Category: News

Over-the-Counter Birth Control Pills: FDA Considering HRA Pharma’s Opill

Why Over-the-Counter Birth Control?

Oral contraceptives have been around since 1960, and their risks and safety profiles have been well-studied throughout the years. According to the Guttmacher Institute, unplanned pregnancies account for 45% of all pregnancies in the US. Furthermore, nearly one-third of individuals who have tried to obtain a prescription for hormonal contraception report difficulty doing so. Polling from Data for Progress in 2022 shows that the majority of Americans, regardless of political affiliation, support making birth control available over the counter. 

The push for over-the-counter (OTC) birth control is driven by the need to expand access to safe and effective contraception. Research shows that women and teens who are uninsured, currently use a less effective contraceptive method, or tried to get a birth control prescription in the past year are more likely to use OTC birth control. Being able to acquire birth control over the counter would especially benefit marginalized communities and individuals who face healthcare barriers, such as transportation, cost, language, and lack of physician access.

Over 100 countries worldwide have approved OTC birth control options, but as of April 2023 the United States is not one of them. The American College of Obstetricians and Gynecologists, American Medical Association, and American Academy of Family Physicians concur that oral contraceptives should be approved for OTC use. In June 2022, the AMA urged the FDA to approve an OTC contraceptive method with no age restriction.

How Do We Get an OTC Birth Control Option?

In order for a drug to be approved for OTC use by the FDA, certain criteria must first be met. The drug must be safe, treat a condition that patients can diagnose by themselves, have a low potential for abuse or misuse, and be available for use without supervision of a healthcare provider. Oral contraception checks all of these boxes.

The next step is having a pharmaceutical company manufacture a product that can be FDA-approved for OTC use. HRA Pharma, a French pharmaceutical company acquired by Perrigo, is working with Ibis Reproductive Health to bring the product Opill to the US market. 

What is Opill?

Opill, the product manufactured by HRA Pharma, is a progestin-only pill for which Ibis and HRA Pharma are seeking FDA approval. If approved, Opill will become the first oral contraceptive available over the counter in the US.

There are two types of oral contraceptives: combination pills (containing both estrogen and progestin) and progestin-only pills. Progestin is a form of the endogenous hormone progesterone, and it plays a key role in the menstrual cycle. Progestin, along with other hormones, helps start and stop the menstrual cycle. Low progestin levels in the body cause shedding of the uterus lining, signaling the start of menstrual bleeding. High progestin levels in the body (i.e., when you’re taking a progestin-only pill) cause the cervical mucus to thicken, making it harder for sperm to enter the uterus and fertilize an egg.

Progestin-only pills are deemed safer than combination oral contraceptives. Due to estrogen’s pro-coagulatory nature, combination oral contraceptives carry the risk of adverse effects related to thromboembolism, or blood clotting. The lack of estrogen in progestin-only pills means it is preferred in individuals who smoke, have high blood pressure, experience migraines with aura, or are otherwise at risk of blood clots.

On July 11, 2022, HRA Pharma submitted their application for FDA approval of Opill. The FDA review process is expected to take about 10 months. Opill has been approved for prescriptive use since 1973, so its safety data has stood the test of time. Traditionally, progestin-only pills must be taken at the same time each day, with only a three-hour window of tolerance before requiring back-up contraception (e.g., male condom). However, recent research has found that there is a larger margin of error than previously believed. Because different progestin-only pills contain different types of progestin, they act on the body through different mechanisms. Thus, some progestin-only pills (including norgestrel-only formulations such as Opill) may not adhere to the strict three-hour window of administration.

When Can We Expect a Decision from the FDA?

Previously, the FDA planned to hold a joint meeting on November 18, 2022 with the Nonprescription Drugs Advisory Committee (NDAC) and the Obstetrics, Reproductive, and Urologic Drugs Advisory Committee (ORUDAC) to review HRA Pharma’s Opill application. This joint meeting was put off indefinitely until March 28th of this year, when the FDA announced that it has rescheduled the advisory committee meeting for May 9-10, 2023. May 9th is also Free the Pill Day, which celebrates the anniversary of the first birth control pill in the US becoming FDA-approved in 1960.

Currently, the nationwide movement involving pharmacists prescribing hormonal contraceptives helps circumvent healthcare barriers and make birth control more accessible. The approval of Opill would further aid in the removal of these barriers and see a monumental expansion of contraceptive access, bringing us one step closer to providing patients with the healthcare they deserve. We look forward to the FDA’s decision as May 2023 draws near.

References

  1. Abrams A. First U.S. application for over-the-counter birth control pill. Time. https://time.com/6195124/birth-control-pill-over-the-counter-fda/. Published July 14, 2022. Accessed April 13, 2023. 
  2. Data For Progress. Files For Progress. Data For Progress. https://www.filesforprogress.org/datasets/2022/5/dfp_22_cai_tabs.pdf. Published 2022. Accessed April 14, 2023. 
  3. Finer L, Zolna M. Declines in unintended pregnancy in the United States. 2008–2011, New England Journal of Medicine, 2016, 374(9):843–852, doi:10.1056/NEJMsa1506575.
  4. Grindlay K, Grossman D. Interest in Over-the-Counter Access to a Progestin-Only Pill among Women in the United States. Womens Health Issues. 2018;28(2):144-151. doi:10.1016/j.whi.2017.11.006
  5. Grindlay K, Grossman D. Prescription Birth Control Access Among U.S. Women at Risk of Unintended Pregnancy. J Womens Health (Larchmt). 2016;25(3):249-254. doi:10.1089/jwh.2015.5312
  6. Wollum A, Zuniga C, Blanchard K, Teal S. A commentary on progestin-only pills and the “three-hour window” guidelines: Timing of ingestion and mechanisms of action [published online ahead of print, 2023 Feb 19]. Contraception. 2023;109978. doi:10.1016/j.contraception.2023.109978.

