Essure Female Sterilization

Essure Product

Essure is a form of permanent birth control that was developed by Conceptus Inc. in 1998 and approved for the US by the FDA in 2002. It consists of a small metal coil resembling a spring, that is placed inside each fallopian tube. Once in place, the body surrounds the implant with scar tissue and creates a barrier so that sperm can not travel into the fallopian tubes and fertilize an egg.

This product was heavily marketed to primary practitioners and OB/GYNs, as well as their patients as a simple non-invasive form of female sterilization. It could be performed in a medical office setting or in an outpatient surgical center without the need for general anesthesia or any incisions. Essure was designed to be an alternative to tubal ligation because it was less expensive and far less invasive than the conventional surgical sterilization with a recovery time of 1-2 days (Essure, 2018).

Essure Timeline

From the time of the FDA approval, there have been clinical study requirements that were attached to the initial review and final approval of the product. This was due to the fact the initial study that was submitted to the FDA was rather short (2 years) and did not involve a large number of participants (745 women). The FDA stipulated that Conceptus would be required to conduct two post-approval studies. The first was to “gather five-year follow up information on the participants in the two premarket clinical trial patient cohorts” and the second consisted of evaluating the rates of bilateral placement by newly trained physicians (FDA, 2018).

2013- Bayer AG of Germany acquired Conceptus. In this same year, patient labeling of the Essure product was updated to include risks of chronic pain and device migration. This was due to increasing concerns among thousands of women that were experiencing severe side effects and surgical removal of the devices.

2014- Bayer sales reportedly topped out over $47 billion.

2016- The FDA required physician and patient labeling changes as well as the requirement of a Patient Decision Checklist (FDA, 2016). A box warning included information about patients having experienced numerous adverse events (persistent pain, perforations of the uterus and fallopian tubes, and migration of the coils into the pelvis or abdomen) and that surgical removal would be necessary to stop these. In the same year, the FDA announced that they were ordering Bayer to conduct post-market studies to determine the benefits and risks associated with the use of Essure.

2017- The European Union suspended the commercial license of Essure for a minimum of three months (Legal Reader, 2017). As a result of this action, authorities in France and Ukraine recalled the device and Bayer voluntarily recalled all implants in Canada, United Kingdom, Finland, and the Netherlands. The FDA also reported in this same year that they had received nearly 12,000 reports of adverse effects related to Essure (Reuters, 2018).

April 2018- The FDA update the physician and patient labeling again. This time, to include a restriction on the sale and distribution of Essure. This product would be restricted to only doctors and hospitals that reviewed the FDA-approved “Patient-Doctor Discussion Checklist – Acceptance of Risk and Informed Decision Acknowledgement” with their patients and got signed consent prior to implanting Essure devices (FDA, 2018). In a letter to Bayer, the FDA stated that they “determined that these restrictions on sale and distribution are necessary to provide reasonable assurance of the safety and effectiveness of the device” (FDA, 2018).

July 2018- The FDA issued a press release stating that the maker of Essure, Bayer, announced that they would halt sales of Essure in the US. The commissioner of the FDA stated that they had been notified by Bayer and “that the Essure permanent birth control device will no longer be sold or distributed after December 31, 2018” (FDA, 2018). Bayer stated that they would withdraw Essure from the US market. The reasoning was not due to safety concerns, but because of declining sales.

Essure Lawsuits

By the middle of 2018, more than 16,000 women had filed lawsuits against Bayer. These suits state that Bayer had knowledge that Essure was a defective product and did not provide proper warnings to those women that had the devices implanted, nor did they provide the necessary training for physicians. They also state that Bayer falsely made statements about the efficacy and safety of Essure in its marketing materials and on its website. Many of the cases include medical problems as stated by the FDA as well as complications ranging from migraines and hair loss to organ perforation from pieces of the device breaking off and unintended or dangerous pregnancies.

In 2018, there were nearly 37,000 women that chronicled their ordeal on the Facebook page Essure Problems, including the side effects and suffering that they attributed to Essure. Today, the site has over 42,000 members (Facebook, 2019).

In the same year, Netflix released “The Bleeding Edge” by Award-nominated filmmakers Kirby Dick and Amy Ziering. The documentary features women who have had a host of debilitating complications as a result of having a “non-invasive” and “medically approved” device implanted in their fallopian tubes to prevent future pregnancy. This film goes on the explain how the medical device industry has released products such as Essure with no concern for the consumers and has driven profits without proper research (Netflix, 2018).

