Drug Injury Watch

Beyaz / Safyral / YAZ / Yasmin: These Drospirenone Containing Birth Control Pills Have A Higher Risk Of Blood Clot Side Effects Than Older Options

New Medical Journal Article Presents "Compelling Evidence" That These Newer Oral Contraceptives Are Associated With More Venous Thromboembolism Events

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Beyaz, Safyral, YAZ, and Yasmin are birth control pills which contain ethinyl estradiol (EE) and the progestin drospirenone (DRSP). These DRSP oral contraceptives have been associated with several different adverse side effects such as:

• Blood Clots
• Deep Vein Thrombosis (DVT)
• Pulmonary Embolism (PE)
• Stroke or Cerebrovascular Accidents (CVA)
• Heart Attack or Myocardial Infarction

From an Editorial piece published May 26, 2015 by the medical journal BMJ, "Fresh evidence confirms links between newer contraceptive pills and higher risk of venous thromboembolism", we get this commentary from Susan S. Jick (a professor of epidemiology at Boston Collaborative Drug Surveillance Program, Boston University School of Public Health):

Notably, Vinogradova and colleagues also looked at the newer oral contraceptives, such as those containing desogestrel, gestodene, and cyproterone, as well as the newest pill containing drospirenone, where data have been limited and the magnitude of effects on the risks of venous thromboembolism remains controversial. They found that the newer contraceptives increased risks by around 3.6- to 4.3-fold compared with non-use, and by around twofold compared with oral contraceptives containing levonorgestrel, norethisterone, or norgestimate. Combined, the results provide compelling evidence that these newer oral contraceptives are associated with a higher risk of venous thromboembolism than older options, despite attempts to develop safer hormonal contraceptives for women.

[Emphasis added]

The important new medical study that Dr. Jick is alluding to above is the subject of this article, "Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases", published in the same edition of the BMJ medical journal.  The lead researcher is Yana Vinogradova ( research fellow in medical statistics at Division of Primary Care, University Park, Nottingham, UK).

___________________________________________________

Beyaz/Safyral/YAZ/Yasmin/Ocella/Gianvi
Free Case Evaluation
Strictly Confidential, No Obligation.

____________________________________________________

 

From the Abstract for this May 2015 medical journal article:

Objective  To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account.

Results  5062 cases of venous thromboembolism from [two nested case-control studies] were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17).

Conclusions  In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.

In order to put this new birth control pill study into context as regards the relative safety of Beyaz, Safyral, YAZ, and Yasmin in terms of blood clot side effects like DVTs and/or PEs,  we return to the May 2015 BMJ Editorial piece by Dr. Jick:

There is controversy surrounding the association between different oral contraceptives and risk of venous thromboembolism, which is due to the variability of case definition and inclusion criteria, and has led to divergent results. Vinogradova and colleagues tried to address differences within previous study designs to help explain the range of results....

Vinogradova’s comprehensive study addresses important questions about the risk of venous thromboembolism in women taking oral contraceptives, concluding that the risk associated with newer pills is around twofold higher than the risk associated with older contraceptives. The risk varies according to case definition of venous thromboembolism, and does not seem to be materially higher for new users of oral contraceptives. These results, combined with those published in a similar study by Lidegaard and colleagues, clarify inconsistencies in earlier studies and provide important guidance for the safe prescribing of oral contraceptives.

[Emphasis added; Footnotes omitted]

Moving from the medical realm to the legal arena, from the PRODUCT-RELATED LITIGATION part of Bayer's Annual Report 2014 (at pg. 311 of the PDF document):

Yasmin™ / yaz™:  As of January 31, 2015, the number of claimants in the pending lawsuits and claims in the United States totaled about 5,000 (excluding claims already settled).  Claimants allege that they have suffered personal injuries, some of them fatal, from the use of Bayer’s drospirenone-containing oral contraceptive products such as Yasmin™ and / or yaz™....

As of January 31, 2015, Bayer had reached agreements, without admission of liability, to settle approximately 9,500 claims in the U.S. for venous clot injuries (deep vein thrombosis or pulmonary embolism) for a total amount of about US$1.9 billion. Bayer will continue to consider the option of settling such claims after a case-specific analysis of medical records. At present, about 2,000 such claims are under review....

Additional lawsuits are anticipated....

We will continue to watch for legal, medical, and regulatory developments as regards Beyaz, Safyral, YAZ, and Yasmin, as well as other DRSP birth control pills such as Gianvi and Ocella.