Photo credit: Image from FreethePill.org


MatissaAbout the Author

Matissa Peng, Pharm.D Candidate, is a 3rd-year student pharmacist in the Class of 2023 at the University of the Pacific Thomas J. Long School of Pharmacy. Matissa completed an elective APPE rotation with Birth Control Pharmacist.

Misoprostol-Only Medication Abortion Regimen

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Political Climate

After the U.S. Supreme Court’s decision to eliminate the constitutional protections for abortion in Dobbs v. Jackson Women’s Health Organization in June 2022, access to mifepristone and abortion services in general are being threatened across the country.

An ongoing anti-abortion lawsuit in Texas seeks to reverse mifepristone’s FDA approval and remove it from the market, even in states where abortion is legal.

This won’t shut down medication abortion altogether, but it will limit treatment options. In the unfortunate case that mifepristone is taken off the market, we need to be prepared to use other regimens such as misoprostol-only.

 

Background

Misoprostol can safely be used alone for medication abortion if mifepristone is not available. It is used off-label for abortion because it is effective at inducing uterine contractions and cervical ripening.

Evidence from a range of sources including randomized control trials, a meta-analysis, a retrospective review and others, shows that misoprostol-only successfully terminates around 80-100% of pregnancies without needing procedural intervention.1 

 

Safety

Side effects for the misoprostol-only regimen are similar to the combined mifepristone and misoprostol regimen, however they may last longer due to the multiple doses.

Beyond vaginal bleeding, other common side effects of misoprostol include nausea, abdominal pain and cramping, diarrhea, and fever/chills. Major complications requiring hospital admission, blood transfusions, or surgery are rare and occur in <1% of cases.1 Patients should seek medical attention if they experience heavy bleeding that soaks 2 full-size pads per hour for 2 consecutive hours, a persistent fever over 100°F that lasts more than 4 hours, severe abdominal pain that is unresponsive to pain medications, or general malaise that lasts over 24 hours after the last misoprostol dose.

It’s critical to acknowledge that self-managed abortions occur and that they may increase, especially in states with severe abortion bans. Available data on self-managed abortions suggest a low prevalence of serious adverse outcomes.2

Pharmacists have been publicly deemed as some of the most trusted healthcare professionals, and it’s important to think about how we can be a safe resource for patients who do seek support for adverse events while protecting them and ourselves from legal repercussions.

 

Sample Protocol

The following sample protocol is endorsed by the Society of Family Planning.3 Providers may use it for guidance when screening patients in-person or through telehealth. Of note, the buccal route of administration is not included in this protocol, but is commonly used as well.

 

Eligibility Criteria 

  • Pregnancy confirmed by urine, serum test, or ultrasound 
  • Gestational age ≤ 12 weeks 
  • None of the following risk factors or symptoms of ectopic pregnancy:
    • Vaginal bleeding or spotting within the past week
    • Pelvic pain within the last week 
    • Prior ectopic pregnancy or tubal surgery
    • IUD currently in uterus or at time of conception
  • No history of hemorrhagic disorder or concurrent anticoagulant therapy
  • No history of allergy to misoprostol or other prostaglandin 
  • Patient has made an informed decision to use misoprostol-only for abortion

Treatment

  • Misoprostol 800 mcg sublingually or vaginally every 3 hours for at least 3-4 doses per clinician judgment
    • Sublingual route: put all 4 pills under the tongue and leave them there for 30 minutes, then swallow what’s left with water
    • Vaginal route: wash hands, lie down, and use finger to insert 4 pills as high up into the vagina as able to and stay lying down for 30 minutes. Moistening each tablet with a few drops of water before insertion may improve effectiveness
  • Analgesics, antipyretic, antiemetics, antidiarrheals as indicated or needed per the clinician

Follow-up

  • Confirm abortion completion by one of the following:
    • Urine pregnancy test 4 weeks after misoprostol use
      • If positive, evaluate with ultrasound or serum HCG tests
    • Ultrasound or pelvic examination 1-2 weeks after misoprostol use 
    • Serial serum HCG testing
      • First test on the day of initial misoprostol ingestion
      • Second test 1-2 weeks later

 

References

  1. Society of Family Planning. (2023). Misoprostol Only is Safe and Effective [fact sheet]. Retrieved from https://societyfp.org/wp-content/uploads/2023/02/SFP_ScienceSays_misoprostol.pdf
  2. Aiken ARA, Romanova EP, Morber JR, Gomperts R. Safety and effectiveness of self-managed medication abortion provided using online telemedicine in the United States: A population based study. Lancet Reg Health Am. 2022;10:100200. doi:10.1016/j.lana.2022.100200 
  3. Raymond EG, Mark A, Grossman D, et al. Medication abortion with misoprostol-only: A sample protocol [published online ahead of print, 2023 Feb 26]. Contraception. 2023;109998. doi:10.1016/j.contraception.2023.109998


michelle (2)About the Author

Michelle Chung, Pharm.D Candidate, is a 4th-year student pharmacist in the Class of 2023 at the University of Washington School of Pharmacy. Michelle completed an elective APPE rotation with Birth Control Pharmacist.

Pharmacists Can Now Dispense Mifepristone Under Updated REMS Program

Mifepristone REMS Update for Pharmacies

What Does the January 2023 Update Mean for Mifepristone Dispensing?

Mifepristone is a medication that is used to end an early pregnancy. It has been available in the United States since 2000 and is widely used as a safe and effective option for ending a pregnancy during the first 10 weeks.

As of January 2023, the US Food and Drug Administration (FDA) announced an update to the Risk Evaluation and Mitigation Strategy (REMS) for mifepristone. One of the most notable changes is the ability for pharmacists to dispense the drug to patients in the community retail setting. Pharmacies must become certified before they can order and dispense mifepristone. Pharmacies can become certified by choosing a designated representative to fill out the Pharmacy Agreement Form and oversee the implementation of the REMS program.

