Drug Safety Developments

Health Canada Issues Safety Review for Xeljanz in April 2021

Xeljanz May Be Linked to Serious Heart-Related Issues and Cancer

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

Health Canada has issued a safety review of Xeljanz and Xeljanz XR -- relatively new drugs commonly used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis -- due to a clinical trial that showed an increased risk of serious heart-related issues and cancers when taking these drugs.

According to an April 2021 alert from Health Canada, "Health Canada has initiated a safety review on Xeljanz and Xeljanz XR (tofacitinib), used to treat arthritis and ulcerative colitis", Health Canada is working with Pfizer, the drug manufacturer, to inform the public about new drug safety findings:

The clinical trial investigated the long-term safety of Xeljanz and Xeljanz XR (tofacitinib) at two doses (5 mg twice a day and 10 mg twice a day) in patients with rheumatoid arthritis, who are at least 50 years of age and have at least one cardiovascular risk factor. Pfizer, the manufacturer of the drug, conducted the trial in multiple countries, including Canada.

The current Canadian label includes serious warnings and precautions for cancer and information on heart attacks, which were the most frequently reported serious heart-related problems in this trial.

Health Canada has not authorized the sale of the higher dose of 10 mg twice a day for rheumatoid arthritis or psoriatic arthritis; this dose is only authorized for patients with ulcerative colitis who have not responded well to other medications. For patients with ulcerative colitis, the Canadian prescribing information recommends that they use the lowest effective dose possible to lower the risk of adverse reactions.

Individuals currently taking Xeljanz should continue to do so, and should not stop or change their dosage of Xeljanz without speaking to their healthcare professional first.

 

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This recent safety alert from Health Canada echoes concerns voiced by the Food and Drug Administration (FDA) in early February 2021.  In this Drug Injury Watch article, "Xeljanz FDA Drug Safety Communication in February 2021 Puts Heightened Scrutiny on Pfizer", we covered the FDA's plans on how to address the Xeljanz safety concerns:

In early February 2021 the FDA doubled-down on these two Xeljanz safety issues: (1) Xeljanz causing heart problems; and (2) Xeljanz causing cancer. This FDA Drug Safety Communication, "Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib)", provided the latest details about these "not-new" Xeljanz safety issues. And what I mean by this characterization is there was already a so-called Black Box Warning that points out reports of Xeljanz causing heart problems and Xeljanz causing cancer which was added to the Xeljanz drug label back in July 2019.

At that time, it was unclear what action the FDA was going to take regarding these concerns, and a February 4, 2021, MedPage Today news report, "No Xeljanz Plan Yet From FDA", reported the FDA was not yet prepared to take action.

Be assured that we will continue to follow this latest Xeljanz drug safety issue as well as watch for possible further FDA regulatory actions, including a possible Xeljanz recall.

 

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Long Term Elmiron Users Are At High Risk For Toxic Maculopathy

Nearly 20% Of Long Term Elmiron Users Diagnosed With Toxic Maculopathy

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

A recent March 2021 article "Update on maculopathy secondary to pentosan polysulfate toxicity" for the Current Opinion in Ophthalmology medical journal shows a strong link between Elmiron, a drug typically used to treat interstitial cystitis (also known as painful bladder syndrome), and toxic maculopathy.  Maculopathy can lead to retinal changes and vision loss.

According to the Abstract for this article, nearly 20% of long-term Elmiron users have been diagnosed with Elmiron-related maculopathy. There is also strong evidence for a correlation between cumulative dosing for Elmiron and the likelihood or severity of the maculopathy:

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%.

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Covered in our most recent March 2021 blog post, "Onset of Maculopathy Due to Elmiron Possible Years After Patients Stopped Use of Elmiron", it is recommended established maculopathy patients be questioned regarding any Elmiron use in the past. The "Update on maculopathy secondary to pentosan polysulfate toxicity" corroborates this recommendation due to the high rate of maculopathy incidences in patients with previous Elmiron use:

Reasonable evidence associates maculopathy with extended exposure to PPS [Elmiron (pentosan polysulfate)], with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS [Elmiron (pentosan polysulfate)] exposure, and patients with known exposure to PPS [Elmiron (pentosan polysulfate)] should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening.

