Drug Injury Watch

Topamax Taken During Pregnancy Associated With A Significant Increased Risk Of Cleft Lip For Infants Born To Those Mothers

Recently Revised Topamax Label Includes Data Of 2014 Annual Report From The North American Antiepileptic Drug (NAAED) Pregnancy Registry

(Posted by Tom Lamb at DrugInjuryWatch.com)

By means of an October 21, 2014 FDA letter to Janssen Pharmaceuticals, Inc. we first learned there was going to be a label change concerning Topamax and cleft lips in infants:

Revisions to Section 8.1 to describe the most recent data pertaining to the risk of oral clefts in infants exposed to topiramate during pregnancy, based on data from the 2014 Annual Report from the North American Antiepileptic Drug (NAAED) Pregnancy Registry.

Here is the revised Topamax (topiramate) Prescribing Information, updated October 2014 (accessed 11/20/14), with the above-referenced revision in section 8 USE IN SPECIFIC POPULATIONS, at 8.1 Pregnancy:

Human Data

Data from the NAAED Pregnancy Registry (425 prospective topiramate monotherapy-exposed pregnancies) indicate an increased risk of oral clefts in infants exposed during the first trimester of pregnancy. The prevalence of oral clefts among topiramate-exposed infants was 1.2% compared to a prevalence of 0.39% for infants exposed to a reference [antiepileptic drug (AED)]. In infants of mothers without epilepsy or treatment with other AEDs, the prevalence was 0.12%. For comparison, the Centers for Disease Control and Prevention (CDC) reviewed available data on oral clefts in the United States and found a similar background rate of 0.17%.

The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 9.6 (95% Confidence Interval [CI] 4.0 – 23.0) as compared to the risk in a background population of untreated women. The UK Epilepsy and Pregnancy Register reported a similarly increased prevalence of oral clefts of 3.2% among infants exposed to topiramate monotherapy. The observed rate of oral clefts was 16 times higher than the background rate in the UK, which is approximately 0.2%.

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We have previously written about the risk of babies being born with cleft lips when their mothers used Topamax during their pregnancy, as seen below:

• Topamax During Pregnancy Increases Risk Of Cleft Lip And/Or Cleft Palate Birth Defects -- Oral Clefts In Babies Are 20 Times More Likely With Women Who Used Topamax (topiramate) After Getting Pregnant [March 2011]
• FDA Seeks Information About Topamax-Related Oral Cleft Birth Defect Cases -- Request For Historical Incidence Data Made In Connection With NDA For New Obesity Drug [February 2011]
• Neurology Journal: Johnson & Johnson's Drug Topamax May Increase Risk of Birth Defects -- Beware If Taking This Seizure Medicine Alone Or With Other Epilepsy Drugs During Pregnancy [July 2008]

We will continue to monitor the safety profile of Topamax as regards children born to mothers who used this antiepileptic drug during their pregnancy.

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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)

Because No Antidote For Eliquis Is Available To Reverse The Effects Of Anticoagulation, There Have Been Irreversible Life-Threatening And Fatal Bleeding Events

 A Reversal Agent For Eliquis Currently Under Development Comes Too Late For People With Trauma-Induced Bleeding Incidents, Some Who Bled To Death

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE: Eliquis Antidote Will Come Too Late For People Who Suffered Serious Bleeding Events, Some Which Caused The Deaths Of Patients 

Advertisements As Well As Prescribing Information / Drug Label Seem To Downplay The Fact That There Is No Reversal Agent For Eliquis, Yet 

(12/21/14) 

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Eliquis (apixaban) was the last of the three "new-generation" anticoagulants to make it to the market. It was approved by the FDA in 2012.  Pfizer and Bristol-Myers Squibb are the two drug companies which share the profits and responsibility for Eliquis.

The first such new blood thinner released was Pradaxa (dabigatran), a direct thrombin inhibitor by Boehringer Ingelheim.  Next came Xarelto (rivaroxaban) by Johnson & Johnson, which was approved in 2011.

