Drug Injury Watch

Beovu Drug Label Change in December 2021 Adds More Information About Vision Loss Side Effects

Provides "risk factors and possible mechanism" for Beovu-related Retinal Vasculitis and Retinal Vascular Occlusion

 

(Posted by Tom Lamb at Drug Injury Watch)

 

We have finally seen the first Beovu drug label change which had been anticipated since Novartis said in May 2021 that the company "will pursue an update to the Beovu prescribing information globally."  As previewed in a Novartis November 2021 "Dear Doctor" letter about Beovu and announced in an MHRA January 2022 Drug Safety Update item for Beovu, there is a revised Beovu Product Information document ("Date of revision of the text: 08 December 2021").  This Beovu drug label change reflects additional information about Beovu vision loss side effects such as intraocular inflammation, including retinal vasculitis and retinal vascular occlusion. We point out, however, that as of this time a similar Beovu drug label change has not been issued by Novartis in the US, yet.

From this Drug Safety Update, "Brolucizumab (Beovu▼): risk of intraocular inflammation and retinal vascular occlusion increased with short dosing intervals", issued January 18, 2022, by the UK's Medicines and Healthcare products Regulatory Agency (MHRA), we get the following:

New information on [the Beovu adverse events retinal vasculitis and retinal vascular occlusion], including risk factors and possible mechanism, was considered in a recent European safety review and ophthalmologists were informed of the new recommendations in a letter in November 2021. The product information of [Beovu (brolucizumab)] will also be updated to reflect this information.

Here are some details about the "risk factors" for those Beovu vision loss side effects from the so-called "Dear Doctor" letter about Beovu that Novartis UK sent on November 2, 2021, to healthcare professionals in the UK:

Risk factors identified

Novartis conducted non‐interventional retrospective real‐world evidence studies in patients with neovascular (wet) age‐related macular degeneration (nAMD) to better understand the incidence of adverse events/safety signal after initiating treatment with [Beovu (brolucizumab)] for up to 6 months. Each of the two studies consisted of retrospective analysis of large United States real‐world databases, the IRIS Registry® [Study HEORUSV201342] and Komodo Healthcare Map™ [Study HEORUSV201368], respectively. Both assessments were conducted in parallel and were nearly identical to the extent the data permitted.

The results of this retrospective analysis in nAMD patients suggest that patients with a medical history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with [Beovu (brolucizumab)] were more likely to present with similar events after [Beovu (brolucizumab)] injection, as compared to nAMD patients with no history of these events.

In addition, a gender difference with a higher risk for IOI (including RV) and/or RO in females has been observed in the two retrospective studies but also in clinical trials. A higher incidence was also observed in Japanese patients.

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And here is some information about the "possible mechanism" for those Beovu vision loss side effects from that same November 2021 Beovu "Dear Doctor" letter:

Immune‐mediated event

Results of the mechanistic study BASICHR0049 based on an analysis of blood samples from five nAMD patients exposed to [Beovu (brolucizumab)] who subsequently developed retinal vasculitis (RV) and/or retinal vascular occlusion (RO), taken together with accumulated data regarding the association of treatment‐emergent immunogenicity and intraocular inflammation (IOI), indicate a causal link between the treatment‐emergent immune reaction against [Beovu (brolucizumab)] and [Beovu-related] “retinal vasculitis and/or retinal vascular occlusion, typically in presence of IOI”.

In this study, blood samples were collected from the five case patients [retinal vasculitis (RV) and/or retinal vascular occlusion(RO)]and from six control patients who had no signs/symptoms of IOI while still receiving [Beovu (brolucizumab)] treatment....

... In the samples from five patients who experienced the RV and/or RO adverse events a humoral and cellular immune response against [Beovu (brolucizumab)] was identified 3‐5 months after the last [Beovu (brolucizumab)] dose and occurrence of the event. Data showed the presence of high titre ADAs, with a polyclonal and diverse IgG‐driven response against multiple B cell epitopes on the [Beovu (brolucizumab)] molecule, as well as memory T cell activation induced by unstressed and heat‐ or mechanically‐stressed [Beovu (brolucizumab)] preparations.

In the samples from patients from the control group, ADAs, when present, had lower titres.

We expect that a similar Beovu drug label change, and a possible associated Beovu "Dear Doctor" letter, will be issued by Novartis here in the US soon.