During the ten years that Essure was marketed and sold in the US, almost 750,000 were implanted with this device (Time, 2018). This medical manufacturing giant currently has a group of 16 cases filed in the U.S. District Court for Eastern Pennsylvania and lawsuit filings are underway in California, Illinois, and Missouri. Many more are expected in the months ahead.

To date, Bayer denies any safety issues associated with Essure and sites that research conducted for nearly two decades confirms Essure’s favorable safety profile. In an interview in 2018, Christopher Loder, a company spokesperson for Bayer, went on to say that even the FDA continues to support the fact that “Essure’s benefits outweigh any potential risks” (Bloomberg, 2018).

References:

http://www.essure.com/what-is-essure

https://www.fda.gov/medicaldevices/productsandmedicalprocedures/implantsandprosthetics/essurepermanentbirthcontrol/ucm452270.htm

https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2016/10/fda-finalizes-guidance-on-boxed-warning,-patient-decision-checklist-for-essure-devices

https://www.fda.gov/downloads/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/UCM488065.pdf

https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/ucm452251.htm

https://www.legalreader.com/essure-loses-commercial-license-in-european-union/

https://medicalxpress.com/news/2017-08-eu-sale-contraceptive-implant.html

https://www.reuters.com/article/us-bayer-essure/bayer-to-phase-out-essure-birth-control-device-in-u-s-idUSKBN1KA2A1

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm604098.htm

https://www.accessdata.fda.gov/cdrh_docs/pdf2/P020014S051A.pdf

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm614123.htm

https://www.washingtonpost.com/news/to-your-health/wp/2018/07/20/sales-of-essure-birth-control-implant-halted-by-bayer-u-s-was-last-to-sell-controversial-device/?utm_term=.c216bba44ddc

https://www.forbes.com/sites/tarahaelle/2018/07/27/bayers-removal-of-contraceptive-device-essure-praised-by-activists/#5bce6eb74a23

https://www.bloomberg.com/news/articles/2018-07-25/bayer-essure-suits-skyrocketed-as-fda-pushed-stronger-warnings

http://time.com/5344646/bayer-essure-birth-control-sales/

https://www.facebook.com/groups/Essureproblems

Tracy R Everhart, MSN, MS CAM

For more than 20 years I've had the opportunity to work in numerous rolls within the medical field, including the last 7 years as a professional medical writer. With an undergraduate degree in biology/microbiology, postgraduate education in allopathic and complementary alternative medicine, my education has afforded me career opportunities with direct patient care, medical research and clinical oversight of statewide projects to improve the health of patients of all ages. I have a broad and deep knowledge of illnesses and conditions that can affect the human body. Even more important is that I have learned traditional treatment methodologies combined with alternative forms, to make the most informed decision about options that may be available.

Uloric Heart Risk

In 2009, Uloric (febuxostat) was the first new drug approved by the FDA for gout in nearly 40 years. Until then, allopurinol (Zyloprim) was the only drug available on the market for preventing the formation of the uric acid crystals that cause gout. However, many patients could not tolerate the recommended therapeutic dose of allopurinol without suffering side effects (sometimes fatal). This new drug did not get overwhelming support by the FDA advisory committee but was ultimately approved.

Clinical Trials for Uloric

Early clinical trials of Uloric showed that at a dose of 80mg, this new drug worked far better than allopurinol and at a 40mg dose, it works equally as well as allopurinol (Clinical Trials, 2005) (Clinical Trials, 2009). Research findings on this drug were submitted with an application to the FDA for approval. The FDA rejected this application sighting that there were slightly more deaths and heart problems with patients taking Uloric than were reported with patients taking allopurinol.

The manufacturer (Takeda) then submitted another application for approval. This 2006 application was denied as well. The committee members noted that 9 of the total 12 deaths among Uloric subjects were attributable to cardiovascular events, whereas no serious adverse cardiovascular (CV) events were linked to allopurinol or the placebo. Taketa then conducted another clinical trial and did not find these same results (Schumacher et al., 2008). They reported that most common side effects seen in these patients were liver function abnormalities, muscle and connective-tissue symptoms, nausea, and rash (FDA Prescribing Info, 2009). The drug was reported as being well tolerated, and the side effects did not increase over long-term use.

