Side Effects Blog

The current version of the Prescribing Information document for Ocaliva (Revised: 5/2022) has a so-called Black Box Warning for cases of serious liver injury involving patients with diagnosed cirrhosis who used Ocaliva. Specifically, this Black Box Warning text was added to this Ocaliva drug label in May 2021:

WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY
BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS

• Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis [see Warnings and Precautions (5.1)].
• OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension [see Contraindications (4)].
• Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension; or experience clinically significant hepatic adverse reactions while on treatment [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].

We will watch to see whether this December 2024 Ocaliva FDA drug safety warning about cases of serious liver injury among patients without pre-existing cirrhosis results in another Ocaliva label change involving the Black Box Warning or other parts of the Prescribing Information document during the first part of 2025.

For some contextual information, we turn to this November 19, 2024 Endpoints News report “Ahead of adcomm, FDA raises safety questions for AstraZeneca’s reversal agent for life-threatening bleeds”, by Zachary Brennan, Senior Editor:

[Andexxa (andexanet)], a recombinant modified human factor Xa protein, is for patients treated with [Xarelto (rivaroxaban)] or [Eliquis (apixaban)] when rapid reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding. That could include, for example, when a patient needed urgent surgery because of a medical emergency or accident.

Last year, AstraZeneca began plans to shift Andexxa to a full approval from its accelerated approval after halting its confirmatory trial early due to these efficacy findings.

But FDA explained how the confirmatory trial, known as ANNEXA-I, revealed “major safety findings” including a “doubling of the rate of thromboses and thrombosis related deaths at Day 30 in the [Andexxa (andexanet)] arm compared with” a standard of care clotting agent known as a prothrombin complex concentrate.

Of the 239 patients treated with [Andexxa (andexanet)], FDA said, 14.6% of patients suffered thrombotic events versus 6.9% in the standard of care arm.

There has been speculation that this increased risk of Andexxa blood clots and clotting-related deaths might lead to an eventual drug recall. For example, the headline for an article published November 20, 2024, by Pink Sheet is “AstraZeneca’s Andexxa Could Be Headed For Withdrawal After US FDA’s Negative Advisory Committee Preview”.

We will continue to monitor this emerging drug safety issue of Andexxa blood clots and clotting-related deaths.

Intracranial meningiomas are mostly non-cancerous or non-malignant tumors. However, cancerous or malignant meningiomas account for 40% of cancers in the central nervous system. Both of these forms of intracranial meningioma are potentially serious medical conditions. Meningiomas grow in layers of tissue covering the brain and spinal cord.

If you are interested in reviewing some general medical information about meningioma, we direct you to the Mayo Clinic’s “Symptoms & causes” and “Diagnosis & treatment” web pages.

This March 2024 BMJ article, “Use of progestogens and the risk of intracranial meningioma: national case-control study”, provides these details about the increased risk of those brain tumors from birth control Depo-Provera injections.

Because the current drug label for Depo-Provera Contraceptive Injection (version “Revised: 7/2024”, accessed 10/16/24) does not include any warning about an increased risk of intracranial meningioma, we are investigating possible drug injury lawsuits seeking legal compensation for women who have been diagnosed with those brain tumors.

That type of lawsuit would be a product liability case filed against the responsible pharmaceutical companies for their failure to warn about brain tumors from birth control Depo-Provera injections. We note that the lawsuit would not be against the woman’s doctors.

Please feel free to contact us to learn more about how the contraceptive injection Depo-Provera being linked to intracranial meningioma might be a drug injury lawsuit seeking legal compensation for women diagnosed with a brain tumor after using this birth control product for years in the past.

A September 20, 2024, Reuters news report, “Court revives more than 500 lawsuits over Fosamax femur fracture risk”, provides a history of prior rulings on the legal defense of federal preemption for the Fosamax MDL femur fracture lawsuits:

The federal litigation stretches back to 2008, and has now been dismissed and revived twice. All of those decisions have hinged on the issue of federal preemption – whether the federal law governing what pharmaceutical companies are required to put on drug labels overrides, or preempts, state law claims that the label fails to warn consumers.

Merck has argued that it does, saying that in 2009 it proposed adding a warning about femur fractures but was initially rejected by the FDA. The warning was eventually added in 2011.

Now-deceased U.S. District Judge Joel Pisano in Trenton, New Jersey, ruled in Merck’s favor on the preemption issue in 2013, but the 3rd Circuit overturned that ruling in 2017, concluding that issue should have been decided by a jury.

The U.S. Supreme Court in 2019 ordered the issue reconsidered once again, saying it was a legal issue for a judge, not a jury.

In 2022, U.S. District Judge Freda Wolfson, who had taken over the case, again sided with Merck on preemption.

The 3rd Circuit on [September 20, 2024], however, again reversed. It said that, even though the FDA had not approved the specific warning proposed by Merck in 2009, it would not necessarily have rejected any warning about femur fractures….

Wolfson has since retired, and the case is now assigned in the trial court to U.S. District Judge Karen Williams. The litigation will return to that court for potential future trials.

We will continue to monitor legal developments for the Fosamax MDL femur fracture lawsuits.

• feeling more tired than usual;
• nausea;
• vomiting;
• unusual itching;
• light-colored stools;
• yellowing of the eyes or skin, called jaundice;
• dark urine;
• swelling in the stomach or belly area, called the abdomen; or,
• pain in the right upper abdomen.

The Veozah liver injury warnings FDA Drug Safety Communication instructed patients and doctors to stop Veozah if signs and symptoms of liver injury occur.

As background, Veozah (fezolinetant) was approved by the FDA in May 2023 to reduce the frequency and severity of moderate to severe hot flashes caused by menopause.

The newly added Veozah liver injury warnings are included in the Veozah Prescribing Information document, or drug label, “Revised: 8/2024” version.  In particular, new warnings about liver toxicity and abnormal liver test results were added to this important part of the Veozah drug label: 5 WARNINGS AND PRECAUTIONS, 5.1 Hepatic Transaminase Elevation and Hepatotoxicity.

There may be some women who were using Veozah and then diagnosed with a serious liver injury at some point between May 2023 and August 2024, the period when the additional information found in those new paragraphs was not in the Veozah drug label. For those women, there are possible drug injury lawsuits that would be filed against Astellas Pharma for failure to adequately warn about liver toxicity and abnormal liver tests associated with Veozah use.

We will continue to monitor developments regarding this new Veozah liver injury warnings drug safety issue.

The American Society of Retina Specialists (ASRS), published a general report on Syfovre retinal-related vision loss, co-authored by the ASRS Research and Safety in Therapeutics (ReST) Committee in December 2023. Their report revealed that at least 13 patients had developed Syfovre retinal-related vision loss earlier in 2023. Specifically, those 13 patients developed retinal vasculitis after their first Syfovre injection.

As mentioned previously, while Syfovre was initially available for use in February 2023, it was not until November 2023 that Apellis added new Syfovre warnings for retinal vascular occlusion and retinal vasculitis cases associated with Syfovre injections to the Syfovre drug label.  This time-lapse is a central part of the Syfovre legal compensation cases that are being filed.

In more detail, Syfovre injection side effects include occlusive retinal vasculitis and non-occlusive retinal vasculitis. These types of eye inflammation result in vision loss and potentially cause blindness.

From this July 19, 2024 news report, “The Syfovre Balancing Act. The Retinal Vasculitis Risk Is Real But Research Also Points to Benefits | ASRS 2024“, we get the most recent findings about patients who were treated with Syfovre and then diagnosed with retinal vasculitis: “The combined results of two real-world evidence studies presented Thursday put the risk of developing retinal vasculitis at about 1 in every 1,330 patients.”

We are handling Syfovre legal compensation cases for retinal vasculitis diagnosed after a patient’s first Syfovre injection. These personal injury cases are drug injury lawsuits filed against Apellis Pharmaceuticals. More precisely, these Syfovre lawsuits are based on product liability law for the alleged failure to warn about retinal vasculitis as a Syfovre side effect promptly. As such, these Syfovre lawsuits are not filed against the patients’ eye doctors.

We have a free online Case Evaluation for these Syfovre legal compensation cases, or you can call us toll-free at 800-426-9535.

Semaglutide-Related Blood Clots Cases: DVT and Pulmonary Embolism

Here are some reports of DVT and pulmonary embolism involving semaglutide drugs we have received in the past several months:

Ozempic – Deep vein thrombosis (DVT) and pulmonary embolism were diagnosed in a 66-year-old woman who had been using Ozempic for 2 months.

Ozempic – Pulmonary embolism (PE) and DVT were diagnosed in a 53-year-old man who had been using Ozempic for 1 year.

Ozempic – Blood clots in both lungs, which is a bilateral pulmonary embolism, were diagnosed in a 46-year-old woman who had been using Ozempic for 2 months.

Rybelsus – DVT was diagnosed in a 62-year-old woman who had been using Rybelsus for 1 month.

Semaglutide-Related Blood Clots Cases: Other Medical Conditions

Here are some reports of other blood clot conditions involving semaglutide drugs we have received in the past several months:

Ozempic – Blood clot in the portal vein, or portal vein thrombosis (PVT), was diagnosed in a 44-year-old woman who had been using Ozempic for 2 weeks.

Wegovy – Ischemic stroke was diagnosed in a 45-year-old man who had been using Wegovy for 3 months.

We are investigating possible Rybelsus, Wegovy, and Ozempic drug injury lawsuits for people diagnosed with deep vein thrombosis (DVT), pulmonary embolism (PE), portal vein thrombosis (PVT), ischemic stroke, or any other blood clot-related side effects.

Let us know if we can assist you or someone you know with a Wegovy, Rybelsus, or Ozempic blood clot case. One way to do this is to submit an online Case Evaluation Form.

The medical study that found the new Ozempic eye problems side effect was presented in this article, “Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide”, which was published on July 3, 2024, by the medical journal JAMA Ophthalmology.

We get an overview of the semaglutide – NAION medical study from this July 3, 2024, STAT news article, “Study links Ozempic to higher risk of eye condition that can cause vision loss”:

A new observational study on [July 3, 2024] reported for the first time a potential link between Novo Nordisk’s GLP-1 drugs Ozempic and Wegovy and an eye condition that can cause vision loss….

NAION, sometimes referred to as an “eye stroke,” occurs from a lack of sufficient blood flow to the optic nerve. It typically causes sudden vision loss and, in severe cases, can lead to blindness. There are currently no proven treatments for the condition.

Some information about the increased risk of these Wegovy, Rybelsus, and Ozempic eye problems side effects was provided in this July 3, 2024, MedPage Today article, “Semaglutide May Be Linked to Condition That Causes Blindness”:

Over a mean follow-up of nearly 3 years, patients with diabetes on semaglutide had more than a fourfold higher risk for developing nonarteritic anterior ischemic optic neuropathy (NAION) compared with patients not on a GLP-1 agonist (HR 4.28, 95% CI 1.62-11.29, P<0.001)….

Those prescribed semaglutide for overweight or obesity had an over sevenfold higher risk for NAION (HR 7.64, 95% CI 2.21-26.36, P<0.001), a significant cause of blindness…

Over 3 years, the cumulative incidence of NAION were 8.9% and 6.7% in the two semaglutide groups, respectively, versus 1.8% and 0.8% for the non-GLP-1 groups. [emphasis added]

Relevant to this recent finding that Ozempic side effects include eye problems with possible vision loss, we point out that in medical records, NAION is sometimes referred to more simply as an “eye stroke” and because it is a form of “optic neuropathy” (an eye disease category) NAION might be noted in short only as optic neuropathy.

Patients who developed NAION following the use of Ozempic, Wegovy, or Rybelsus may be entitled to legal compensation by filing a drug injury lawsuit against Novo Nordisk, the pharmaceutical company responsible for Ozempic, Wegovy, and Rybelsus.

From this Fierce Pharma June 28, 2024 article, “EU’s drug regulator again rejects Apellis’ eye med….”, we get the latest on what is happening with Syfovre in Europe:

For the second time in six months, Europe’s Committee for Medicinal Products for Human Use (CHMP) has given a thumbs down to Apellis’ Syfovre for the treatment of patients with geographic atrophy (GA) caused by age-related macular degeneration….

“Although the studies showed that Syfovre slowed the growth of geographic atrophy lesions, this did not lead to clinically meaningful benefits for patients,” the CHMP said. “It was noted that benefits of a treatment should impact patients’ everyday functioning, and this was not demonstrated in the studies.”

“In terms of safety,” the CHMP continued, “regular injections into the eye carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, that could further worsen vision.”

In January of this year, the CHMP adopted its first negative opinion on Syfovre….

We have been monitoring this Syfovre drug safety issue since July 2023 on Drug Injury Watch, and these are the four most recent articles:

• Syfovre Retinal Vaso-occlusive Vasculitis Case Report Involving 78-year Old Woman With Vision Loss (4/24/2024)
• Syfovre Case Report: Occlusive Retinal Vasculitis Shortly After Patient’s First Syfovre Injection (3/6/2024)
• Syfovre Safety Issues Need More Attention Before This Relatively New Eye Drug Gets Widely Prescribed (12/27/2023)
• Syfovre Update: New Warnings About Retinal Vasculitis and/or Retinal Vascular Occlusion After Syfovre Injections (12/4/2023)

We continue to investigate possible Syfovre drug injury lawsuits for patients who developed retinal vasculitis or retinal vascular occlusion with resulting vision loss or blindness after their Syfovre injection.

• Whether Novo Nordisk knew or should have known that its semaglutide-containing drugs Wegovy, Rybelsus, and Ozempic can cause ischemic strokes (which are strokes caused by blood clots), pulmonary embolism (PE), or deep vein thrombosis (DVT) — as opposed to gastroparesis, gastric stasis, stomach paralysis, and other semaglutide-related stomach conditions;
• Whether Novo Nordisk adequately warned the patient or their prescribing doctor about the alleged increased risk of blood clots of Wegovy, Rybelsus, Ozempic that can lead to a stroke, PE, or DVT; and,
• Whether Novo Nordisk made false, misleading, or incomplete representations regarding the drug safety of Wegovy, Rybelsus, and Ozempic.

In more detail, drug injury lawsuits for people using Wegovy, Rybelsus, or Ozempic diagnosed with gastroparesis, gastric stasis, stomach paralysis, and other semaglutide-related stomach conditions are in this federal court MDL: IN RE: GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS (GLP-1 RAS) PRODUCTS LIABILITY LITIGATION, MDL No. 3094.

However, drug injury lawsuits involving a stroke, pulmonary embolism, or deep vein thrombosis when using Wegovy, Rybelsus, or Ozempic would not be part of federal court MDL No. 3094 as currently configured in the February 2024 Transfer Order because that federal court MDL does not include stroke, PE, and DVT cases.

We have been investigating possible drug injury lawsuits against Novo Nordisk involving strokes caused by blood clots as well as PEs and DVTs in patients using Wegovy, Rybelsus, or Ozempic.

If we can assist you or someone you know, our Drug Injury Case Evaluation Form is available online, or you can call us at (800) 426-9535 to discuss a possible Wegovy, Rybelsus, or Ozempic case.