Be assured we will continue to monitor the drug safety regulatory sector for further developments regarding Beovu vision loss side effects such as intraocular inflammation, retinal vasculitis, and retinal vascular occlusion.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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Xeljanz Risks of Cardiovascular Events, as Well as Cancers, Cause More Xeljanz Use Limitations

October 2021 UK's MHRA Xeljanz Action Follows September 2021 FDA Xeljanz Drug Safety Communication Update

 

(Posted by Tom Lamb at Drug Injury Watch)

 

On September 1, 2021, we posted this article, "Xeljanz: FDA Warnings Updated: There are Higher Rates of Blood Clots and Deaths for Both Doses of Xeljanz, Now", in which we listed the five Drug Injury Watch articles we wrote earlier in 2021 about Xeljanz drug safety developments. Now we are covering the latest drug regulatory action taken due to the Xeljanz risk of cardiovascular events as well as the Xeljanz risk of cancers, or malignancies, this one by the UK's Medicines and Healthcare products Regulatory Agency (MHRA).

This Drug Safety Update document, "Tofacitinib (Xeljanz▼): new measures to minimise risk of major adverse cardiovascular events and malignancies", issued by the MHRA on October 6, 2021, states that Xeljanz should not be used by these patients in the groups identified below unless there is no suitable drug treatment alternative:

• 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.

As regards the Xeljanz side effects findings underlying these new Xeljanz use limitations, from the Safety Review part of this October 2021 MHRA Xeljanz document:

Study ORAL Surveillance (A3921133) was a large, randomised, active-controlled, clinical safety trial to evaluate the safety of tofacitinib versus tumour necrosis factor (TNF)-alpha inhibitors....

The co-primary endpoints of study A3921133 were adjudicated major adverse cardiac events and adjudicated malignancies (with the analysis excluding non-melanoma skin cancer)....

In 2021, final results from study A3921133 showed tofacitinib to be associated with an increased incidence of non-fatal myocardial infarction and malignancies, particularly lung cancer and lymphoma.

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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. Feel free to send me an email if we can be of assistance to you or someone you know.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Products Recall: Philips Bi-Level PAP, CPAP, and Mechanical Ventilator Devices Using PE-PUR Sound Abatement Foam

For Patients with Polyester-based Polyurethane (PE-PUR) Exposures, Potential Health Risks Include Cancers and Organ Failures

 

(Posted by Tom Lamb at Drug Injury Watch)

 

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UPDATE: On June 30, 2021 the FDA issued this document to alert and inform patients, "Certain Philips Respironics Ventilators, BiPAP, and CPAP Machines Recalled Due to Potential Health Risks: FDA Safety Communication", which listed the Philips Respironics ventilators, BiPAP, and CPAP machines manufactured between 2009 and April 26, 2021 that are covered by the June 2021 Philips products recall.

(6/30/2021)

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In June 2021, the healthcare technology company Royal Philips issued a products recall for certain Philips Bi-Level PAP, CPAP, and Mechanical Ventilator devices due to possible toxic exposures from the polyester-based polyurethane (PE-PUR) sound abatement foam component in these Philips products.  From our perspective,  a few cancers and some organ failures are the most serious possible medical conditions for patients with toxic exposures of PE-PUR from these Philips products.

We start with this June 14, 2021 document, "Philips issues recall notification* to mitigate potential health risks related to the sound abatement foam component in certain sleep and respiratory care devices", with this stated purpose at the outset:

[P]rovides an update on the recall notification* for specific Philips Bi-Level Positive Airway Pressure (Bi-Level PAP), Continuous Positive Airway Pressure (CPAP), and mechanical ventilator devices to address identified potential health risks related to the polyester-based polyurethane (PE-PUR) sound abatement foam component in these devices.

From these excerpts from that June 2021 Philips recall notification, we get some important details:

• Philips determined based on testing that there are possible risks to users related to this type of foam. The risks include that the PE-PUR foam may degrade into particles which may enter the device’s air pathway and be ingested or inhaled by the user, and the foam may off-gas certain chemicals.
• Philips has received reports of possible patient impact due to foam degradation. The potential risks of particulate exposure include headache, irritation, inflammation, respiratory issues, and possible toxic and carcinogenic effects. The potential risks of chemical exposure due to off-gassing include headache, irritation, hypersensitivity, nausea/vomiting, and possible toxic and carcinogenic effects.

