By: Bhojranie Brahmanand, PharmD Candidate c/o 2025

Traditionally, a prescription has always been required for contraceptives such as birth control. However, on July 13, 2023, the Food and Drug Administration (FDA) approved Perrigo’s Opill®, a daily progestin-only oral contraceptive (POC) as the first over-the-counter (OTC) birth control pill.¹ This drug was originally approved for prescription (Rx) use in 1973. It is indicated for use in women capable of reproduction to prevent pregnancy and has a 93% effective rate.² Each Opill® tablet contains 0.075 mg of norgestrel, a synthetic progestogen. POCs work by thickening the cervical mucus to impede sperm penetration, lowering the midcycle luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peaks accountable for decelerating the ovum’s passage within the fallopian tubes and altering the endometrium. Approximately two hours after oral administration of this medication, serum progestin levels reach their peak followed by rapid distribution and elimination. Around 24 hours after drug ingestion, serum levels return close to the initial baseline suggesting that efficacy is dependent upon rigid adherence to the dosing schedule.²

Justification for the Rx-to-OTC Switch

The primary motivation to switch Opill® from an Rx-only to OTC medication arose from the recent implementation of abortion laws across the United States (US), making it increasingly difficult for women to obtain access to abortion care. In 2011, 75% of all unplanned pregnancies in the US occurred in women aged 15 to 49 years.³ Those at risk of unintended pregnancy include women who reported either current use of a contraceptive method (with potential for failure of treatment) or no current contraceptive method (despite being sexually active). For many women, the need to obtain a prescription or visit the doctor can be challenging and time-consuming. In a study that assessed women’s perspectives on having OTC access to a POC, it was found that many women supported this decision since it offered convenience and discretion.⁴

The ACCESS Study

The Adherence with Continuous-dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) study played a crucial role in granting Opill® OTC status. ACCESS was a single-arm, open-label, multicenter, 24-week prospective study that involved assessing patient use of Opill® as an OTC product.⁵ The purpose of this study was to evaluate the adequacy of the OTC label in guiding appropriate consumer selection. Among the 883 women in the user population, six participants reported pregnancies in which conception was estimated to have occurred during the use of Opill®, and five participants reported pregnancies in which Opill® was discontinued prior to the estimated day of conception.⁵

Previous Clinical Trials

Since Opill ® had previously been approved by the FDA for prescription use by females of reproductive potential to prevent pregnancy, no new clinical trials assessing product efficacy were conducted as part of the switch development program. Its efficacy as a POC was demonstrated in eight clinical studies held in the US. Those included in these studies were women aged 15 to 49 years. These studies involved a total of 2,173 participants who completed at least one treatment cycle and 648 participants who had completed at least 13 cycles, providing a total of 21,856 28-day cycles of exposure to the drug. The observed pregnancy rate in these studies was approximately 2 pregnancies per 100 woman-years.⁶ HRA Pharma also conducted its own meta-analysis of eight separate clinical trials that assessed the efficacy of norgestrel 0.075 mg tablets. From a population of 7,584 participants across 66,409 cycles, 98 pregnancies were reported [95% confidence interval (Cl), 1.09 to 3.49].⁵ It was estimated that 7% of women will experience an unintended pregnancy during the first year of typical use.⁷

The most common side effects that participants in these studies experienced included headache, dizziness, nausea, fatigue, and acne. Additionally, use of Opill® may be associated with an increased risk of delayed follicular atresia, menstrual irregularity, changes in menstrual flow, and prolonged bleeding. Opill® tablets are contraindicated for use by women who might have a suspected pregnancy, suspected carcinoma of the breast, abnormal uterine bleeding, or liver tumors.^6,8 However, because Opill® only contains progestin, it presents no risk of venous thromboembolism compared to contraceptives containing estrogen. Hence, it is considered much safer and more appropriate for a broader population of women.

Conclusion

Birth control pills are an easy method to prevent pregnancy. They provide consistent contraception and help women stay in control of their fertility. Any of women at risk of unintended pregnancy in the US could benefit from the use of an easily accessible and effective contraceptive option at some point over the course of their reproductive lives. Opill® is expected be sold at pharmacies, convenience stores, and online in early 2024. Perrigo has not yet released pricing information but plans to in the coming months. Overall, Opill® has a promising future as a reliable and convenient oral contraceptive option.

References

1. FDA approves first nonprescription daily oral contraceptive. News release. Food and Drug Administration. Published July 13, 2023. Accessed December 14, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nonprescription-daily-oral-contraceptive.
2. Brenner PF, Mishell DR Jr, Stanczyk FZ, Goebelsmann U. Serum levels of d-norgestrel, luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone in women during and following ingestion of combination oral contraceptives containing dl-norgestrel. Am J Obstet Gynecol. 1977;129(2):133-140. doi:10.1016/0002-9378(77)90733-5
3. Unintended Pregnancy. Centers for Disease Control and Prevention. Division of Reproductive Health. Last Reviewed March 27, 2023. Accessed August 25, 2023. https://www.cdc.gov/reproductivehealth/contraception/unintendedpregnancy/.
4. Baum S, Burns B, Davis L, et al. Perspectives among a diverse sample of women on the possibility of obtaining oral contraceptives over the counter: a qualitative study. Womens Health Issues. 2016;26(2):147-152. doi:10.1016/j.whi.2015.08.007
5. Opill (norgestrel 0.075 mg tablets) for Rx-to-OTC switch. Joint Meeting Of The Nonprescription Drugs Advisory Committee And The Obstetrics, Reproductive, And Urologic Drugs Advisory Committee. May 9-10, 2023. https://www.fda.gov/media/167893/download.
6. Opill (norgestrel). Package insert. HRA Pharma; August 2017.
7. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83(5):397-404. doi:10.1016/j.contraception.2011.01.021
8. Kapp N. WHO provider brief on hormonal contraception and liver disease. Contraception. 2009;80(4):325-326. doi:10.1016/j.contraception.2009.01.020

Published by Rho Chi Post