norgestrel

Norgestrel is a progestin-only oral contraceptive that FDA approved on July 13, 2023 as a nonprescription birth control pill, the first time a daily oral contraceptive has been made available over the counter (OTC) in the U.S. Norgestrel is a synthetic formulation of the female sex hormone progesterone, taken to prevent pregnancy. Progesterone, along with estrogens, another group of hormones, regulates the reproductive cycle in women. Norgestrel interferes with the normal hormonal balance during the menstrual cycle to prevent pregnancy.

Progesterone plays a vital role in the regulation of menstruation, ovulation, implantation, maintenance of pregnancy, and fetal growth. Estrogen stimulates the growth of endometrium, the inner uterus lining, while progesterone prepares it for implantation and pregnancy. Progesterone stimulates the growth of breast tissue, readying it for lactation. In the absence of conception, hormone levels fall, leading to menstruation and beginning of a new cycle.

The reproductive cycle is regulated by a system known as the hypothalamic-pituitary-gonadal axis. The hypothalamus secretes gonadotropin releasing hormone (GnRH), which stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH stimulate ovulation and the production of estrogen and progesterone at the appropriate times during the cycle to enable conception and pregnancy.

Norgestrel works by binding to progesterone receptors, protein molecules in cells that respond to progesterone. Norgestrel prevents pregnancy by suppressing ovulation in approximately half the users. Other effects of norgestrel that help prevent pregnancy are as follows:

• Thickens the cervical mucus, hindering the passage of sperm into the uterus
• Lowers the mid-cycle peaks in FSH and LH that enable follicle maturation and ovulation
• Slows the movement of ovum through the fallopian tubes
• Prevents implantation by thinning the endometrium

• Do not use norgestrel if you are hypersensitive to any of its components.
• Do not use norgestrel in the following conditions:
  • Known or suspected pregnancy
  • Known or suspected breast or other progestin-sensitive cancers or a history of these cancers
  • Undiagnosed abnormal uterine bleeding
  • Benign or malignant liver tumors
  • Acute liver disease
• Up to 10% of pregnancies that occurred in norgestrel users during clinical trials were ectopic. Consider the possibility of ectopic pregnancy in women who become pregnant or experience lower abdominal pain while taking norgestrel.
• Sometimes, follicular degeneration (atresia) may be delayed and the follicle may become larger than normal. These enlarged follicles are generally asymptomatic or may cause mild abdominal pain and disappear spontaneously, but may rarely twist and rupture, requiring surgical intervention.
• Norgestrel use may cause menstrual irregularities including spotting, breakthrough bleeding, or absence of menstruation (amenorrhea).
  • Evaluate women for undiagnosed abnormal uterine bleeding before prescribing norgestrel.
  • Test for pregnancy in women with amenorrhea.
  • If uterine bleeding together with the clinical history suggests infection, malignancy, pregnancy, or other conditions, perform tests to rule out these conditions.
• Discontinue norgestrel if you develop symptoms of liver function disturbances or jaundice. Do not resume norgestrel until liver function returns to normal and the cause is established to be not related to norgestrel.
• Evaluate women who experience new onset or exacerbation of migraine or severe, persistent or recurrent headaches, because they are at increased risk for stroke.
• Norgestrel contains FD and C yellow No.5 (tartrazine) as a color additive, which may cause allergic reactions in susceptible people. Individuals with aspirin hypersensitivity are more likely to be hypersensitive to tartrazine. Discontinue norgestrel if you develop allergic reactions, and seek immediate medical attention.
• Diarrhea and/or vomiting within 4 hours of taking norgestrel can reduce its absorption. Women must use non-hormonal methods of contraception as a backup for the next 48 hours.
• Norgestrel may cause slight changes in glucose tolerance and increase in plasma levels of insulin, although women with diabetes mellitus do not generally experience changes in insulin requirement.
• Occasionally, some women may experience mild changes in lipid and carbohydrate metabolism that have not generally been found to be clinically significant.
• Norgestrel may increase the risk of developing breast cancer, which is likely related to the duration of use, particularly at a younger age.
• Strong or moderate CYP3A4 inhibitor medications may increase the blood concentration of norgestrel and increase the risk of adverse effects.
• Strong or moderate CYP3A4 inducers may reduce norgestrel efficacy and lead to contraceptive failure.
• Norgestrel may affect some endocrine lab tests including decrease in sex hormone-binding globulin concentrations, and decrease in thyroxine concentration because of decrease in thyroid-binding globulin.

