Drug Injury Watch

August 2017 ED Drugs Label Change Warns That Some Users Of Cialis, Levitra, And Viagra Have Developed NAION Vision Loss

There Is An Approximate Two Times Increased Risk Of NAION According To Recent Medical Study, Which Is Consistent With Some Earlier Medical Research

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

As reported previously, the erectile dysfunction (ED) drugs Cialis (tadalafil), Levitra (vardenafil hydrochloride), and Viagra (sildenafil citrate) have been associated with a type of sudden vision loss called Nonarteritic Anterior Ischemic Optic Neuropathy (NAION).

In July 2005 the FDA ordered warnings be put on the package insert labels of these ED drugs, or impotence drugs, to the effect that some users of Cialis, Levitra, and Viagra have developed NAION, a form of blindness. At the same time, however, the FDA stated that it is impossible at present to know if NAION is a side effect of these ED drugs, or an unrelated medical condition.

In June 2006 Health Canada issued a Public Communication alerting Canadians that the drug companies Eli Lilly (Cialis), Bayer (Levitra), and Pfizer (Viagra) were in the process of sending a so-called "Dear Doctor" letter to inform healthcare providers in Canada about changes to the respective package insert, or label, for these drugs regarding this vision loss, or NAION, side effect.

Now, 11 years later, in August 2017, there is some additional information about the increased risk of developing the eye or vision side effect NAION which is included in a recent label change for Viagra, Cialis, and Levitra.

 

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From a comparison of the relevant parts of the two most recent drug labels for Levitra, below, you can see what was added by means of this August 2017 label change concerning NAION as a possible adverse drug event or adverse reaction (in the second and third paragraphs of the current drug label).

 

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FULL PRESCRIBING INFORMATION document for Levitra (Revision Date: 9/2015)

5.4 Effects on the Eye

Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including LEVITRA, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 in males aged ≥50. An observational study evaluated whether recent use of PDE5 inhibitors, as a class, was associated with acute onset of NAION. The results suggest an approximate 2 fold increase in the risk of NAION within 5 half-lives of PDE5 inhibitor use. From this information, it is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2)]. 

 

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FULL PRESCRIBING INFORMATION document for Levitra (Revision Date: 8/2017)

 

5.4 Effects on the Eye

Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including LEVITRA, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 in males aged ≥50.

An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies.

Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see Adverse Reactions (6.2)].

 

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We will continue to monitor the safety profile of Viagra, Cialis, and Levitra as regard the vision-loss condition NAION as well as other possible ED drugs side effects.

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

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Prilosec / Prevacid / Nexium Federal Court Lawsuits For Kidney Injury Consolidated By MDL Established In August 2017

These Proton-Pump Inhibitors (PPIs) Are Linked To Acute Interstitial Nephritis, Chronic Kidney Disease, End Stage Renal Disease, And Kidney Failure

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In February 2017 the United States Judicial Panel on Multidistrict Litigation (JPML) denied a motion for centralization or consolidation of federal court lawsuits brought by plaintiffs in six proton-pump inhibitors (PPIs) cases alleging kidney injury. All of the defendant pharmaceutical companies in those lawsuits opposed that first effort to set up a Multidistrict Litigation (MDL) for these cases.

But six months later, with more Prilosec, Prevacid, and Nexium cases filed and with some of the drug companies no longer in opposition, the JPML established IN RE: PROTON-PUMP INHIBITOR PRODUCTS LIABILITY LITIGATION (NO. II) – MDL No. 2789.

From the JPML’s Transfer Order filed on August 2, 2017 we get these details:

In the complaints in these 161 personal injury and wrongful death actions, plaintiffs allege that as a result of taking one or more proton-pump inhibitors (PPIs), they or their decedents suffered kidney injury (e.g., chronic kidney disease (CKD), acute interstitial nephritis, end stage renal disease, or kidney failure). Plaintiffs allege that defendants failed to adequately warn of the negative effects and risks associated with PPIs....

