farxiga (dapagliflozin)], 38% of patients were prescribed [Jardiance (empagliflozin)] and 1% of patients were prescribed [Invokana (canagliflozin)].

Researchers observed a more than twofold increased risk for both lower-limb amputation and diabetic ketoacidosis for patients prescribed an SGLT2 inhibitor vs. a GLP-1 receptor agonist. For lower-limb amputation, the HR was 2.32 (95% CI, 1.37-3.91) for SGLT2 vs. GLP-1 receptor agonist use, with the largest absolute risk increases observed for those with a history of peripheral artery disease in the cohort (absolute risk difference, 14.9; 95% CI, 0.7-43.8), Ueda said.

We continue to investigate drug injury lawsuits against the responsible pharmaceutical companies for diabetes patients who have had lower extremity amputations (legs, feet, toes) while using Invokana, Jardiance, Farxiga, or one of the other SGLT-2 inhibitors.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)

Diabetes Drug Tradjenta Associated With Bullous Pemphigoid, A Chronic Blistering Skin Condition

Bullous Pemphigoid (BP) Is An Auto-Immune Skin Disease Which Can Be Fatal, Particularly In Patients Who Are Debilitated

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Three relatively new medical studies add weight to an emerging drug safety issue involving Tradjenta (linagliptin), which is part of the dipeptidyl peptidase 4 (DPP-4) inhibitors class of type 2 diabetes drugs.

Before getting to the recent medical journal articles which seem to show that an increased risk of bullous pemphigoid (BP) is a side effect associated with Tradjenta, we point out that at least three other diabetes drugs also contain linagliptin, which is the active ingredient in Tradjenta:

• Glyxambi (empagliflozin and linagliptin)
• Jentadueto (linagliptin and metformin hydrochloride)
• Jentadueto XR (linagliptin and metformin hydrochloride)

The first medical journal article, "Association of Bullous Pemphigoid With Dipeptidyl-Peptidase 4 Inhibitors in Patients With Diabetes", provides findings from a retrospective case-control study, and was published online August 8, 2018 in the medical journal JAMA Dermatology.

From the Abstract for this first article we get the following Tradjenta safety information:

Importance:  The association of bullous pemphigoid (BP) with the use of dipeptidyl-peptidase 4 (DPP-4) inhibitors among patients with diabetes has recently emerged. The risk of developing BP during treatment with new DPP-4 inhibitor agents like [Tradjenta (linagliptin)] is yet to be established....

Results:  Eighty-two patients with BP and 328 age- and sex-matched control participants were enrolled; mean (SD) age, 79.1 (9.1) years; and 44 patients were female (53.7%). Overall, DPP-4 inhibitor intake was associated with a 3-fold increased risk for BP (adjusted odds ratio [OR], 3.2; 95% CI, 1.9-5.4). The adjusted ORs for [Galvus (vildagliptin)] and [Tradjenta (linagliptin)] were 10.7 (95% CI, 5.1-22.4) and 6.7 (95% CI, 2.2-19.7), respectively.... Discontinuation of DPP-4 inhibitor treatment was followed by improved clinical outcomes.

__________________________________________________________________

Tradjenta

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

We note that Galvus is not FDA-approved at this time, i.e., 8/20/2018.

The second medical journal article, "Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Disproportionality Analysis Based on the Japanese Adverse Drug Event Report Database", was published online July 12, 2018 in the medical journal Diabetes Care.

For this second article, we get a concise summary of relevant points from an August 9, 2018 Medscape report, "Type 2 Diabetes Drugs Linked to Bullous Pemphigoid":

In the earlier Diabetes Care study, Masanori Arai, MD, of the department of endocrinology and metabolism, Graduate School of Medicine, Yokohama City University, Japan, and colleagues, identified 546 bullous pemphigoid cases from the Japanese Adverse Drug Event Report (JADER) database, of which 392 were associated with DPP4 inhibitor use.

The JADER contains all pharmacovigilance data spontaneously reported to Japan's Pharmaceuticals and Medical Devices Agency since April 2004.

In an adjusted analysis, reported odds ratios for bullous pemphigoid by individual DPP4 inhibitor were 2.67 for [Tradjenta (linagliptin)]... and 12.09 for [Galvus (vildagliptin)].

The third article, "Dipeptidyl peptidase‐4 inhibitors‐associated bullous pemphigoid: A retrospective study of 168 pemphigoid and 9,304 diabetes mellitus patients", was published June 19, 2018 by the Journal of Diabetes Investigation (JDI).

From the Abstract for this third article we get some general background information which is relevant to the Tradjenta - bullous pemphigoid drug safety issue:

Aims/Introduction:  Bullous pemphigoid (BP) might be drug‐induced. The present study evaluated the relationship between BP and dipeptidyl peptidase‐4 inhibitors (DPP4Is).

Conclusions:  The positive rate of anti‐BP180NC16a antibody was lower in BP patients with DPP4I than without DPP4I, regardless of type 2 diabetes mellitus. The antibody titer was low in both the overall and type 2 diabetes mellitus populations. The prevalence of BP in 9,304 patients receiving DPP4Is was 0.0859%, which is higher than that in the general population. As DPP4Is are common diabetes treatments, we must be aware of the risk of BP.

We will continue to monitor the medical literature for further developments concerning Tradjenta (linagliptin) drug-induced bullous pemphigoid (BP) as a potential side effect of this popular diabetes drug.  We will also watch to see whether there is any increased risks of bullous pemphigoid associated with Glyxambi (empagliflozin and linagliptin) or Jentadueto (linagliptin and metformin hydrochloride).