The FDA grouped the finding from all of the studies conducted by Takeda and could not determine “with much confidence” that Uloric posed a greater risk of CV events than did allopurinol. They ultimately approved the use of Uloric in the chronic management of hyperuricemia (elevated levels of uric acid) in patients with gout. With this use granted, they also stipulated that the manufacturer (Takeda) was required to conduct additional post-marketing clinical trial to determine:

Whether the use of Uloric is associated with a moderate increase in the risk of serious adverse cardiovascular outcomes when compared to allopurinol.
Any drug-drug interactions with Uloric and a single, oral dose of theophylline.

The results of these clinical trials also needed to be reported to the FDA according to a set schedule. The Final Report Submission for the drug-drug interaction with theophylline was due on May 31, 2010, and the Final Report Submission for cardiovascular risks was due on January 31, 2015 (FDA, 2009). They were also required to include drug warning labels.

Uloric Marketing

According to a report in The Pharma Letter, in the decade since Uloric was approved, the medication has been aggressively marketed to consumers and providers (Pharma Letter, 2018). Takeda reported $1.9 billion in US sales of febuxostat from fiscal years 2012 through 2017. For the one-year period ending in June 2015, there were 1.3 million US prescriptions for Uloric, making it the 46th most prescribed brand-name medication in the USA at the time. The retail price of a 30-day supply of Uloric is also roughly 20-25 times higher than allopurinol when compared on the GoodRx website (3/2019).

Uloric Cardiovascular Concerns

In 2017, serious concerns started to surface about the CV risks associated with the use of Uloric. November of that year, the FDA announced that they had received the preliminary results from the required clinical trials from Takeda and were alerting the public that they showed an increased risk of heart-related death with febuxostat (Uloric) compared to allopurinol. They stated that once the Final Report Submission was received, the information would undergo a comprehensive review. Once that was complete, they would notify the public of any additional findings (FDA, 2017).

The results of the study known as CARES was presented in March 2018, at an annual meeting of the American College of Cardiology in Orlando. This long term study compared the risk of CV events with the use of Uloric to allopurinol. They concluded that the rates were comparable for major CV events (non-fatal heart attack, stroke, rhythm problems and hospitalization for heart failure) between the two drugs (American College of Cardiology, 2018).

Following this announcement, a nonprofit consumer advocacy organization called Public Citizen Health Research Group petitioned the FDA to remove the gout medication Uloric. According to the agency’s director “The FDA almost certainly would have denied approval of febuxostat if data from this post-market trial had been available at the time of the initial submission. The only justifiable course of action to prevent further cardiovascular deaths is obvious: This medication must be removed from the U.S. market immediately.”( Public Citizen, 2018)

In February 2019, the FDA released the results of their advisory committee review. The committee members overwhelmingly voted 19 to 2 (with one abstention) to approve a Boxed Warning for Uloric due to increased risk of heart-related death and death from all causes with the use of this drug. The FDA also stated that providers should “reserve Uloric for use only in patients who have failed or do not tolerate allopurinol. Counsel patients about the cardiovascular risk with Uloric and advise them to seek medical attention immediately if they experience the symptoms” such as:

Chest pain
Shortness of breath
Rapid or irregular heartbeat
Numbness or weakness on one side of your body
Dizziness
Trouble talking
Sudden severe headache

Taketa’s View of the CV Risks of Uloric

Taketa’s most recent clinical study of Uloric revealed that there were 15 deaths per year from heart-related causes and 26 deaths per year from any cause per 1,000 patients were observed (FDA, 2019). The president of Takeda responded to the FDA announcement in January 2019 by saying “We have studied the safety of Uloric for more than 15 years and remain confident in Uloric as an important option for the chronic management of hyperuricemia in gout. We look forward to additional discussions with the FDA regarding these CARES data.”

Since the risk of CV events is increased in patients with gout, it is troubling to know that Takeda presented report after report of the findings of their drug Uloric, stating that there was a risk of adverse effects that include CV events. Despite this information and additionally required clinical trials, they aggressively marketed this drug to providers and to consumers that were already at risk. This led to hundreds of thousands of patients being prescribed the drug, who were unaware of the potential dangers associated with it.

