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. 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.

Present and Future Pharmacist Roles in Medication Abortion Care

Medication Abortion Pharmacist

Educational programming for pharmacy students and practicing pharmacists on medication abortion is limited.

Twenty years ago, the FDA approved mifepristone. Since then, medication has transformed the accessibility of abortion. In 2017, about 39% of abortions in the United States were medication abortions, reflecting many people’s preference for this option.1 As reproductive health services are transforming, it is important that pharmacy services become adaptive to them.

What is medication abortion?

A medication abortion is the use of medications to end a pregnancy. There are a couple of medication abortion regimens, but the only regimen approved by the FDA is a combination of mifepristone and misoprostol to end a pregnancy up to 70 days gestation.2

First, a patient takes 200 mg of mifepristone orally followed by 800 mcg of misoprostol buccally, 24-48 hours after the mifepristone dose. After 7-14 days, the patient must follow-up with a health care provider.2

Mifepristone works by binding competitively to the intracellular progesterone receptor, thus blocking the effects of progesterone that support the pregnancy.3 Misoprostol works by inducing contractions in the myometrium as well as relaxation of the cervix.4

According to a systematic review performed by the American College of Obstetrics and Gynecology (ACOG), medication abortion was 97% effective up to 70 days after gestation.5

Present pharmacist roles with medication abortion

Right now, the pharmacist role with medication abortion is minimal as patients receive their dose of mifepristone in the clinic to take either at that time or at home. A prescription for misoprostol may be filled at a pharmacy to be picked up by the patient. Pharmacists will counsel patients on how to take the misoprostol and what to expect with this medication.

Mifepristone is only able to be dispensed at a clinic as a result of restrictions in place as part of the Risk Evaluation and Mitigation Strategies, or REMS, with an exception allowing mail order during the pandemic. The purpose of REMS is to assure that a medication’s benefits outweigh its risks. Recently, there have been studies on the safety of mifepristone to determine whether the REMS requirements are necessary or not.

Future pharmacist roles with medication abortion

According to articles published in the New England Journal of Medicine and Journal of the American Pharmacists Association, the REMS restrictions on mifepristone use have been deemed medically unnecessary as the rates of adverse events and mortality are extremely low. Since its approval, only 19 deaths have been reported to the FDA out of over 3 million patients who had taken mifepristone giving it a mortality rate of 0.00063%.6 Additionally, analysis of data from studies of over 423,000 women, which demonstrated that nonfatal serious adverse events from mifepristone use ranged from 0.01-0.7% and were almost always able to be treated.6

There are research studies underway to evaluate no-test medication abortion protocols, medication abortion telehealth services, and pharmacy dispensing of mifepristone. As new information emerges, there will be more opportunities for pharmacists to have a role in medication abortion care.

Educational programming for pharmacy students and practicing pharmacists on medication abortion is limited. The University of California San Francisco’s Advancing New Standards in Reproductive Health (ANSIRH) recently released a home study continuing pharmacy education program titled “Pharmacists’ Role in Medication Abortionthat is free and open to all. Birth Control Pharmacist has an open access introductory curriculum that can be integrated into pharmacy curricula.

Conclusion

In summary, medication abortion is a critical and common component of women’s health and reproductive health services. Although there are currently restrictions on the ways that patients can obtain a medication abortion, this many soon change and pharmacists will be an important part of access.

This article was originally published in Pharmacy Times.

REFERENCES

  1. Jones RK, Witwer E and Jerman J, Abortion Incidence and Service Availability in the United States, 2017, New York: Guttmacher Institute, 2019, Accessed September 8, 2020. https://www.guttmacher.org/report/abortion-incidence-service-availability-us-2017
  2. U.S. Food and Drug Administration (FDA), Mifeprex (mifepristone) information, 2018. Accessed September 20, 2020. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/mifeprex-mifepristone-information
  3. Mifeprex (mifepristone) [prescribing information]. New York, NY: Danco Laboratories, LLC; April 2019.
  4. Cytotec (misoprostol) [prescribing information]. New York, NY: Pfizer; February 2018.
  5. Chen, MJ, Creinin, MD. Mifepristone with buccal misoprostol for medical abortion: A systematic review. Obstetrics and gynecology, 2015;126(1), 12-21. Retrieved from https://escholarship.org/uc/item/0v4749ss.
  6. Mifeprex REMS Study Group, Sixteen years of overregulation: time to unburden Mifeprex, N Eng J Med, 2017;376(8):790-794,https://www.nejm.org/doi/full/10.1056/NEJMsb1612526.
  7. Raifman S, Orlando M, Rafie S, Grossman D. Medication abortion: potential for improved patient access through pharmacies. 2018;58(4):377-81.


