Side Effects Blog

In June 2021 it was reported that Invokana, Farxiga, Jardiance, and other drugs in the Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors class, are associated with an increased risk of retinal vein occlusion. This new SGLT2 inhibitors side effect was the subject of a presentation at the 81st Scientific Sessions of the American Diabetes Association which was based on the first study to examine the potential association of retinal vein occlusion with the use of SGLT2 inhibitors.

From this news report published on the PracticeUpdate website (free registration required), “ADA 2021: SGLT2 Inhibitors May Increase the Risk of Retinal Vein Occlusion”, we get these details:

In a subgroup analysis, significant interactions were evident with use SGLT2 inhibitors and risk of retinal vein occlusion concerning age ≥ 60 years (hazard ratio 1.53, 95% confidence interval 1.20–1.94, P =.0135) and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (hazard ratio 3.13, 95% confidence interval 155–6.32, P = .0083). No significant interactions were evident for sex, age, body mass index, presence of comorbidities, multiple lifestyle factors, or use of other anti-diabetes agents.

[The researchers concluded] “In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of retinal vein occlusion. The elderly and patients with chronic kidney disease were at higher risk for retinal vein occlusion,”….

Of course, we will continue to monitor the medical literature for more about this new SGLT2 inhibitors side effect related to vision/eyes, retinal vein occlusion.

In postponing Rinvoq, the FDA said it’s still reviewing those Pfizer data, according to AbbVie. In February, the agency alerted patients and doctors of Xeljanz’s safety signal. At that time, it said it would dig into the results and consider what moves to take.

Existing JAK inhibitors, including Rinvoq, already bear warnings of increased risk of blood clots on their U.S. labels. Xeljanz’s cardiovascular red flag obviously made the FDA nervous about it being a class-wide problem for all JAK drugs.

For some additional perspective, we turn to this June 25, 2021, EndpointNews article, “FDA pushes back decisions on AbbVie’s Rinvoq sNDAs to further review a failed Pfizer trial”:

The regulator’s continued evaluation of the Pfizer trial shows those safety concerns have not abated. Pfizer announced in January that ORAL Surveillance, its six-year post-marketing trial for its JAK inhibitor Xeljanz, had failed. Across 4,362 patients, those who received either a low or high dose of Xeljanz experienced more major cardiovascular events — such as stroke and heart attack — than those on Humira or Enbrel. They also had higher rates of cancer, with Pfizer failing to hit non-inferiority on both primary endpoints.

We will continue to watch for further developments and indications concerning an FDA Advisory Committee for Xeljanz, Rinvoq, and other JAK inhibitors so that outside experts to review their risk/benefit profiles as regards new indications such as atopic dermatitis. If this comes to be, we expect that FDA Advisory Committee would be discussing the new JAK inhibitors heart side effects and cancer risks issues which were flagged by means of the earlier Xeljanz safety signal.

Tasigna has been linked to atherosclerosis, which is a disease that results in thickening, hardening, and blocking of the arteries due to the buildup of plaque. In turn, strokes, heart attacks, and lower limbs amputations can be Tasigna side effects as these are serious medical conditions that can result from, or are secondary to, atherosclerosis-related diseases.

In more detail, the following medical conditions are considered to be atherosclerosis-related diseases:

• peripheral arterial disease (PAD) involving lower limbs;
• peripheral arterial occlusive disease (PAOD);
• ischemic heart disease; and
• ischemic cerebrovascular disease.

As background, in Canada the drug company Novartis Pharmaceuticals has issued stronger warnings about atherosclerosis-related diseases being Tasigna side effects — compared to what is found on the US version of the Tasigna drug label. This situation has given rise to the contention that warnings about Tasigna side effects in the current US drug label are insufficient, or a failure to adequately warn. In turn, Tasigna drug injury lawsuits have been filed against Novartis here in the U.S.

Novartis has proactively communicated these data to health authorities and will pursue an update to the Beovu prescribing information globally.

We are watching for this forecasted Beovu label change which will, presumably, add new and updated warnings about Beovu vision loss side effects.

