Drug Safety Developments

New Anticoagulant BevyxXa Approved by the FDA

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

On June 23, 2017, a new anticoagulant drug called BevyxXa (betrixaban) was approved by the FDA for the prevention of venous thromboembolism and pulmonary embolism.

This drug acts as a direct Factor Xa inhibitor, similar to the other anticoagulant drugs Eliquis, Savaysa, and Xarelto.

Unlike the anticoagulant Pradaxa, which is a direct thrombin inhibitor, none of the Factor Xa inhibitors currently have FDA-approved reversal agents.

The article "Still No Approved Reversal Agents Or Antidotes For Eliquis, Savaysa, And Xarelto To Stop Acute Bleeding" by attorney Thomas Lamb provides additional information on this topic.

Due to the lack of adequate reversal agents for these drugs, many Eliquis, Savaysa, and Xarelto lawsuits across the country have been filed by those who have suffered life-threatening uncontrollable bleeding, or by the families of those that have lost their lives as a result of such bleeding.

The current drug label for BevyxXa (6/23/17) already includes the following warning regarding its risk of bleeding events, excerpted from the "Warnings and Precautions" section of the label:

BEVYXXA increases the risk of bleeding and can cause serious and potentially fatal bleeding. Promptly evaluate any signs or symptoms of blood loss...

Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions (7.2)].

Advise patients of signs and symptoms of blood loss and to report them immediately and seek emergency care. Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement. Discontinue BEVYXXA in patients with active pathological bleeding.

There is no established way to reverse the anticoagulant effect of BEVYXXA, which can be expected to persist for at least 72 hours after the last dose. It is unknown whether hemodialysis removes BEVYXXA. Protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant activity of BEVYXXA.

Even though recent drug labels for Eliquis, Savaysa, and Xarelto contain similar warnings, many people believe that such warnings are insufficient, and need to be strengthened by making them "black-box warnings."  These are the strictest warnings put in the labeling of prescription drugs or drug products by the Food and Drug Administration (FDA) when there is reasonable evidence of an association of a serious hazard with the drug.

Additionally, it is particularly worrisome that the anticoagulant effects of BevyxXa can last for up to 72 hours after the last dose.  To put this into perspective, the effects of Eliquis, Savaysa, and Xarelto only last up to 24 hours after the last dose is taken.

While this may not seem significant, it can make the difference between being able to perform a life-saving surgical procedure within 24 hours versus 72 hours on a patient who is uncontrollably bleeding due to one of these drugs.

Given that the most common adverse reactions with BevyxXa in clinical trials so far have been bleeding events, one may expect lawsuits similar to those of other anticoagulant drugs arise after the drug is released this year.

We will continue to monitor the medical literature concerning BevyxXa and its risk of bleeding, and continue to report additional findings.

 

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Can SGLT-2 Inhibitor Diabetes Drugs Increase Your Risk of Stroke?

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

While we have frequently discussed DKA, kidney damage, and amputations as possible side effects of diabetes drugs in the SGLT-2 inhibitors class -- such as Farxiga, Invokana, Jardiance -- strokes and thromboembolic events are also considered potential harmful effects of these drugs.

Based on FAERS reports received during the second quarter of 2015, posted in early 2016, the FDA identified both strokes and thromboembolic events as a "potential signal of a serious risk" for SGLT-2 inhibitors, and stated that they are "evaluating the need for regulatory action."

This warning applies to the following SGLT-2 inhibitors:

• Farxiga (dapagliflozin)
• Invokana (canagliflozin)
• Jardiance (empagliflozin)
• Glyxambi (empagliflozin/linagliptin)
• Invokamet (canagliflozin/metformin HCl)
• Synjardy (empagliflozin/metformin HCl)
• Xigduo XR (dapagliflozin/metformin HCl) 

Though this information was provided back in January 2016, hardly any new information on these possible side effects has been provided.

The CANagliflozin cardioVascular Assessment Study (CANVAS) studied the effects of Invokana "compared to placebo on CV events including CV death, heart attack, and stroke in patients with T2DM."  While this study has recently been completed, the actual study results have yet to be posted.

Additionally, a similar study concerning Jardiance has already been completed, and there is also an ongoing study concerning Farxiga, which will be completed in approximately 2020.

The Abstract of a recent article, titled "Impact of glucose-lowering therapies on risk of stroke in type 2 diabetes," provides the following information:

As for DPP-4 inhibitors, there was a non-significant trend towards benefit for stroke, whereas a possible increased risk of stroke with SGLT2 inhibitors—and in particular, [Jardiance (empagliflozin)] in the EMPA-REG OUTCOME trial—has been suggested and requires clarification...

In summary, the effects of antidiabetic drugs on risk of stroke appear to be heterogeneous, with some therapies (pioglitazone, GLP-1 receptor agonists) conferring possible protection against ischaemic stroke, other classes showing a neutral impact (DPP-4 inhibitors, insulin) and some glucose-lowering agents being associated with an increased risk of stroke (sulphonylureas, possibly SGLT2 inhibitors, high-dose insulin in the presence of insulin resistance).

