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

2020 CDC Update for Contraceptive Use in Women at High Risk for HIV

What is the significance?

Women who have unprotected sex or have multiple partners have not only an increased the risk of sexually transmitted infections (STIs also known as STDs) but also have a risk of pregnancy. Aside from condoms, other contraceptive methods do not protect against HIV and other STIs but can effectively prevent an unintended pregnancy with potential complications and perinatal transmission associated with HIV infection.  Based on the new 2019 recommendations by the World Health Organization (WHO), the CDC published updated guidelines to the 2016 U.S. Medical Eligibility Criteria (US MEC) for Contraceptive Use regarding women at high risk for HIV infection in April 2020.

 

What changed?

The following updates were made to the US MEC for Contraceptive Use, 20161:

Women at high risk for HIV:

There are no restrictions for use (MEC Category 1) of all contraception methods, now including IUDs and depot medroxyprogesterone acetate (DMPA) injection. Previously, high risk for HIV was a condition for which copper-containing and progesterone-releasing IUD and DMPA use was MEC Category 2 (benefits generally outweigh the risks of the condition).

Women on antiretroviral (ARV) therapy:

The CDC has clarified that their recommendations for contraception in women taking nucleoside reverse transcriptase inhibitors (NRTIs) applies to all NRTI indications: prevention (PrEP) or treatment of HIV infection. Most contraceptive methods are MEC Category 1 except initiation of IUDs in women whose HIV viral loads are not controlled or are not ARV therapy due to the risk of pelvic inflammatory disease due to the risk of pelvic inflammatory disease with IUD insertion (MEC Category 2).

See Table 1 for a summary of recommendation changes.

 

Summary of Clinical Evidence

The US MEC recommendations are based on a review of clinical evidence, the WHO recommendations, and epidemiological information regarding unintended pregnancy, contraceptive use, HIV infection, and maternal morbidity and mortality in the US.2 In the previous 2017 US MEC update, intramuscular DMPA (DMPA-IM) use changed from a category 1 to a category 2 based on evidence of possible increased risk for HIV acquisition in women using DMPA who are already at high risk of infection.2,3 However, in August 2019, the WHO published the following updates regarding recommendations for contraceptive use in this population:

Women with high HIV risk are eligible to use all methods of contraception without restriction (category 1)4

    • All progestin-only methods, including progestin-only pills (POPs), intramuscular and subcutaneous DMPA, levonorgestrel (LNG) implants, and etonogestrel (ETG) implants
    • Copper and LNG intrauterine devices (IUDs)
    • All combined hormonal contraceptive methods, including combined oral contraceptives (COCs), combined contraceptive patches, and combined vaginal rings

These recommendations for this patient population have been made in light of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, which aimed to determine the risk of HIV incidence with the use of DMPA-IM, copper IUD, and LNG implant contraceptives. The randomized, multicenter, open-label trial included 7,839 non-pregnant, HIV-seronegative African females aged 16 to 35 years seeking effective contraception who were placed into 3 groups of contraceptive methods: DMPA-IM, copper IUD, and LNG implant.3 After 18 months, 397 HIV infections were observed: 36% in the DMPA-IM group, 35% in the copper IUD group, and 29% in the LNG implant group with no significant statistical differences between each method.3 Therefore, DMPA-IM copper IUD, or LNG implant use does not further increase the risk of getting HIV in patients already at high risk for HIV. In addition, patients younger than 25 years were associated with higher HIV incidence than those 25 years or older, and herpes simplex virus-2 (HSV-2) seropositive patients were associated with higher HIV incidence than those who were HSV-2 seronegative.3 However, age and HSV-2 status did not significantly alter the relationship between contraceptive use and HIV acquisition.3

Although the ECHO trial did not assess other hormonal methods (e.g., COCs, subcutaneous DMPA, hormonal IUDs), WHO also made their recommendations based on low/low-to-moderate quality studies or extrapolation from other studies indicating no increased risk for HIV acquisition with these methods.3,4 A consensus was also made that “no biological or clinical reasons” were evident “that a lower hormonal dose, different delivery mechanism, or different progestin” would affect HIV risk.”3

 

References

  1. Tepper NK, Curtis KM, Cox S, Whiteman MK. Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection. MMWR Morb Mortal Wkly Rep 2020;69:405–410. Available from:http://dx.doi.org/10.15585/mmwr.mm6914a3
  2. Tepper NK, Krashin JW, Curtis KM, et al. “Update to CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection.” MMWR Morb Mortal Wkly Rep. 2017;66(37):990-994.
  3. Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet. 2019;394(10195):303-313.
  4. Contraceptive eligibility for women at high risk of HIV. Guidance statement: recommendations on contraceptive methods used by women at high risk of HIV. Geneva: World Health Organization; 2019. License: CC BY-NC-SA 3.0 IGO.

Marjorie Valdez Student PharmacistAbout the Authors

Marjorie Valdez is a fourth-year pharmacy student at the UC San Diego School of Pharmacy and Pharmaceutical Sciences.

Cydnee Ng, PharmD completed her pharmacy training at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences in 2019. She is currently a community pharmacist at Walgreens in the San Francisco Bay Area.