As we have reported previously on our Elmiron Information Page, as well as in our previous blog post, "Onset of Maculopathy Due to Elmiron Possible Years After Patients Stopped Use of Elmiron", 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, even potentially years, before a medical doctor was able to diagnose their eye problem.

We are currently investigating possible Elmiron lawsuits for patients with past Elmiron use diagnosed with eye problems such as:

• Vision Loss / Blindness
• Maculopathy (retinal or pigmentation)
• Retinal Pigmentary Endothelium Injury (RPE)
• Pigmentation Maculitis
• Macular Degeneration (pigmentation or dry)

If we can be of assistance to you or someone else regarding an Elmiron vision loss case, you can send an email to Tom Lamb or you can call us on our toll-free number: 800-426-9535.

 

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Onset of Maculopathy Due to Elmiron Possible Years After Patients Stopped Use of Elmiron

New Medical Article About Elmiron-Related Vision Loss 3 Years After Elmiron Use

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

A November 2020 article, "Potential new onset clinically detectable pentosan polysulfate maculopathy years after drug cessation", shows new research that further supports the idea that Elmiron-related vision loss can occur years after ending the use of Elmiron.

According to the Abstract for this recent article published by the Retinal Cases & Brief Reports medical journal, a 44-year-old female demonstrated signs of vision loss related to her Elmiron use which had ended nearly three years prior to her suspected diagnosis of maculopathy due to Elmiron:

A 44-year-old female with a 435g cumulative exposure to [Elmiron (pentosan polysulfate sodium)] presented 38-months after drug cessation with six months of worsening metamorphopsia and prolonged dark adaptation. Fundus exam and multimodal fundus imaging demonstrated characteristic features of [Elmiron (pentosan polysulfate)] maculopathy, and molecular testing was unremarkable. In contrast, color fundus photos of the same patient acquired at an outside facility 25 months prior did not display features consistent with [Elmiron (pentosan polysulfate)] maculopathy.

These findings are significant, as it shows the duration of time between the time a patient has stopped using Elmiron and the onset of Elmiron-related vision loss may be much longer than initially thought. 

Additionally, as we have reported previously in our January 2021 blog post, "Elmiron Maculopathy Secondary to Pentosan Polysulfate (PPS) Toxicity: Medical Journal Article", it had been suggested that established maculopathy patients should be questioned regarding any Elmiron use in the past.  This seems incredibly important now, as the onset of Elmiron-related vision loss may take place years after a patient has stopped using Elmiron.

 

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As we have reported previously on our Elmiron Information Page, 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, now potentially years, before a medical doctor was able to diagnose their eye problem.

Our law firm is investigating possible Elmiron lawsuits for patients who have suffered vision loss due to Elmiron maculopathy. If we can be of assistance to you or someone else regarding an Elmiron vision loss case, you can send an email to Tom Lamb or you can call us on our toll-free number: 800-426-9535.

 

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Increased Risk of Myelodysplastic Syndrome and AML Associated with PARP Inhibitors

Alternative Options to PARP Inhibitors May Be Available

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

Recent studies of Poly (ADP-ribose) polymerase, or PARP, inhibitors shows this class of drug may be linked to an increased risk of secondary myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) in patients with cancer.

PARP inhibitors are used to treat several different types of cancers, including ovarian, breast, pancreatic, and prostate cancers.  PARP inhibitors work by stopping the PARP protein found in our cells from repairing the cells, essentially inhibiting cancer cells any further growth, and subsequently killing them off.