For a more in-depth view of this latest development as regards Beovu safety issues, we turn to this June 1, 2021, FiercePharma news report, “Novartis calls off 3 Beovu trials testing more frequent dosing on concerns of vision-threatening side effect”:

[In the MERLIN clinical trial] Beovu doubled the rate of intraocular inflammation compared with [Eylea], with 9.3% percent of patients suffering the complication in the Beovu trial arm. That compared with 4.5% for Eylea. None of the Eylea patients developed reginal vasculitis or retinal vascular occlusion, while those side effects happened in 0.8% and 2% of Beovu patients, respectively. The problem could potentially damage a person’s vision.In Merlin, the rate of vision loss from any cause was 4.8% for Beovu patients and 1.7% for Eylea patients….

The company has yet to identify the root cause behind Beovu’s safety problem.

As we have reported previously, Beovu lawsuits for our clients have been filed starting in January 2021, alleging Novartis failed to warn doctors and patients about these Beovu safety issues. Our law firm began investigating drug injury lawsuits against Novartis for Beovu back in February 2020, and we continue to accept Beovu cases that involve vision loss and blindness due to occlusive retinal vasculitis, retinal artery occlusion, and intraocular inflammation.

From the May 2021 Ocaliva FDA Drug Safety Communication we get this statement about what the FDA is doing:

We added a new Contraindication, FDA’s strongest warning, to the Ocaliva prescribing information and patient Medication Guide stating that Ocaliva should not be used in PBC patients with advanced cirrhosis. Advanced cirrhosis is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia). We also revised the Boxed Warning, our most prominent warning, to include this information along with related warnings about this risk.

And later in the May 2021 Ocaliva FDA Drug Safety Communication about a “new” Ocaliva-related liver injury and the Ocaliva label change, here is what the FDA found during its Ocaliva liver safety evaluation:

In the five years since Ocaliva’s accelerated approval, FDA identified 25 cases of serious liver injury leading to liver decompensation or liver failure associated with Ocaliva in PBC patients with cirrhosis, both in those without clinical signs of cirrhosis (compensated) or in those with clinical signs of cirrhosis (decompensated). Many of these PBC patients had advanced cirrhosis before starting Ocaliva…. After starting Ocaliva, the pace of the liver decompensation or failure reported suggested these adverse events, which resulted in liver transplant in a small number of cases, were related to the drug rather than progression of the underlying PBC.

We are investigating possible Ocaliva drug injury lawsuits that would be filed against Intercept Pharmaceuticals, the responsible drug company, for patients who have been diagnosed with these serious possible Ocaliva side effects.

Purpose of review: The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to [Elmiron, or pentosan polysulfate sodium (PPS)].

Recent findings: [Elmiron (PPS) toxicity] was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1–2 kg and 10–15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%.

It is important to know that a patient does not need to have current Elmiron use right up until the time when their pigmentary maculopathy is diagnosed for it to be considered Elmiron-related eye damage.

We are currently investigating possible Elmiron lawsuits for patients with past Elmiron use diagnosed with pigmentary maculopathy. If we can assist you with an Elmiron-related eye damage legal case, you can submit an online Elmiron Case Evaluation Form or call us on our toll-free number: 800-426-9535.

Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver transplantation. The role of systemic corticosteroids is controversial, but they may be administered when a liver injury event cannot be distinguished between autoimmune hepatitis or DILI or when a DILI event presents with prominent autoimmune hepatitis features.

For an easier read (than the full medical journal article) about the significance of these updated DILI clinical practice guidelines, we refer you to this May 3, 2021, Healio news report, “ACG releases guidelines for managing suspected drug-induced liver injury”.

Conclusions and Relevance: In this case report, [progressive multifocal leukoencephalopathy (PML)] occurrence was likely a result of the immunomodulatory function of [Ocrevus] as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of [Ocrevus], especially in patients at higher risk for infections such as elderly patients.

We get some interesting additional information about this Ocrevus PML case report from a March 16, 2021, Medpage Today article, “PML Reported in Ocrelizumab-Treated MS Patient”:

This case, first noted by Genentech in October 2019 but with many details lacking, is the only one associated with [Ocrevus] alone.