This only affects the dispensing aspect of mifepristone use. The requirements associated with the safe prescribing of this medication remain the same. This update is expected to alleviate the burden on patients and make medication abortion care more accessible. This revision to the REMS program is a step in the right direction for reproductive health access. 

The other component of the medication abortion regimen is misoprostol. Pharmacies have been dispensing misoprostol for medication abortion as well as other indications, so they can continue to do so without any changes.

 

Certification Requirements

Here are some of the most important steps to the certification process that pharmacists should know about.

  • Decide who will become the authorized representative(s). This individual(s) will oversee compliance with the REMS program.
  • Choose one Pharmacy Agreement Form from either Danco Laboratories or GenProBio to complete. You should pick the form that corresponds to the product — brand or generic — you plan to dispense most often.
  • Develop a record-keeping system for prescriber agreement forms. You can keep a binder with the physical forms or create a digital folder on the pharmacy computer. You will need a Prescriber Agreement Form (for either manufacturer) from each prescriber prior to filling the first prescription issued by them.
  • Record the NDC and lot number from each medication package dispensed in the patient’s record.
  • Mifepristone must be dispensed to the patient within four calendar days of the date the pharmacy receives the prescription.
    • If patients are set to receive the drug >4 days after the pharmacy received the prescription, confirm the appropriateness of dispensing with the prescriber.
    • If the pharmacy is mailing mifepristone, they must use a shipping service that provides tracking information.

 

How Should Pharmacists Counsel Patients?

  • Learn about the side effects, contraindications, counseling strategies, and follow-up needs related to mifepristone and misoprostol.

 

Why Is This Important?

Pharmacists play an integral role in medication abortion by ensuring that patients receive the correct medications in a timely manner and providing education on the proper use of the drugs. By providing guidance on other aspects of the abortion process, such as follow-up care and contraception options, pharmacists help to ensure that patients have a safe and successful abortion experience. It is important for pharmacists to be aware of these changes to ensure that they are providing their patients with the best care possible and following the requirements for dispensing mifepristone. 

 

Frequently Asked Questions

Can mifepristone be processed through prescription drug insurance?

There is no information yet on whether it is covered as a pharmacy benefit with the various health plans. Pharmacies should process the claims in hopes of coverage, and if not it will put the need for coverage on the radar for these health plans. For now, explain to patients it may be an out-of-pocket expense until their health plans align with the update. If any pharmacists have connections with health plans, this is an important issue to advocate for.

Federal Medicaid funding only pays for abortions when the pregnancy is a result of rape or incest or a threat to the pregnant person’s life. Sixteen states have opted to use their own state funds to pay for medication abortions, for Medicaid enrollees.

  • Alaska, California, Connecticut, Hawaii, Illinois, Maine, Maryland, Massachusetts, Minnesota, Montana, New Jersey, New Mexico, New York, Oregon, Vermont, and Washington

Private insurance coverage of abortion services is variable and depends on the type of insurance plan, the policyholder’s state of residence, and employer coverage decisions. Pharmacists should encourage patients to contact their insurance provider if they have questions about whether a particular insurance provider will cover the cost of the drug. 

 

Can a pharmacist refuse to dispense mifepristone or misoprostol?

Pharmacists can legally refuse to fill prescriptions due to religious or personal values in most states that have conscience laws. However, some states require that pharmacists avoid neglecting or abandoning the patient’s needs. In other words, you have to ensure the patient is still able to get the medications elsewhere in a timely fashion if you are not going to fill the prescription. Check your state policy.

 

Are there any special storage or handling requirements for mifepristone?

No, but it is important to note that:

  • MIFEPREX is supplied as light yellow, cylindrical, and bi-convex tablets imprinted on one side with “MF.” One tablet is individually blistered on one blister card that is packaged in an individual package.
  • The generic mifepristone is light yellow, circular, and is also packaged individually.
  • Both should be stored at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F).

 

Where can pharmacists receive training to dispense medication abortion tablets?

Located on our website is a continuing pharmacy education course that can help teach pharmacists about everything they need to know about medication abortion and the dispensing implications. It is a 1-hour home-study activity with no charge to participate, complements of UCSF’s ANSIRH, and it has received no commercial support.

 

How can a pharmacist support patients seeking medication abortion tablets, particularly in areas where access to such services may be limited?

If a pharmacy is not yet certified to dispense mifepristone, they can refer their patients to mail-order pharmacies. Here are three safe online options they can utilize: Honeybee Health, American Mail Order Pharmacy, and ManifestRx.

 

How will state bans affect pharmacy dispensing?

While pharmacies in any state may complete the pharmacy agreement for Danco or GenBioPro, they would not be able to legally dispense mifepristone for medication abortion if they are in a state that has banned medication abortion. Check your state policies.

 

How to know if a pharmacy is certified to dispense?

Pharmacies can inform their local providers when they’re enrolled to let them know about their certification. Pharmacies can consider proudly displaying signage in stores and on their social media to raise awareness about the availability of medication abortion care. We have some social media graphics that you are welcome to use. Patients are encouraged to call ahead to ask about a pharmacy’s status.

Some chains, like CVS and Walgreens, have stated they are in the works of becoming certified, but this doesn’t ensure every location will implement the program at the same rate.

 


Amanda IdusuyiAbout the Author

Amanda Idusuyi, Pharm.D Candidate, is a 4th-year student pharmacist in the Class of 2023 at the University of Connecticut School of Pharmacy. Amanda completed an elective APPE rotation with Birth Control Pharmacist.