Common side effects of norgestrel include:

• Delay in follicular atresia, a process of degeneration and resorption of follicles that do not mature into ova
• Menstrual irregularity
• Changes in menstrual flow
• Breakthrough spotting and bleeding
• Prolonged bleeding
• Absence of menstrual bleeding (amenorrhea)
• Painful menstruation (dysmenorrhea)
• Vaginal discharge
• Headache
• Dizziness
• Nausea
• Increase in appetite
• Abdominal pain and cramps
• Bloating
• Fatigue
• Backache
• Breast discomfort
• Acne
• Nervousness

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 0.075 mg in 28-day calendar packs
• All tablets contain active drug

Adult and Pediatric:

Contraception

• Progestin-only oral contraceptive indicated to prevent pregnancy in women and adolescent girls who have started menstruating (menarche)
• 1 tablet (0.075 mg) orally at same time every day
• Administration is continuous with no interruption between pill packs
• See Administration for information regarding missed pills and when to use backup contraceptive methods

Starting norgestrel

• Start first pack on any day
• If switching from another oral contraceptive, vaginal ring, or patch, start taking the day after stopping other method
• Use condom (or another barrier method) for each intercourse during the first 2 days after initiating

Dosing Considerations

• NOT an emergency contraceptive (morning after pill); do not take to try to prevent pregnancy after unprotected sex because it is ineffective
• Does NOT protect against HIV/AIDS or other sexually transmitted diseases (STDs); use condoms to protect against STDs

Oral Administration

• Take 1 tablet at the same time every day; take even when bleeding or spotting
• Do NOT use as an emergency contraceptive
• Continue to see healthcare provider for routine healthcare visits
• Use a condom or another barrier method if taking tablet more than 3 hours late or missing a tablet on 1 or more days

Missed or vomited dose

• Missed tablet by 3 hours or less
  • Take 1 tablet immediately and go back to usual schedule
• Missed tablet by more than 3 hours or missed 1 or more tablets
  • Take 1 tablet immediately, as soon as remembered; then go back to usual schedule
  • This may mean taking 2 tablets in 1 day
  • Use a condom (or another barrier method) during intercourse for next 48 hours after restarting norgestrel
  • Instruct patient to take a pregnancy test or contact physician if menses is late after missing any tablets in the past month
• Vomiting or severe diarrhea within 4 hours of dose
  • Use a condom (or another barrier method) during intercourse for next 48 hours
  • On the next day, take daily tablet at usual time

Overdose

Norgestrel overdose may cause nausea, vomiting, breast tenderness, dizziness, drowsiness, fatigue and withdrawal bleeding in women. Norgestrel has no specific antidote and overdose is treated with symptomatic care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Norgestrel has no known severe interactions with other drugs.
• Serious interactions of norgestrel include:
  • apalutamide
  • carbamazepine
  • enzalutamide
  • fosphenytoin
  • mifepristone
  • phenobarbital
  • phenytoin
  • primidone
  • rifampin
  • St John’s Wort
• Norgestrel has interactions with at least 98 different drugs.
• Norgestrel has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Norgestrel is for prevention of pregnancy and is not indicated for pregnant women. Suspected pregnancy should be ruled out before starting any hormonal contraceptive including norgestrel. Discontinue norgestrel if pregnancy is confirmed.
• Published studies do not report any adverse effects on fetal development from long-term use of progestin-only oral contraceptives in pregnant women.
• Limited available data indicate that normal ovulation and fertility return soon after discontinuation of norgestrel.
• Small amounts of norgestrel are excreted in breastmilk. There have been very rare reports of adverse effects in the breastfed infant, including jaundice.
• According to the LactMed database, progestin-only contraceptives such as norgestrel are considered the hormonal contraceptives of choice in nursing mothers.
• Decision to breastfeed should be based on the nursing mother’s clinical need for norgestrel, health and developmental benefits of breastfeeding, and potential risks to the breastfed infant from exposure to the drug or the mother’s underlying condition.

• Take norgestrel exactly as instructed, at the same time every day, including throughout all bleeding episodes.
• Use an additional non-hormonal method of contraception for 48 hours, if the daily dose is delayed for 3 or more hours, or if you have vomiting and/or diarrhea.
• Avoid smoking cigarettes while taking norgestrel. Smoking increases the risk for serious cardiovascular disease, stroke and heart attack. Smoking while taking norgestrel also increases the risk for breast cancer, cancer of the reproductive organs, liver tumor and changes in carbohydrate and lipid metabolism.
• Norgestrel use may alter normal menstrual bleeding patterns. However, if you have missed two consecutive periods or miss one period and have missed norgestrel doses, take a pregnancy test.
• Report to your obstetrician/gynecologist if you experience repeated vaginal bleeding after sexual intercourse, prolonged episodes of bleeding, absence of periods or development of severe abdominal pain.
• Norgestrel does not protect against human immunodeficiency virus (HIV) infection or other sexually transmitted diseases.
• Store norgestrel safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.