 

What The Studies Show

According to February 2021 article, "PARP inhibitors may increase risk for myelodysplastic syndrome, AML", recent studies show patients using PARP inhibitors are at nearly double the risk for developing MDS/AML compared to the placebo group:

According to results of the analysis, use of PARP inhibitors significantly increased risk for myelodysplastic syndrome and AML compared with placebo (OR = 2.63; 95% CI, 1.13-6.14).

The analysis of data from VigiBase showed 99 cases of myelodysplastic syndrome and 79 cases of AML associated with PARP inhibitor use.

Among 96 patients with available data, median treatment duration was 9.8 months (interquartile range [IQR], 3.6-17.4), and among 58 patients with available data, median latency period since first exposure to a PARP inhibitor was 17.8 months (IQR, 8.4-29.2). Researchers observed a high rate of mortality (45%) among 104 patients with reported outcomes. Cytopenia was co-reported in 71 (40%) of the 178 cases of myelodysplastic syndrome or AML, of which anemia was most frequent type (34%).

The study included PARP inhibitor drugs such as Lynparza (olaparib), Zejula (veliparib), Rubraca (rucaparib) and ABT-888 (veliparib).  Researchers acknowledge the number of MDS/AML incidences in correlation with PARP inhibitors may be underestimated in the study, and further research is needed to confirm the results.

 

PARP Inhibitors Not The Only Option for Cancer Treatment

Interestingly, PARP inhibitors are not the only class of drug available for treatment of cancer patients.  As we have reported in earlier articles, Vascular Endothelial Growth Factor (VEGF inhibitors) and immune checkpoint inhibitors have also been used "off-label" for treatment of cancer patients.

In our August 2020 article, "Vascular Endothelial Growth Factor (VEGF) Inhibitors: Increased Risk Of Aneurysm And Artery Dissection", we address the risks associated with VEGF inhibitors, such as aneurysm and artery dissection.  VEGF inhibitors include drugs such as Avastin (bevacizumab), Iclusig (ponatinib), Ofev (nintedanib), and many others.  You can find a more comprehensive list of VEGF inhibitors in our previously mentioned August 2020 article.

We will continue to monitor the safety profiles for these PARP inhibitors, including whether the FDA mandates any label changes which add warnings about an increased risk of MDS/AML.

 

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Imbruvica's Cardiotoxicity Claims Furthered by Recent Chronic Lymphocytic Leukemia Study

Could Lower Dose of Imbruvica Help Mitigate Adverse Events?

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

Imbruvica (ibrutinib) has been associated with cardiotoxic properties, and in some cases, even death.  A recent November 2020 article, "Ibrutinib’s Cardiotoxicity - An Opportunity for Postmarketing Regulation” published in JAMA Oncology, highlights a study of chronic lymphocytic leukemia (CLL) in relation to Imbruvica.  The study found a significant increase in death rate for those using Imbruvica when compared to the controlled factor:

This drug is known to have cardiotoxic properties, probably due to off-target inhibition of another kinase. While in randomized trials ibrutinib [Imbruvica] has been demonstrated to increase survival, some studies have demonstrated fatal toxic effects associated with the drug. This was most obvious in a 3-arm study of CLL in which the 2 ibrutinib [Imbruvica] arms were associated with a 7% rate of death during treatment or within 30 days after treatment cessation, compared with a 1% rate of death in the control arm.

Similar toxicity reports have been found in another Bruton tyrosine kinase (BTK) inhibitor drug, Calquence (acalabrutinib), although the labeling for this drug does include a warning regarding the risk of atrial fibrillation and flutter.  Another study conducted by the World Health Organization (WHO), and analyzed by the Food and Drug Administration (FDA) reviews the 303 Imbruvica deaths and their causes from 2015-2017:

This analysis included 13,572 reports involving ibrutinib [Imbruvica] as of January 2018, primarily in patients receiving treatment for CLL. More than 97% of the events were from 2015-2017 and included 303 ibrutinib [Imbruvica] associated deaths. Of total deaths, 103 were due to arrhythmias, and 90 were due to central nervous system hemorrhage. Conduction disorders (mainly high-grade atrioventricular block) were also notable.