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)

Some Newer Diabetes Drugs Linked To Lower Limb Amputations: "Significantly Increased Risk"

New Study Suggests Possible Drug Class Side Effects Of SGLT-2 Inhibitors Such As Invokana, Jardiance, And Farxiga

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors) are relatively new medicines used to treat Type-2 diabetes. Included in this drug class are Invokana, Farxiga, and Jardiance, as well as Invokamet, Xigduo, Glyxambi, Synjardy, Qtern, Steglatro, Steglujan, and Segluromet.

A new medical study found that SGLT-2 inhibitors have a higher risk of leg, feet, and toe amputations when compared to older diabetes drugs such as sulfonylureas, metformin, and thiazolidinediones.

In more detail, this article "Association Between Sodium-Glucose Cotransporter 2 Inhibitors and Lower Extremity Amputation Among Patients With Type 2 Diabetes", by Hsien-Yen Chang, PhD, et al., was published online August 13, 2018 by the medical journal JAMA Internal Medicine.

Among the results stated by medical researchers involved with a recently concluded retrospective cohort study and reported in this medical journal article:

• [N]ew use of sodium-glucose cotransporter 2 inhibitors was associated with a statistically significant increased risk of amputation compared with use of metformin, sulfonylureas, and thiazolidinediones.
• New use of SGLT-2 inhibitors was statistically significantly associated with amputation compared with sulfonylureas, metformin, or thiazolidinediones (adjusted hazard ratio, 2.12; 95% CI, 1.19-3.77).

____________________________________________

Invokana / Farxiga / Jardiance

Free Case Evaluation

Strictly Confidential, No Obligation.

____________________________________________

 

For some commentary and observations about this recently concluded medical study we draw from a MedPage Today report, "Mixed Data on SGLT-2 Inhibitors' Amputation Risk":

"The rate of amputation found by Chang et al is strikingly lower than the rate found in the [Canagliflozin Cardiovascular Assessment Study (CANVAS)] program (6.3 per 1000 person-years), reflecting important differences between the populations in each study," commented Michael Fralick, MD, of Brigham and Women's Hospital in Boston, and two colleagues in an accompanying commentary, highlighting how the current study's population was generally younger, and fewer participants had a history of ischemic heart disease, history of amputation, or use of insulin compared with those in CANVAS.

"These differences in baseline comorbidities likely explain, at least in part, why the incidence rate of amputation was much lower than that detected in CANVAS," they suggested.

Interestingly in contrast, the recent OBSERVE-4D study reported new users on canagliflozin didn't have any increased risk for below-knee amputations when compared with other SGLT-2 inhibitors....

"The study by Chang et al helps to contextualize the risk in a relatively low-risk patient population, but does not settle the debate," expressed the commentators, stating how it's still unclear if this elevated amputation risk is attributed to a class effect with SGLT-2 inhibitors.

We have written previously about this apparent amputations side effect of these newer diabetes drugs: 

• Jardiance – Lower Limb Amputations Drug Safety Issue Remains Uncertain
• Invokana – Amputations: No Explanation Yet As Regards “How” And “Why”
• FDA Reports Show Extent And Nature of Invokana-Amputation Side Effect
  
• Invokana Gets “Black-Box Warning” For Risk Of Leg And Foot Amputations

We are currently investigating possible drug injury lawsuits against the responsible pharmaceutical companies for diabetes patients who have had lower limb amputations (legs, feet, toes) while using Invokana, Jardiance, Farxiga, or one of the other SGLT-2 inhibitors.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)

Actemra Side Effects: Pulmonary Hypertension, Interstitial Lung Disease, Pulmonary Alveolar Proteinosis

FDA Watch List Includes Actemra: Evaluating Regulatory Action Based On Possible Signs Of Serious Risk, New Safety Information

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In July 2018 the FDA issued this document, "Potential Signals of Serious Risks/New Safety Information Identified from the FDA Adverse Event Reporting System (FAERS): January - March 2018", which is sometimes generally referred to as the "FDA Watch List".

Included on this July 2018 FDA Watch List is the Actemra (tocilizumab) injection.

In particular, the FDA is evaluating the need for Actemra drug safety regulatory action due to adverse event reports involving these three medical conditions:

• pulmonary hypertension;
• interstitial lung disease; and,
• pulmonary alveolar proteinosis.

These pulmonary or lung conditions are listed under the heading "Potential Signal of a Serious Risk/New Safety Information" for Actemra on this FDA Watch List. Put otherwise, these pulmonary or lung conditions may be Actemra side effects.

__________________________________________________________________

Actemra

Free Case Evaluation

Strictly Confidential, No Obligation.

__________________________________________________________________

 

As background, Actemra is approved by the FDA for the treatment of several different medical conditions:

1. Moderately to severely active rheumatoid arthritis in adult patients who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs);
2. Giant Cell Arteritis (GCA) in adult patients;
3. Polyarticular Juvenile Idiopathic Arthritis (PJIA) in patients 2 years of age and older; and,
4. Systemic Juvenile Idiopathic Arthritis (SJIA) in patients 2 years of age and older.

The responsible drug company is Genentech, Inc.

We first wrote about Actemra back in June 2017 as regards another possible Actemra side effect: "Despite The High Number Of Actemra - Pancreatitis Cases Reported To FDA, No Warning Added To Drug Label".

We will continue to monitor the FDA for any regulatory action concerning Actemra regarding pulmonary hypertension, interstitial lung disease, and pulmonary alveolar proteinosis, as well as pancreatitis.

Of course, if you have any experiences or observations relevant to Actemra which you would like to share, you can post a Comment below or you can email me.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)