Contraception for Your Transgender Patients

Terminology

Navigating through a discussion about gender and sexuality with the many terms used today can be confusing. Here is a brief introduction to terminology regarding the multifaceted gender spectrum.1

  • Cisgender: Gender identity matches assigned gender at birth2
  • Transgender: Gender identity differs from assigned gender at birth2
  • Gender nonbinary/queer/fluid: Individuals do not identify with a male-female binary and may have a fluid, multifaceted gender identity2

Now let’s review contraception for transgender patients…with a focus on transgender men (male gender identity and female assigned gender at birth)…

Considerations for contraception care

Gender affirmation therapy does not take the place of contraception.

Each patient may prefer different gender affirmation methods, which may affect their contraceptive needs.Methods include hormone therapy with testosterone, surgery, or no intervention. For patients undergoing testosterone therapy or no intervention who desire contraception, an additional contraceptive method becomes necessary. On the other hand, patients who undergo reaffirming surgery may or may not need additional contraception to reduce risk of pregnancy, depending on the extent of surgery performed.

 

There are knowledge gaps around fertility and contraceptive needs amongst transgender patients and their providers.

Some transgender men and providers have a lack of knowledge regarding their reproductive potential and risk of pregnancy if sexually active with a capable partner.3 Misperceptions include testosterone as effective contraception (may decrease fertility, but does not eliminate pregnancy risk) and midlife patients as infertile (presumed menopausal).3,4,5

 A transgender man has reproductive potential if they have an intact uterus and ovaries and until menopause or surgical sterilization.3 In addition, testosterone use may not completely suppress ovarian function, causing irregular or suppressed periods, which should not be confused with perimenopause in midlife patients.3,5 It is important to note there is still a risk of pregnancy despite a lack of menstruation. In a study of 41 transgender men who had been pregnant and given birth, one-third of pregnancies were unintended.Contraception use prior to pregnancy was lower in patients who used testosterone compared to those who did not.6 Use of a contraceptive is still necessary even with testosterone therapy.

 

Transgender patients have barriers to care that may prevent provision of adequate sexual and contraceptive care

Examples of barriers include stigmatization and feeling unsafe in health care settings.Health care teams should provide a supportive, open, and safe environment for transgender patients by accepting their gender identity and sexual orientation and using their preferred name and pronouns. Providers should ask if patients have an intact uterus and ovaries, are sexually active with a partner that may result in pregnancy, have a history of sexual violence, are at risk of sexually transmitted infections (STIs), and use gender affirmation methods.3

 

There is a lack of research on pregnancy risk and fertility in transgender patients, and consequently, contraceptive guidelines for this patient population.3

 

Contraception for transgender men

All transgender men with reproductive potential should be offered contraception.5 Patients should decide which contraceptive they prefer to use, if any. 

 

Reversible contraceptives

Reversible methods are most appropriate for patients who have not decided or do not want to make long-term or irreversible decisions regarding their reproductive potential.3

 

Progestin-only contraceptives

Progestin-only methods do not interfere with testosterone use. Regardless of testosterone use, patients who continue to have menstrual cycles may prefer this method due to high rates of amenorrhea and potential for masculinizing effects (e.g., increased hair growth).5,7

Traditional progestin-only pills (POP) containing norethindrone have a risk of low patient adherence due to its strict 3-hour window, which by missing correct timing of doses, may compromise contraceptive efficacy.However, the new POP, Slynd, allows for a 24-hour missed pill window.9 Irregular bleeding may occur, which patients may want to avoid.8

For patients seeking longer acting methods, the progestin-only injectable and long-acting reversible contraceptive devices — implant and IUDs — may be more convenient and have higher rates of amenorrhea.

 

Combination hormonal contraceptives

There is a lack of evidence regarding combined hormonal contraceptives including pills, patches, and vaginal rings) for transgender men as the estrogen may or may not interfere with testosterone therapy. At this time, there are no contraindications to concurrent use.5 Though patients can choose combination hormonal contraceptives, some may not prefer this method due to concerns about having estrogen in their system and the potential for female traits to appear.5,10 Other available and acceptable methods should be considered before considering combination hormonal contraceptives.5

 

Nonhormonal contraceptives

Although the copper IUD does not interfere with testosterone, there is a risk of increasing any existing menstrual bleeding.5 Patients with an intact uterus who want to avoid both progestins and estrogens and who are already amenorrheic may prefer this method.5

The contraceptive effectiveness of external and internal condoms is lower than hormonal methods and LARCs, however they are essential to prevent HIV and other STDs.3

Permanent surgical options are available for patients who do not want to get pregnant at all.3,7

 

Contraceptives for transgender women

For patients with a female gender identity and male sex assigned at birth taking estrogen, condoms may be used as well as permanent options, including orchiectomy (removal of testicles) and vasectomy (blockage of vas deferens tubes, preventing sperm from reaching testicles).7

 

For more information regarding transgender care and terminology, please visit the UCSF Transgender Care Navigation Program website at transcare.ucsf.edu/guidelines.

 

References

  1. Justice for Sisters. “Update: Gender Bear Now in BM, Chinese Language & English.” Accessed on September 5, 2019. Available at: https://justiceforsisters.wordpress.com/2016/07/13/updated-gender-bear-in-bm-chinese-language-english/.
  2. UCSF Transgender Care Navigation Program. “Terminology and definitions.” UCSF Transgender Care Navigation Program. June 17, 2016. Accessed on September 11, 2019. Available at: https://transcare.ucsf.edu/guidelines/terminology.
  3. Francis A, Jasani S, Bachmann G. Contraceptive challenges and the transgender individual. Womens Midlife Health. 2018;4:12.
  4. Amato P. “Fertility options for transgender persons.” UCSF Transgender Care Navigation Program. June 17, 2016. Accessed on September 11, 2019. Available at: https://transcare.ucsf.edu/guidelines/fertility.
  5. Boudreau D, Mukerjee R. Contraception care for transmasculine individuals on testosterone therapy. J Midwifery Womens Health. 2019;64(4):395-402.
  6. Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124(6):1120-1127.
  7. Shah M. “Birth control across the gender spectrum.” Bedsider. 2017. Accessed on September 11, 2019. Available at: https://www.bedsider.org/features/1070-birth-control-across-the-gender-spectrum.
  8. Jones K, Wood M, Stephens L. Contraception choices for transgender males. J Fam Plann Reprod Health Care. 2017;43(3):239-240.
  9. Exeltis USA, Inc. “Exeltis USA, Inc. announces the approval of Slynd, the first and only progestin-only pill providing pregnancy prevention with a 24/4 dosing regimen and 24-hour missed pill window.” Exeltis USA, Inc. June 6, 2019. Accessed on November 19, 2019. Available at: https://www.prnewswire.com/news-releases/exeltis-usa-inc-announces-the-approval-of-slynd-the-first-and-only-progestin-only-pill-providing-pregnancy-prevention-with-a-244-dosing-regimen-and-24-hour-missed-pill-window-300863390.html.
  10. Reproductive Health Access Project. “Birth control across the gender spectrum.” Reproductive Health Access Project. 2019. Accessed on September 11, 2019. Available at: https://www.reproductiveaccess.org/wp-content/uploads/2018/06/bc-across-gender-spectrum.pdf
  11.  

About the Author

Cydnee Ng, PharmD completed her pharmacy training at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences in 2019. She is currently a community pharmacist at Walgreens in the San Francisco Bay Area.

Twirla: A New Contraceptive Patch

What is Twirla?

Twirla is a new contraceptive patch designed for patients who want freedom from the daily pill without committing to a longer acting method. This transdermal patch delivers 120mcg of levonorgestrel and 30mcg of ethinyl estradiol through Agile’s Skinfusion® patch, which consists of five layers and serve as the reservoir for the active and inactive ingredients, as well as a barrier to prevent accumulation of debris from daily wear. Twirla is designed to be applied once weekly for three weeks, followed by one patch free week for menstruation.

Currently there is only one hormonal contraceptive patch available for consumer use called Xulane (norelgestromin 150mcg/ethinyl estradiol 35mcg). Women who use this patch have higher blood serum concentrations of estrogen compared to oral methods (AUC0-∞ 37.7±5.6 vs. 22.7±2.8), which is associated with health concerns such as increased risk of blood clots in the legs and lungs. Agile Therapeutics, the women’s healthcare company behind Twirla, saw an unmet need in the market for a low-dose hormonal contraceptive patch. This market gap lead to the development of their newly formulated contraceptive patch, Twirla.

 

What are the pros and cons of Twirla?

This patch provides another option for women who desire an alternative from a daily pill, without the constraints of a longer acting method. Twirla is applied once weekly, meaning women only have to remember their birth control about three times a month rather than every day. With various daily activities and responsibilities, a weekly patch liberates women from one of those daily routines. There are other birth control options such as the Depo-Provera injection, IUDs, or implants that serve as alternatives to the pill but some women perceive these methods as more invasive compared to the patch. Additionally, given the lower dose of estrogen, Twirla appears to have a lower risk of blood clots as shown in comparator studies but remains equally effective in regulating menstrual cycles and preventing pregnancies as compared to the existing patch option.

Although the convenience of a patch is desirable, there are several noteworthy considerations with this product. As previously mentioned, Twirla’s formulation lowers the risk of blood clots, but there remains a risk of blood clots with hormonal patches compared to oral methods.  Additional side effects reported with Twirla include unscheduled vaginal bleeding, weight gain, headache, and abdominal cramps.  Women have also reported skin irritation when applying and removing the patch. Regarding size, Twirla is round and slightly larger (28cm2) than the Xulane (14 cm²) patch. Additionally, both Twirla and Xulane are currently only produced in one neutral shade of beige. For many women, this prevents the possibility of a discrete form of birth control which may make this a less desirable option.

 

Are there different considerations with a patch compared to other contraceptive methods?

Given the hormones in Twirla, the patch works just like the pill in terms of preventing pregnancy by delaying ovulation.  It can be applied on the upper arm, buttocks, back, or lower abdomen. The patch is designed to withstand activities such as exercising, swimming, showering, etc. If the patch does happen to fall off during the week, it can be reapplied or a new patch may be used in its place. If the patch has been off more than 24 hours, a back up method such as condoms should be used for the next seven days of the new patch cycle. Although it’s rare (<2% of the time), healthcare providers recommend daily checks to ensure the patch has not accidentally fallen off. Patches should not be worn longer than the week they are intended and consequences of doing so include bleeding, spotting, and increased risk for unintended pregnancy. If a patient is more than 48 hours late transitioning from the existing patch to a new patch, then a back up should be used for seven days. Like all other birth control methods, Twirla does not protect against sexually transmitted diseases or HIV.