In a separate document, "Medical Device recall notification (U.S. only) / field safety notice (International Markets)", from Philips Respironics, there is some product identification information about the various Philips Bi-Level PAP, CPAP, and Mechanical Ventilator devices affected by this June 2021 Philips products recall -- as well as what Philips products are not affected by this recall, and why.

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For another viewpoint on this Philips medical device safety issue, we refer you to this June 23, 2021 document issued by the United Kingdom's Medicines and Healthcare products Regulatory Agency, "National Patient Safety Alert: Philips ventilator, CPAP and BiPAP devices: Potential for patient harm due to inhalation of particles and volatile organic compounds".

Based on current information, here are the most serious possible related medical conditions for a patient with past harmful particulate exposures and/or chemical exposures from the polyester-based polyurethane (PE-PUR) sound abatement foam component in the recalled Philips Bi-Level PAP, CPAP, and Mechanical Ventilator devices:

Cancers, such as:

-- Lung Cancer
-- Liver Cancer
-- Kidney Cancer

Organ Failures, such as:

-- Liver Failure
-- Kidney Failure

We are investigating product liability lawsuits against Philips for patients with toxic exposures from the polyester-based polyurethane (PE-PUR) sound abatement foam component in the Philips products recalled in June 2021.  These lawsuits could be personal injury cases or wrongful death cases, depending on the facts.

If you or someone you know used one of the recalled Philips Bi-Level PAP, Philips CPAP, or Philips Mechanical Ventilator devices and, in turn, developed cancer or experienced organ failure, we are providing free case evaluations for possible lawsuits against Philips. You can use our online Philips Breathing Devices Case Evaluation Form or, if you prefer, call us on our toll-free number, 800-426-9535.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Gilenya Liver Injury Risk Warnings Are Increased, Again, This Time in Canada

Similar Gilenya Drug Label Changes Were Made in Europe and UK During Past Few Months

 

(Posted by Tom Lamb at Drug Injury Watch)

 

On January 18, 2021 Health Canada posted a Gilenya drug safety alert about patients developing Gilenya-associated liver injury, including acute liver failure requiring liver transplant. In the final two months of 2020 we saw similar Gilenya liver risk warnings announced by drug regulators in Europe and the United Kingdom (UK).

This Health Canada Dear Healthcare Professional Letter, "GILENYA (fingolimod) - Risk of Liver Injury", presented this Gilenya drug safety issue as follows:

Post-market cases of clinically significant liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have been reported in multiple sclerosis (MS) patients treated with GILENYA. Some of these cases have resulted in acute liver failure requiring a liver transplant.

Health Canada provided some background, as well as adding new information, in that January 2021 Gilenya drug safety alert:

The most recent periodic review of international safety data identified cases of liver failure, some requiring liver transplant, in patients treated with GILENYA. Other cases of clinically significant liver injury were also reported in patients treated with GILENYA. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have appeared shortly following the initiation of treatment as well as after prolonged use.

During clinical trials, an increase in hepatic enzymes was identified as a very common adverse drug reaction associated with GILENYA. Given the seriousness and severity of recently reported post-market cases, the Canadian Product Monograph (CPM) for GILENYA has been updated to further inform on the risk of liver injury and to include revised guidance for monitoring liver function and criteria for treatment interruption and/or discontinuation.

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We have written about the Gilenya drug label changes with increased liver risk warnings added in Europe and the UK in these previous articles:

• Gilenya Safety Alert November 2020: Cases of Acute Liver Failure Requiring Liver Transplant -- European Medicines Agency (EMA) and Novartis Issue Dear Doctor Letter About Gilenya Label Change
• 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

In the US, the Gilenya drug label was revised back in November to add warnings about Gilenya-associated liver injury, including acute liver failure requiring a liver transplant. See 5 WARNINGS AND PRECAUTIONS, 5.5 Liver Injury.

