Side Effects Blog

The Health Canada Xeljanz Advisory gives some more detailed information in a section intended for healthcare professionals but, no doubt, of interest to patients using Xeljanz — as well as Olumiant or Rinvoq, perhaps:

• Inform patients that Xeljanz/Xeljanz XR may increase their risk of major adverse cardiovascular events including non-fatal myocardial infarction. Instruct all patients, especially geriatric patients, current or past smokers, or patients with other cardiovascular risk factors, to be alert for signs and symptoms of cardiovascular events.
• Inform patients that Xeljanz/Xeljanz XR may increase their risk of certain cancers, and that lung cancer, lymphoma and other cancers have been observed in patients taking Xeljanz. Instruct patients to inform their healthcare provider if they have ever had any type of cancer.

Our law firm is investigating possible drug injury lawsuits for patients who used Xeljanz, Olumiant, or Rinvoq and then suffered one of the serious side effects associated with these JAK inhibitors drugs. In particular, heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as cancers such as lymphoma and lung cancer.

Some patients with [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy may unfortunately experience difficulty with dark adaptation, reading, contrast sensitivity, and changes in mesopic microperimetry. In the current study, the [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy group was more likely to have complaints of difficulty with their visual field, reading, dark adaptation, and visual acuity….

There is currently no treatment for [Pentosan Polysulfate Sodium / Elmiron]-associated maculopathy, and the retinopathy can progress even after discontinuing [Pentosan Polysulfate Sodium / Elmiron]. In a multicenter study of 11 patients who had discontinued [Pentosan Polysulfate Sodium / Elmiron], 77% continued to experience progression, with the RPE atrophy growing at a rate of 0.32mm per year, and 9% developing worsening vision over 12 months…. [footnotes omitted]

We are handling Elmiron lawsuits for patients who have developed Elmiron-associated retinopathy, retinal pigmentary changes, or pigmentary maculopathy due to their past use of Elmiron. These Elmiron lawsuits are filed against the drug companies responsible for Elmiron. This is because — despite a growing number of Elmiron-related vision loss case reports in the medical literature over the years — it was not until June 2020 that any warning about these eye problem side effects was included in the Elmiron drug label here in the US.

It is important to know that our Elmiron lawsuits for patients who have suffered any of these Elmiron eye problem side effects are filed only against the pharmaceutical companies responsible for Elmiron — not the doctors who prescribed the Elmiron as a treatment for their bladder diseases.

Significantly, it is not necessary for the patient to have been using Elmiron regularly right up until the time when their Elmiron-related vision loss was diagnosed in order to file an Elmiron lawsuit. That is, unlike most other drug injury cases, the patient could have stopped using Elmiron months before a medical doctor was able to diagnose their Elmiron-associated retinopathy, for example.

From the Abstract for this November 2021 JAMA Ophthalmology article, we point out these selected parts:

• Importance: Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu).
• Objective: To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent [Beovu (brolucizumab)] treatment. Additionally, potential risk factors associated with these adverse events were evaluated.
• Conclusions and Relevance: The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first [Beovu (brolucizumab)] injection had the highest observed risk rate for IOI and/or RO in the early months after the first [Beovu (brolucizumab)] treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with [Beovu (brolucizumab)] cannot be assessed.

There was also an Invited Commentary piece related to the above medical journal article which was also published by the medical journal JAMA Ophthalmology titled “Risk Factors for Intraocular Inflammation After Brolucizumab Treatment”, fromw which we get this guidance for ophthalmologists that use Beovu for their AMD patients:

Clinicians should maintain heightened awareness for RO and/or RV with IOI after [Beovu (brolucizumab)] and be familiar with diagnostic imaging protocols especially widefield fluorescein angiography and recommended treatment algorithms. Based on the current literature, same-day bilateral [Beovu (brolucizumab)] injections should be avoided and [Beovu (brolucizumab)] is contraindicated in eyes with active IOI or a history of IOI related to [Beovu (brolucizumab)]. Based on the study from Khanani and colleagues, a recent history of IOI and/or RO should be considered as another potential risk factor for [Beovu (brolucizumab)]-related IOI.