Sources:

https://clinicaltrials.gov/ct2/show/NCT00102440

https://onlinelibrary.wiley.com/doi/full/10.1002/art.24209

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_Approv.pdf

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021856s011lbl.pdf

https://worldhistoryproject.org/2009/2/13/fda-approves-takeda-pharms-uloric

https://www.medicinenet.com/script/main/art.asp?articlekey=94500

https://www.medscape.com/viewarticle/898600

https://www.webmd.com/arthritis/news/20090216/fda-oks-new-gout-drug-uloric

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000TOC.cfm

https://clinicaltrials.gov/ct2/show/results/NCT00174915?view=results

https://www.fda.gov/downloads/drugs/drugsafety/ucm584803.pdf

https://www.healio.com/rheumatology/gout/news/online/%7b5eff7ca8-878e-48de-aad2-6770ee0ef1d9%7d/fda-to-examine-heart-related-deaths-associated-with-febuxostat

https://www.acc.org/latest-in-cardiology/articles/2018/03/07/15/53/mon-8am-cares-cv-safety-of-febuxostat-and-allopurinol-in-patients-with-gout-and-cv-comorbidities-acc-2018

https://www.reuters.com/article/us-health-heart-gout-drug/newer-gout-drug-poses-risk-to-heart-patients-idUSKCN1GO26V

Tracy R Everhart, MSN, MS CAM

Opioid Crisis

An epidemic of addiction and death across the United States.

The use of opioid drugs has reached epidemic levels and has spread to every race, gender, socioeconomic class and nearly every age group of people in the United States. The Centers for Disease Control and Prevention (CDC) reports that these addictive drugs claim about 130 American lives on a daily basis and the numbers continue to increase annually. The question is, how did we as a nation get to this point and why?

What are opioids?

According to the National Institute of Health’s National Institute on Drug Abuse, “Opioids are a class of drugs that include the illegal drug heroin, synthetic opioids such as fentanyl, and pain relievers available legally by prescription, such as oxycodone (OxyContin), hydrocodone (Vicodin), codeine, morphine, and many others”.

Opium

Opium became available in the US in 1775, but we believe that it has used by man since 3400 B.C. when it was first recorded in writing. The drug comes from the opium poppy (Papaver somniferum) seed pod sap, that contains various amounts of alkaloids such as morphine, codeine, thebaine, and papaverine. In the U.S. in the 1800s, opium dens started to spring up in the west (San Francisco’s Chinatown) and quickly spread east to New York. This was because of immigration and trading with other countries that cultivated the poppies and then supplied the drug. Opioids (morphine) were used to treat soldiers in the 1860s during the civil war and many soldiers became addicted to them. The US Congress banned opium in 1905 and in the following year they passed the Pure Food and Drug Act. This act required labeling of the contents on all medications.

Heroin

The Bayer Company was the first to produce heroin and in 1898, there were producing and distributing this new “miracle drug” on a commercial scale. It was found that it controlled pain levels better than codeine and morphine. However, it was also discovered that patients were developing a tolerance to the drug and quickly becoming addicted. It was eventually banned but it’s use gradually increased until the 1970s. Since that time we have seen a ten-fold increase in heroin use in the U.S.

Prescription Opioids

The Harrison Narcotics Act in 1914 regulated opioids (and coca leaves) to limit their recreational usage and by the 1970s, the stigma of addiction led doctors to avoid prescribing opioids. They opted for surgical procedures to block pain signals instead. However, in the 1980s and 1990s, opioids began to be used again to treat pain from chronic diseases. This when we saw a spike in new pain medications being approved and prescribed.

Here, we can look at the timeline of opioids that have been approved by the US Food and Drug Administration (FDA) over the years:

1947 Methadone (methadone hydrochloride) was approved as an antitussive and analgesic. In 1972 it was approved for opioid addiction treatment.

1957 Darvon (propoxyphene hydrochloride) was approved.*

1972 Darvocet (propoxyphene napsylate, acetaminophen) was approved.*

1983 Vicodin (hydrocodone bitartrate, acetaminophen) was approved.

1987 MS Contin (morphine sulfate) was approved. First opioid that allowed dosing every 12 hours instead of every 4-6 hours.

1989 Percodan (oxycodone HCI, aspirin) was approved.

1990 Duragesic (fentanyl transdermal system) was approved. First opioid “patch” that was designed to be worn for 3 days.

1995 OxyContin (oxycodone controlled-release) was approved. The first formulation of oxycodone that allowed dosing every 12 hours instead of every 4 to 6 hours.