Upcoming Changes to the Mifepristone REMS Program: Implications for Pharmacy Practice

Mifepristone REMS Change

Pharmacists in the community setting may soon have the opportunity to ease access to medication abortion in the United States. In the coming months, mifepristone (Mifeprex) is anticipated to have an updated Risk Evaluation and Mitigation Strategy (REMS) Program that allows dispensing through local brick-and-mortar and mail-order pharmacies. This change will integrate pharmacists into abortion care and bring them to the forefront of the national discussion about reproductive rights. Staying up to date on new regulations and their legal implications is paramount for successfully navigating this new role pharmacists can play in reproductive health and providing the best patient care.

Background

Mifepristone (Mifeprex) and misoprostol (Cytotec) are used together for medication abortion, or drug-induced interuterine pregnancy termination. Since 2000, this medication combination has provided pregnant patients with a safe, noninvasive means to end an unwanted but otherwise uncomplicated pregnancy. Patients first take mifepristone, followed by misoprostol in 24 to 48 hours. While misoprostol is dispensed at the prescriber’s office or a local pharmacy, there have historically been strict dispensing regulations on mifepristone.

In order to access medication abortion, patients must first make an appointment with a reproductive healthcare provider to ensure that there are no contraindications to this method of pregnancy termination. Prior to the coronavirus-19 pandemic, the prescriber of mifepristone was the only individual allowed to dispense this medication. Patients were required to be physically present with the prescriber to obtain mifepristone. Appointments to receive this medication often occur after the initial pregnancy screenings, and barriers to abortion such as intimidation by protestors and geographical proximity to clinics severely limited patient access to this service. 

During the coronavirus pandemic, enforcement of the in-person dispensing requirement has been relaxed with the condition that adherence to all other requirements included in the Patient Agreement Form be maintained, allowing for the utilization of mail to dispense mifepristone, either mailed to the patient from the clinic or a partner mail-order pharmacy. This temporary change has not only allowed greater access to medication abortion, but has led to increased calls for the permanent modification of the REMS Program associated with mifepristone.

More information on medication abortion can be found here.

Forthcoming FDA Update to the Mifepristone REMS Program

The success of the pandemic-spurred dispense by mail model emboldened advocacy for adjusting the provisions associated with mifepristone. Though no formal announcement was made, the FDA’s question and answer webpage on mifepristone was updated on December 16, 2021 to include upcoming changes. After a comprehensive review of the safety data collected through mifepristone’s REMS Program, the FDA indicated that an updated REMS is appropriate and should include pharmacy dispensing of this medication. 

While this change brings a groundbreaking transformation to safe abortion access in the United States, there are limitations on its timely implementation into pharmacy practice. Customary with the FDA’s policies for updating REMS requirements, REMS modification notification letters have been sent to the manufacturers of Mifeprex and generic mifepristone. The manufacturers, Danco Laboratories and GenBioPro, will draft an updated REMS Program and submit it to the FDA for approval. Once approved, the modifications to the REMS Program will be in effect. Pharmacies will need to be certified to dispense mifepristone.

This change will only affect the dispensing aspect of mifepristone use. The requirements associated with the safe prescribing of this medication will likely remain the same.

How to Prepare for Changes to Pharmacy Practice 

Though the details of the updated REMS Program are not yet public, there are steps that pharmacists can take in order to prepare for this change.

  • Become familiar with the websites for Mifeprex and mifepristone from Danco Laboratories and GenBioPro. The current process for prescribers to certify to prescribe and dispense this product, the Prescriber Agreement Form, is relatively straightforward. It is likely that the certification process for pharmacies will be similar.

  • Complete a continuing pharmacy education program on medication abortion to get acquainted with the adverse events, contraindications, counseling points, and follow up requirements associated with mifepristone and misoprostol.

  • Develop pharmacy policies regarding the dispensing of this medication. If a pharmacist on staff is not willing to verify and dispense a mifepristone prescription, there should be reasonable alternatives in place to ensure patient access to this medication.

  • Identify local resources for patients. In states where abortion restrictions are in place, it is incredibly important to stay up to date on the options that patients have for safe and effective reproductive care. 

Conclusions

Pharmacists have been and continue to be the most accessible healthcare providers to patients. With the upcoming modification to mifepristone’s REMS Program, pharmacists can play a larger role in patients’ reproductive health. Commitment to lifelong learning is an essential component of effective pharmacy practice. Regardless of personal beliefs, we as healthcare providers have a responsibility to practice in an educated way that is respectful of our patients’ autonomy and right to care within the law.

 


MuscatAbout the Author

 

Jacqueline Muscat is a pharmacy student in the Class of 2023 at University of Michigan College of Pharmacy.

Nextstellis®: A new drug update 

 

A new combined oral contraceptive was approved by the FDA (Nextstellis®) in April 2021.1 Nextstellis contains estetrol, an estrogen that can be manufactured from plants and that was originally derived naturally during pregnancy from the fetus liver, and drospirenone, a progestin found in other currently available contraceptives. Drospirenone has antiandrogenic and anti-mineralocorticoid activity.2 Estetrol differs from ethinyl estradiol in that has selective antagonistic and agonistic estrogen receptor activity, while ethinyl estradiol has exclusively agonist activity. With perfect use, Nextstellis is effective as a contraceptive for females between the ages of sixteen and fifty. These results are supported by data from two Phase III trials which obtained the drug’s safety and success over an extensive trial program. This research consisted of 3632 women between the ages of sixteen and fifty with 23% of patients having a BMI of 30-35 kg/m2. In the North American Phase III trial alone, 1524 women between the ages of sixteen to thirty-five years were tested over 12 months for 13 menstrual cycles and the clinical endpoint was that Nextstellis is 98% effective in preventing pregnancy when taken correctly.1

nextstellis packThe current recommended dosing is one tablet by mouth daily in the order provided by the blister pack for 28 days. The blister pack contains twenty-four active ingredient pills followed by four inert pills. The first active tablet should be taken on the first day of the menstrual cycle daily at the same time every day. If Nextstellis is not taken on the first day of menses an additional non-hormonal contraceptive method should be used for the first seven days.1 Nextstellis can be taken with or without food.2