We will continue to monitor the medical journals for Beovu safety developments and, in particular, intraocular inflammation and retinal vascular occlusion associated with Beovu.

Xeljanz is a Pfizer drug, Rinvoq is an AbbVie drug, and Olumiant is an Eli Lilly drug. The pharmaceutical companies AbbieVie and Eli Lilly have attempted to distinguish the safety profile of their respective JAK inhibitors drug product from the various adverse drug reactions that have been observed in the Xeljanz clinical trial that have driven the FDA regulatory actions driving these December drug label changes.

One pharmaceutical industry commentator wrote after the latest Xeljanz, Olumiant, and Rinvoq label changes said he thinks that AbbVie may have an advantage in “market share” going forward as regards the three JAK inhibitors drugs approved for the treatment of rheumatoid arthritis, given some details of the new drug label for Rinvoq.

Our law firm is investigating possible Xeljanz, Olumiant, and Rinvoq lawsuits for patients who have suffered serious side effects or adverse drug reactions while using one of these JAK inhibitors. In particular, we are reviewing cases of cancers, blood clots, heart problems, and deaths associated with Xeljanz, Olumiant, and Rinvoq.

If we can be of assistance to you or someone you know, please feel free to contact us, at your convenience.

For example, there is this Lilly News Release document, “OLUMIANT® Long-Term Safety Profile Established Up to 9.3 Years in Integrated Analysis of More Than 3,700 Patients with Rheumatoid Arthritis”, which was issued on November 9, 2021.

For some analysis and context about that November 2021 Olumiant press release from Eli Lilly, we refer you to this Fierce Pharma news report, “Eli Lilly touts long-term safety data for Olumiant amid classwide scrutiny on JAK meds”, published on November 10, 2021.

In the new pooled analysis, the incidence of major adverse cardiovascular events (MACE) for Olumiant was 0.51 per 100 patient-years of exposure, which Lilly said falls within the range in the general rheumatoid arthritis population as described in epidemiological studies….

In a subgroup of patients over 50 years old who had at least one existing heart risk factor, the incidence rate of MACE [for Olumiant] was higher at 0.77 per 100 patient-years.

That latter patient population was targeted in Pfizer’s postmarketing safety study for Xeljanz. As [Pfizer] disclosed earlier this year, Xeljanz’s MACE incidence rate was 0.91 per 100 person-years at the 5 mg dose….

As for the cancer rates, the age-adjusted number for Olumiant was 0.92 per 100 person-years, which Lilly again said appeared similar to the general U.S. population. In the Pfizer trial, Xeljanz recorded a cancer rate of 1.13….

The FDA is still considering the details of the JAK inhibitors drug class “Black-Box” warnings label change it announced in September 2021.

Our law firm is investigating possible drug injury lawsuits for patients who used Olumiant, Rinvoq, or Xeljanz and then suffered serious side effects associated with JAK inhibitors drugs. These include heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as cancers such as lymphoma and lung cancer.

The patient was scheduled to receive [Padcev (enfortumab vedotin)] on days 1, 8, and 15 of a 28-day cycle at the M.D. Anderson Cancer Center. He tolerated day 1 of his medication well; however, after his day 8 infusion, an erythematous rash with associated skin sloughing developed on <20% of his body…. @His medication list was reviewed for the identification of a potential cause of SJS/TEN…. Based on his recent initiation of [Padcev (enfortumab vedotin)] and his rapid-onset development of the rash, the drug was deemed to be the cause and was discontinued, and he was started on a topical steroid. A biopsy was performed, and the pathology revealed interface dermatitis with central areas of full-thickness epidermal necrosis, consistent with an SJS/TEN overlap (Fig 3).

… His rash progressed to involve >30% of his skin, and he was diagnosed with TEN…. The patient died 20 days after admission on February 27, 2020.