 

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)

May 2015 Diabetes Drugs - Ketoacidosis Link Warning By FDA Covers Invokana, Farxiga, And Jardiance, With Label Changes Possible

Case Reports Of These Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors Causing Diabetic Ketoacidosis (DKA) Presented At Recent Medical Meeting

 

 (Posted by Tom Lamb at DrugInjuryWatch.com)

 ________________________________________________________________________________

UPDATE: "Health Canada Warns About Link Between DKA & Popular Diabetes Drugs"

(5/19/16)

 ________________________________________________________________________________

 

The FDA is investigating a connection between a certain class of diabetes medicines and diabetic ketoacidosis (DKA), ketoacidosis, or ketosis.  From "FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood", issued on May 15, 2015:

The U.S. Food and Drug Administration (FDA) is warning that the type 2 diabetes medicines [Invokana (canagliflozin), Farxiga (dapagliflozin), and Jardiance (empagliflozin)] may lead to ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones that may require hospitalization. We are continuing to investigate this safety issue and will determine whether changes are needed in the prescribing information for this class of drugs, called sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Patients should pay close attention for any signs of ketoacidosis and seek medical attention immediately if they experience symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness....

A search of the FDA Adverse Event Reporting System (FAERS) database identified 20 cases of acidosis reported as diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients treated with SGLT2 inhibitors from March 2013 to June 6, 2014 (see Data Summary). All patients required emergency room visits or hospitalization to treat the ketoacidosis. Since June 2014, we have continued to receive additional FAERS reports for DKA and ketoacidosis in patients treated with SGLT2 inhibitors.

__________________________________________

Invokana / Farxiga / Jardiance
Free Case Evaluation
Strictly Confidential, No Obligation.

___________________________________________

 

In addition, at least one study presented at the 2015 annual meeting of the American Association of Clinical Endocrinologists found a connection between the SGLT2 inhibitors and diabetic ketoacidosis (DKA).  From this MedPage Today news report, "Three Diabetes Drugs Linked to Ketoacidosis, FDA Warns":

In one of the studies presented [this May 2015 meeting of the American Association of Clinical Endocrinologists (AACE)], researchers led by Foiqa Chaudhry, MD, an endocrinology fellow at the University of Florida, described two cases of DKA that developed after the patients were taking SGLT2 inhibitors. An 18-year-old female presented with persistent vomiting and abdominal pain for the last 24 hours. She'd had type 2 diabetes since she was 8, but had never had ketoacidosis.

She had started taking metformin and [Invokana (canagliflozin)] 3 weeks earlier, and her primary care physician increased the dosage from 100 mg to 300 mg one week earlier. She was treated for diabetic ketoacidosis with an insulin drip and an IVF, and was eventually discharged.

In the other case, a 55-year-old man presented with dizziness. It was found that he had recently started taking glipizide and [Farxiga (dapagliflozin)]. He was treated for mild DKA and sent home. The authors of the paper said that the safety of SGLT2 therapy warrants further study.

We will continue to monitor the safety profile of these SGLT2 inhibitors -- Invokana (canagliflozin), Farxiga (dapagliflozin), and Jardiance (empagliflozin) -- as regards side effects such as cases of acidosis reported as diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients using these drugs as diabetes treatments.

 

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)

Testosterone Injections Or Shots Such As Depo-Testosterone Might Have Higher Risks Of Heart Attacks, Strokes, And Deaths

New Medical Research Suggests The Safety Of A Testosterone Drug Might Depend On Its Form: Injections / Shots; Creams / Gels; Skin Patches

 

 (Posted by Tom Lamb at DrugInjuryWatch.com)

 

On March 3, 2015 an FDA Drug Safety Communication about testosterone products was issued requiring drug companies to make a “labeling change to inform of possible increased risk of heart attack and stroke with use”.

Now, according to a large retrospective cohort medical study published online by the JAMA Internal Medicine journal in May 2015, we learn that short-acting testosterone injections or shots -- such as the Depo-Testosterone (testosterone cypionate) injection from Pharmacia and Upjohn Company (a division of Pfizer) -- are associated with a higher risk of cardiovascular events, hospitalizations, and deaths when compared with gels or patches.

From the Abstract for "Comparative Safety of Testosterone Dosage Forms" (an Online First article), we get this overview of the new medical research:

Importance  Increases in testosterone use and mixed reports of adverse events have raised concerns about the cardiovascular safety of testosterone. Testosterone is available in several delivery mechanisms with varying pharmacokinetics; injections cause spikes in testosterone levels, and transdermal patches and gels cause more subtle but sustained increases. The comparative cardiovascular safety of gels, injections, and patches has not been studied.