Regardless of the studies that have been completed, the FDA does not appear to have made a definitive decision regarding the relationship between SGLT-2 inhibitors and strokes or thromboembolic events such as pulmonary embolism (PE) and deep vein thrombosis (DVT).

We will continue to monitor the medical literature and news concerning the FDA's determination regarding the SGLT-2 inhibitors class of diabetes drugs and the possible increased risk of stroke and thromboembolic events.

In the meantime, we invite you visit our website, and to submit a free case evaluation if you or someone you know has experienced one of the following side effects after using a brand-name SGLT-2 inhibitor (see earlier list):

• Acute Kidney Injury
• Kidney Failure or damage
• Diabetic Ketoacidosis (DKA)
• Ketoacidosis
• Ketosis
• Ischemic Stroke / Cerebrovascular Accident (CVA)
• Deep Vein Thrombosis (DVT)
• Pulmonary Embolism (PE)
• Leg Amputation
• Foot or Toe(s) Amputation

 

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Invokana Shown to Have Heart Benefits, but Elevated Amputation Risks

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

Type 2 diabetes drug Invokana (canagliflozin) was the subject of the Canagliflozin Cardiovascular Assessment Study (CANVAS) and the CANVAS renal-end-points trial (CANVAS-R).  While it was recently shown to have significant cardiovascular benefits, it also carries double the risk of lower-limb amputations.

In terms of cardiovascular event reduction, Invokana was shown to result in "a 14% reduction in risk for a composite score on CV mortality as well as nonfatal myocardial infarction and stroke, with each measure contributing to the positive score," according to a recent article on the topic.

This 14% risk reduction perfectly matches that of Jardiance (empagliflozin), another type 2 diabetes drug belonging to the SGLT2 inhibitors class of drugs.  This suggests that there may be a similar effect for other drugs in this class, such as Farxiga (dapagliflozin).  However, we won't know for sure until 2019 when the results of the Farxiga study are released.

Additionally, when comparing Jardiance and Invokana, "Jardiance was more effective in cutting the risk of death (-38%) compared to a much more modest 13% reduction for Invokana."

Invokana was also "linked to a significantly higher risk of amputations, a safety concern that has already triggered a black box warning."  While the total number of amputations was small, it was double that of the placebo group.  For more information on this topic, see my previous article, "Risk of Lower Limb Amputations Doubled with Invokana and Invokamet Use."

A recent Forbes article provides more information on the cardiac benefits and amputation risks:

For every three heart attacks, strokes, or cardiovascular deaths prevented by Invokana, there were two amputations, 71% of them of toes or the lower foot, according to the results of the 10,142-patient study, which was funded by Johnson & Johnson...

Heart attacks were far more common than amputations. For every year patients took the drug, there were 31.5 heart attacks, strokes, or cardiovascular deaths per 1,000 patients in the placebo group and 26.9 in the group that took Invokana, a 14% decrease. But, there would be 3.4 amputations per 1,000 patients in the placebo group and 6.3 amputations per 1,000 patients among those who received Invokana – a doubling of risk that held true for both minor amputations (think toes) and major ones (think legs).

John Buse, the chief of endocrinology at UNC - Chapel Hill provided his opinion on the matter, "Personally, I would much rather have a small heart attack than lose a toe...And I think I would much rather have a big heart attack than lose a leg.”  He anticipates a significant debate, saying that the benefits and harms are most likely "over- and under-estimated in each study."

We will continue to monitor the medical literature on the potential risks and benefits of Invokana and similar SGLT2 drugs.

Currently, we are investigating cases concerning Invokana / Farxiga / Jardiance / Invokamet / Xigduo / Glyxambi / Synjardy / Qtern.  See our website for more information on these drugs, and for our free case evaluation.

 

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AbbVie Required to Pay Depakote Victim $15 Million for Birth Defect

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

AbbVie, which spun out of Abbott Laboratories in 2013, was recently held responsible for failing to adequately warn that their bipolar disorder drug, Depakote (valproic acid), could cause severe birth defects when taken by pregnant women.

The $15 million will be awarded to a 10-year-old boy, Stevie Gonzalez, who was born with spina bifida after his mother took Depakote while pregnant.  

As a result of the Depakote-related birth defect, Gonzalez is confined to a wheelchair and has already undergone twelve surgeries.  The money was awarded to Gonzalez in order to pay for past and future medical bills and care.

Though AbbVie claimed the potential side effects of Depakote were properly disclosed, the jurors in federal court in Illinois decided otherwise.

While AbbVie was held responsible for inadequately warning of Depakote's potential for birth defects, they were not required to pay punitive damages as well.  In other words, the did not think that the Plaintiffs provided clear and convincing evidence that AbbVie's conduct concerning Depakote amounted to malice, oppression, or fraud.

At this time, there are nearly 700 similar cases pending in U.S. courts against AbbVie concerning Depakote-related birth defects.

In addition, drugs similar to Depakote--such as Depakene, Depacon, and Stavzor--have also been shown to cause birth defects when taken during pregnancy.