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Could Lowering Imbruvica's Recommended Dosage Impact Adverse Events?

Some discussion has occurred over whether a lower dosage of Imbruvica would have any affect on the adverse events and deaths associated with the drug. According to the same November 2020 article, "Ibrutinib’s Cardiotoxicity - An Opportunity for Postmarketing Regulation”:

In analyzing the original application, the FDA reviewers included the following comment to the sponsor: “We recommend you evaluate lower doses in future clinical development as data from the phase 1 trial PCYC-04753 showed that maximum BTK occupancy and maximum response were achieved at doses of 2.5mg/kg.”

Furthermore, a 2019 study reiterated the need for a lower dosage of Imbruvica:

A 2019 preclinical study that tested the effects of ibrutinib [Imbruvica] on stem cell–derived cardiomyocytes differentiated into “atrial-like” cardiomyocytes found that ibrutinib [Imbruvica] caused a dose-dependent decrease in action potential duration and cardiomyocyte viability that was associated with an increase in calcium transient duration. These preclinical results are consistent with recent evidence regarding the serious cardiac adverse events associated with ibrutinib [Imbruvica] use.

However, no further studies have been performed by the manufacturer, despite FDA recommendations for additional testing of Imbruvica at lower doses.  Due to a lack of data on the effects of Imbruvica dosage and the role it plays in the adverse events cause by the drug, it is currently unclear if the lower dose would have an impact, and susceptible patients may still have an adverse reaction, despite taking Imbruvica at a lower dose.

We will continue to monitor the drug safety profile of Imbruvica and report significant developments, including any additional Imbruvica drug label changes, here.

 

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Xeljanz Safety Trial Results Which May Lead to Xeljanz Recall

Other JAK Inhibitors May Be Negatively Affected by Xeljanz Study Results, Too

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

On February 5, 2021, we reported on a potential upcoming Xeljanz recall following a Drug Safety Communication from the U.S. Food and Drug Administration (FDA) regarding new evidence about Xeljanz adverse events in our article, "Will There Be a Xeljanz Recall in the Future?".  We will now provide you with a more in-depth look into the results of the Xeljanz safety trial, or Xeljanz study, that prompted the February 2021 FDA Drug Safety Communication about Xeljanz.

 

Xeljanz Study Results 

On Wednesday, January 27, 2021, Pfizer announced the results from the FDA-mandated Xeljanz safety trial.  This Xeljanz study was composed of a randomized group of 4,362 patients who all had at least one cardiovascular risk factor and were taking either a 5 or 10 mg/day dosage of Xeljanz or a tumor necrosis factor (TNF) inhibitor.  The study found patients taking Xeljanz showed significantly higher rates of adjudicated malignancies when compared with patients taking TNF inhibitors.  Similarly, those taking Xeljanz saw significantly higher rates of major adverse cardiovascular events (MACE) compared to TNF inhibitors. 

According to January 27, 2021 article, "JAK Inhibitor Mises Endpoint in Safety Study. Now What?":

Adverse events were pooled for the two [Xeljanz (tofacitinib)] doses for evaluating the primary endpoints. Incidence rates for MACE were slightly higher with the 10-mg versus 5-mg dose (10.5 vs 9.1 per 1,000 person-years); rates of malignancies did not differ between dosages. Following a signal for increased risk of pulmonary embolism and mortality at the higher dose, patients in the 10-mg arm were moved to the 5-mg dose in early 2019.

Cancer and MACE safety signals had been noted in the drug's clinical trials and later postmarketing reports, leading to cautions on tofacitinib's label, including boxed warning about increased mortality, thrombosis, and lymphoma and other malignancies.

While the complete analysis of the Xeljanz study conducted by Pfizer has not yet been published, the company reports they are working with the FDA to review the Xeljanz safety trial results as they become available.  It is expected the results of the study will yield further data on Xeljanz and pulmonary embolism, mortality, and comparative effectiveness.

