Drug Injury Watch

A New Case Of Progressive Multifocal Leukoencephalopathy (PML) In A Patient Using Gilenya Is Reported By Novartis In Canada

Company Is Investigating This Gilenya - PML Case To See Whether Brain Disease Might Be A Side Effect Of Its MS Drug

(Posted by Tom Lamb at DrugInjuryWatch.com) 

Gilenya (fingolimod) capsules were approved by the FDA in 2010 and by Health Canada in 2011.

We posted this article about Gilenya last week, on February 16, "Various Drug Safety Issues Continue To Be Associated With Novartis Multiple Sclerosis (MS) Medication Gilenya".  In that article we looked at the cardiac-related risks associated with Gilenya.

A few days later we saw this news report on the website for the Multiple Sclerosis Society of Canada, "Case of PML reported in patient treated with Gilenya®", and from from that article we get this more recent drug safety information:

Pharmaceutical company Novartis has reported a case of PML (progressive multifocal leukoencephalopathy) in an individual who had received Gilenya® (fingolimod) for more than 4 years for the treatment of relapsing-remitting multiple sclerosis (RRMS). Novartis has informed the regulatory authorities of this case, and is investigating whether treatment with Gilenya® contributed to the development of PML....

This is the third case of PML observed for Gilenya®. The first case was reported in 2012, wherein Novartis had noted that the case was likely associated to previous treatment with Tysabri. However, they did not rule out Gilenya® as a contributor to the development of PML. The second case occurred in 2013 in an individual who received Gilenya® for 7 months following treatment with immunosuppressive drugs and multiple courses of high dose corticosteroids. Both cases occurred outside of Canada.

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We have written numerous times in the past about reports of progressive multifocal leukoencephalopathy (PML) being associated with the older MS drug Tysabri (which articles can be found by putting "PML" in the search engine box that is on the home page for Drug Injury Watch, in the right side bar).

For a brief summary of PML and its symptoms, we go back the the February 2015 MS Society of Canada news report about Gilenya:

PML is a rare, generally fatal brain disease caused by the JC virus. It is primarily associated with severely suppressed immune systems. Symptoms of PML can include: progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, changes in thinking, memory and orientation, confusion and personality changes.

We will continue to monitor the safety profile of this controversial Novartis MS drug and to watch for any more reports of PML in patients using Gilenya.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb) 

Various Drug Safety Issues Continue To Be Associated With Novartis Multiple Sclerosis (MS) Medication Gilenya

ISMP QuarterWatch Report From 2014 States Adverse Events Reports Show That Gilenya Cardiac Risks "were neither rare nor hypothetical"

(Posted by Tom Lamb at DrugInjuryWatch.com)

The safety profile for the Novartis drug Gilenya (fingolimod) has been controversial for some time now, and the concerns about adverse reactions and side effects continue.

As background, in August 2012 we posted this article, "Multiple Sclerosis (MS) Medication Gilenya: Timeline Of Actions Taken In US, Canada, And Europe".

And over the past several years we have been monitoring news reports about Gilenya adverse reactions and suspected side effects at our Pharmaceutical Drug Litigations Updates site.

Last fall, from the September 24, 2014 edition of the ISMP QuarterWatch publication, we received more data and information about the various safety risks associated with Gilenya.

We start with this overview from "Update on Fingolimod (GILENYA)" in the Executive Summary section:

... three years of postmarket and new published data highlight four important safety risks of [Gilenya (fingolimod)].... Adverse event reports for the most recent 12 months showed the cardiac risks were neither rare nor hypothetical.... Also identified was a large group of cases (n = 348) indicating macular degeneration or less specific adverse effects on the eye. .... A third concern was increased infection risk because of the effect of [Gilenya (fingolimod)] on lymphocytes.... Finally, pregnancy risks were a substantial premarketing concern based on animal studies linking the target [Gilenya (fingolimod)] receptor to vascular malformations in rodents and human fetal abnormalities 5/66 (7.6%) of known pregnancies in clinical studies....

