Side Effects Blog

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.

As regards the pigmentary maculopathy Elmiron side effect, the new Elmiron Medication Guide includes the following:

Changes in the retina of the eye (pigmentary maculopathy). Taking ELMIRON may be associated with pigment changes in the retina of the eye that may continue even after stopping treatment with ELMIRON. Tell your healthcare provider including your eye doctor right away if you have any vision changes including any of these symptoms:

• difficulty reading
• your vision takes longer to adjust to low or reduced light
• blurred vision

Throughout your treatment, regular eye examinations that include retinal examinations are suggested for early detection of retinal/macular changes….

As we have stated previously, the June 2020 Elmiron label change that finally added warnings concerning vision problems such as retinal pigmentary changes and pigmentary maculopathy was overdue from our perspective. Accordingly, there have been Elmiron lawsuits filed by patients who have suffered vision loss against the pharmaceutical companies responsible for Elmiron.

We are currently investigating possible Elmiron lawsuits for patients with past Elmiron use diagnosed with retinal pigmentary eye problems such as the pigmentary maculopathy Elmiron side effect.

If we can be of assistance to you or someone you know with Elmiron-related eye damage, you can send an email to Tom Lamb or you can call us on our toll-free number: 800-426-9535. Or, if you prefer, simply submit an online Elmiron Case Evaluation Form — it is free, confidential, and there is no obligation.

(1) We started investigating these Beovu eye problems soon after the American Society of Retinal Specialists (ASRS) issued a Beovu drug safety alert to its members in February 2020. In fact, our February 27, 2020 article, “Beovu Side Effects Include Retinal Vasculitis, Eye Inflammation: Safety Issues For Macular Degeneration Drug“, was one of the first articles written about these Beovu eye problems.

(2) During the past 13 months — from February 2020 to March 2021 — we have closely monitored this Beovu drug safety issue and written many more articles about the circumstances surrounding various Beovu eye injection reactions causing vision loss and blindness such as:

• Retinal Vasculitis
• Occlusive Retinal Vasculitis
• Retinal Artery Occlusion
• Retinal Vascular Occlusion

(3) The first three Beovu vision loss lawsuits filed in the US were for clients of our law firm. Each of those three women had their Beovu lawsuit filed as an individual case. The basic liability allegations in those Beovu lawsuits, as well as other Beovu cases concerning Beovu eye problems, are:

• Novartis misrepresented that Beovu was a safe treatment for age-related macular degeneration; and,
• Novartis failed to warn about Beovu eye injection reactions causing vision loss and blindness.

If we can be of assistance to you or someone else regarding a possible Beovu lawsuit for vision loss or blindness due to Beovu eye injection reactions, you can submit a Beovu Case Evaluation Form online or you can call us on our toll-free number: 800-426-9535.

Again, we point out the important fact that these Beovu vision loss lawsuits are filed as individual cases. There will not be any Beovu class actions for Beovu eye problems. As such, people with Beovu eye injection reactions must contact a lawyer or law firm to have their Beovu lawsuit filed so they can get legal compensation from Novartis for their Beovu drug injury.

We respectfully suggest those people should contact our law firm for the 3 reasons set forth above.

The article, “Pentosan Polysulfate and Vision: Findings from an International Survey of Exposed Individuals”, was published in December 2020 by the Retina medical journal. From the Abstract for this article we get these facts about high levels of Elmiron use:

Purpose: To investigate patient-reported visual function in individuals taking [Elmiron (pentosan polysulfate sodium, or PPS)] for interstitial cystitis.

Results: … Respondents in the highest [Elmiron (pentosan polysulfate sodium, or PPS)] exposure tertile were more likely to report difficulty with reading small print (adjusted OR 2.29, 95%CI 1.15-4.57) and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted OR 2.41, 95%CI 1.44-4.03) than unexposed respondents.

It is important to know that a patient does not have to have current Elmiron use right up until the time when their pigmentary maculopathy or macular degeneration is diagnosed in order for those conditions to be considered Elmiron-related eye damage.

We are currently investigating possible Elmiron lawsuits for patients with past Elmiron use diagnosed with pigmentary maculopathy or macular degeneration.

If we can be of assistance to you or someone you know with Elmiron-related eye damage, you can submit an online Elmiron Case Evaluation Form or you can call us on our toll-free number: 800-426-9535.

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)”, announce the new Xeljanz warnings. It is the ORAL Surveillance Xeljanz safety trial data that is the basis for those new Xeljanz warnings as well as some Xeljanz drug safety alerts issued by the FDA during the past few years.

For some commentary on this Xeljanz safety trial, which started in March 2104 and was completed in July 2020, we go to this February 16, 2021, Healio Rheumatology article, “‘We need to see the data’: FDA’s Xeljanz safety warning stirs concerns for JAK inhibitors”:

[Stanley Cohen, MD, clinical professor in the department of internal medicine at the University of Texas Southwestern Medical School, and medical codirector of the Metroplex Clinical Research Center, told Healio Rheumatology] the fact that ORAL Surveillance was a head-to-head trial suggests there is “certainly a signal” for major cardiovascular events and cancer with [Xeljanz (tofacitinib)].

“I do think these results are serious,” Cohen said. “I think it’s something we have to look at critically, and again, with just the topline — what can you say? We need to look at all the data and better understand the data.

As mentioned above, the February 2021 FDA safety alert about Xeljanz having increased risks for serious heart-related problems and cancers raises the issue of whether all JAK inhibitors share these side effect risks:

According to Cohen, Pfizer’s results with Xeljanz indicate that other companies that produce JAK inhibitors should likely go back and examine their clinical trial programs, selecting out those patients with the same risk factors to see if there was any imbalance in MACE or malignancies.

As such, besides just watching for more data from the Xeljanz safety trial showing an increased risk of serious heart-related problems and cancer associated with Xeljanz, we will look for any indication that the new Xeljanz warnings might be added to Olumiant and Rinvoq, also.

As to what the FDA did not say in that 2021 Xeljanz FDA Drug Safety Communication — but what seems to be indicated by this latest Xeljanz FDA action — we refer you to this February 4, 2021, MedPage Today news report, “No Xeljanz Plan Yet From FDA”:

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.

For the time being, at least, it appears that Pfizer is not inclined to withdraw Xeljanz from the market given that there was a Xeljanz television advertisement that ran in my part of the country during the national nightly news a couple of days after this “new” 2021 FDA drug safety alert about Xeljanz side effects was issued.

One wonders how the FDA might react to this “direct to consumer” advertisement for Xeljanz which Pfizer was still running after the February 2021 FDA Xeljanz Drug Safety Communication about Xeljanz causing heart problems and Xeljanz causing cancer.

It seems within the realm of possibility that the FDA may mandate a Xeljanz recall in the future, but this remains to be seen.

Of course, we will be vigilant as, with the FDA, we wait for “further information” from the safety clinical trial showing an increased risk of serious heart-related problems and cancer associated with Xeljanz.