About the AuthorBreanna Headshot

Breanna Failla is a pharmacy student in the Class of 2022 at Midwestern University in Illinois. Breanna completed a summer internship with Birth Control Pharmacist.

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. 

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.

Putting Policy into Practice: Contraception Care in San Francisco Pharmacies

Contraception Care in San Francisco Pharmacies

What makes some pharmacies more successful than others at implementing pharmacist-prescribed contraception care? To answer this question, we conducted a study to determine the extent of hormonal contraceptive prescribing, also referred to as furnishing in California, among San Francisco community pharmacies, and identify the factors that led to successful implementation.

Implementation in San Francisco pharmacies 

After calling all 113 community and independent pharmacies located in San Francisco, we identified 21 locations (19%) that furnished hormonal contraception. Only one of these was an independent pharmacy; the rest were chain community pharmacies. Half or more of Costco, CVS, and Safeway locations furnished hormonal contraception, while less than 5% of Walgreens and independent pharmacies did so. 

Factors associated with successful adoption

Within the control of pharmacies

We identified three main factors that led to successful implementation that were within pharmacy control. The first was a company protocol—respondents stated that having an established precedent and administrative support, and paying for pharmacists’ training, was crucial for successful implementation. The second was advertising, due to the community’s limited awareness of this service. Lastly, the accessibility of pharmacists played a role in increasing access to services and to hormonal contraception. 

Relating to the setting or larger community

We also identified factors leading to successful implementation outside the control of pharmacies. These included the location of the pharmacy and its patient population, as well as collaboration with local clinics. Pharmacies in proximity to students and other younger and short-term residents found there was more need for hormonal contraceptive furnishing services. One pharmacy had an existing collaboration with a local clinic and its providers that acted as a bridge to the service. 

Barriers to service adoption 

Respondents also reported several barriers to successful implementation. The cost of consultation for patients was a widespread concern. Lack of time was another barrier reported by many pharmacists, which could be resolved through scheduled appointments or more overlaps of pharmacist shifts. The last identified barrier was patient privacy. Many respondents expressed a need for a private consultation room in order to provide a confidential service, and those that had a private consultation room acknowledged this as a benefit. 

Effect of COVID-19 on furnishing 

Our data collection began in April 2020, shortly after the introduction of San Francisco’s shelter-in-place order. We asked study participants to comment on whether practices or demand for hormonal contraception had changed under the shelter-in-place order and responses were mixed. While some pharmacies reported an increase in demand for hormonal contraceptive furnishing, others reposted a decrease. 

Implications for the future

We found an increase in participation among pharmacies in San Francisco that were furnishing hormonal contraception than previously reported in California overall; 19% in San Francisco in 2020 versus 11% statewide in 2017. This finding could reflect either pharmacies adding this service gradually over time or a local phenomenon. However, CVS pharmacists reported that a new corporate protocol was initiated in 2020, suggesting the higher rate of furnishing we identified could be reflected statewide. Our results detailed successful strategies used by San Francisco community pharmacies that could serve as a model for expanding this service to other pharmacies. In the words of one respondent:

“The pharmacist is the most overtrained and underutilized health care professional we have.”

With more widespread implementation of this service, community pharmacists can increase their scope of practice, improve quality and continuity of care for patients, and expand access to hormonal contraception to improve reproductive health.

Link to the full paper.

References

  1. California Board of Pharmacy 1746.1: Protocol for pharmacists furnishing self- administered hormonal contraception. Link.
  2. Chen L, Lim J, Jeong A, & Apollonio D. Implementation of hormonal contraceptive furnishing in San Francisco community pharmacies, 2020. Journal of American Pharmacists Association. doi:https://doi.org/10.1016/j.japh.2020.07.019
  3. Gomez AM. Availability of pharmacist-prescribed contraception in California, 2017. JAMA. 2017;318(22):2253e2254. 

Chen Lim Jeong ApollonioAbout the Authors

Lauren Chen, Julie Lim, and Asher Jeong are third-year doctoral students at the University of California San Francisco (UCSF) School of Pharmacy. Dorie Apollonio is a professor in the UCSF Department of Clinical Pharmacy.

Finding Gluten-Free Oral Contraceptive Options for Your Patients

Patients with celiac disease or who otherwise follow a gluten-free diet need to be aware of potential sources of gluten, especially in medications such as oral contraceptives. The FDA defines gluten as “proteins that naturally occur in [wheat, barley, and rye or their crossbred hybrids] and that may cause adverse health effects in persons with celiac disease”. Potential sources of gluten can come from excipient ingredients, which are used to bind pills. Starches used in excipients are typically derived from corn, potato, rice or tapioca which don’t contain gluten, but some starches may also be derived from wheat.

Besides the type of starch, the amount of starch in a pill can vary. While the FDA strictly regulates the active ingredients of drug products, drug manufacturers are allowed to use any quantity and type of FDA-approved excipient. Another factor to consider is that generic products only require the active ingredient to be identical to the brand and do not have to use the same excipient or inactive ingredients. So while a brand name medication may be gluten-free, the generic formulation isn’t guaranteed to also be gluten-free.

Determining if a Medication is Gluten-Free

If you’re looking for what ingredients are included in a medication, you can find them listed on the package insert, also known as the prescribing information. If the ingredients listed on the package insert don’t include what source they are derived from, such as ‘starch’ instead of ‘cornstarch’, then you should call the manufacturer to confirm the source.

Examples of both gluten-free and gluten-containing excipient ingredients include:

  • Pregelatinized starch, sodium starch glycolate: derived from corn, potato, rice, or wheat but chemically processed so gluten remaining is unlikely
  • Dextrans, dextrose: derived from corn and potato starch so they do not contain gluten
  • Dextrates, dextrins: derived from any starch source so you would have to call the manufacturer to confirm if gluten is included
  • Starch alcohols (xylitol, maltitol, and mannitol): some are derived from wheat but they are purified to no longer contain gluten

Another issue that can arise is cross-contamination. The FDA has stated that although they don’t collect data in regards to contamination with gluten, “the amount of gluten would be well below the levels we have estimated an inactive ingredient, such as wheat starch, could potentially contribute to an oral drug product”. If wheat happens to be an impurity in a drug listed as gluten-free, the FDA estimates that it could contain no more than 0.5 mg of gluten per pill (for reference, a slice of bread labeled ‘gluten-free’ may contain up to 0.57 mg of gluten and still meet FDA criteria for being considered gluten-free).

Drug Information Resources

DailyMed (https://dailymed.nlm.nih.gov/dailymed/) is a reputable online resource for pharmacists to use as you are able to see the active and inactive ingredients in each geneic formulation of a drug. This may be a complicated resource for patients, so make sure to limit this resource to your own education.

Currently, there are several oral contraceptive options available that are gluten-free. To be 100% certain, it is best to consult either DailyMed or the package insert for the ingredient lists.

Patient Counseling

Ultimately, it is up to the patient to decide if they feel comfortable taking their particular oral contraceptive. If there is any uncertainty about a medication’s gluten-free status, contacting the manufacturer directly is the best way to clarify. Other birth control methods that don’t include gluten are non-oral options such as the Depo-Provera® shot, Nexplanon® implant, vaginal rings, condoms (depending on lubricant used), diaphragms, IUDs, transdermal patches and more.

As pharmacists, it is important to make note of patient allergies on their profiles as well as counsel patients on the inactive ingredients in their medications so that patients can feel more confident and at ease while taking their medications. You can apply your skills when caring for patients by keeping track if generic manufacturers change and informing patients if they are able to continue taking their medications.

References

  1. United States, Congress, Food and Drug Administration. “Gluten in Drug Products and Associated Labeling Recommendations: Draft Guidance for Industry .” Gluten in Drug Products and Associated Labeling Recommendations: Draft Guidance for Industry, 2017, pp. 1–12.
  2. Parrish, Carol. “Medications and Celiac Disease- Tips from a Pharmacist.” Celiac.org, Jan. 2007, celiac.org/main/wp-content/uploads/2009/11/Medications_and_Celiac_Disease.pdf.

About the Author

birth control pharmacist headshots (2)Niamh O’Grady, PharmD Candidate, is a pharmacy student in the Class of 2021 at the University of California San Francisco School of Pharmacy.

Article reviewed by Breanna Failla, PharmD Candidate and Brooke Griffin PharmD, BCACP

Contraception During COVID-19: Pharmacy Best Practices

Pharmacists should not allow postponed or cancelled appointments to keep patients from accessing birth control. It’s important that patients understand how their pharmacy can continue to meet their contraceptive needs during the coronavirus disease 2019 (COVID-19) pandemic.

Pharmacists should inform patients that even though clinics and providers’ offices might be closed, their pharmacy is still able to facilitate refills, provide emergency contraception, and, in some states, prescribe hormonal contraception.

The following tips can help ensure your pharmacy is meeting patients’ contraceptive needs during COVID-19, while keeping your patients and pharmacy staff safe.

1. Encourage Contactless Communications and Dispensing 

Prevent patients from missing doses or going without contraception by preemptively contacting them via texts, emails, and calls to assess their needs. Encourage patients to utilize contactless communication to get in touch with the pharmacy for prescriptions or other items they want to order.

Pharmacies can provide contactless contraceptive care during COVID-19 by encouraging patients to obtain birth control prescriptions and products via mail, drive-through, or curbside pick-up services.


2. Promote and Supply Over-the-Counter Products

Visits to the pharmacy may be very limited for patients because of stay-at-home orders, social distancing, and other COVID-19-related barriers. Preemptively supplying prescriptions for emergency contraception can avert out of pocket costs while mitigating stress for patients that experience method failure and are unable to access the pharmacy in a timely manner.2 Encourage patients to have a pregnancy test on hand, in addition to over-the-counter contraceptive options, to ensure that patients’ contraceptive needs are met when routine visits to the pharmacy are not feasible.


3. Optimize Prescriptions and Anticipate Patient Needs

To maintain social distancing and the health of patients and employees, encourage providers to transmit new prescriptions electronically or via telephone.

Prescriptions for birth control should include maximum quantities and refills for a full year’s supply.2 Some states require health plans to cover dispensing a 12-month supply of birth control.3 Dispense the maximum amount allowed by the patient’s insurance and share the cash price if a patient desires paying out-of-pocket to limit visits to the pharmacy or clinic.

Pharmacy staff can proactively review patients’ profiles to anticipate upcoming refills and ensure the pharmacy’s birth control inventory is adequate to fulfill patient needs.

Check with your state’s COVID-19 pharmacy executive orders to ensure permitted emergency refills are being authorized.


4. Adapt Pharmacist Prescribing

Utilize Telehealth for Birth Control Visits

Patients are turning to telehealth services to access contraception during COVID-19. Transitioning your contraception service to telehealth wherever possible will ensure continuity of care while protecting the health and safety of patients and employees. Pharmacists can utilize telehealth to initiate contraception, assess and switch current methods, and adjust therapy as needed.

Due to COVID-19, some telehealth HIPAA regulations have loosened and health insurance plans are beginning to cover telehealth services.

Offer Methods that Don’t Require Blood Pressure Screening

Encourage patients to consider a progestin-only contraceptive if they’re unable to visit the pharmacy for a blood pressure screening.

Progestin-only contraceptive methods do not require a blood pressure screening in order to be safely prescribed, making them a feasible option when prescribing birth control via telehealth. Progestin-only options that can be prescribed by pharmacists and dispensed at the pharmacy include progestin-only pills (containing norethindrone or drospirenone) and depot medroxyprogesterone acetate injections (subcutaneous or intramuscular formulations).

Blood pressure measurement is required prior to initiating combined hormonal contraceptives—containing both estrogen and progestin hormones—due to the increased risk of stroke and myocardial infarction in patients with hypertension or without blood pressure measurements.

This article was co-written by Whitney Russell, a student pharmacist at University of Kentucky College of Pharmacy, and Kailey Hifumi, a student pharmacist at the Pacific University School of Pharmacy.

This article was originally published in Pharmacy Times.

Click image to view and download our COVID guide.

Find out more about providing contraceptive care during COVID-19 on our COVID resource page

References

  1. CDC. Guidance for pharmacies during COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/pharmacies.html; Published April 14, 2020. Accessed May 15, 2020.
  2. Family Planning National Training Center. What family planning providers can do to meet client needs during COVID-19. https://www.fpntc.org/resources/what-family-planning-providers-can-do-meet-client-needs-during-covid-19. Accessed May 15, 2020.
  3. Kaiser Family Foundation. Oral contraceptive pills. Available at: https://www.kff.org/womens-health-policy/fact-sheet/oral-contraceptive-pills/. Published May 23, 2019. Accessed May 15, 2020.
  4. Beyond the Pill. Contraceptive care during COVID-19. https://beyondthepill.ucsf.edu/contraceptive-care-during-covid-19. Accessed May 15, 2020.

Contraception During COVID: California’s Medi-Cal and FamilyPACT Programs Cover Depo-SubQ Provera

We recently wrote about the importance of offering patients subcutaneous depot medroxyprogesterone acetate (DMPA-SQ) as a contactless form of contraception during the COVID-19 public health emergency. California pharmacists can prescribe DMPA-SQ under statewide protocol upon completing the required training program and obtain payment for the visit for Medi-Cal patients.

As of April 9, 2020, California’s Medi-Cal, FamilyPACT, and managed Medi-Cal health plans are covering DMPA-SQ under pharmacy benefits.

To facilitate compliance with state and federal guidelines for sheltering in place and physical distancing, DHCS will temporarily allow for pharmacy dispensing of DMPA-SQ directly to patients for self-administration at home. This is in addition to current Medi-Cal policy that allows administration by a health care professional. Self-administration of DMPA-SQ would be at the option of the Medi-Cal recipient after individualized discussions and decision-making between the prescriber and the recipient. The prescribing provider is responsible for ensuring proper training of the recipient in administering the drug, potential side effects, and proper disposal of the pre-filled syringe.

The FamilyPACT system updates to allow for claim reimbursement of DMPA-SQ will not be implemented until May 15, 2020 for pharmacy dispensing, with a retro-effective date on or after April 9, 2020.  Pharmacies may re-process their denied claims after the implementation date and it should process successfully at that time. FamilyPACT always recommend that pharmacies validate eligibility, process the claim, get the denial, dispense the medication, and reprocess the claim after May 15 for payment. The reprocessed claim will show payment for the actual date of service as long as it is not before April 9.

Additionally, a reminder that a Medi-Cal beneficiary should not be required to pay for a covered medication until all avenues of successful processing have been explored and the department denies the service (for example the provider tries obtaining a TAR) and only if the patient requests to purchase the medication out of pocket. 

The full policy document is published on the COVID-19 webpage at: Direct-to-Patient Dispensing of Subcutaneous Depot Medroxyprogesterone Acetate – COVID-19 Emergency. This temporary policy change is effective immediately and remains in effect until further notice.

Clinical Considerations for Contraception During COVID: Patient Self-Administration

During the COVID-19 pandemic and beyond, patients may desire a contactless method of contraception. The subcutaneous (SQ) formulation of depot medroxyprogesterone acetate (DMPA), Depo-SubQ Provera, is an important option to offer patients. This may be of particular interest among patients who currently come in to the pharmacy or go to a clinic for their intramuscular (IM) injection.

Formulation Differences

While patients are able to self-administer both subcutaneous and intramuscular injections for a variety of purposes (e.g., insulin, fertility medications), patients may prefer the SQ formulation of DMPA since it is associated with less pain and higher continuation rates than the IM formulation.

Differences between the two formulations are summarized in the table below.

Intramuscular (IM)Subcutaneous (SQ)
Dose150 mg104 mg
Duration13 weeks
(up to 15 weeks)
12-14 weeks
Generic AvailabilityYesNo
Cost at Pharmacy$70-100>$200

Another important consideration is insurance coverage of these products. Some health plans cover the IM formulation as a medical benefit but have not yet included it as a pharmacy benefit. Some health plans are now covering the SQ formulation as a pharmacy benefit due to COVID-19, while others cover it as a pharmacy benefit but require a prior authorization.

How to Initiate or Switch

There is no physical assessment or blood pressure measurement required for eligibility of DMPA.

If your patient is not currently using a method of hormonal contraception, they can begin using either the IM or SQ at any time during the menstrual cycle if it is reasonably certain that patient is not pregnant. A backup method of contraception should be used for 7 days.

If your patient is currently using IM DMPA, the SQ DMPA can be administered when she is due for her next injection. No backup contraception is needed.

If your patient is currently using any other hormonal contraception (i.e., progestin only-pill, hormonal IUD, combination hormonal pill, patch or ring) or a copper IUD, the DMPA should be administered 7 days before stopping the other method. No backup contraception is needed.

References