We will watch to see whether the FDA mandates any further Gilenya drug label changes with increased liver risk warnings here in the US going forward.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Vascular Endothelial Growth Factor (VEGF) Inhibitors: Increased Risk Of Aneurysm And Artery Dissection

New Warnings Added To Drug Labels For All VEGF Inhibitors By UK's MHRA Already; FDA Is Evaluating Need For Regulatory Action

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

On July 31, 2020 the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) issued this Drug Safety Update, "Systemically administered VEGF pathway inhibitors: risk of aneurysm and artery dissection", which began as follows:

Before initiating systemic vascular endothelial growth factor (VEGF) pathway inhibitors, carefully consider the risk of aneurysm and artery dissection in patients with risk factors. In patients who receive a systemic VEGF pathway inhibitor, reduce as far as possible any modifiable risk factors such as hypertension.

This July 2020 MHRA Drug Safety Update presented these two points in the "Update for healthcare professionals" section:

• use of systemically administered VEGF pathway inhibitors (see list in background) in patients with or without hypertension may promote the formation of aneurysms or artery dissections
• aneurysms or artery dissections are thought to occur infrequently in patients taking systemic VEGF pathway inhibitors, but some fatal cases have been reported, mainly in relation to aortic aneurysm rupture and aortic dissection

From the "European review of cases of aneurysm and artery dissection" part of that MHRA document we get these details:

A recent European review concluded that all systemically administered VEGF pathway inhibitors may promote the formation of aneurysm and artery dissection. The product information for all systemically administered VEGF pathway inhibitors has been updated to include a warning about the risk of aneurysm and artery dissection and to recommend carefully considering these risks before initiating in patients with risk factors, such as hypertension.

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Here in the US , meanwhile, 16 brand name VEGF inhibitors appeared on the "January - March 2020 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS)", which is sometimes called the FDA Watch List.

These are the VEGF inhibitors identified in this most recent FDA Watch List:

Inlyta (axitinib)
Avastin (bevacizumab)
Cabometyx (cabozantinib)
Caprelsa (vandetanib)
Cometriq (cabozantinib)
Cyramza (ramucirumab)
Iclusig (ponatinib)
Lenvima (lenvatinib)
Mvasi (bevacizumab-awwb)
Nexavar (sorafenib tosylate)
Ofev (nintedanib)
Stivarga (regorafenib)
Sutent (sunitinib malate)
Votrient (pazopanib)
Zaltrap (ziv-aflibercept)
Zirabev (bevacizumab-bvzr)

As regards those VEGF inhibitors, the FDA Watch List document states:

• Potential Signal of a Serious Risk / New Safety Information -- Aneurysm and artery dissection
• Additional Information (as of June 12, 2020) -- FDA is evaluating the need for regulatory action.

We will continue to monitor the safety profiles for these VEGF inhibitors, including whether the FDA mandates any label changes which add warnings about an increased risk of aneurysm and artery dissection for this class of drugs.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Xeljanz Side Effects Include Serious, Potentially Fatal Infections As Well As Blood Clots And Venous Thromboembolism

March 2020: UK Drug Regulator MHRA Issues Safety Guidance And New Measures To Minimize Risks For Certain Patients

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

We have written about Xeljanz drug safety several times in the past, with an emphasis on the risk of Xeljanz-related blood clots. Recently, however, there was some attention directed to a clinical trial finding which shows Xeljanz increases infection risks, with pneumonia, cellulitis, herpes zoster, and urinary tract infections.

For some background on the Xeljanz-related blood clots issue, you can read our previous articles:

• "Xeljanz Recommended Dosage For Ulcerative Colitis Patients May Increase Risk Of Pulmonary Embolism", posted in February 2019; and,
• "European Medicines Agency (EMA) Warns Xeljanz Increases Risk Of Pulmonary Embolism (PE) And Deep Vein Thrombosis (DVT)", posted in November 2019.

In the March 2020 edition of their Drug Safety Update publication, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) published this report, "Tofacitinib (Xeljanz▼): new measures to minimise risk of venous thromboembolism and of serious and fatal infections".

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As we are focusing in this article on the fact that Xeljanz increases infection risks, we limit our review to that aspect of the MHRA Xeljanz Drug Safety Update report. In relevant part, here is what is being pointed out:

[Xeljanz (tofacitinib)] is known to increase the risk of serious and fatal infections such as pneumonia, cellulitis, herpes zoster, and urinary tract infections. Existing advice contraindicates use of [Xeljanz (tofacitinib)] in patients with active infections, and advises healthcare professionals to consider the benefits and risks in patients with recurrent infections, a history of serious or opportunistic infection, or travel to areas of endemic mycoses, and in those who have underlying conditions that may predispose them to infection.