Our next Padcev skin reaction case report was found in an article published by the medical journal Frontiers in Oncology. The lengthy title of that article is “Case Report: Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Case Series on the Clinical and Histopathologic Spectrum of Adverse Cutaneous Reactions From Fatal Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis to Dermal Hypersensitivity Reaction”. This Padcev-induced TEN case report concerns a 71-year-old male, whose case was described in relevant part as follows:

He received [Padcev (enfortumab vedotin)] 1.25 mg/kg on days 1 and 8 of the first cycle. Within 24 h of the day 8 infusion [of Padcev], he experienced diffuse pruritus. Four days after the infusion, he presented to the emergency department with fevers to 101°F and mouth pain but was otherwise hemodynamically stable with unremarkable cardiac and pulmonary exams. His dermatologic exam on admission revealed a small ulceration on the right lateral upper lip, well-demarcated erythema of the inferior tongue tip, and tender erythema of the axillae, flanks, inguinal region, and soles of feet…. The clinical and histologic findings were compatible with early changes of SJS/TEN….

ICU transfer with IV methylprednisolone treatment was initiated on day 3 for involvement of 18% total body surface area and high SCORETEN of 7…. He subsequently was transferred to the burn unit at a nearby hospital, but the patient expired several days later.

We are investigating Padcev-induced TEN / SJS cases for patients who suffered these serious and sometimes fatal Padcev side effects as possible drug injury lawsuits to filed against Astellas Pharma US, Inc., the manufacturer of Padcev.

• people older than 65 years of age;
• people who are current or past smokers;
• people with other cardiovascular risk factors, such as diabetes or coronary artery disease;
• people with pre-existing cancer or malignancy risk factors.

About the Xeljanz risk of cardiovascular events, we find this important information in the October 2021 MHRA Xeljanz document:

Predictive factors for development of myocardial infarction (fatal and non-fatal) were identified using a multivariate Cox model with backward selection. These factors were age older than 65 years, male sex, current or past smoking, history of diabetes, and history of coronary artery disease (which includes past myocardial infarction, coronary heart disease, stable angina pectoris, or past coronary artery procedures).

And about the Xeljanz risk of cancers, that document provides this information:

Predictive factors for development of malignancies (excluding non-melanoma skin cancer) were identified using a multivariate Cox model with backward selection. These were age older than 65 years and current or past smoking.

We will watch for possible additional drug regulatory actions due to the Xeljanz risk of cardiovascular events as well as the Xeljanz risk of cancers, and report significant developments here.

Our law firm is handling Xeljanz drug injury lawsuits for patients with cases of Xeljanz causing heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as Xeljanz causing lymphoma, lung cancer, and other cancers.

[Chronic lymphocytic leukemia (CLL)] is a disease of the elderly. Real-world evaluations suggest many patients initiated on [Imbruvica (ibrutinib)] have significant comorbidities, many of them cardiovascular.

Hypertension — an important risk factor for the development of atrial fibrillation — may occur at a much higher rate in real-world practice settings than reported in clinical trials.

Patients should be monitored for the development of new or worsened hypertension, particularly early in the therapy course.

Second, we have a June 2021 report from ThePharmaLetter, “Imbruvica: new safety signal for use with rituximab and ACE inhibitors” about the European Medicines Agency (EMA) issuing a new safety signal for Imbruvica with rituximab:

As part of its advice on safety-related aspects to other European Medicines Agency committees, the Pharmacovigilance Risk Assessment Committee (PRAC) last week discussed a direct healthcare professional communication (DHPC) containing important safety information for Imbruvica (ibrutinib).

This DHPC aims to inform healthcare professionals about a new safety signal of sudden or cardiac death with Imbruvica when used in combination with rituximab and angiotensin-converting enzyme (ACE) inhibitors. The signal was recognized following a review of the findings of a clinical trial….

Third, and most recent, is a September 2021 MedPage Today news report, “Ibrutinib for CLL Tied to Higher Heart Risks vs Chemotherapy”, about there being increased risks for atrial fibrillation, bleeding, and heart failure seen in a Canadian cohort of patients using Imbruvica:

Use of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica) was linked with cardiovascular risks in patients with chronic lymphocytic leukemia (CLL), according to results of a population-based cohort study.