Significantly, none of these three blood thinners -- Pradaxa, Xarelto, and Eliquis -- currently have an approved antidote for a patient experiencing a trauma-induced bleeding event or needing emergency surgery.

We wrote about this drug safety problem in this article, "Eliquis And Xarelto, Like Pradaxa, Linked To Serious Bleeding Events Due To Fact No Antidote Available", which we posted back in September 2014.

Now we have an update on this drug safety situation as regards Eliquis, at least.

We start with the fundamental fact that Eliquis is a Factor Xa inhibitor.

In response to the "no-antidote" Eliquis issue, the company Portola Pharmaceuticals has developed a new product, Andexanet alfa, which reverses the effects of Factor Xa inhibitors.

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Not surprisingly Portola is collaborating with Pfizer and Bristol-Myers Squibb on the product's development insofar that Eliquis sales numbers would likely increase with Portola's new Xa antidote coming on the market.

From a November 17, 2014 Seeking Alpha business news report, "Adexanet Alfa reverses anticoagulant effect of Eliquis in first stage of Phase 3":

In the first part of the ANNEXA-A Phase 3 study, andexanet alfa produced a rapid and almost complete reversal (94%) (p<0.0001) compared to placebo of the anticoagulant effect of Eliquis (apixaban) in healthy volunteers ages 50 - 75 as measured by anti-Factor Xa activity. The results will be presented today at the American Heart Association meeting in Chicago.

Given that Xarelto is a Factor Xa inhibitor, also, this advancement by Portola with its new Xa antidote shoud benefit Boehringer Ingelheim, which has been the subject of recent lawsuits concerning serious bleeding events, some of which have been fatal.

Although Xarelto lawsuits are getting more attention, including law firm TV ads, Eliquis cases for side effects such as trauma-induced atypical and irreversible bleeding events have the same factual basis: lack of an effective reversal agent, or antidote.

We are investigating Eliquis-related death cases which involve excessive bleeding as well as other Eliquis side effects such as gastrointestinal (GI) bleeds, rectal bleeding, and brain hemorrhages or intracranial hemorrhages.

To reiterate, as stated in the above Seeking Alpha report:

Currently, there is no antidote to Eliquis despite the need for a method to reverse its anticoagulation effects in certain clinical situations such as a major bleeding event or emergency surgery.

While Portola's Factor Xa antidote will someday help patients suffering an acute bleed, and should lead to fewer Xarelto and Eliquis lawsuits in the future, unfortunately, its eventual and much anticipated FDA-approval is too late for some people who suffered serious bleeding events or bled to death, already.

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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)

Xarelto: Drug-Induced Liver Injury Warning Should Be Added To Drug Label Prescribing Information For Xarelto Say Medical Researchers

Medical Journal Article Reports On Two Patients Who Experienced Severe Liver Damage Onset During Xarelto Treatment

(Posted by Tom Lamb at DrugInjuryWatch.com)

Most adverse drug reaction case reports associated with the still relatively new anticoagulant Xarelto (rivaroxaban) involve serious bleeding side effects such as gastrointestinal (GI) bleeds and rectal bleeding as well as irreversible life-threatening trauma-induced atypical bleeding incidents.

A recent article, however, published by the medical journal JAMA Internal Medicine, "Symptomatic Hepatocellular Liver Injury With Hyperbilirubinemia in Two Patients Treated With Rivaroxaban", discusses a different serious Xarelto side effect: drug-induced liver injury / liver damage.