Xeljanz is classified as a JAK inhibitor, which works by blocking Janus kinases (JAKs), which is an enzyme that regulates immune cells.  This allows for Xeljanz to fight inflammatory diseases such as rheumatoid arthritis and ulcerative colitis.  Recent studies like the Pfizer report on Xeljanz look into the concern JAK inhibitors may impair the body's ability to fight off dangerous microbes or cancer.

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How Xeljanz Fares Against TNF Inhibitors and Other JAK Inhibitors

According to January 27, 2021 article, "Safety finding weighs on Pfizer's inflammation drug, and could spell trouble for others", the results of the Xeljanz study could have impacts on other JAK inhibitors, and even TNF inhibitors:

Results show that among Xeljanz-treated patients, 98, or 3.37%, had a major cardiovascular event sometime between when they started treatment to 60 days after they stopped. In the TNF group, 37, or 2.55%, experienced such an event. Malignancies, excluding non-melanoma skin cancer, were seen in 122, or 4.19%, of patients given Xeljanz and 42, or 2.89%, of patients given a TNF inhibitor. With regard to Xeljanz, Pfizer said heart attack and lung cancer were the most frequently reported major cardiovascular events and malignancies, again excluding non-melanoma skin cancer.

Other JAK inhibitors since Xeljanz have also been approved for use by the FDA, though some of them also carry Black Box Warnings about infections, thrombosis, and cancer risk.

According to January 27, 2021 article, "Pfizer's big blockbuster Xeljanz flunks its post-marketing safety study, renewing harsh questions for JAK class", Xeljanz may not fare well against TNF inhibitors:

And on Wednesday, Pfizer announced that the six-year study 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.

However, overall it seems we do not have enough data to come to a conclusion about a possible Xeljanz recall or other JAK inhibitors recalls.  According to the same January 27, 2021 article, "Pfizer's big blockbuster Xeljanz flunks its post-marketing safety study, renewing harsh questions for JAK class":

It’s also not yet clear how the new findings will impact JAK inhibitors more broadly. In a note to investors, RBC’s Brian Abrahams said physicians already take safety issues into account when considering JAK inhibitors, but that the new data could make the FDA “even more risk-averse on labeling for the class going forward.” That could impact Incyte as they await the FDA’s decision on a topical formulation for Jakafi, one of the only JAK inhibitors that does not yet have a black box warning.

 

Current FDA Recommendations

Although the FDA has released a safety alert warning patients about the associated risks of Xeljanz, physicians are currently still recommended to continue to follow the recommendations listed in the drug's prescribing information.  Patients are advised not to discontinue Xeljanz use without first consulting their physician.

According to February 2, 2021 article, "FDA warns of increased risk for heart-related issues, cancer linked to Xeljanz", Pfizer is committed to a continued review of results from the recent Xeljanz study:

“Providing information on the safe and effective use of our medicines is imperative,” Tamas Koncz, MD, PhD, chief medical officer for Inflammation and Immunology at Pfizer, said in a company release. “We believe that extensive additional analyses of these study data, and communicating them as soon as possible, will further clarify the benefit and risk profile of tofacitinib to help inform medical decision-making and patient care.”

The FDA is currently recommending health care providers report any adverse events related to Xeljanz to the FDA's MedWatch Safety Information and Adverse Events Reporting Program.

 

Be assured that we will continue to follow this latest Xeljanz drug safety issue as well as watch for possible further FDA regulatory actions, including a possible Xeljanz recall.

 

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Will There Be a Xeljanz Recall in the Future?

FDA Issues New Safety Alert for Serious Heart-Related Problems and Cancer

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

A possible Xeljanz recall may be on the horizon following the release of a February 4, 2021, Drug Safety Communication from the U.S. Food and Drug Administration (FDA) regarding new evidence about Xeljanz adverse events.  This FDA Xeljanz safety alert was issued following the recent release of findings from a safety clinical trial that shows an increased risk of serious heart-related problems and cancer being associated with Xeljanz.