1998 Actiq (fentanyl citrate) was approved. First pain medicine approved to treat cancer breakthrough pain.

1999 Percocet (oxycodone and acetaminophen) was approved.

*Darvon and Darvocet were banned in 2010.

Most of these have become common household names, but they didn’t start that way. Many were originally designed and prescribed for severe acute pain. Prescriptions were written in very limited quantities or were mainly used in hospital settings. But by the period of 2012-2016, the sales data that was analyzed by the FDA shows that products that were sold from manufacturers to pharmacies and other settings, revealed that sales to retail settings accounted for the majority of the annual opioid analgesic sales (>80%) and injectable formulations accounted for less than 0.2% of those sales. This means that there has been an enormous shift in the sales of these drugs from in-patient settings (hospitals) to outpatient settings (pharmacies), to then be dispensed to the general public. This peaked in 2011 with doctors writing 238 million opioid analgesic prescriptions annually.

Opioid Addiction

There are some staggering statistics when we look at the number of individuals that are diagnosed with opioid use disorder (addiction) in the United States. The National Institute on Drug Abuse provides us with annual figures that include the effects that this has on public health and social and economic welfare. They estimate that nearly 1.7 million people in the United States suffer from substance use disorders related to prescription opioid pain relievers and 21 to 29 percent of all patients that are prescribed opioids for chronic pain will misuse them. Unfortunately, opioid deaths are the reality of opioid drug misuse. The CDC also has stated that around 68% of the more than 70,200 US drug overdose deaths in 2017 involved an opioid.

Opioid Deaths

We know that in the 1990s there was growing pressure in the health care industry to treat pain more aggressively and as a result, pharmaceutical companies focused on the development of new pain medications. These companies also marketed the drug aggressively to doctors. They were marketed as safe medications that provided long-term relief. These doctors were told that less than 1% of all patients that were prescribed medications abused them and they should be prescribing more to help their patient in pain. Many critics believe that there was a concerted effort by the pharmaceutical companies to mislead the public and physicians about the dangers.

Since then, millions of Americans have abused prescription opioids. The federal government reports that more than 130 people now die each day from opioid overdoses, though not all of those drugs were obtained by prescription. A study published in the Harvard Review of Psychiatry found that the death rate from opioid misuse is 6 to 20 time greater than that the general population.

The CDC estimates that the total “economic burden” of just prescription opioid misuse in the United States is $78.5 billion a year. This includes the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement. Because of this economic burden, local and state governments believe that the pharmaceutical companies should pay for the cost associated with this epidemic. Public officials hope for an outcome similar to the massive tobacco settlement of the 1990s.

Opioid Lawsuits

In an effort to reduce risk and maximize the benefits of available pain treatment options, the CDC issued comprehensive guidelines for prescribing opioids for chronic pain outside of cancer treatment, palliative care, and end-of-life care. These prescribing recommendations stated that non-opioid treatments are preferred as the first step for treatment of chronic pain. As a result of the attempts by the CDC to change opioid prescribing patterns, they have been opposed primarily by indirect intervention. This has been done by the pharmaceutical industry through lobbying and advocacy groups.

A coalition of 41 states’ attorneys general has filed lawsuits against five major opioid manufacturers (Endo International, Janssen Pharmaceuticals, Teva Pharmaceutical Industries Ltd./Cephalon Inc. and Allergan). Subpoenas have been served and they are seeking information about how these companies marketed and sold prescription opioids. This group also served a supplemental investigative subpoena to Purdue Pharma.

The coalition is also demanding documents and information related to distribution practices from three drug distributors (AmerisourceBergen, Cardinal Health and McKesson). According to reports by the Drug Channels Institute, these three companies had more than $400 billion in revenue in 2016 and manage about 90% of the country’s national drug distribution.

Forbes recently published an article that stated that they believe that “opioid lawsuits on par to the become largest civil litigation agreement in U.S. history”. To date, there are numerous lawsuits that have been filed in relation to the opioid crisis. The largest case to date is one filed in the US District Court of Ohio, in which municipalities from across the country are seeking damages from this opioid crisis. The judge, in this case, Dan A. Polster, has called the opioid epidemic a “man-made plague, twenty years in the making” and has refused a motion by drug companies to dismiss the case. He is urging both sides to come to an agreement in what could amount to billions of dollars.