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From a medical site summary about this recent Xarelto liver safety study, "Rivaroxaban and Liver Injury: Case Studies Add to Safety Questions", we get these facts:

A case study in JAMA Internal Medicine reports on two patients that experienced severe liver injury onset during treatment with the oral anticoagulant [Xarelto (rivaroxaban)]. The first patient was a 52-year-old man who developed severe lobular hepatitis two months after initiation of [Xarelto (rivaroxaban)] 10mg/day for the prevention of deep vein thrombosis (DVT) after internal fixation of a tibia fracture. The preserved lobular architecture and lack of fibrosis of portal tract were consistent with a drug-related liver injury....   The second patient, a 73-year-old woman prescribed 10mg/day of [Xarelto (rivaroxaban)] after a total knee replacement for the prevention of DVT, experienced mixed liver injury but liver enzyme levels and bilirubin concentration restored to normal levels after 14 days of [Xarelto (rivaroxaban)] cessation....  The authors speculate that [Xarelto (rivaroxaban)] was most likely the cause of drug-induced liver injury (DILI) in both patients and that physicians should be aware of this potentially severe adverse drug reaction. They also emphasize that a warning regarding symptomatic liver injury should be included in the drug label.

We will continue to watch for liver failure, drug-induced hepatitis, and liver damage drug injury cases possibly associated with Xarelto blood thinner treatment.

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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)

The Link Between Popular Erectile Dysfunction (ED) Drug Viagra And Melanoma Has A Potential Molecular Basis According To Medical Expert Who Reviewed Recent Study

Finding Applies Also To ED Drugs Cialis, Levitra, Staxyn, and Stendra, As Well As Pulmonary Arterial Hypertension (PAH) Medications Revatio And Adcirca

(Posted by Tom Lamb at DrugInjuryWatch.com)

About six months ago we posted this item, "Viagra May Increase Risk Of Melanoma In Men Who Have Used This ED Drug, According To An April 2014 Medical Journal Article", in which we reported that Viagra (sildenafil), a popular erectile dysfunction (ED), appeared to increase the risk for malignant melanoma, a potentially fatal form of skin cancer.

That medical journal article, "Sildenafil Use and Increased Risk of Incident Melanoma in US Men: A Prospective Cohort Study", was published by JAMA Internal Medicine in April 2014.

Since then, there has been some commentary pieces written by medical reporters about this Viagra - melanoma study.

First, from the American Council on Science and Health (ACSH) web site, there is "Viagra and melanoma correlation: Is it real?".  From that article, we get this apparent validation of the underlying medical study:

Unlike many of the junk studies we routinely lambaste here, this one is well run and also has a biologically plausible mechanism to explain the findings. It is also a prospective study—one planned in advance to explore a theory—rather than a retrospective study, (often called data dredging) where data from past studies are analyzed to find some kind of correlation between two events. The former is almost always more scientifically valid compared to the latter....

ACSH’s Dr. Josh Bloom says, “The mechanism that the authors propose is very complicated, but this is to be expected. The processes of cell proliferation and survival are dependent upon a large number of interdependent biochemical events, all falling under the general topic called cell signalling. Although not proven, the proposed role of [Viagra (sildenafil)] in these processes is reasonable, and this does help support their findings.”

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Next, from a MedPage Today article, "Viagra Frisky Might Be Melanoma Risky", there is some more medical support for this still relatively new finding:

Though just an association -- not proof of causality -- the link between [Viagra (sildenafil)] and melanoma does have a potential molecular basis, said Ryan Sullivan, MD, of Massachusetts General Hospital in Boston.

"[Viagra (sildenafil)] may promote tumor growth, at least in tumor cells," Sullivan told MedPage Today. "There's plausibility, but this not causation as of yet. There's still a lot of work that needs to be done before we can definitively say that drugs for erectile dysfunction cause melanoma."

If the association proves to be a real relationship, then the effect on melanoma risk probably applies to all drugs in the PDE5-inhibitor class, he added.  [Emphasis added]

As such, this new drug injury finding which also seems to apply to the erectile dysfunction (ED) drugs Viagra, Cialis, Levitra, Staxyn, and Stendra, as well as the pulmonary arterial hypertension (PAH) medications Revatio and Adcirca -- all being phosphodiesterase 5 (PDE5) inhibitors.

We will continue to monitor this malignant melanoma side effect of Viagra as well as Cialis, Levitra, and other drugs in the PDE5-inhibitor class.

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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)