M&D Clinical Corner: Community Pharmacist’s Guide to OTC Contraceptive Pill: Opill®

The Clinical Corner is a monthly feature that highlights a variety of important pharmacist topics that is written by Morris & Dickson’s staff pharmacist, Paula Belle (RPh).

This month’s Clinical Corner will provide information on the recent Food and Drug Administration (FDA) approval of the first over-the-counter oral contraceptive.

• Background
• The Pharmacist’s Role
• Understanding Opill®
• Counseling Patients
• Resources for Pharmacists
• Resources for Patients

BACKGROUND

• Norgestrel 0.075 mg tablets (Opill®) will be the first daily oral contraceptive to make the Rx-to-OTC switch. [1]
• Norgestrel 0.075 mg tablet was originally approved as a daily oral contraceptive in 1973. [2]
• The product was marketed under the brand name Ovrette® until 2005, when distribution was stopped by the company for marketing reasons, and not for reasons of safety or effectiveness. [2]
• Beginning in 2015, HRA Pharma (now owned by Perrigo) met with FDA multiple times to obtain advice on a nonprescription development program. [2]
• In a non-binding decision, the U.S. Food and Drug Administration’s (FDA) Nonprescription Drugs Advisory Committee (NDAC) and the Obstetrics, Reproductive, and Urologic Drugs Advisory Committee (ORUDAC) voted unanimously 17 to 0, with no abstentions, that the benefits of making Opill®, a progestin-only daily oral contraceptive, available for over-the-counter (OTC) use outweighs the risks. [3]
• At the May 9-10, 2023, public Advisory Committee meeting, advisors voted unanimously that, in their opinion, the potential benefits of nonprescription norgestrel 0.075 mg daily tablet contraception availability outweighed the potential risks. [2]
• According to the drug’s maker, Perrigo, Opill®, sometimes called the minipill, will be available for purchase online and in stores in the first quarter of 2024, without a prescription. [4]
• It is too soon to say if cost or coverage will be a barrier for patients. [1]

THE PHARMACIST’S ROLE
Understanding OPILL®

• Opill® is a progestin-only and estrogen-free contraceptive pill [5] as opposed to a combination pill containing estrogen and progestin. [4]
• It is suitable for most people, including those who have a contraindication to estrogen and people who are smokers, breast-feeding, and have a history of migraines. [5]
• Opill prevents conception by thickening the cervical mucus to inhibit sperm penetration and suppressing or disrupting ovulation. [6]
• The daily oral contraceptive pill is currently the most common form of contraception used in the US. [5]
• Prescription progestin-only pills like Opill® have been used for nearly 50 years to prevent pregnancy. [5]
• The FDA review team’s most notable risk concerns for norgestrel tablets included :
  • Use of the product by people with progestin-sensitive cancers, with the risk for worsening the clinical course of the cancer, or increasing risk of recurrence. [2]
  • The high frequency of vaginal bleeding with the product, with the risk that people using the product will attribute vaginal bleeding to the product and not recognize the need to seek evaluation for serious conditions that manifest with vaginal bleeding. [2]
  • The potential for reduction in bone mineral density, and perhaps increased fracture risk, with very long-term use of the product. [2]
• For each of these concerns, the FDA review council recognized the following [2]:
  • Progestin-sensitive Cancers
    • The FDA review council acknowledged that progestin-sensitive cancers are uncommon in people under age 40 years, and the population using norgestrel tablet for contraception would likely overwhelmingly be under the age of 40 years. [2]
    • For an individual consumer of the product, the risk is very low, and almost nonexistent if they read and follow the labeling. [2]
    • Overall, the total public health impact of the potential harm related to incorrect use by people with progestin-sensitive cancer is likely outweighed by the probable larger public health impact of prevention of a large number of unintended pregnancies with all their attendant harms. [2]
  • Abnormal Uterine Bleeding
    • In the age group most likely to use norgestrel tablet contraception, serious conditions associated with abnormal uterine bleeding are uncommon. Per SEER 2019 data, endometrial cancer is rare in women of reproductive age, occurring in only 0.037% of women under age 50 years. [2]
    • Consistent daily use and consistent timing of dosing are considered important for optimal effectiveness of norgestrel tablet contraception, and may reduce the occurrence of breakthrough vaginal bleeding. [2]
  • Reduction in Bone Mineral Density
    • Norgestrel 0.075 mg/day does not strongly suppress estrogen. [2]
    • While the long-term effect on bone density and risk of fracture is not completely characterized for norgestrel 0.075 mg daily, the preservation of some degree of estrogen secretion would be expected to be somewhat protective. [2]
    • In the reviewed literature, norgestrel itself has not been associated with decreased bone mineral density or increased fracture risk. [2]
    • The prescription labeling for progestin-only oral contraceptives does not recommend monitoring of bone mineral density. [2]