... the large volume of reports of serious injury (n = 2,716) equals approximately 17% per patient-year of exposure, showing that [Gilenya (fingolimod)] remains a high-risk drug with multiple toxicities. Additional detail about this calculation and Novartis’ views are discussed in the main report.  [emphasis added]

Given the extent and severity of the adverse events reports about Gilenya disrupting normal heart rhythm, we want to go into more depth on the cardiac-related risks associated with this still relatively new MS drug from Novartis.

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From the Results, or main report, section of the September 2014 QuarterWatch from ISMP, we get this additional information about the heart-related problems patients have had when using Gilenya:

Cardiac Rhythm Risks

Severe and fatal cardiac rhythm disturbances were observed during preapproval testing of [Gilenya (fingolimod)], primarily bradycardia and heart block occurring soon after initiating treatment. Several fatalities in testing occurred at higher than the currently approved dose. In response to this risk [Gilenya (fingolimod)] was approved with a recommendation that the first dose be administered with monitoring and observation for the first 6 hours. In the QuarterWatch adverse event data, cardiac arrhythmias were the largest subcategory of reported serious adverse drug events. We identified 473 cases in the cardiac arrhythmia SMQ, including 13 patient deaths, 11 cases classified as life threatening and 141 resulting in hospitalization. While “decreased heart rate” was the most common manifestation reported (n = 175) other cases indicated loss of consciousness or syncope (n = 58) and various heart blocks (n = 62). One case could have report terms in multiple categories. Adverse event data show that cardiac adverse events proved to be a major hazard of this drug in clinical practice.  [footnote omitted]

We will continue to watch for reports of heart-related side effects with Gilenya and monitor the activity of drug regulators in the US, Canada, and Europe as regards the safety profile of this controversial Novartis MS drug.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb) 

Zofran Associated With Birth Defects When Used During Pregnancy As An "Off-Label" Morning Sickness Treatment

Medical Researchers Find Increased Risk Of Heart Defects And Cleft Palates In Babies Born To Women Using Zofran

(Posted by Tom Lamb at DrugInjuryWatch.com)

Women with severe morning sickness who were prescribed Zofran (ondansetron) -- a GlaxoSmithKline drug approved by FDA for the prevention of nausea and vomiting associated with chemotherapy and radiotherapy -- have had babies born with heart-related birth defects and other congenital malformations such as cleft palate and/or cleft lip.

For some background facts regarding this emerging drug-safety issue we begin with a June 2014 investigative news report, "Birth defects blamed on unapproved morning sickness treatment", which was published by the Toronto Star newspaper.  Here are three important points taken from that article:

[#1]  Because most women experience nausea and vomiting during the first trimester, they would be taking the drug at the same time the fetus is most vulnerable to developing malformations and deformities.

Roughly 10 to 15 per cent of pregnant women receive drugs to treat morning sickness, according to a recent U.S. study.

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[#2]  In 2012, the U.S. Department of Justice reached a $3-billion settlement with GlaxoSmithKline after the government alleged the company promoted the off-label uses of several drugs, including Zofran, the company’s brand-name version of ondansetron.

Court documents alleged the company gave doctors kickbacks to prescribe the drug for morning sickness and disseminated false information about Zofran’s safety and effectiveness.

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[#3]  The Star contacted [GlaxoSmithKline about] the side-effect reports.

Glaxo said “the safety of [Zofran (ondansetron)] for use in human pregnancy has not been established. . . . (The company) monitors and reports all adverse event reports . . . and works closely with regulatory authorities in Canada to include relevant safety information for physicians and patients within our product labels.”

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The most concerning medical study to date about the association of Zofran with birth defects is by a group of Danish doctors, "Ondansetron use in early pregnancy and the risk of congenital malformations – a register based nationwide cohort study", which was first presented in 2013.

From a document describing that Zofran - birth defects medical research:

Background

... Only limited data concerning the safety of [Zofran (ondansetron)] in pregnancy is available.

Therefore we conducted a nationwide cohort study testing the hypothesis use of [Zofran (ondansetron)] during the first trimester was associated with a higher prevalence of congenital malformations.

Methods

The study included all women giving birth in Denmark 1997 and 2010.... The primary outcome was the prevalence of major congenital malformations according to the EUROCAT classification system and subgrouping among first trimester users of [Zofran (ondansetron)] compared to non-users. Exposure was defined redemption of one prescription of [Zofran (ondansetron)] in the first trimester of pregnancy.