 

Is Twirla a good option for everyone?

There is no one-size fits all method that is right for all women. Some women might be at greater risk for adverse effects with the patch. Agile reported reduced efficacy in preventing pregnancy for women who weigh 202 pounds (92kg) or more, or who have a BMI of 30 kg/m2 or greater. As a result, the drug company initially issued a Limitation of Usestatement in their product labeling that documented this clinical outcome.  Since gaining FDA approval, this limitation has transitioned to a listed contraindication. Xulane’s package insert lists the same contraindication, yet is regularly prescribed in women with a BMI >30 kg/m2. Studies have shown that the decrease in efficacy does not preclude the use of these patches in obese women. To combat the associated risks, additional counseling to emphasize the importance of strict compliance with the patch for optimal protection is necessary. Studies have also shown an increased risk in blood clots in women who are overweight and those who smoke. Additional contraindications for using Twirla include women with a high risk of thrombotic disease, who experience migraine with aura, who have liver disease, or who have undiagnosed abnormal uterine bleeding.

 

Is Twirla available now?

Twirla was approved by the FDA earlier this month on February 14, 2020. As part of the approval process, the FDA is requiring Agile to conduct a long term, observational post-marketing study to further evaluate the risks of blood clots in new users of Twirla. With its recent approval, the manufacturer is now focusing their attention on commercializing Twirla for consumer use. They hope to complete the manufacturing process and expect to ship the initial product to wholesalers as early as the end of this year.

With patient needs and safety in mind, the approval of this medication further expands the range of contraceptive options available for women. Given that there have only been three non-daily combined hormonal contraceptive methods made available since 2001, this is a valuable and timely option for women who seek alternative methods.

References

  1. FDA Approves Agile Therapeutics, Inc.’s Twirla® (levonorgestrel and ethinyl estradiol) Transdermal System – A New Weekly Contraceptive Patch Delivering a 30 mcg Daily Dose of Estrogen and 120 mcg Daily Dose of Progestin. (2020, February 14). Retrieved February 23, 2020, from https://ir.agiletherapeutics.com/news-releases/news-release-details/fda-approves-agile-therapeutics-incs-twirlar-levonorgestrel-and
  2. Efficacy, Safety and Tolerability Study of Agile AG200-15 Transdermal Contraceptive Delivery System – Full Text View. (2017, September 25). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02158572?term=AG200-15&draw=2&rank=1
  3. Therapeutics, A. (n.d.). Results From the SECURE Trial, a Phase 3 Study of the… : Obstetrics & Gynecology. Retrieved from https://journals.lww.com/greenjournal/Abstract/2017/05001/Results_From_the_SECURE_Trial,_a_Phase_3_Study_of.46.aspx
  4. Hatcher, R. A. et. al (2018). Contraceptive technology. New York, NY: Ayer Company Publishers, Inc.
  5. Van den Heuvel et. al, M. W. (2005). Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception72(3). Retrieved from https://www-sciencedirect-com.proxy-remote.galib.uga.edu/science/article/pii/S0010782405000971 

About the AuthorBirth Control Pharmacist Headshots

Savannah Gross is a third-year pharmacy student at the University of Georgia College of Pharmacy. 

Article reviewed by Rebecca Stone, PharmD, BCPS, BCACP

Endometriosis Basics and How Contraception Can Help

What is endometriosis?

Endometriosis is characterized as a condition in which endometrial tissue, which normally lines the uterus, develops outside of the uterine cavity in abnormal locations such as the ovaries, fallopian tubes and abdominal cavity.1 Endometriosis is a common cause of chronic pelvic pain in women and can sometimes be associated with infertility.2 It is estimated that 1 in 10 women suffer from endometriosis (with percentages even higher in women with chronic pelvic pain and infertility).  On average, it takes anywhere from 3 to 11 years from the onset of pain symptoms for women to be accurately diagnosed with endometriosis.3

As pharmacists, it is important to establish our role in patient care and to be aware of this underdiagnosed condition and the role of hormonal contraception in managing symptoms and the disease. We can assist patients with endometriosis by having confidence in the medication they were prescribed and keeping in mind the individual treatment goals in each patient. While there is no definitive cure for endometriosis, there are pharmacological approaches in the management of the associated pain. While there are many different options available for women with endometriosis, this article will be focusing on the use of hormonal contraceptives in endometriosis pain management. Additionally, it is important to keep in mind that no hormones are free of side effects and severity and tolerability can vary significantly; not all types of endometrial pain respond equally to hormonal treatment.4

 

What is the role of hormonal contraceptives in endometriosis treatment?  

Combined hormonal contraceptives (CHCs) and progesterone only pills (POPs) have been used for pain management associated with endometriosis. Hormonal contraceptives help to slow the growth of new endometrial tissue and may prevent formation of new adhesions which can help decrease the pain patients have. However, hormonal contraceptives will not eradicate any endometrial tissue that currently exists in the patient.5

There are a few differences in tolerability and the level of evidence for each treatment. For assessing the different types of contraceptive treatment for endometriosis, the European Society of Human Reproduction and Embryology (ESHRE) has created a grading scale as part of their justification for treatment:

Grading Scale

Grade A: treatment has been backed by meta-analysis, systemic review or multiple RCTs (high quality). 