 

Contraindications of Nextstellis

Patients should avoid use of Nextstellis prior to menarche or if they are postmenopausal.2 Nextstellis has a black box warning for women over the age of 35 who smoke.  Like other estrogen-containing contraceptives, this drug is contraindicated in women with a high risk, or current diagnosis, of thrombotic diseases. Nextstellis is also contraindicated in patients who have a history, or current diagnosis, of hormonal cancers such as breast cancer, renal impairment, adrenal insufficiency, and certain liver diseases: hepatic adenoma, hepatocellular carcinoma, acute hepatitis, or decompensated cirrhosis. Additionally, this drug cannot be administered in conjunction with hepatitis C drugs that contain ombitasvir/ paritaprevir/ ritonavir. Drug interactions for Nextstellis include CYP3A inducers and the patient should use an alternative contraception method for up to 28 days after the last dose of a CYP3A inducer. 2 Lastly, Nextstellis should not be used when there is undiagnosed and abnormal vaginal bleeding.1  

 

Other warnings and precautions include gallbladder disease, cholestasis, and liver disease in which case the drug should be discontinued. If hypertension or hyperkalemia occurs, monitor periodically and discontinue if levels persist outside of normal parameters. Additionally, Nextstellis should be discontinued if migraines are new, persistent, and severe to the patient.1 Females with prediabetes and diabetes should monitor their blood glucose levels, and females with hypertriglyceridemia should consider a different birth control as this may increase the risk of pancreatitis.2

   

Limitations of Use

The limitations of Nextstellis is that it could be less effective in obese patients with a body mass index equal to or greater than 30 kg/ m2. Within the studied population, 23% accounted for women with a BMI between 30- 35 kg/ m 2. The Pearl Index for women with a BMI <30 was 2.57, and it was 2.94 for women with a BMI between >30 and 35. 1 The Pearl Index is equal to the number of women that get pregnant out of 100 women per year. As the BMI increased in the women participating in the study, the Pearl Index also increased. The lower the Pearl Index, the more effective the use of contraceptives. 2

 

Adverse Reactions

The most common adverse reactions (>2%) were bleeding irregularities, dysmenorrhea, headaches, mood disturbance, increase weight, acne, decrease libido and breast symptoms.1 Mood disturbances were classified as irritability, anxiety, insomnia, panic disorder, restlessness and suicidal ideation. Breast symptoms included breast enlargement and sensitivity.2   These side effects are common in all combination oral contraceptives. Prescribers and dispensers should educate their patients that these symptoms are likely to occur, and most side effects will begin to resolve after three to five months of therapy when the body has adjusted to the hormonal changes. 3

 

Unique Features

While there are several other combination oral contraceptives on the market, Nextstellis has unique features that distinguishes it from other oral contraceptives. First, the estrogen component is estetrol, whereas most other contraceptives contain ethinyl estradiol. According to Grandi and colleagues  the selective actions of estetrol can lead to fewer side effect because the half-life of estetrol is 20- 28 hours, whereas other estrogens like estriol have a half-life of 10- 20 minutes and estradiol has a half-life of 1-2 hours. Estetrol is also minimally converted to estriol and estradiol. The longer half-life and the minimal metabolism to other estrogen forms, allows this drug to be  available for a longer period of time to bind at the receptor sites.4 Specifically, Nextstellis selectively binds to the nuclear estrogen receptor and it is described to be a native estrogen with selective action in tissues. 1 In pharmacologic studies, it was proven that estetrol acts as an estrogen in bones, uterus, and vagina. 5 

 

Clinical Trials

In addition to providing a contraceptive option for women who are unable to tolerate ethinyl estradiol, Nextstellis has demonstrated overall low rates of common side effects found in oral contraceptives such as acne, libido changes and breast pain in two Phase III studies (North American trial and the EU/Russian study).1 Animal data demonstrated that estetrol had a 100 times weaker effect on breast tissue proliferation in vitro human cells along with in vivo mouse mammary glands than estradiol.3 Although early animal studies have shown that estetrol has less of a damaging effect on breast tissue and may have a lower impact on the risk of breast cancer for humans, there needs to be more studies to solidify this data. 4

 

Interventional studies on Nextstellis have demonstrated less outcomes of deterrent side effects common to hormonal contraceptives such as breakthrough bleeding. Less than 2% of patients in the Phase III study experienced unscheduled bleeding episodes after cycle 2.1 In the FIESTA study it was shown that estetrol combined with drospirenone (E4/DRSP) compared with  quadriphasic estradiol valerate and dienogest (E2 V/DNG) had different frequencies for unscheduled bleeding. Breakthrough bleeding was present in 33.8% of the E4/DRSP group group versus 47.8% of the E2 V/DNG group. There was an additional study that showed overall satisfaction of being on E4/DRSP was higher than E2 V/DNG when patients took a self-reported Subject Satisfaction and Health-Related Questionare.4

 

Environmental Impact           

Estetrol is beneficial because it is less likely to contribute to water pollution and harm to the environment than estradiol (E2) or ethinyl estradiol (EE2).6 Nextstellis is metabolized in a unique way where less of the drug ends up being in the urine and therefore less of it ends up in our water system. This drug is made through a plant-based procedure, unlike other estrogens. Estrogens like ethinyl estradiol are not metabolized well, leading to build up in the body. Ethinyl estradiol is excreted in the urine and ends up in bodies of water, where it can lead to damage to marine life’s growth and ability to reproduce, whereas estetrol’s ability to be decomposed more quickly can be more environmentally friendly. According to Mirtha Women’s Health Pharmaceutics, levels as low as 1ng/L of E2 and EE2 in fish environments can lead to adverse effects and are far more potent than having 32,000 ng/L of estetrol. Adverse side effects, including reduced testicular growth, development of ova-testes in males, reduced egg production, delayed maturation, and the population ratio skewed towards females. are severely affecting the fishes reproductive health6.

 

In conclusion, Nextstellis is a recent FDA-approved oral contraceptive that offers patients another alternative for birth control. Nextstellis’ active estrogen is estetrol which is unique compared to other combination oral contraceptives. While not stated in the current package insert, data are emerging that support fewer breast tissue effects and breakthrough bleeding than older oral contraceptives. Overall, Nextstellis is a safe and effective contraceptive option. 

 

REFERENCES

  1. NEXTSTELLIS® (DRSP/E4): Now Available for Pregnancy Prevention. https://www.nextstellis.com/. Accessed June 25, 2021.
  2. Nextstellis (Drospirenone and Estetrol) [package insert]. U.S Food and Drug Administration website. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf. Accessed April 2021. 
  3. Grossman Barr, Nancy. “Managing Adverse Effects of Hormonal Contraceptives.” American Family Physician, U.S. National Library of Medicine, 15 Dec. 2010, pubmed.ncbi.nlm.nih.gov/21166370/.
  4. Grandi G, Chiara Del Savio M, Lopes da Silva-Filho A, Facchinetti F. Estetrol (E4): the new estrogenic component of combined oral contraceptives. Taylor & Francis. https://www.tandfonline.com/doi/full/10.1080/17512433.2020.1750365. Published April 7, 2020. Accessed June 25, 2021.
  5. Singer, Christian F., et al. “Antiestrogenic Effects of the Fetal Estrogen Estetrol in Women with Estrogen-Receptor Positive Early Breast Cancer.” OUP Academic, Oxford University Press, 5 July 2014, academic.oup.com/carcin/article/35/11/2447/416699.
  6. Mithra Pharmaceuticals. “E4 Paves the Road towards a Revolutionary Era of Environmental FRIENDLY MEDICINES.” GlobeNewswire News Room, Mithra Pharmaceuticals, 10 Jan. 2020, http://www.globenewswire.com/news-release/2020/01/10/1968775/0/en/E4-Paves-the-Road-Towards-a-Revolutionary-Era-of-Environmental-Friendly-Medicines.html


About the Authors

AthinaAthina Herrera Ng, PharmD Candidate 2023, is currently in her third year of pharmacy school at Midwestern University College of Pharmacy-Downers Grove. She holds the Event Chair position for Pharmacy and Pediatrics and is invested in learning more about women and children’s health. She is passionate about creating art in her free time as well as helping others heal through expressive therapy.

 

KaylaKayla Mitzel, PharmD Candidate 2023, is currently in her second year of pharmacy school at Midwestern University College of Pharmacy – Downers Grove. She is serving as the President Elect for APhA-ASP, and the Member at Large for CPNP. Her hobbies include running and biking. 

Reviewed by Brooke Griffin, PharmD, BCACP.

Updated Report on State Policy Efforts to Expand Access to Contraception in Pharmacies

Free 22-page report describing the current landscape of direct pharmacy access to contraception in pharmacies, state policy approaches and experiences, as well as implementation.

The 2020 report includes information for policy efforts in 2020, along with emphasis on definitions of reimbursement vs. payment and a new appendix with model bill elements. 

Subscribe and download PDF report

Levonorgestrel Intrauterine Device for Emergency Contraception

Levonorgestrel IUD for EC

A New Emergency Contraception Option

A recent study set out to assess the one-month pregnancy risk with the levonorgestrel 52-mg intrauterine device (IUD, Liletta®) as compared with the copper IUD (Paragard®) for emergency contraception (EC). The study included adults up to 35 years old who requested EC after unprotected sexual intercourse. Unprotected sexual intercourse must have occurred within the previous five days, but participants were not excluded if unprotected sexual intercourse also occurred up to 14 days prior. Participants were instructed to follow-up one month after IUD insertion for a urine pregnancy test, but even if they did not follow-up, their medical records for the following six months were reviewed to verify if a pregnancy was ever detected.1

 

Why the Levonorgestrel IUD?

Although not currently approved by the FDA for EC, the copper IUD, has substantial evidence supporting its use for EC. The failure rate of the copper IUD as EC is much lower than that of oral EC options.2-4 However, when compared to the copper IUD, the levonorgestrel IUD is more popular for long-term contraception, likely due to its other benefits, including decreased menstrual bleeding and pain.5-7

 

Failure Rates and Adverse Events

Of 638 total participants who received an IUD, only one patient experienced an EC failure. The patient had received a levonorgestrel IUD and the pregnancy ended in a spontaneous abortion at ten weeks with the IUD still in place. Statistical analysis of the data showed that the levonorgestrel 52-mg IUD was non-inferior to the copper IUD as EC. Rates of adverse events that required medical attention during the first month of IUD use were similar among both groups and very low overall.1

 

What Does This Mean for Patients?

This evidence means there is a new highly effective option for patients seeking EC and ongoing long-term contraception within five days of unprotected sexual intercourse. Although Liletta® was the levonorgestrel IUD used in this study, Mirena® is another levonorgestrel 52-mg IUD that releases the same daily dose of levonorgestrel. Other levonorgestrel IUDs release varying amounts of levonorgestrel, so we cannot necessarily expand these results to other options at this time. It is also possible the levonorgestrel IUD could be effective in preventing pregnancy when used up to 14 days after unprotected sexual intercourse, but more research is needed in this patient population.1

 

What Does This Mean for Pharmacists?

Pharmacists should be aware of this new option when counseling and referring patients who request EC after unprotected sexual intercourse. Of course, pharmacists should also know when it would be appropriate to utilize other EC options and if their state allows them to prescribe oral EC.

 

For more information: 

References

  1. Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs. copper intrauterine devices for emergency contraception. N Engl J Med. 2021; 384:335-44.
  2. Cleland K, Zhu H, Goldstuck N, et al. The efficacy of intrauterine devices for emergency contraception: a systematic review of 35 years of experience. Hum Reprod. 2012; 27:1994-2000.
  3. Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomized non-inferiority trial and meta-analysis. Lancet. 2010; 375:555-62.
  4. von Hertzen H, Piaggio G, Ding J, et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicenter randomized trial. Lancet. 2002; 360:1803-10.
  5. Diedrich JT, Desai S, Zhao Q, et al. Association of short-term bleeding and cramping patterns with long-acting reversible contraceptive method satisfaction. Am J Obstet Gynecol. 2015; 212:50-8.
  6. Sanders JN, Myers K, Gawron LM, et al. Contraceptive method use during the community wide HER Salt Lake contraceptive initiative. Am J Public Health. 2018; 108:550-6.
  7. Peipert JF, Zhao Q, Allsworth JE, et al. Continuation and satisfaction of reversible contraception. Obstet Gynecol. 2011; 117:1105-13.


About the AuthorKatie Hood

Katie Hood, PharmD Candidate is a pharmacy student in the Class of 2021 at Shenandoah University Bernard J. Dunn School of Pharmacy and Pharmaceutical Sciences. Katie completed an elective APPE rotation with Birth Control Pharmacist.

Medication Abortion Curriculum: A Pharmacy Student Perspective

The topics of reproductive health and particularly abortion remains stigmatized in today’s society despite 1 in 4 women having an abortion in their lifetime. Pharmacy school curriculums across the nation reflect this predicament, since abortion is omitted in the standard curriculum of many, if not all, pharmacy schools. Which brings up a question of how knowledgeable are student pharmacists, future medication specialists, with this subject?

Medication Abortion Curriculum was developed by the expert pharmacy educators at Birth Control Pharmacist in an attempt to better familiarize pharmacy students with the topic of medication abortion. This open access curriculum is a PowerPoint deck that is intended to be added or incorporated within a standard, larger lecture such as contraception. The slides provide the basics on medication abortion and prepare pharmacy students to dispense medications and counsel patients appropriately.

Medication abortion with a regimen of mifepristone and misoprostol has been shown to be safe and effective for decades, and is becoming increasingly utilized and acceptable to women across the world.1 Despite the growing use of these medications to induce termination of early pregnancy, the U.S. pharmacist involvement in abortion care is currently limited due to FDA imposed restrictions on how mifepristone can be distributed and dispensed.2 However, in some countries both medications are allowed to be dispensed by pharmacies rather than being limited to clinics and doctor’s offices, improving accessibility for people in need.3,4 Current research has shown great benefits of expanding the types of clinicians providing services, which may eventually lead to FDA lifting unnecessary restrictions to increase access to medication abortion through pharmacies.5

Diversification of skills and areas of expertise is necessary for any future pharmacists who want to stay relevant in tomorrow’s healthcare. Pharmacists need to be prepared to dispense and counsel on misoprostol now and may be able to offer additional patient-centered care in the future. For these reasons, pharmacists should be capable of providing patients with sufficient information, education, and safe and convenient care.

If you’re a pharmacy educator or a student who wants to advocate for medication abortion to be included in your school’s curriculum, check out the slide deck on the Resources page under Pharmacist Education and Training. 

Medication Abortion Curriculum Open Access for Pharmacy Educators

References

  1. Beaman J, Prifti C, Schwarz EB, et al. Medication to Manage Abortion and Miscarriage. J Gen Intern Med. 2020;35(8):2398-2405. doi:10.1007/s11606-020-05836-9.
  2. Raifman S, Orlando M, Rafie S, et al. Medication abortion: Potential for improved patient access through pharmacies. J Am Pharm Assoc (2003). 2018;58(4):377-381.doi:10.1016/j.japh.2018.04.011.
  3. Tamang A, Puri M, Masud S, et al. Medical abortion can be provided safely and effectively
    by pharmacy workers trained within a harm reduction framework: Nepal. Contraception. 2018;97(2):137-143. doi:10.1016/j.contraception.2017.09.004.
  4. Rogers C, Sapkota S, Paudel R, et al. Medical abortion in Nepal: a qualitative study on women’s experiences at safe abortion services and pharmacies. Reprod Health. 2019;16(1):105. doi:10.1186/s12978-019-0755-0.
  5. Weaver G, Schiavon R, Collado ME, et al. Misoprostol knowledge and distribution in Mexico City after the change in abortion law: a survey of pharmacy staff. BMJ Sex Reprod Health. 2019;46(1):46-50. doi:10.1136/bmjsrh-2019-200394.


About the AuthorEugenia

Eugenia A. Haire, PharmD Candidate is a pharmacy student in the Class of 2021 at the Shenandoah University Bernard J. Dunn School of Pharmacy. Eugenia completed an elective APPE rotation with Birth Control Pharmacist.

Webinar Introduces Pharmacists to New Hormonal Contraceptives

New drugs are constantly being approved by the FDA, and it is important for practicing pharmacists to stay up to date on new contraceptives. There are now over 50 unique contraceptives available, and pharmacists need to be aware of these and incorporate them into their practices. Birth Control Pharmacist recently hosted a webinar that aimed to educate pharmacists, pharmacy staff members, and other healthcare providers to feel more comfortable with the new contraceptive options they could prescribe or dispense.

The faculty speaker, Shareen El-Ibiary, PharmD, BCPS, FCCP, is a professor and chair of the Department of Pharmacy Practice at Midwestern University, College of Pharmacy. She is also a consultant for Birth Control Pharmacist.