Counseling Patients

• Patients should not use Opill® if they have ever had breast cancer; are already pregnant; or are concomitantly using another birth control pill, vaginal ring, patch, implant, injection, or intrauterine device. [7]
• Patients should be advised to use a condom, or another barrier method, every time they have sex during the first 2 days of use. It takes 48 hours for this product to begin working. [7]
• If a patient opts to use OTC Opill ®, pharmacists should add this drug to patient profiles and be aware of and review for drug interactions such as CYP3A4 inducers (phenytoin, etc.) that may reduce the efficacy of pill, patch or ring. [1]
• Pharmacists can counsel patients regarding the long safety track record of norgestrel with fewer risks than oral contraceptives with estrogen. [1] Nearly 50 years of use and scientific evidence show that progestin-only pills such as Opill® are effective at preventing pregnancy and are safe for most women to use. [3]
• Pharmacists should remind patients that should they miss a dose, progestin-only pills are less forgiving than other oral contraceptives that contain estrogen. [1]
• Strict adherence should be emphasized including the use of alarms and/or apps to ensure that Opill® is taken at the same time each day. [1]
• Pharmacists should explain that taking Opill® at the same time each day is a more effective method of contraception than other OTC options such as condoms and spermicides. [1]
• Recommend backup contraception for 2 days after starting the first pack, if a dose is more than 3 hours late, or if a patient vomits or has severe diarrhea within 4 hours of taking a dose. [1]
• Opill® will come in multiple 28-day pill pack options. These are likely to include a 1, 2, 3, or 6-month supply. Patients should be advised to take a pill at the same time every day, continuously with no breaks between packs. [1]
• Patient counseling should include the note that irregular menstrual bleeding is common with progestin-only pills and to continue taking norgestrel if this happens. [1]
• Patients should also be aware that Opill® is NOT an emergency contraceptive and it will not protect against sexually transmitted infections. [1]

RESOURCES FOR PHARMACISTS

• Access to the FDA’s database of drug effects on CYP enzymes and transporter systems is available at: CYP Enzyme-Transporter Systems Drug Interactions
• Various resources that include general contraceptive guidance, selected practice recommendations, social media tools, and family planning for healthcare providers is available at: Contraceptive Guidance for Healthcare Providers
• Evidence-based guidance to help health care providers offer help to patients including choosing the most appropriate contraceptive method for individual circumstances and using that method correctly, consistently, and continuously to maximize effectiveness is available at U.S. Medical Eligibility Criteria for Contraceptive Use
• Health care providers can play a critical role in educating female patients with intellectual disabilities and their caregivers about contraceptive topics. Guidance is available at: Counseling Female Patients With Intellectual Disabilities

RESOURCES FOR PATIENTS

• The CDC offers information to patients about contraception at: Contraception
• Consumer oriented information about various contraceptives is available at: Birth Control Methods
• Emergency Contraception information for patients is available at: Emergency Contraception

SOURCES

1. Center, T.R., Prepare for Opill, the First OTC Oral Contraceptive. 2024.
2. Murry, K.M. Decisional Memorandum New Drug Application 17031 Supplement 41 Application for Full Prescription-to-Nonprescription Switch of Norgestrel Tablets 0.075 mg. 2023 [cited 2024 January 23]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/017031Orig1s041SumR.pdf.
3. Perrigo Company. Press release. 2024 [cited 2024 January 23]; Available from: https://opillhcp.com/pages/press-release.
4. WebMD. What Families Should Know About the New OTC Birth Control Pill. 2024 [cited 2024 January 25]; Available from: https://www.webmd.com/sex/birth-control/news/20231006/what-to-know-about-opill-otc-birth-control.
5. Perrigo Company. About Opill For HCP. 2024 [cited 2024 January 25]; Available from: https://opillhcp.com/pages/about-opill.
6. Perrigo Company. OPILL (NORGESTREL 0.075 MG TABLETS) FOR RX-TO-OTC SWITCH SPONSOR BRIEFING DOCUMENT. 2023 [cited 2024 January 25]; Available from: https://www.fda.gov/media/167893/download.
7. American Pharmacists Association. Updates from FDA. 2024 [cited 2024 January 23]; Available from: http://www.pharmacist.com/Publications/Pharmacy-Today/Article/updates-from-fda-15.