Over 3 years, the incidence of atrial fibrillation (AF)-related healthcare contact was 22.7% in patients treated with [Imbruvica (ibrutinib)] compared with 11.7% in patients who received chemotherapy, risk of hospital-diagnosed bleeding was 8.8% and 3.1%, respectively, and risk of heart failure (HF) was 7.7% and 3.6%, reported Husam Abdel-Qadir, MD, PhD, of Women’s College Hospital in Toronto, and colleagues.

We will continue to monitor the medical literature for more reports of heart-related Imbruvica side effects, as well as watch for possible regulatory action by the FDA or the EMA.

According to the FDA, as of September 2021 some of the generally recognized Xeljanz side effects and Xeljanz adverse events are:

Heart Attacks
Myocardial Infarction (MI)
Strokes — Ischemic / due to a blood clot
Deep Vein Thrombosis (DVT)
Pulmonary Embolism (PE)
Arterial Thrombosis
Lymphoma
Lung Cancer
Other Cancers
Death

We will continue to monitor the medical literature for developments regarding serious Xeljanz-related peripheral neuropathy and other Xeljanz adverse event reports.

At the present time, our law firm is investigating Xeljanz lawsuits filed against Pfizer, the pharmaceutical company responsible for Xeljanz, for patients with cases of Xeljanz causing heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as Xeljanz causing lymphoma, lung cancer, and other cancers. Please feel free to contact us if we can help you or someone you know with a Xeljanz drug injury case.

Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious skin reactions that can be life-threatening and even fatal. In people who have developed SJS), the more severe skin reaction TEN is diagnosed when more than 30% of the skin surface is affected and the moist linings of the body (mucous membranes) have extensive damage. Put otherwise, toxic epidermal necrolysis (TEN) is a severe form of Stevens-Johnson syndrome (SJS). And, significantly, TEN is such a serious skin reaction that it can be fatal, causing patient deaths in some situations.

In the initial Padcev drug label (“Revised: 12/2019”) there was a warning about general, low-level Padcev skin side effects in the Warnings and Precautions section at 5.4 Skin Reactions.

The first label change to add warnings for the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) came in March 2021. From the “Revised: 3/2021” Padcev drug label at 5.1 Skin Reactions:

Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

But only four months later, in July 2021, the FDA mandated increased warnings about the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), in the form of a so-called “Black Box” warning with the bolded title WARNING: SERIOUS SKIN REACTIONS

Our law firm is investigating cases for patients who have suffered the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) as possible drug injury lawsuits to be filed against Astellas Pharma US, Inc., the manufacturer of Padcev.

First, from the Abstract for this study report published in the September 1, 2021 edition of The Journal of Urology, “PD01-09 PATIENT PERCEPTION OF OCULAR RISK IN PENTOSAN POLYSULFATE USE FOR INTERSTITIAL CYSTITIS”:

• CONCLUSIONS: While the mechanism of maculopathy in [Elmiron] use is not fully understood, this risk must be weighed against its potential benefit as a treatment for interstitial cystitis. Physicians should counsel patients on risk of ocular complication in long term and high dose [Elmiron] use, and consider alternative therapies and early ophthalmologic referral in patients with lifetime cumulative doses [of Elmiron] greater than 500 g.

Second, from the Abstract for this study report published in the February 11, 2021 edition of the medical journal Clinical Ophthalmology, “Maculopathy Secondary to Pentosan Polysulfate Use: A Single-Center Experience”:

• Conclusion: A novel drug-induced maculopathy has been associated with [Elmiron] use with a distinct clinical constellation that can be accurately identified with multimodal imaging.

Of course, we will continue to monitor this still-emerging drug safety issue of Elmiron and maculopathy.

Our law firm is investigating possible Elmiron drug injury lawsuits for cases of an Elmiron vision side effect such as retinal pigmentary changes and pigmentary maculopathy resulting in vision loss.