 

Summary of Xeljanz History

In 2012 Xeljanz was approved by the FDA to treat adults with rheumatoid arthritis, and in 2017 the drug was approved by the FDA to treat psoriatic arthritis.  Shortly thereafter, in 2018, the drug was approved by the FDA to treat ulcerative colitis.

By February 2019 through July 2019, safety clinical trials conducted by Xeljanz manufacturer, Pfizer, began to show an increased risk of blood clots and death when taking the drug at a higher dosage of 10mg twice daily.  Patients included in the study were at least 50 years old, and were required to have at least one cardiovascular risk factor.

We reported on the risks of Xeljanz at the higher dosage on our Drug Injury Watch blog in a February 2019 article, "Xeljanz Recommended Dosage For Ulcerative Colitis Patients May Increase Risk Of Pulmonary Embolism":

There appears to be a somewhat "under the radar" drug-safety issue with the 10 mg twice daily recommended dosage of Xeljanz for patients with ulcerative colitis (UC), according to this February 20, 2019 article, "FDA cites an ‘ongoing review’ for Pfizer’s blockbuster Xeljanz, with implications for the class", published by Endpoint News [free subscription required]. 

Given the results of those 2019 safety clinical trials, the FDA mandated a Black Box Warning label for Xeljanz, in part cautioning doctors about the increased risk of blood clots and death associated with Xeljanz.

According to this February 4, 2021, FDA Drug Safety Communication, "Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib)", while the recent safety clinical trial is complete, the FDA is awaiting additional results:

The clinical trial is now complete and initial results show a higher occurrence of serious heart-related events and cancer in RA patients treated with both doses of tofacitinib compared to patients treated with a TNF inhibitor. FDA is awaiting additional results from the trial.

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Plans for a Xeljanz Recall in the Near Future?

The February 2021 Drug Safety Communication about Xeljanz and its association with heart-related problems as well cancer risks is very concerning because it comes on top of the 2019 Xeljanz Black Box Warning.  However, the FDA reportedly will await further information before making any additional Xeljanz label changes or take any other regulatory actions.

According to this February 4, 2021 news report, "No Xeljanz Plan Yet From FDA", it is possible that a Xeljanz recall may be coming in the future, but as of now the FDA is not ready to take action:

But the FDA is not yet prepared to take action, which could include ordering new label language, requiring a risk evaluation and mitigation strategy (REMS), or even pulling the drug from the market [i.e., a Xeljanz recall.]

For now, the agency is content with "alerting the public that preliminary results from a safety clinical trial show an increased risk of serious heart-related problems and cancer" relative to tumor necrosis factor (TNF) inhibitors.

Since the analysis of the clinical trials is not yet complete, the FDA has reported it will evaluate the results once received and will communicate its final conclusions and recommendations once the review has been completed.

In the same MedPage Today report, "No Xeljanz Plan Yet From FDA", the Black Box Warning is referenced yet again, though there is no mention of when, or even if, a Xeljanz recall will occur:

[Xeljanz (tofacitinib)] and two other JAK inhibitors already carry boxed warnings about increased mortality, thrombosis, and lymphoma and other malignancies. These were mandated after clinical trials showed numerically higher rates of these events with the drug versus placebo or other comparators. The FDA also ordered a dedicated safety study for [Xeljanz (tofacitinib)] to better understand the risks; it did the same for one of the other JAK inhibitors, baricitinib (Olumiant). It did not do so for the third, upadacitinib (Rinvoq).

Under a REMS, drugmakers might be ordered to provide training for prescribers about the risks, develop special educational materials for patients, and/or require patients to certify they received the materials and understand them.

 

Current Recommendations from the FDA

According to February 2021 Xeljanz Drug Safety Communication issued by the FDA, "Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib)", the current recommendations for Xeljanz are as follows:

Patients should not stop taking [Xeljanz (tofacitinib)] without first consulting with your health care professionals, as doing so may worsen your condition. Talk to your health care professionals if you have any questions or concerns.