Grade B: treatment has been backed by a meta-analysis, systemic review or multiple RCTs (moderate quality), single RCT, large non-randomized trial, case-control or cohort studies (high quality). 

Grade C: treatment has been backed by a single RCT, large non-randomized trial, case-control or cohort studies (moderate quality).4

CHCs may considered as it can reduce endometriosis-associated dyspareunia, dysmenorrhea and non-menstrual pain.4 Oral CHCs are considered “Grade B”.4 It is important to note that endometriosis is considered to be a predominantly estrogen-dependent disease. It is possible that the estrogen component of CHCs may mask the effect of the progestin by possibly activating the disease. However, it has been argued that ethinylestradiol doses are too low to reach an activating threshold.4 According to the American College of Obstetricians and Gynecologists (ACOG) guidelines, CHCs showed significant decrease in pain in patients and if that therapy is not tolerated patient could move on to progestins. Unlike the ESHRE, they did not differentiate between types of contraceptives and their related effectiveness.5 

Among the CHCs, it is important to recognize that different dosage forms have different grades of evidence of efficacy in the ESHRE guidelines. Continuous CHCs (active tablets only) were given a “Grade C”.  Vaginal contraceptive rings and transdermal patches were also given a “C”.4

Progestin-only pills are considered “Grade A” by the ESHRE guidelines because they have the most evidence to date in reducing endometriosis-related pain. Additionally, while Levonorgestrel-containing IUDs are not FDA approved as treatment for endometriosis, they are given a “Grade B” as an option to reduce pain related to the disease.4 Additionally, the ACOG guidelines recognize the use of levonogersterol-containing IUDs to reduce endometriosis related pelvic pain, but emphasized that potential side effects like irregular bleeding and weight gain are common.5  

Another type of progestin contraceptive that can be used for endometriosis-associated pain is Depot medroxyprogesterone (DMPA). DMPA works to prevent follicular growth preventing ovulation.6 ACOG recognizes DMPA as a suitable treatment as it has been approved by the FDA for treatment of endometriosis-associated pain.5 Furthermore, ESHRE gave DMPA a “Grade A” as an option to reduce endometriosis-related pain.4

As pharmacists, we serve a vital role in the patient care plan and can be there to help patients recognize the types of treatment options available to them. As a patient, it may be hard navigating through the different contraceptive options that they have for endometriosis pain management. Pharmacists can help patients navigate these options in order to help improve their quality of life.

References

    1. Noncontraceptive benefits of birth control pills: fact sheet. ASRM (American Society for Reproductive Medicine). Available from: https://www.reproductivefacts.org/globalassets/rf/news-and-publications/bookletsfact-sheets/english-fact-sheets-and-info-booklets/noncontraceptive_benefits_of_bcp_factsheet.pdf. Accessed January 16, 2020
    2. Leyland N, Casper R, Laberge P, Singh SS, SOGC. Endometriosis: diagnosis and management. J Obstet Gynaecol Can 2010;7 (Suppl 2):S1–32.
    3. Husby GK, Haugen RS, Moen MH. Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand. 2003;82(7):649–53. 
    4. Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et, al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400-12.
    5. Committee on Gynecologic Practice. ACOG Practice Bulletin No. 114: Management of endometriosis. Obstet Gynecol. 2010;116(1):223–36.
    6. Depo-Provera CI (medroxyprogesterone acetate) [package insert]. U.S Food and Drug Administration website. Revised October 2010. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020246s036lbl.pdf. Accessed February 10, 2020

About the Author

Breanna HeadshotBreanna Failla, PharmD Candidate is in her second year of pharmacy school at Midwestern University Chicago College of Pharmacy. She serves as APhA-ASP Chapter President and Midyear Regional Meeting Coordinator for Region 4. 

Article reviewed by Brooke Griffin, PharmD, BCACP

Should We Offer Preconception Services in Community Pharmacies?

Why is preconception care important?

Roughly 4 million pregnancies occur in the United States annually.1 A common misconception is that preconception care is only a health care need when there is an intention to become pregnant. However, because nearly half of all pregnancies in the United States are unplanned, most birth defects occur within the first 3 months of pregnancy, and nearly one-fifth of pregnant women in in the United States receive no prenatal care before the end of their first trimester, preconception care is a serious population health issue deserving of attention.2-4

Why should pharmacists consider being involved?

Although preconception care is recommended to be routinely provided to all women of reproductive potential, gaps exist. With an estimated 90% of Americans living within 5 miles of a community pharmacy, community pharmacists have been proposed as an ideal provider of selected preconception care services to help fill these gaps and support preconception care initiatives.5,6

Where do we even start?

My PGY-1 community pharmacy residency was an incredible year filled with many great experiences that truly helped sculpt my professional practice during my first year as a pharmacist. One of the requirements was to develop and implement a research project; the topic chosen was preconception care. In full disclosure, I did not know much about it when I started the project and quickly found I had more questions than answers. However, I rapidly realized how deserving it is of continued attention.

Our primary objective was to perform a needs assessment using modified evidence-based core indicators:

Preconception Services in the Pharmacy

The above parameters were assessed with the use of a 1-page patient survey, retrospective chart review, and vaccine database review.3,7

Of the 110 patients who were asked to complete the survey, 99 patients took the survey and were included in the study for analysis. More than 75% of the patient population reported being sexually active and only about 50% of participants indicated they used some form of contraception, highlighting a large proportion of the population with the potential to become pregnant, as well as for unplanned pregnancy.

96% of study participants were found to have at least one health concern that could adversely affect a pregnancy if she were to become pregnant. The majority of study participants reported at least one of the following:

  • Abnormal BMI
  • Missing documentation of at least one assessed vaccination
  • No form of daily multivitamin that contained folic acid

Additionally, roughly half of survey participants were on at least one medication with potentially teratogenic effects.

Not only was preconception care need established across the majority of survey participants, but needs were found to span multiple preconception care parameters as well as differing demographics. However, despite the demonstrated need, 78.8% of the survey participants indicated they were not interested in receiving more information on preconception care. Therefore, pharmacists must play an active role in identifying and educating eligible patients.

Are you ready to begin implementing preconception care services within the community pharmacy setting?

If the answer is yes — and I hope it is — what are the next steps?

In identifying these concerns, we hoped that the results could be used in developing new clinical services to support preconception care needs.

Pharmacists already provide non-dispensing services via multiple service models, therefore preconception care services may be built within existing frameworks.6,8,9,10 This support can include:

  • Screening for preconception parameters
  • Optimizing pharmaceutical care plans for adequate disease state management
  • Counseling for prescription and over-the-counter (OTC) products to assist in family planning
  • Prescription contraception via statewide protocol or collaborative practice agreement (depending on state/scope of practice)

As we continue to learn more about the need for and how preconception care fits into community pharmacy practice, I leave you with one final question:

Where might preconception care services fit within your pharmacy workflow and how might you implement these types of services to better the health of the patients you serve?

References

For the original research article, please visit: https://www.ncbi.nlm.nih.gov/pubmed/31010784

  1. Centers for Disease Control and Prevention. Births and natality. Available at: https://www.cdc.gov/nchs/fastats/births.htm; March 31, 2017. 
  2. Centers for Disease Control and Prevention. Preconception health and healthcare. Available at: https://www.cdc.gov/preconception/index.html; February 13, 2017. 
  3. Johnson K, Posner SF, Biermann J, et al. Recommendations to improve preconception health and health caredUnited States. A report of the CDC/ATSDR Preconception Care Work Group and Select Panel on Preconception Care. MMWR Morb Mortal Wkly Rep. 2006;55(RR06):1e23.
  4. Korenbrot CC, Steinberg A, Bender C, Newberry S. Preconception care: a systematic review. Matern Child Health J. 2002;6(2):75e88.
  5. Frederick J. By the numbers: how community pharmacists measure up. Drugstore News;March 13, 2015. Available from:http://www.drugstorenews. com/article/numbers-how-community-pharmacists-measure. 
  6. DiPietro NA, Bright DR. Medication therapy management and preconception care: opportunities for pharmacist intervention. Inov Pharm. 2014;5(1):141.
  7. Frayne DJ, Verbiest SV, Chelmow D, et al. Health system measures to advance preconception wellness: consensus recommendations of the Clinical Workgroup of the National Preconception Health and Health Care initiative. Obstet Gynecol. 2016;127:863e872.
  8. DiPietro Mager NA. Fulfilling an unmet need: roles for clinical pharmacists in preconception care. Pharmacotherapy. 2016;36(2): 141e151.
  9. El-Ibiary SY, Raney EC, Moos MK. The pharmacist’s role in promoting preconception health. J Am Pharm Assoc. 2014;54:e288ee303.

Birth Control Pharmacist HeadshotsAbout the Author

Mollie Reidenbach, PharmD is a clinical care coordinator with SpartanNash, a chain community pharmacy primarily based in Michigan, embedded within a physician group to provide medication therapy support for both their patients and providers.

Teratogenic Medications and Contraception Management

Teratogenic Medications and Contraception

The use of prescription medications by pregnant women has increased over the past 30 years and with the usage comes an increased associated risk of exposing the fetus to the drugs. These medications can cause fetal abnormalities during a pregnancy. Often, for unique reasons, women are not concomitantly prescribed contraception or are not educated regarding the importance of using contraception while taking these high risk medications. Although, the use of teratogenic medications may be necessary for a woman’s health it is important to use birth control while on these drugs to prevent exposure during a pregnancy. 

What are teratogenic medications?

Teratogens are agents that interfere with fetal development when exposed during pregnancy and cause abnormalities. Examples of these teratogens include, but are not limited to alcohol, smoking, and various prescription medications. 

The thalidomide tragedy is an unfortunate example of what teratogenic drugs can do to the development of fetuses. In the late 1950s and early 1960s, thalidomide was widely used for the treatment of nausea in pregnant women soon after, it became apparent that the treatment caused malformations of the arms and legs. Currently, the drug is limited to use for the treatment for various conditions such as skin lesions caused by leprosy and multiple myeloma.

Why is it important to take contraception while on these medications?