Objective  To determine the comparative cardiovascular safety of testosterone injections, patches, and gels.

Conclusions and Relevance  Testosterone injections were associated with a greater risk of cardiovascular events, hospitalizations, and deaths compared with gels. Patches and gels had similar risk profiles. However, this study did not assess whether patients met criteria for use of testosterone and did not assess the safety of testosterone among users compared with nonusers of the drug.

___________________________________________________

Free Testosterone Drugs Case Evaluation
Strictly Confidential, No Obligation.

___________________________________________________

 

From a May 11, 2015 news report, "Testosterone Shots: Riskier Than Gels or Patches?" -- with this sub-headline: "Spike in T levels from bolus injections may explain higher adverse outcome rates" -- published online by MedPage Today, we get the following summary information and commentary about this testosterone drugs safety study:

Compared with men using gels, those receiving injections had a greater risk for the composite of cardiovascular outcomes (MI, unstable angina, and stroke) (HR 1.26, 95% CI 1.18-1.35), hospitalization (HR 1.16, 95% CI 1.13-1.19), and death (HR 1.34, 95% CI 1.15-1.56) but not VTE (HR 0.92, 95% CI 0.76-1.11).

When testosterone patches were compared with gels, the investigator did not find any increased risk for cardiovascular events (HR 1.10, 95% CI 0.94-1.29), hospitalization (HR 1.04, 95% CI 1.00-1.08), death (HR 1.02, 95% CI 0.77-1.33), or VTE (HR 1.08, 95% CI 0.79-1.47).

"Different dosage forms lead to different serum testosterone levels over time -- injections result in spikes and super-normal levels -- possibly accounting for the observed risk of cardiovascular disease," [J. Bradley Layton, PhD, an epidemiologist at the University of North Carolina Chapel Hill] and colleagues wrote....

The study is well-designed and done by a reputable group, said Bradley Anawalt, MD, an endocrinologist and professor of medicine at the University of Washington Medical Center, in an email to MedPage Today. But it only included short-acting forms of injectable testosterone (testosterone cypionate, enanthate, and propionate) and not the longer-acting testosterone undecanoate which is the most common form used in Europe and which was recently approved in the U.S.

The short-acting forms of injectable testosterone are associated with higher spikes in testosterone levels, said Anawalt, who was not involved with the study.

"I don't think we should change our practice based on this study," Anawalt said. However, he added that for those using short-acting testosterone injections, the study suggests it may be prudent to use lower doses at more frequent intervals.

For more about what is currently know about testosterone drugs like Axiron, AndroGel, Testim, Depo-Testosterone, see this website page Testosterone Therapy Drugs.

We will continue to watch for new medical research about testosterone drugs safety especially as regards heart attacks or myocardial infarction (MI), strokes, and cardiovascular deaths which might be caused by so-called "Low-T" testosterone therapy products such as Depo-Testosterone injections or shots.

 

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)

Long-Term Combined Plavix - Effient Use May Be Associated With An Increased Overall Risk Of Non-Cardiovascular Death Compared To Shorter Therapy Period

FDA Drug Safety Communication Issued In November 2014 About The Dual Antiplatelet Therapy (DAPT) Trial Which Was Published In The New England Journal of Medicine

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

Plavix (clopidogrel) and Effient (prasugrel) are important antiplatelet blood-thinning medicines used to prevent heart attacks, strokes, and other clot-related diseases.

The Dual Antiplatelet Therapy (DAPT) trial was published by the New England Journal of Medicine (NEJM) on November 16, 2014 in this article, "Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents".

That same day came this related item, "FDA Drug Safety Communication: FDA reviews long-term antiplatelet therapy as preliminary trial data shows benefits but a higher risk of non-cardiovascular death", from which we get this information:

FDA is evaluating preliminary data from a clinical trial showing that treatment for 30 months with dual antiplatelet blood-thinning therapy decreased the risk of heart attacks and clot formation in stents, but there was an increased overall risk of death compared to 12 months of treatment. The clinical trial compared 30 months versus 12 months of treatment with dual antiplatelet therapy consisting of aspirin plus either clopidogrel (Plavix) or prasugrel (Effient), following implantation of drug-eluting coronary stents....

FDA has not reviewed the trial results or reached any conclusions based on the findings from this clinical trial. We are communicating this safety information while we continue to evaluate the results from this trial and other available data. We will communicate our final conclusions and recommendations when our evaluation is complete.

We will watch for the FDA's follow-up communication as regards this Plavix - Effient drug safety investigation and report significant developments here.

 

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)