We will continue to monitor the medical literature as well as the legal news concerning the pending and upcoming Depakote - birth defect cases.

If you or someone you know has given birth to a child with spina bifida or other neurological birth defects after taking Depakote, Depacon, Depakene, or Stavzor while pregnant, we invite you to complete our free case evaluation.

You may also view our website for more information on Depakote / Depakene / Depacon / Stavzor.

 

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FDA Warns of Serious Pancreatitis Risk in Some Patients Taking Viberzi

 

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Related Article:  Viberzi - Pancreatitis Side Effects Can Develop At Any Time While Taking This IBS Drug, According To FDA Safety Warning

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Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

In March of this year, the FDA released a Drug Safety Communication concerning the increased risk of serious pancreatitis in patients without a gallbladder who use the irritable bowel syndrome drug, Viberzi (eluxadoline).

Viberzi is a relatively new drug manufactured by Allergan used to treat irritable bowel syndrome in adults when the main symptom is diarrhea (IBS-D).

The FDA reported that pancreatitis developed as a result of taking Viberzi without having a gallbladder can result in hospitalization and even death: 

From May 2015, when Viberzi was first approved, through February 2017, FDA received 120 reports of serious cases of pancreatitis or death.* Among the 68 patients who reported their gallbladder status, 56 of them did not have a gallbladder and received the currently recommended dosage of Viberzi. Seventy-six patients were hospitalized, of which two patients died. These two patients did not have a gallbladder. Some cases of serious pancreatitis or death also reported sphincter of Oddi spasm (n=6) or abdomen pain (n=16) (see Data Summary).

They also note that pancreatitis can develop in patients who have had as few as one or two doses of Viberzi.  In fact, the two patients who died had only one dose of Viberzi, and "the patient who experienced pancreatitis died within 3 days of taking the initial Viberzi dose."

A new drug label was released on April 20, 2017, which added lack of a gallbladder to the contraindication section, as well as the following warnings:

5 Warnings and Precautions

5.1 Pancreatitis

(Additions and/or revisions are underlined)

Pancreatitis, with or without sphincter of Oddi spasm, has been reported in patients taking either the 75 mg or 100 mg dosage of VIBERZI, including serious cases resulting in hospitalization, primarily in patients without a gallbladder. Fatal cases have also been reported in patients without a gallbladder. VIBERZI is contraindicated in patients without a gallbladder.   Most of the reported cases of serious pancreatitis occurred within a week of starting treatment with VIBERZI and some developed symptoms after one to two doses.

In patients with a gallbladder, evaluate a patient’s alcohol intake prior to starting VIBERZI. Instruct patients to avoid chronic or acute excessive alcohol use while taking VIBERZI. Monitor for new or worsening abdominal pain that may radiate to the back or shoulder, with or without nausea and vomiting.  Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of pancreatitis such as acute abdominal or epigastric pain radiating to the back or shoulder associated with elevations of pancreatic enzymes with or without nausea and vomiting.

 

5.2 Sphincter of Oddi Spasm

(Additions and/or revisions are underlined)

There is a risk of sphincter of Oddi spasm, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain (e.g., biliary-type pain) in patients taking VIBERZI. Postmarketing serious adverse reactions of sphincter of Oddi spasm with or without pancreatitis resulting in hospitalization have been reported, primarily in patients without a gallbladder. Most of the reported cases of serious sphincter of Oddi spasm occurred within a week of starting treatment with VIBERZI and some developed symptoms after one to two doses.  VIBERZI is contraindicated inpatients without a gallbladder.

Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of sphincter of Oddi spasm such as acute worsening of abdominal pain,…

We will continue to monitor the medical literature for more information concerning the link between Viberzi use in patients without a gallbladder and severe pancreatitis.

 

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Type 2 Diabetes Drugs Linked to Severe Joint Pain

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

Health Canada recently warned about the risk of severe, debilitating joint pain as a result of taking type 2 diabetes medications called dipeptidylpeptidase-4 (DPP-4) inhibitors.  

This DPP-4 inhibitors class of drugs includes the following:

• Onglyza
• Kombiglyze XR
• Nesina
• Kazano
• Oseni
• Glyxambi
• Janumet (XR)
• Januvia
• Jentadueto
• Tradjenta
• Qtern

The FDA also issued a Drug Safety Communication in August of 2015 concerning the association of DPP-4 inhibitors and severe joint pain.  They soon added the following warning to the labels for these drugs:

Severe and Disabling Arthralgia

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.

The FDA's warning and subsequent label change concerning DPP-4 inhibitors sparked an extensive review of the existing medical literature on the relationship between these drugs and severe joint pain.

Based on this literature review, as well as the FDA's actions and their Adverse Event Reporting System, Health Canada is following suit and "working with manufacturers to update the product safety information for all DPP-4 inhibitors to communicate the risk of developing severe and disabling joint pain with the use of these drugs."

It will be interesting to see if Health Canada decides to use a strengthened version of the FDA's warning against disabling joint pain in their own warnings.

We will continue to monitor medical news and publications for new and increased warnings of the link between severe joint pain and the DPP-4 inhibitor class of drugs.

 

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