In support of this new motion, plaintiffs, AstraZeneca, and Pfizer argue that the number of involved actions, districts, and plaintiffs’ counsel has increased significantly since [our ruling in February], that many more cases likely will be filed, that there now are a significant number of related state court actions, and that informal coordination and cooperation are not practicable to manage litigation of this scope. After careful review of the record, we agree with this assessment. [footnotes omitted]

 

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Notably, during this second time around the drug company Takeda was still opposed to the creation of any PPIs federal court MDL for various reasons. But the JPML was not convinced by their arguments, as seen from this excerpt from the Transfer Order:

And, although it is true that AstraZeneca is sued in far more actions than Takeda, a significant number of actions are “mixed use” cases in which the plaintiffs allege use of more than one PPI, and sue Takeda and one or more other PPI manufacturers, including AstraZeneca. The prospect of additional cases against Takeda does not seem far-fetched [10]. Given these circumstances, including the seemingly indivisible nature of plaintiffs’ alleged injuries in the “mixed use” cases, we decline to carve out from the MDL cases or claims against Takeda. [footnotes omitted]

Lastly, this point – which may have been a factor for the JPML when ruling this time on the Prilosec / Prevacid / Nexium federal court MDL consolidation – was mentioned in a footnote for the August 2017 Transfer Order:  "The variety of alleged kidney injuries arguably has diminished, as most plaintiffs allege that they suffer from [chronic kidney disease (CKD)]...."

We are currently investigating Prilosec, Prevacid, Nexium, and other brand name proton pump inhibitors (PPIs) heartburn drugs, by prescription and/or over-the-counter, involving:

• Acute Interstitial Nephritis
• Chronic Kidney Disease (CKD)
• End-Stage Renal Disease (ESRD)
• Severe Renal Impairment
• Kidney / Renal Failure
• Acute Kidney Injury

We encourage you to submit a Nexium / Prilosec / Prevacid Case Evaluation online – it is free, confidential, and there is no obligation.

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

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Analysis Of FDA Adverse Event Reports Describes Extent And Nature of Invokamet / Invokana - Amputation Side Effect

This New Medical Research Was Published Just Before "Black-Box Warning" About Lower Limb Amputations Added To Drug Labels

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In the final week of July 2017, the FDA issued a notification that it had approved a revised drug label for Invokana and Invokamet, as well as a revised Medication Guide for these two diabetes drugs from Janssen Pharmaceuticals. This label change was previewed in a May 2017 FDA Drug Safety Communication about an increased risk of leg and foot amputations. For more information on this recent development, see this earlier article: "Invokana - Amputation Side Effect Gets "Black-Box Warning" On Revised Drug Label Issued In July 2017".

Just before this Invokamet / Invokana label change was finally done, The Lancet Diabetes & Endocrinology medical journal published this Correspondence item on July 18, 2017, "SGTL2 inhibitors and amputations in the US FDA Adverse Event Reporting System".

From that item, we get these two excerpts:

• In summary, this pharmacovigilance analysis confirms that use of canagliflozin, but not dapagliflozin or empagliflozin, might be associated with an increased risk of amputations. However, [the US Food and Drug Administration (FDA) adverse event Reporting System (FAERS)] data analysis has important limitations because there is no definite causal link between drug exposure and adverse event.... [footnote omitted]
• Most of the available reports (57 [86%] of [66 SGLT2 inhibitor-associated amputations]) listed canagliflozin as a suspect or concomitant drug. Average and detailed report information is provided in the appendix. On average, patients were aged about 60 years, and most were men. In 57 (89%) of 64 cases (two reports could not be retrieved for detailed analysis), an SGLT2 inhibitor was the primary suspect and average treatment duration was about 1·5 years. Based on indications, 11% of patients had diabetic foot or wounds, but concomitant adverse events included wound, necrosis, gangrene, or ischaemia in 14 cases, and osteomyelitis or other infections in 15 cases. Cumulatively, in 23 (36%) of 64 cases there was at least one of such features of diabetic foot syndrome. The most common level of amputation was the toe, but there were 13 above-ankle leg or limb amputations, two multiple amputations, one hand amputation, and three fatal cases.

 

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In early August 2017 an article with some additional contextual information, "FDA Reports Further Support for Canagliflozin-Amputation Link", was published on the Medscape website (free registration required). From that article we get the following points:

Among 66 reports of SGLT2-inhibitor–associated amputations, 57 (86%) involved canagliflozin. Moreover, two-thirds of those reports were among people with no discernible risk factors for amputation, "which, worryingly, points to an unpredictable effect of the drug," [Gian Paolo Fadini, MD, PhD, of the division of metabolic diseases, department of medicine, University of Padova, Italy] told Medscape Medical News....

Thus far, the FDA has not extended the label warning about amputations to other drugs in the class [e.g., Jardiance (empagliflozin) and Farxiga (dapagliflozin)], although the European Medicines Agency (EMA) has, pending further investigation.

"Our data are the first to confirm the warning originated from CANVAS and tends to suggest this is not a class effect," Dr Fadini told Medscape Medical News.

We are currently investigating possible drug injury cases against the responsible drug company, Janssen Pharmaceuticals, where a patient who used Invokana or Invokamet had to have a lower limb amputation.

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European Drug Regulator EMA Suspends Use Of MRI Drugs Magnevist, Omniscan, And OptiMARK In July 2017

The Drug Safety Concern Is That Use Of These Gadolinium Contrast Agents Can Leave Gadolinium Deposits In Brain Tissues

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

The European Medicines Agency (EMA) recently announced it is taking regulatory action on certain magnetic resonance imaging (MRI) contrast drugs containing gadolinium a couple of months after the U.S. Food and Drug Administration (FDA) decided otherwise.

To understand these divergent paths, we start with the timeline of events giving rise to the EMA's suspension of the MRI drugs Magnevist, Omniscan, and OptiMARK in July 2017.

In March 2017, following its assessment of gadolinium agents used in body scans, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended the suspension of certain MRI drugs. This action was based on a review which found evidence of gadolinium deposits in the brain after MRI body scans, but no signs of harm.

According to an April 2017 update to "PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension for some marketing authorisations":

Following the PRAC’s March 2017 recommendation, some of the marketing authorisation holders concerned by this referral procedure have requested a re-examination. Upon receipt of the grounds for their requests, the PRAC will start a re-examination, which is expected to conclude in July 2017

Next came this July 7, 2017 EMA document, "PRAC confirms restrictions on the use of linear gadolinium agents", which included this statement: "No specific conditions linked to gadolinium deposition in the brain have been identified, but the clinical consequences are unknown."

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Lastly, in its July 21, 2017 document, "EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans", we get this further elaboration on that statement:

There is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions for some intravenous linear agents in order to prevent any risks that could potentially be associated with gadolinium brain deposition....

No adverse neurological effects, such as cognitive or movement disorders, have been attributed to gadolinium deposition in the brain with any gadolinium agents.

We turn now to the FDA's treatment of this drug-safety assessment of Magnevist, Omniscan, and OptiMARK, as well as the several other gadolinium-based contrast agents (GBCAs).

From its "FDA Drug Safety Communication: FDA identifies no harmful effects to date with brain retention of gadolinium-based contrast agents for MRIs; review to continue" we get this explanation of why no regulatory action is necessary -- at least not yet:

All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because we identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future....

There are two types of GBCAs based on their chemical structures, linear GBCAs and macrocyclic GBCAs....

The [scientific publications we evaluated] show that linear GBCAs retain more gadolinium in the brain than macrocyclic GBCAs. However, our review did not identify adverse health effects related to this brain retention....

The manufacturer of OptiMARK (gadoversetamide), a linear GBCA, updated its label with information about gadolinium retention in various body organs such as the brain, skin, and other organs. We are reviewing the labels of other GBCAs to determine if changes are needed.

We will be watching for the "public meeting to discuss this issue in the future" mentioned by the FDA -- which, perhaps, will be a so-called Advisory Committee Meeting.

In addition, we will monitor the medical literature for "any risks that could potentially be associated with gadolinium brain deposition" mentioned by the EMA.

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

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