Tag: progestin-only pill

Meet Slynd: A Novel Progestin-Only Pill

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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.

An OTC Birth Control Pill Could Become a Reality

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over-the-counter-birth-control-pillsAn over-the-counter (OTC) birth control pill is finally on the horizon. HRA Pharma, a French pharmaceutical company, has recently formed a partnership with the nonprofit research organization Ibis Reproductive Health to conduct the research needed to prepare and submit a new drug application for an OTC progestin-only pill to the FDA. While the approval may be several years away, at least we are on the way. More than 70% of women support OTC access to birth control.1

This is an exciting prospect that could make birth control pills more widely available and easier for people to access and use. Ultimately, it may make a dent in our high rate of unintended pregnancies (45% of all pregnancies in the United States).2

All birth control pills – combined and progestin-only – are currently available by prescription only. Some states, such as California and Oregon, have enacted state laws allowing pharmacists to prescribe hormonal birth control. The more resources and options people have to obtain their birth control, the more likely they are to use it to effectively control if and when they have a pregnancy.

The birth control options currently available OTC are spermicides, condoms, and levonorgestrel emergency contraception. Progestin-only pills are much more effective at preventing pregnancy than any of these other methods. The pill—including progestin-only and combined—is one of the most effective birth control methods available. Both pill types are about 99% effective when used exactly as directed and 91% effective with typical use.3 Progestin- only pills have about the same effectiveness as combination estrogen and progestin pills, rings, and patches.

While combined hormonal birth control pills are generally more popular, the estrogen component results in some serious contraindications and precautions.3 Women with high blood pressure, migraines with aura, and other medical conditions should be avoiding estrogen. On the other hand, the progestin-only pill does not have the same concerns and can be safely used by most women. An OTC progestin-only pill is expected to follow in the footsteps of levonorgestrel – a progestin-only emergency contraceptive pill.

Many professional medical associations have expressed support for OTC birth control pills, including the American Medical Association, American College of Obstetricians and Gynecologists, American Academy of Family Physicians, and the American College of Clinical Pharmacy Women’s Health Practice and Research Network.4-7 It’s even a bipartisan issue, although there are disagreements on who should pay for an OTC birth control pill among different political parties.

Pharmacists and other providers have expressed concerns about expanding access to birth control and how that might impact other necessary health services.8,9 We must trust women to continue to seek and obtain related preventive health care and health maintenance from their primary care physicians, obstetricians/gynecologists, or other health care providers. There is no evidence to suggest that birth control pills should be held hostage to make women go to the doctor. Pap smears and other preventive health care procedures are important, and access to birth control pills is important, but the 2 are independents and do not need to be linked.3

For more information, see the Oral Contraceptives Over-the-Counter (OCs OTC) Working Group websites: http://ocsotc.org/ and http://freethepill.org/.

References:

  1. Grossman D, Grindlay K, Li R, Potter JE, et al. Interest in over-the-counter access to oral contraceptives among women in the United States. Contraception. 2013;88(4):544-52.
  2. Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008–2011. N Engl J Med. 2016; 374(9): 843-52
  3. US Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2016. MMWR. 2016;65(4):1-66.
  4. American Academy of Family Physicians (AAFP) Resolution No 501: Endorse access without age restriction to over-the-counter oral contraceptive pills. April 2016.
  5. American College of Obstetricians and Gynecologists Committee Opinion No 615: Access to contraception. Obstetrics and Gynecology. 2015; 125(1):250–5.
  6. American Medical Association Resolution D-75.995 (Sub. Res. 507, A-13): Over-the-counter access to oral contraceptives. American Medical Association. 2013.
  7. McIntosh J, Rafie S, Wasik M, McBane S, Lodise NM, El-Ibiary SY, et al. Changing oral contraceptives from prescription to over-the-counter status: An opinion statement of the Women’s Health Practice and Research Network of the American College of Clinical Pharmacy. Pharmacotherapy. 2011;31(4):424-37.
  8. Rafie S, Kelly S, Gray EK, et al. Provider opinions regarding expanding access to hormonal contraception in pharmacies. Womens Health Issues. 2016;26(2):153-60.
  9. Rafie S, Haycock M, Rafie S, Yen S, Harper CC. Direct pharmacy access to hormonal contraception: California physician and advanced practice clinician views. Contraception. 2012;86(6):687-93.

This article was originally published in Pharmacy Times.