The program focused on three new hormonal contraceptives – Annovera, Twirla, and Slynd – along with one new nonhormonal contraceptive – Phexxi.

What is Annovera?

Annovera is a new contraceptive vaginal ring that contains segesterone and ethinyl estradiol. It is different from NuvaRing because it is used for 13 consecutive cycles, as opposed to just one cycle. It is not refrigerated.

What is Twirla?

Twirla is a new contraceptive patch that contains levonorgestrel and ethinyl estradiol. It is very similar to Xulane in terms of application, but Twirla has lower rates of headache, nausea, and breast tenderness.

What is Slynd?

Slynd is a new progestin-only oral contraceptive that contains drospirenone. In each pack of 28 tablets, there are 24 active tablets and four inactive tablets. The main benefit of Slynd over norethindrone is less opportunity for missed doses. Unlike norethindrone’s 3-hour window to take a dose, patients on Slynd have up to a 24-hour window to take a dose before it is considered a missed dose. Pharmacists need to be aware of the unique drug interactions associated with Slynd.

What is Phexxi?

Phexxi is a new prescription-only contraceptive gel that does not contain nonoxynol-9. Instead, it contains lactic acid, citric acid, and potassium bitartrate. Phexxi should be applied vaginally within one hour before each episode of intercourse. It should not be used by patients who have recurrent urinary tract infections or urinary tract abnormalities.

Dr. El-Ibiary wrapped up the program by reviewing patient cases, and she even demonstrated a patient interaction within a pharmacy. This helped bring the concepts from the lecture portion to life and allowed participants to practice incorporating these new hormonal contraceptive into their counseling and other practices.

Fortunately, if you missed the webinar, the video recording and materials are available for home study online at https://birthcontrolpharmacist.com/newhc/. The course material is available to all, with pharmacists having the opportunity to obtain Continuing Pharmacy Education credit. This material provides education to participants to increase their comfort in prescribing, dispensing, or counseling patients on the new contraceptive options available.

Participants provided feedback at the conclusion. Keep reading to see their positive reviews and gain a better idea of what to expect from the online course:

 “As a P1, I appreciate how Dr. El-Ibiary explained everything clearly. It helped me better understand the content and I now have a much better understanding of contraceptives.”

“Very practical, real-life patient case scenarios were used as effective teaching points.”

“Amazing presentation. Very informative and easy to follow.”

“Thank you for providing this CE! It was both helpful & thorough.”

New Hormonal Contraceptives Home Study CPE

Katie HoodAbout the Author

Katie Hood, PharmD Candidate is a pharmacy student in the Class of 2021 at Shenandoah University Bernard J. Dunn School of Pharmacy and Pharmaceutical Sciences. Katie completed an elective APPE rotation with Birth Control Pharmacist.

Webinar Equips Pharmacists to Provide Contraception Care During COVID-19

During the COVID-19 worldwide pandemic it has been quite the adjustment to deliver safe and quality patient care. Specifically, for contraception care, pharmacists have been working extra hard to continue their direct patient care with how accessible they are. Birth Control Pharmacist recently hosted a webinar that facilitated an educational program and discussion for pharmacy staff members to feel more equipped to deliver contraception and emergency contraception services during COVID-19.

We had multiple speakers of diverse backgrounds in order to give different perspectives on the effects of COVID-19 on contraception care and how pharmacists can best help their patients. The panel speakers were Jennifer Karlin, MD, PhD an attending physician in Family & Community Medicine at UC Davis and Sonya Frausto, PharmD who is the pharmacist-in-charge at Ten Acres Pharmacy, an independent community pharmacy.

What is the healthcare landscape during the COVID-19 pandemic?

Laying out the landscape during the COVID-19 pandemic helped paint a picture to participants about the extensive effects on contraception care. Whether that be loss of insurance or fear of infection from going to healthcare facilities, it highlighted how important it can be for pharmacists to assist their patients with contraception while following national guidelines.

How can pharmacists prescribe birth control safely?

National guidelines covered prescribing birth control and also social distancing to reduce the risk of spreading the virus. Telehealth has been a useful service in adhering to social distancing, while also maintaining face-to-face encounters. This helps patients maintain a personal relationship with their pharmacist.

What are some best practices within the pharmacy?

There are many useful suggestions throughout the webinar, but a useful tool they referenced is the Contraceptive Care Best Practices During COVID-19 best practices guide for pharmacies created by Birth Control Pharmacist.

Dr. Frausto wrapped up the program by reviewing useful tools and resources to use while in the pharmacy. Then she demonstrated a patient interaction within a pharmacy. This helped really bring the whole webinar together with a real-world example and solidified that this webinar is well worth the watch.

Fortunately, if you missed the webinar, the video recording and materials are available for home study online at https://birthcontrolpharmacist.com/careduringcovid/. The course material is available to all, with pharmacists having an opportunity to obtain Continuing Pharmacy Education credit. This material provides education to participants to increase their comfort in providing contraception care, including prescribing hormonal contraception, in community pharmacies during the COVID-19 public health emergency.

Participants provided feedback at the conclusion. Keep reading to see their positive reviews and gain a better idea of what to expect from the online course:

“I loved this CE. Very informative, the speakers were great and passionate about the topic!”

“As a newer pharmacist, this type of information helps me to feel better prepared to provide these kinds of services to patients.”

“Loved the topic, very timely for COVID.”

“I was coming from a state where pharmacists did not prescribe birth control so this was a new perspective for me.”

pharmacy-based-contraception-care-during-covid-19-online-cpe-program-1

About the Author

Samantha ThompsonSamantha Thompson, PharmD Candidate is a pharmacy student in the Class of 2023 at University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. Samantha completed a summer internship with Birth Control Pharmacist.