Many women take potentially teratogenic medications for health conditions such as hypertension, diabetes, cholesterol, etc. and taking these medications while pregnant increases the risk of fetal malformations and spontaneous abortions. The use of contraception while taking these medications reduces the risk of having pregnancies with abnormalities. 

A study was conducted to evaluate teratogenic medications and associated prescription of contraception in the primary care setting. They found that 25% of the patients that participated in the study were prescribed at least 1 high risk medication from Table 1 and of those patients over half did not have contraceptive management. Ondansetron, often used for nausea in pregnancy, was excluded from the second analysis resulting in 10% of the patients on a high-risk medication and 61.9% of those patients were found to be without any use of contraception management.

The table below summarizes the medications that were used in a study and the teratogenic risks associated with them.

Table 1. Common teratogenic medications and related potential fetal effects

Medication Name Potential Fetal Effects
Atorvastatin, Simvastatin, Pravastatin Congenital abnormalities in infants and skeletal malformations in rats and mice
Topiramate Cleft lip/palate and hypospadias
Valproic Acid Facial dysmorphology, congenital heart defects, spina bifida, cleft lip/palate, development delays
Ondansetron Cardiac malformations
Paroxetine Cardiac malformations and pulmonary hypertension
Lisinopril Spontaneous abortion, oligohydramnios, newborn renal dysfunction

Who is at risk? 

Women who were less than 25 years of age had a low probability of receiving contraception when prescribed a teratogenic medication compared to patients who were of advanced maternal age (over 35 years old). Demographically, among all women who participated in the study, 60% belonged to a minority group compared to the 40% who were not in a minority group which suggests that minorities may be prescribed teratogenic medications more frequently compared to their non-minority counterparts.

Why is this a problem?

The study did not explore why this trend was seen. There are multiple challenges that family physicians face regarding contraception and teratogenic medication management. The first is that physicians may not be able to identify their patients’ family planning intentions, making appropriate counseling challenging. Second, they may experience difficulty finding clinically relevant information on the teratogenic medications. Additionally, while some medications are monitored strictly such as isotretinoin (Accutane), most are not, which makes it difficult for the provider to regularly re-evaluate reproductive plans when patients do not make frequent office visits. Lastly, specialists might prescribe these medications and fail to communicate with the primary care physician leaving the management of contraception up to the patient.

What can pharmacists do? 

It is important to practice interprofessional collaboration which results in safer prescribing practices. Pharmacists are now able to prescribe birth control in some states and can educate patients about contraception use while on teratogenic medications and directly provide contraception if needed and document it.

References

  1. Panchal, BD, Cash, R, Moreno, C, et al. (2019). High-Risk Medication Prescriptions in Primary Care for Women Without Documented Contraception. The Journal of the American Board of Family Medicine 2019;32(4):474–480.
  2. Kim, JH, Scialli, AR. “Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease.” Toxicological Sciences 2011;122(1):1–6.
  3. “Thalidomide: Research Advances in Cancer and More.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 25 May 2019. Available at: https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/thalidomide/art-20046534

About the Author

Sara Shaikh, PharmD Candidate is a pharmacy student at the University of California San Francisco School of Pharmacy in San Francisco, California.

Meet Slynd: A Novel Progestin-Only Pill

What’s this new pill?

Slynd® is the new progestin-only oral contraceptive approved by the FDA in May 2019. This novel progestin-only pill (POP) contains drospirenone 4 mg in each active tablet, which is a higher dose than what is found in drospirenone-containing combined oral contraceptives (COCs). 

Table 1. Products with drospirenone.

Product Name

Medication Doses

Regimen

Yasmin, Zarah, Syeda, Ocella

Drospirenone 3 mg, ethinyl estradiol 30 mcg

21/7

Safyral

Drospirenone 3 mg, ethinyl estradiol 30 mcg, levomefolate calcium 451 mcg

21/7

Yaz, Gianvi, Loryna

Drospirenone 3 mg, ethinyl estradiol 20 mcg

24/4

Beyaz

Drospirenone 3 mg, ethinyl estradiol 20 mcg, levomefolate calcium 451 mcg

24/4

Slynd

Drospirenone 4 mg

24/4

This will be the second POP formulation available, in addition to the many norethindrone 0.35 mg products currently available.

What are the features of this new pill?

This pill provides pregnancy prevention with a 24/4 dose regimen. In the ongoing evolution of contraception, the goal has always been to improve efficacy as well as minimizing adverse events. Estrogen dose reduction and shortening of hormone-free intervals have been helpful to meet these goals. As a result, Slynd was developed with a 24/4 dose regimen which provides a more stable hormonal timeframe compared to traditional 21/7 dose regimens, achieving greater pituitary and ovarian suppression. For this reason, the 24/4 regimen has less hormone withdrawal effect and improves pelvic pain, headaches, breast tenderness, and bloating symptoms that are reported during the hormone-free days with 21/7 regimens.  

Slynd pill pack

Figure 1. Slynd pill pack containing 24 active pills and 4 inactive pills.

(Image credit: slynd.com)

Slynd also allows a 24-hour missed pill window which improves reliability and bleeding profiles in the event of a missed dose. One study compared two arms — one with four missed doses (four 24-hour delays) and the other with no missed dose during the cycle. Even with four missed doses in the cycle, there was adequate ovarian suppression and the same follicular size was observed in both arms.