Study A3921133 showed incidence of non-fatal serious infections to be higher in patients with rheumatoid arthritis receiving [Xeljanz (tofacitinib)] than in those receiving a TNF inhibitor (see letter for study data). The risk of serious infections and fatal infections was further increased in older patients aged 65 years or older, as compared to younger patients (aged 50–64 years) – see letter for data.

We will continue to watch for significant Xeljanz drug safety developments in the medical literature and the drug regulatory realm.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Lemtrada Cardiovascular Reactions Can Occur Within 1-3 Days Of Infusions In People Without Any Identifiable Risk Factors

Unpredictable And Potentially Fatal Immune-Mediated Reactions Can Occur Within Months And Up To At Least 4 Years After Lemtrada Treatments

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has completed its review of Lemtrada (alemtuzumab) in the treatment of multiple sclerosis patients. Significant Lemtrada safety findings include the early risks of cardiovascular events with Lemtrada use and Lemtrada-related thrombocytopenia around the time of infusion, as well as long-delayed immune-mediated reactions involving Lemtrada years after its use.

The MHRA issued its review document, "Lemtrada▼ (alemtuzumab): updated restrictions and strengthened monitoring requirements following review of serious cardiovascular and immune-mediated reactions", on February 12, 2020. Here are its Lemtrada safety findings as regards the risks of cardiovascular events with Lemtrada use and immune-mediated reactions involving Lemtrada:

The review concluded that serious cardiovascular reactions can rarely occur within 1 to 3 days of [Lemtrada (alemtuzumab)] infusions in people without any identifiable risk factors. Reactions included myocardial ischaemia, cerebral haemorrhage, arterial dissection of the cervicocephalic arteries, pulmonary alveolar haemorrhage, and non-immune thrombocytopenia.

The review also found unpredictable and potentially fatal immune-mediated reactions can occur within months and up to at least 4 years after treatment with [Lemtrada (alemtuzumab)]. Reactions included autoimmune hepatitis, haemophagocytic lymphohistiocytosis, and acquired haemophilia A. The review also identified serious cases of Epstein-Barr virus reactivation reported after treatment, including hepatitis. Some patients developed more than one autoimmune disorder following treatment.

Lemtrada is a monoclonal antibody (mAb) authorized for the treatment of adults with relapsing-remitting multiple sclerosis.

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We have written several times previously about Lemtrada safety findings pointed out by the FDA and other drug regulatory agencies in the past couple of years:

• In December 2018 we published this article, "Lemtrada: Warnings About Strokes And Arterial Dissections / Blood Vessel Lining Damage Added To Drug Label", which covered a November 2018 FDA Drug Safety Communication about Lemtrada.
• In July 2019 we published this article, "Lemtrada: Reports Of Serious Cardiovascular Events And Immune-Mediated Reactions Under Investigation", to inform the MHRA had established new use restrictions and requiring increased monitoring of patients using this Lemtrada.
• In October 2019 we published this article, "Lemtrada Adverse Events May Occur More Frequently Than Previously Noted By Drug Safety Regulators And Researchers", which pointed out a study that found six additional deaths related to Lemtrada use that had not been reported before.

Soon after that last article, a "Dear Healthcare Professional Letter" was sent out by sanofi-aventis Canada Inc., "LEMTRADA (alemtuzumab) - Risk of Autoimmune Hepatitis, Haemophagocytic Lymphohistiocytosis, and Associated Serious Cardiovascular Reactions".

We will continue to monitor the medical literature for reports of cardiovascular events with Lemtrada use and immune-mediated reactions involving Lemtrada.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Gilenya Birth Defects Warnings Issued By Drug Safety Regulators In Canada And Europe -- But Not By FDA In The US

Gilenya Increased Risk of Major Congenital Malformations Such As Renal / Kidney And Musculoskeletal Abnormalities, Atrial Septal Defects

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

On December 19, 2019 Health Canada issued a Dear Healthcare Professional Letter, "GILENYA (fingolimod) - Risk of Congenital Malformations", which warned about certain birth defects associated with Gilenya.  The Key Messages part of that document starts with these two points:

• When used during pregnancy, GILENYA (fingolimod) has been associated with an increased risk of major congenital malformations, including congenital heart disease such as atrial septal defect, and renal and musculoskeletal abnormalities.
• GILENYA is now contraindicated in women who are pregnant or in women of childbearing potential who are not using effective contraception.

This December 2019 Health Canada warning about Gilenya birth defects goes on to provide the following more detailed information:

Available human data (post-marketing data and pregnancy registry information) supported by animal data suggest that use of GILENYA is associated with an increased risk of overall major congenital malformation (approximately 5%) when administered during pregnancy in comparison with the prevalence observed in the general population (2-4%).

... [A]n increased prevalence of the following specific major malformations was noted:

• congenital heart disease such as atrial septal defects;
• renal abnormalities; and
• musculoskeletal abnormalities.

The Contraindications, Warnings and Precautions, and Consumer Information sections of Canadian Product Monograph (CPM) for GILENYA has been updated to include the new contraindication and new safety information regarding the risk of congenital malformations.

This Gilenya label change mandated by Health Canada in December 2019 comes after some earlier drug safety regulatory actions in Europe.

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First, in July 2019 the European Medicines Agency (EMA) published this document, "Updated restrictions for Gilenya: multiple sclerosis medicine not to be used in pregnancy", which begins with this Gilenya pregnancy warning:

EMA has recommended that the multiple sclerosis medicine Gilenya (fingolimod) must not be used in pregnant women and in women able to have children who are not using effective contraception.... This is because the active substance in Gilenya, fingolimod, can harm the unborn baby and may cause birth defects....

These recommendations follow a review triggered by reports suggesting that the risk of birth defects in infants who have been exposed to Gilenya during pregnancy is twice as high as the 2 to 3% risk observed in the general population. The most frequently reported birth defects in infants exposed to Gilenya were those affecting the heart, kidneys, bones and muscles.

Second, in September 2019 the Medicines and Healthcare products Regulatory Agency (MHRA) issued this Drug Safety Update, "Fingolimod (Gilenya▼): increased risk of congenital malformations; new contraindication during pregnancy and in women of childbearing potential not using effective contraception", which had this summary at the start:

Fingolimod is associated with an increased risk of major congenital malformations including cardiac, renal, and musculoskeletal defects, when used in pregnancy. Women of childbearing potential must use effective contraception during fingolimod treatment and for 2 months after discontinuation.

In connection with those actions by European drug safety regulators, Novartis Pharmaceuticals UK Ltd. sent out a Direct Healthcare Professional Communication titled "Gilenya ▼ (fingolimod) – New contraindication in pregnant women and in women of childbearing potential not using effective contraception".

As an aside, one wonders why there has been no FDA action regarding this Gilenya birth defects issue and why there has been no "Dear Doctor Letter" about pregnant women using Gilenya sent out by Novartis Pharmaceuticals Corporation in the US as of this date (i.e., December 19, 2019).

We will continue to monitor this developing drug safety issue involving Gilenya birth defects, specifically the increased risk of major congenital malformations, including congenital heart disease such as atrial septal defect, renal / kidney abnormalities, and musculoskeletal abnormalities.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Uloric Side Effects Lead To An Increased Risk of Patient Cardiovascular Deaths, Says Health Canada

Drug Safety Warning: Watch For Myocardial Infarction, Stroke, And Cardiac Failure In People Who Are Taking Uloric

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In early November 2019 Health Canada warned that in a post-market study, Cardiovascular Safety of [Uloric (Febuxostat)] and Allopurinol in Participants With Gout and Cardiovascular Comorbidities (the CARES trial), a higher rate of cardiovascular deaths has been reported in patients with gout who also had cardiovascular disease when treated with Uloric, compared to those treated with the more-established gout drug allopurinol.

Based on the results of the CARES study, Health Canada mandated an Uloric label change to the effect that Uloric is now only approved for use in Canada as a treatment "to lower serum uric acid levels in patients with gout who have an inadequate response or intolerance to allopurinol, or for whom treatment with allopurinol is inappropriate (a second-line therapy)."

That information is from this Health Canada document, "ULORIC ® (febuxostat) - Increased Risk of Cardiovascular Fatal Outcomes", which goes to provide these details:

The [ULORIC drug label] was revised to enhance the safe use of ULORIC based on evidence identified in [the CARES trial]. This study was conducted to evaluate the CV risk of ULORIC in patients with gout who had a history of major CV disease, cerebrovascular disease, or diabetes mellitus with micro- and/or macrovascular disease. The study compared the risk of major adverse CV events between patients treated with ULORIC (N=3098) and allopurinol-treated patients (N=3092). There was a higher rate of CV death in patients treated with ULORIC (134 CV deaths of 3098) compared to patients treated with allopurinol (100 CV deaths of 3092). All-cause mortality was higher in the ULORIC group (243 deaths of 3098) than the allopurinol group (199 deaths of 3092) due to a higher rate of CV deaths (see Table 1 for details). Sudden cardiac death was the most common cause of adjudicated CV deaths in the ULORIC group (83 of 3098; 2.7%) as compared to the allopurinol group (56 of 3092; 1.8%).

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This recent drug safety regulatory action by Health Canada is similar to a Drug Safety Update for Uloric issued July 17, 2019 by the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA), which we reported on in this article, "Uloric Use By Patients With Major Cardiovascular Disease Associated With Higher Risk Of Deaths".

Here is a list of our earlier 2019 Uloric articles:

• Uloric Lawsuits Involving Heart Attacks And Strokes Follow Recent FDA Warnings About Cardiovascular Deaths (April 2019)
• Uloric "Black-Box Warning" For Increased Risks Of Heart-Related Deaths And Cardiovascular Side Effects (March 2019)
• Uloric Recall, "Black-Box Warning", And Limited Use Discussed By FDA Advisory Committees In January 2019 (January 2019)

We are investigating Uloric drug injury cases against Takeda Pharmaceuticals America, Inc., which is responsible for Uloric in the US. For additional information, you can see the Uloric Side Effects page on our Drug Injury Law website.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Lemtrada Adverse Events May Occur More Frequently Than Previously Noted By Drug Safety Regulators And Researchers

Ten Deaths Identified As Being Most Probably Related To Lemtrada, With Six Of These Cases Not Previously Reported, According To New Study

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

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UPDATE: "Dear Healthcare Professional Letter" sent  October 15, 2019 by sanofi-aventis Canada Inc.: LEMTRADA (alemtuzumab) - Risk of Autoimmune Hepatitis, Haemophagocytic Lymphohistiocytosis, and Associated Serious Cardiovascular Reactions

(10/16/19)

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Lemtrada adverse events have been on our radar for about the past year, and now there is some new drug safety information about Lemtrada use to report.

Back in December 2018 we published this article, "Lemtrada: Warnings About Strokes And Arterial Dissections / Blood Vessel Lining Damage Added To Drug Label".  It covered this November 2018 FDA Drug Safety Communication, "FDA warns about rare but serious risks of stroke and blood vessel wall tears with multiple sclerosis drug Lemtrada (alemtuzumab)"

Then in July 2019 we posted this article, "Lemtrada: Reports Of Serious Cardiovascular Events And Immune-Mediated Reactions Under Investigation", to inform the UK's Medicines and Healthcare products Regulatory Agency (MHRA) had taken regulatory action in May 2019 regarding Lemtrada. Specifically, the MHRA established new use restrictions and requiring increased monitoring of patients using this multiple sclerosis (MS) drug.

Now we are learning fatal adverse events (AEs) associated with Lemtrada may occur more frequently than previously understood, according to medical researchers.

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This finding by those researchers was published in this medical journal article, "Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis", published August 12, 2019 by BMC Research Notes. From the Abstract for this recent Lemtrada study report we get the following:

Results:  We identified nine cases with a probable and one case with a possible causal relationship between [Lemtrada (alemtuzumab)] treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of [Lemtrada (alemtuzumab)] from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with [Lemtrada (alemtuzumab)] occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.

The underlying Lemtrada study is discussed in this August 29, 2019 piece, "Link Between Lemtrada, Mortality More Common Than Previously Reported", found on the Multiple Sclerosis News Today web site. When this piece was viewed on October 9, 2019 there were six Comments posted, including some from and about actual MS patients who used Lemtrada and experienced apparent adverse events.

Of course, we will continue to monitor the drug safety profile of Lemtrada in the US and Europe. If you have any Lemtrada adverse events or other relevant information which you would like to share, you can submit a Comment below.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)