So pharmaceutical company Genentech knew about this first monotherapy Ocrevus PML case no later than October 2019, but important details about the subject patient and its ramifications in terms of Ocrevus drug safety just came to light in March 2021.

We will continue to monitor this “new” Ocrevus drug safety issue involving PML as well as watch for any explanation from Genentech about an almost one-and-a-half-year delay in making this Ocrevus PML case report available to the public.

Last week we saw this April 8, 2021, Endpoints News article with a telling headline, “Series of JAK inhibitor delays may signal an upcoming FDA adcomm”, by Zachary Brennan, from which we get the following insights:

Three-month review delays from the FDA have become the norm in recent days for JAK inhibitors, some of which are seeking label expansions.

But the pushback of these action dates for AbbVie’s Rinvoq, Pfizer’s Xeljanz and abrocitinib, and Eli Lilly’s Olumiant may be a sign that the FDA is preparing to hold an advisory committee of outside experts to review the risk/benefit profiles of JAK inhibitors for atopic dermatitis, according to Leerink analyst Geoffrey Porges. This wouldn’t be the first time this year that the FDA wants to review a series of drugs before an adcomm as the agency is holding such a review later this month for cancer drugs that have previously won accelerated approvals.

We will continue to watch for new information about an increased risk of serious heart-related problems and cancer associated with Xeljanz. And we will look for any related developments concerning the JAK inhibitors class of drugs, such as the possible FDA Advisory Committee Meeting for Xeljanz, Olumiant, and Rinvoq mentioned above.

At the present time, our law firm is investigating possible Xeljanz drug injury lawsuits for people who have been diagnosed with heart-related problems or cancer.

From the Summary section of that 2021 Federal Register Notice:

The Food and Drug Administration (FDA or Agency) has determined that BELVIQ (lorcaserin hydrochloride) tablets, 10 milligrams (mg), and BELVIQ XR (lorcaserin hydrochloride) extended-release tablets, 20 mg, were withdrawn from sale for reasons of safety or effectiveness. The Agency will not accept or approve abbreviated new drug applications (ANDAs) for lorcaserin hydrochloride tablets, 10 mg and 20 mg.

According to that 2021 Federal Register Notice, this further FDA action regarding Belviq means:

[The FDA] will remove BELVIQ (lorcaserin hydrochloride) tablets, 10 mg, and BELVIQ XR (lorcaserin hydrochloride) extended-release tablets, 20 mg, from the list of drug products published in the Orange Book. FDA will not accept or approve ANDAs that refer to this drug product.

Going back to the February 2020 FDA Drug Safety Communication announcing the Belviq drug recall, “FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market”, these are some of the specific types of cancer associated with Belviq:

Pancreatic Cancer
Colorectal Cancer
Colon Cancer
Rectal Cancer
Lung Cancer

Our law firm is investigating possible Belviq lawsuits where patients have been diagnosed with cancer, including but not limited to the types listed above.

One indication of this concern is found in a March 18, 2021, BioPharma news report, “AbbVie’s approval delay raises further concerns about JAK drugs”, from which we get the following:

The Food and Drug Administration may take up to three months longer to review an application from AbbVie to get Rinvoq, its marketed medicine for rheumatoid arthritis, also approved to treat active psoriatic arthritis. The company now expects a decision toward the end of the second quarter.

AbbVie gave few details about the reasons for the delay in a Wednesday statement, noting only that the FDA had requested new information on the drug’s benefits and risks in psoriatic arthritis patients. But after speaking with the company, Vamil Divan, an analyst at Mizuho Securities, learned the requests were for long-term safety data similar to what Pfizer recently showed for Xeljanz, a rival drug that works like Rinvoq.

We will continue to watch for newly released information from the Xeljanz safety clinical trial that showed Xeljanz-associated heart problems and possible Xeljanz-related cancers and which is the basis for the February 2021 Xeljanz FDA Drug Safety Communication. In addition, for the reasons stated above, we will monitor the safety profile of Rinvoq and Olumiant to see whether those are JAK inhibitors drug class adverse drug events and side effects risks.