Drospirenone inhibits ovulation by suppressing luteinizing hormone (LH) secretion. Additionally, by modifying cervical mucus, it reduces sperm transport and thus prevents fertilization. Unlike other conventional synthetic progestins, drospirenone has a similar profile to endogenous progesterone. As an analogue of 17-alpha spironolactone, drospirenone has anti-mineralocorticoid and anti-androgenic activity. Due to the anti-mineralocorticoid activity, it increases urinary sodium and serum aldosterone. Therefore, compared to other COCs causing fluid retention and edema, drospirenone has an ability to reduce blood pressure. 

 

Should we be worried about blood clots with drospirenone?

Drospirenone was first introduced to the market in combination with low dose ethinyl estradiol as a contraceptive well suited for women with premenstrual dysphoric disorder (PMDD), moderate acne, polycystic ovarian syndrome and hirsutism. 

While the FDA is concerned about the potential correlation between contraceptives containing drospirenone and blood clots, the overall result of two prospective multicenter phase III studies reported no single case of venous thromboembolism (VTE) in patients who used POP. FDA has funded a study to investigate the correlation, and still is reviewing other clinical trials. In 2011, the FDA reported that “preliminary results of the FDA-funded study suggest an approximately 1.5-fold increase in the risk of blood clots for women who use drospirenone-containing birth control pills compared to users of other hormonal contraceptives.” 

Other studies have shown use of drospirenone-containing COCs was not associated with increased risk of thromboembolic events compared to other COCs containing other progestins. Due to data limitations, the causality is still unclear, and FDA will provide updates once available. 

While there is an increase in the relative risk of this rare adverse event with COCs containing drospirenone, the incidence is still very low and much lower than pregnancy and postpartum periods. ACOG’s Committee on Gynecologic Practice has concluded that the risk of thromboembolism in patients who use drospirenone-containing COCs is very low.  

It is unknown whether Slynd increases the risk of VTEs, however, any potential risk with this POP is expected to be lower than COCs containing drospirenone. 

 

Which patients should not use this pill?

Drospirenone is contraindicated in women with positive or unknown antiphospholipid antibodies, ischemic heart disease, stroke, current or history of breast cancer, hepatocellular adenoma, malignant hepatoma, and severe hepatitis. Clinicians should use this medication with caution in patients who are taking other medications that can predispose them to hyperkalemia, or monitor potassium level.

The drug interaction profile is similar to drospirenone-containing COCs. Although drospirenone is metabolized independently of P450 enzymes, it is a minor substrate of CYP3A4. It is recommended to avoid use in patients taking strong 3A4 inhibitors to prevent hyperkalemia. Strong P450 and P-glycoprotein transporter inhibitors and inducers can affect the serum concentration, efficacy, and adverse effects. 

 

What’s the bottom line for place in therapy?

In conclusion, Slynd can be used in most patients and will be an important option for patients with contraindications to estrogen — including history of high blood pressure or smoking above age 35 — PMDD, as well as patients desiring contraception without androgenic effects, such as those with acne or polycystic ovary syndrome (PCOS).

 

References:

  1. Mishell DR. “YAZ and the Novel Progestin Drospirenone.” The Journal of Reproductive Medicine 2008.
  2. Machado RB, et al. “Drospirenone/Ethinylestradiol: A Review on Efficacy and Noncontraceptive Benefits.” Womens Health 2011;7(1)19–30.
  3. Bachmann G, Kopacz S. “Drospirenone/Ethinyl Estradiol 3 Mg/20 Mug (24/4 Day Regimen): Hormonal Contraceptive Choices – Use of a Fourth-Generation Progestin.” Patient Preference and Adherence, 2009 
  4. Palacios S, et al. “Multicenter, Phase III Trials on the Contraceptive Efficacy, Tolerability and Safety of a New Drospirenone‐Only Pill.” Acta Obstetricia Et Gynecologica Scandinavica 2019.
  5. Center for Drug Evaluation and Research. “Risk of Blood Clots with Birth Control Pills Containing Drospirenone.” FDA Website Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-possible-increased-risk-blood-clots-birth-control.
  6. American College of Obstetricians and Gynecologists. Risk of venous thromboembolism among users of drospirenone-containing oral contraceptive pills. Committee Opinion No. 540. Obstet Gynecol 2012;120:1239–42. Available at: https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Risk-of-Venous-Thromboembolism.
  7. Drugs.com. Exeltis USA, Inc. Announces the Approval of Slynd (drospirenone), the First and Only Progestin-Only Pill Providing Pregnancy Prevention with a 24/4 Dosing Regimen and 24-hour Missed Pill Window. 2019. [online]
  8. Slynd (drospirenone) [prescribing information]. Florham Park, NJ; Exeltis USA, Inc.; May 2019.
  9. Duijkers IJ, Heger-Mahn D, Drouin D, Colli E, Skouby S. Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake. Contraception 2016;93(4):303–309.
  10. CDC. US Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016;65Available at: https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/appendixc_tableC1.html

Lida Binesheian - Slynd Article on Birth Control Pharmacist

About the Author:

Lida Binesheian, PharmD, CACP is a Clinical Pharmacist and Certified Anticoagulation Care Provider based in Austin, Texas.