Health care professionals should consider the benefits and risks of [Xeljanz (tofacitinib)] when deciding whether to prescribe or continue patients on the medicine. Continue to follow the recommendations in the [Xeljanz (tofacitinib)] prescribing information.

Be assured that we will continue to follow this latest Xeljanz drug safety issue as well as watch for possible further FDA regulatory actions, including a possible Xeljanz recall.

 

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Boston Children's Hospital Offers Alternatives to MiraLAX for Constipation Treatment

MiraLAX Has Been Associated With Neuropsychiatric Problems in Children

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

For the past few years, we have reported on the popular over-the-counter constipation drug MiraLAX, and its adverse side effects in children. While the Food and Drug Administration (FDA) continues to fund research for a potential connection between the two, few advancements have been made in the research.

 

MiraLAX Overview

While many pediatricians have recommended parents use MiraLAX to treat chronic childhood constipation, the drug has yet to be approved by the FDA for use in children.  However, the drug quickly became a topic of discussion amongst parents, as many parents report behavioral and neurological issues in their children that they claim stem from the child's use of MiraLAX.

MiraLAX is typically mixed with eight ounces of water and is meant to be used one to two times daily to treat constipation.  Some individuals notice common side effects, such as loose bowel movements, bloating or nausea, although these side effects typically improve with a dosing adjustment.

 

Boston Children's Hospital Makes Recommendations to MiraLAX Alternatives

The Boston Children's Hospital offers alternatives to MiraLAX, claiming the drug is simply one of the many options when treating chronic childhood constipation.  According to the hospital, lifestyle modification should be the first form of treatment.  This includes increased hydration, high-fiber diets and regular exercise.

According to the Boston Children's Hospital's page entitled, "Division of Gastroenterology, Hepatology and Nutrition - MiraLAX and Other Options for Treating Constipation", other medication alternatives to MiraLAX are also available for constipation treatment:

When lifestyle modifications have been exhausted, medication options for treating constipation include:

• MiraLAX
• lactulose (a non-absorbable sugar)
• magnesium hydroxide (aka Milk of Magnesia)
• senna (an herbal extract that stimulates bowel motions)
• mineral oil 

The hospital stresses these products should only be used if recommended by a trained healthcare professional.

 

Additional Information and Sources

While few advancements have been made in terms of PEG 3350 research in relation to MiraLAX use by children, parents and other family members may find comfort in joining the Facebook group "Parents Against MiraLAX".  Additionally, you may want to consider referring to our February 2020 article, "MiraLAX: The Quest to Get Answers from the FDA"  for more information of past PEG 3350 studies.

As always, we will continue to monitor the issues surrounding MiraLAX and will provide you with any new or relevant information. Please feel free to share any relevant information with us, as well.

 

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Gilenya Associated with Cases of Liver Injury, Including Acute Hepatic Failure Requiring Liver Transplant

January 2021 Drug Safety Update for Gilenya Issued by Medicines and Healthcare products Regulatory Agency

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

Gilenya, a medication used to treat different forms of multiple sclerosis (MS), has updated its advice about the risks of serious liver injury and herpes meningoencephalitis in the UK.  According to a January 2021 Drug Safety Alert issued by the UK's Medicines and Healthcare products Regulatory Agency (MHRA), "Fingolimod (Gilenya▼): updated advice about the risks of serious liver injury and herpes meningoencephalitis", serious and some fatal cases of liver injury, including acute hepatic failure requiring liver transplant have been associated with Gilenya:

A recent European review of safety data identified 7 cases of clinically significant liver injury that developed between 10 days and 5 years after the start of fingolimod treatment, including 3 post-marketing reports of acute hepatic failure requiring liver transplantation. Liver samples showed submassive hepatic necrosis in 2 patients, and one of these samples also contained features of acute hepatitis.