Results

We identified 897 018 births in the study period. 1248 women redeemed a prescription of [Zofran (ondansetron)] in the first trimester of which 58 (4.7%) had offspring with a congenital malformation compared to 31357 (3.5 %) in the unexposed group. The odds ratio (OR) of having an offspring with a major malformation after exposure to [Zofran (ondansetron)] was 1.3 (CI95% 1.0-1.7). This was mainly caused by an increased prevalence of heart defects (OR=2.0 (CI95% 1.3-3.1)....

Conclusion

We found a doubling in the prevalence of major congenital heart defects in children whose mothers redeemed a prescription of [Zofran (ondansetron)] in the first trimester of pregnancy.

An earlier medical journal article from 2011, "Medications Used to Treat Nausea and Vomiting of Pregnancy and the Risk of Selected Birth Defects", indicated that Zofran use as a morning-sickness drug during pregnancy results in an increased risk of cleft palate (CP).

An update on the 2013 Danish medical research presentation about Zofran use during pregnancy was provided in the June 2014 Toronto Star news report:

Those researchers... have since expanded the study to include more births and arrived at the same conclusion; they recently submitted their results to an academic journal, the lead researcher told the Star.

We will continue to monitor this relatively new drug-safety issue of Zofran use by pregnant women being linked to birth defects such as congenital heart defects and cleft palate, as well as possibly other congenital malformations in children born to those women.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb) 

Viagra / Cialis / Levitra: Prostate Cancer Recurrence When Used After Radical Prostatectomy Surgery

Researchers Surprised By Their Finding As Earlier Medical Studies Suggested Anticancer Effect In Prostate

(Posted by Tom Lamb at DrugInjuryWatch.com)

Findings about increased cancer risks being associated with the use of erectile dysfunction (ED) drugs such as Viagra, Cialis, and Levitra are not new, as those relatively popular drugs and others had been associated with melanoma.  For more about that drug side effect see our Viagra / Cialis / Levitra / Staxyn / Stendra / Revatio / Adcirca drug information page.

The February 2015 edition of The Journal of Urology includes this article, "Use of Phosphodiesterase Type 5 Inhibitors May Adversely Impact Biochemical Recurrence after Radical Prostatectomy", which was published online back in September 2014.

From the Abstract for this recent medical journal article about Viagra, Cialis, and Levitra:

• Purpose

Experimental evidence suggests that phosphodiesterase type 5 inhibitors may suppress tumor growth, postpone metastasis and prolong survival, but clinical data are lacking. We studied the effect of phosphodiesterase type 5 inhibitors on biochemical recurrence after radical prostatectomy for prostate cancer.

• Conclusions

Contrary to experimental data, the use of phosphodiesterase type 5 inhibitors after radical prostatectomy may adversely impact biochemical recurrence. Further studies are needed to validate our results.

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For some contextual information we get the following from a January 27, 2015 Medscape Medical News article, "Docs 'Astonished': ED Drugs Tied to Prostate Cancer Return":

The study is the first of its kind. No other research has looked at the use of these drugs after prostate cancer surgery and their impact on biochemical recurrence.

However, a previous observational study showed that the use of PDE5 inhibitors in men with ED (and no history of prostate cancer) was associated with a decreased incidence in the rate of prostate cancer (Asian J Androl. 2013;15:246-248). The investigators from Scott & White Healthcare in Temple, Texas, explain that men treated with PDE5 inhibitors might ejaculate more often than untreated men, which has been demonstrated to have a protective effect against prostate cancer (JAMA. 2004;291:1578-1586).

There have also been multiple reports from labs that these drugs might thwart cancer prostate cancer growth and postpone metastasis.

In fact, lab evidence on ED drugs in prostate and other cancers has prompted some investigators to call for the "repurposing" of PDE5 inhibitors for adjuvant chemotherapy (Front Pharmacol. 2013;4:82).

As the researchers cautioned in their medical journal article, the association between Viagra / Cialis / Levitra and prostate cancer recurrence after radical prostatectomy needs to be studied further.

Be assured that we will be watching for further developments concerning this possible new side effect of erectile dysfunction (ED) drugs.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb)