Review of the First Over-the-Counter Oral Contraceptive (2025)

Norgestrel, (Opill) is the first over-the-counter (OTC) oral contraceptive to be approved by The Food and Drug Administration (FDA) in the United States. A progestin-only oral contraceptive, each pill contains 0.075 mg of norgestrel and is available in 28-day packs. There is no estrogen component in the pill, which should be taken daily at the same time for maximal efficacy. ¹

While a prescription is unnecessary, patient education is important. A consumer information leaflet comes with the medication, and patients should review this before using the product. The FDA advises that patients re-read the instructions each time the product is purchased.²

How it Works

Norgestrel acts on the endocrine feedback system between the ovaries, pituitary gland, and hypothalamus. Once norgestrel reaches the therapeutic level in the bloodstream, feedback signals to the hypothalamus and pituitary suppress ovulation. Norgestrel decreases the release of the gonadotropin-releasing hormone (GnRH) from the hypothalamus and blunts the pre-ovulatory luteinizing hormone (LH) surge from the pituitary gland. The loss of the LH surge suppresses ovulation. Norgestrel also increases the thickness of cervical mucus, making it less permeable to sperm, and makes the endometrium resistant to implantation.^3,4

Usage and Efficacy

The Opill can be started anytime during the menstrual cycle. Guidelines recommend taking norgestrel at the same time each day. Once 1 pack of pills is finished, the next pack should be started. Backup contraception or avoidance of sexual intercourse is recommended for the first 48 hours if progestin-only pills are started later than the first 5 days after the beginning of the menstrual cycle.⁵

Norgestrel has a short half-life and serum levels decline to near baseline by 24 hours. A pill taken more than 3 hours late (27 hours after the prior dose) is considered a “missed” pill. Missed pills can result in ‘escape ovulation’ and require the use of backup contraception to prevent pregnancy.⁶

If there is a missed dose of norgestrel or vomiting after taking the pill, the recommended course of action involves taking the missed pill as soon as possible and continuing with the remaining pills as scheduled. To ensure pregnancy prevention with a missed dose, backup contraception is recommended, such as condoms, for 48 hours after the missed dose or after vomiting.¹

When taken as directed, norgestrel has 98% efficacy in preventing pregnancy in individuals who are adherent to the daily regimen. To attain 98% efficacy, the patient must take 1 tablet every day and at the same time each day without any breaks between monthly packs. The FDA recommends using a backup birth control method, such as a condom when the person misses or is delayed in taking the daily tablet for more than 3 hours.⁷

Studies show that the failure rate of typical “real world” use, which accounts for inconsistent or incorrect use, is approximately 7%. The failure rate is the same with estrogen-progestin combination birth control pills. Comparatively,long-acting reversible contraceptives (LARCS), the intrauterine device (IUD), and the progestin implant have the lowest failure rates of all contraceptive methods (<1%), while condoms and spermicide carry the highest probabilities of failure (13% and 21%, respectively).^8,9

Drug Interactions and Adverse Effects

There may be drug interactions that lessen the effect of the Opill. Drug interactions may occur with anticonvulsants, anti-tuberculosis agents, anti-retroviral agents, medications to treat pulmonary hypertension, and St. John’s Wort.

Norgestrel may interact with ulipristal acetate (the “morning-after “pill), and it is not an emergency contraceptive. The Opill does not protect against sexually transmitted diseases (STIs).¹

The most common adverse side effects¹⁰ reported included:

• Acne
• Bloating
• Breast tenderness
• Change in appetite
• Diarrhea
• Dizziness
• Fatigue
• Headache
• Heavy or light menstrual bleeding
• Nausea
• Spotting or bleeding between menstrual cycles
• Vomiting

Serious side effects¹⁰ that require notification of a health care provider include:

• Dark-colored urine
• Fever
• Loss of appetite
• New or worsening migraine headache
• Rash; hives; itching
• Shortness of breath
• Sudden, severe, or persistent lower abdominal pain
• Swelling of the face, eyes, or mouth
• Tiredness
• Unusual vaginal bleeding or menstrual bleeding that is unusually heavy or that lasts a long time
• Wheezing
• Yellowing of the skin or eyes

Discussion

Although previous studies have suggested that hormonal contraceptives may have reduced effectiveness in women who are overweight or obese compared with women who are not overweight, a meta-analysis found that most of these studies had low evidence for a correlation between body weight and the efficacy of norgestrel.¹¹

Studies have suggested that there is significant variability in adherence behavior among users of oral contraceptives.^12,13 One study investigated adherence to the norgestrel regimen in a group of women that reflected the diversity of the US population at risk for unintended pregnancy and prior hormonal contraception experience. The study found that 85% of participants had greater than 85% adherence to the daily pill. They also reported taking their dose within 3 hours of their scheduled dosing time 96% of the time.When a pill was missed, 97% of users reported using a condom for 48 hours as directed by the OTC label and instructions.⁴

According to the manufacturer, Opill should not be used in women who are pregnant or have a history of breast cancer or liver disease. It should not be taken together with another birth control pill, vaginal ring, patch, implant, injection, or an intrauterine device.¹

The FDA recommends that individuals who miss 2 periods (or have missed a single period and have missed doses of the Opill) or suspect they may be pregnant should take a pregnancy test. Consumers should discontinue the use of the Opill if a pregnancy is confirmed.¹²

Adolescent patients can begin taking Opill after the onset of menarche. In such cases, clinicians should educate the patient and their caregiver (eg, parent) about expectations for the first menstrual period and normal cycle length, frequency, and volume for subsequent periods.¹³

Key points:

• Primary care clinicians need to be knowledgeable about OTC oral contraceptives, as many patients may need counseling and education.
• Patients need to understand the importance of consistent, strict adherence to a daily schedule for the complete effectiveness of the pill.
• Clinicians should inquire about current medications and allergies.
• Counseling should be individualized based on the patient’s health history, other medications in the patient’s drug regimen, and risk factors for adverse events.