This January 2021 safety update comes after the European Medicines Agency released a review of Gilenya safety data in November 2020, as discussed in our recent blog post, "Gilenya Safety Alert November 2020: Cases of Acute Liver Failure Requiring Liver Transplant".

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According to January 2021 Gilenya MHRA alert, the current advice for healthcare professionals is to monitor liver function tests routinely, both before, during, and after treatment with Gilenya.  Additionally, the article provides advice both for patients exhibiting signs of liver injury, and those without signs of liver injury:

• in patients without signs and symptoms of liver injury, the updated advice is:
  • monitor liver function tests more frequently if serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels exceed 3-times the upper limit of normal (ULN) but less than 5-times ULN with a normal bilirubin level
  • discontinue fingolimod if ALT or AST levels exceed 5-times ULN or if they are at least 3-times the ULN and bilirubin is increased – fingolimod may be re-started following a careful benefit-risk assessment of the underlying cause when serum levels have returned to normal
• in patients with symptoms or signs of hepatic dysfunction:
  • check liver function tests urgently
  • discontinue fingolimod if significant hepatic injury is confirmed; further treatment with fingolimod may be considered following recovery only if an alternative cause of hepatic dysfunction is established

We will continue to monitor the Gilenya safety profile with special attention to cases of Gilenya-related liver failure following drug-induced liver injury associated with Gilenya.

 

Drug Injury Watch: Side Effects News & Reports

Drug Injury Law: Medical & Legal Information

Pre-existing Eye Conditions Linked to Beovu-related Adverse Events

Case Study Further Supports Link Between Beovu and Adverse Events

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

Novartis has recently identified patients with pre-existing eye conditions prior to being treated with Beovu as being at higher risk of potentially suffering from vision-threatening adverse events caused by the drug in a recent review. The discovery comes following a February 2020 warning issued by the American Society of Retinal Specialists warning patients of severe vision loss linked to the use of Beovu.

 

What the Novartis Review Found

In the review issued by Novartis, the main risk of experiencing vision-altering side effects such as retinal vasculitis and/or retinal vascular occlusion within the six months after the first administration of Beovu was prior intraocular inflammation and/or vascular occlusion in the year prior to the first injection of Beovu.

In more detail, according to this November 14, 2020, Reuters article, "Novartis identifies possible risk factors for Beovu patients":

The observed overall risk rate of 0.46% for all Beovu-treated patients increased to 3.97% in people who had the conditions before treatment, Novartis said.

Around the world, drug regulators are approving updated safety guidelines aimed at identifying ways to prevent severe vision loss when using Beovu. Novartis continues to uphold its position that Beovu is a valuable and important treatment option for patients with wet AMD, with an overall favorable benefit/risk profile.

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Beovu Case Study: Adverse Events Related to Beovu Injection

As mentioned previously, Beovu has been related to cases of retinal vasculitis and severe vision loss, especially with patients who have a medical history of retinal vasculitis and/or retinal vascular occlusion.  A case study published in the American Journal of Ophthalmology Case Reports in December 2020 outlines the complications a 76-year old had following her Beovu injections.

Approximately one week following her third administration of Beovu, the woman experienced pain, decreased vision, and increased floaters. One month after her last Beovu injection, the patient was switched to Lucentis, a drug also aimed at treating wet AMD. Three weeks following the switch in medication, the patient experienced several adverse side effects including photophobia, pain, and decreased vision. 

According to the December 2020 American Journal of Ophthalmology Case Reports article, "Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: A clinicopathologic case study", several adverse side effects were reported:

Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200....

Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers.

Additionally, in the same article, it was concluded the adverse events were in relation to Beovu, with no mention of Lucentis causing the vision-related issues:

Treatment with brolucizumab [Beovu] can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.

 

For a complete list of side effects or more information on Beovu, please visit our Beovu Drug Information Page. 

We will continue to monitor the issues surrounding Beovu and provide you with any new or relevant information.  Please feel free to share any information with us as well.

 

Drug Injury Watch: Side Effects News & Reports

Drug Injury Law: Medical & Legal Information