Norgestrel

Introduction Overview

Generic Name

norgestrel

Brand Name

Opill

Dosage Form

tablet (0.075 mg)

Drug Class

Progestins

Pharmacokinetics

Absorption:
Norgestrel, the active ingredient in Opill, is rapidly and extensively absorbed from the gastrointestinal tract following oral administration. Peak plasma concentrations of norgestrel are typically reached within 1 to 2 hours post-dose. The bioavailability of oral norgestrel is high due to limited first-pass metabolism, allowing effective systemic hormone levels after a single tablet ingestion. Food intake does not significantly impact the absorption kinetics, thus Opill may be taken with or without meals, providing flexibility and ease of use. The absorption process is generally consistent among diverse patient populations; however, gastrointestinal disturbances such as vomiting or severe diarrhea within 4 hours of dosing can reduce effective absorption, necessitating the use of additional contraceptive precautions.

Distribution:
Norgestrel is extensively bound to plasma proteins, predominantly sex hormone-binding globulin (SHBG) and albumin. Approximately 98% of the hormone in circulation is protein-bound, with only a small fraction existing in the free biologically active form. The drug distributes widely to reproductive tissues where it exerts its contraceptive action, and measurable concentrations can be detected in breast milk, indicating passage through biological membranes. The volume of distribution reflects moderate tissue uptake, consistent with its lipophilic steroid structure. The protein-binding characteristic contributes to a relatively stable plasma half-life and a steady pharmacodynamic effect when administered daily.

Metabolism:
Norgestrel undergoes extensive hepatic metabolism primarily via cytochrome P450 enzymes, particularly CYP3A4 isoforms. It is biotransformed into multiple inactive metabolites through reduction, hydroxylation, and conjugation pathways including glucuronidation and sulfation, which facilitate renal and biliary elimination. Some of the metabolites can be detected in plasma and urine but lack progestogenic activity. The metabolism is subject to induction or inhibition by concomitant medications such as anticonvulsants (e.g., phenytoin, carbamazepine) and antibiotics (e.g., rifampin), which can reduce plasma levels of norgestrel and potentially compromise contraceptive efficacy. Genetic variations in metabolic enzymes may also influence individual pharmacokinetic profiles.

Elimination:
Excretion of norgestrel and its metabolites occurs primarily via the urine and feces with a minor component eliminated unchanged. The elimination half-life after a single dose ranges between 13 to 20 hours, supporting once-daily dosing regimens. Steady-state plasma concentrations are achieved within 2 to 3 days of continuous administration. Renal or hepatic impairment could affect metabolism and elimination rates, although clinical data suggest that standard dosing remains appropriate in most cases without dose adjustment. The drug’s clearance ensures maintenance of effective plasma concentrations when taken daily and on time, underscoring the critical importance of adherence for contraceptive reliability.

Dosage Forms

Available Dosage Forms:
Opill is available exclusively as an oral tablet containing 0.075 mg (75 micrograms) of norgestrel. This single-dose tablet is formulated for daily ingestion and is designed for consistent systemic hormone delivery. The product does not contain estrogen and is characterized as a progestin-only pill (POP), commonly referred to as a minipill.

Dosages for Adults and Adolescents:
The recommended dosing schedule for Opill is the administration of one 0.075 mg tablet once daily, taken at the same time each day without interruption between packs. The regimen involves continuous dosing without placebo or hormone-free intervals, providing steady contraceptive coverage. Initiation can occur on any day of the menstrual cycle, but barrier contraception should be used for the first 48 hours after initial dosing to ensure protection. Adherence to timing within a 3-hour window daily is essential because even minor delays increase pregnancy risk.

Specific Patient Populations:
Opill is approved for use in adult women and adolescents who require contraception and is especially appropriate for those who prefer or require estrogen-free contraception, such as breastfeeding women or individuals with contraindications to estrogen. The safety profile in breastfeeding has been well established, with no deleterious effects on milk production or infant health. Dose adjustments are generally not required for renal or hepatic impairment, though clinical judgment is advised. Use in patients with a history of hormone-sensitive cancers, liver disease, or unexplained vaginal bleeding requires prior medical evaluation to mitigate risks.

Clinical Guidelines:
Opill is designed for over-the-counter availability, providing accessible contraception without prescription barriers. The continuous daily dosing without breaks and strict adherence timing differentiates it from combined oral contraceptives, emphasizing the need for patient education on missed doses, delays, and gastrointestinal disturbances affecting absorption. Use in conjunction with additional barrier methods during initiation, missed doses, or potential malabsorption episodes is recommended to maintain contraceptive efficacy.

Mechanism Of Action

Norgestrel, the active hormonal component in Opill, functions primarily as a synthetic progestin that mimics the activity of natural progesterone, selectively binding to progesterone receptors in target tissues to exert its contraceptive effects. The principal mechanism involves thickening the cervical mucus, which forms a viscoelastic barrier that significantly impedes sperm penetration through the cervical canal. This immediate alteration in cervical mucus rheology reduces sperm motility and viability, effectively preventing sperm from reaching and fertilizing the ovum.

Additionally, norgestrel exerts suppressive effects, albeit variable, on the hypothalamic-pituitary-ovarian axis. It may partially inhibit the mid-cycle surge of luteinizing hormone (LH), thereby reducing or delaying ovulation in some users. However, ovulation suppression is not as consistent as with combined oral contraceptives, and its efficacy predominantly relies on mucus changes and endometrial modifications.

On the endometrial level, norgestrel induces alterations that render the uterine lining less receptive to implantation. These morphological and biochemical changes include stromal decidualization and suppression of glandular development, creating an inhospitable environment for embryo implantation in the event fertilization occurs. While this is a secondary mode of action, it may contribute to overall contraceptive effectiveness.

Comparatively, unlike combined estrogen-progestin contraceptives which target multiple points of the reproductive axis, progestin-only pills like Opill depend mainly on cervical mucus thickening and less reliably prevent ovulation. Clinical studies have confirmed that when taken exactly as prescribed, these mechanisms yield a pregnancy prevention rate of approximately 98%, underscoring the significance of strict adherence. Opill’s low-dose progestin formulation minimizes estrogen-related side effects while providing effective contraception through these multi-faceted biological pathways.

Pharmacological Actions

Progestogenic activity through selective binding to progesterone receptors.
Thickening of cervical mucus to inhibit sperm penetration and mobility.
Partial suppression or delay of ovulation via hypothalamic-pituitary-ovarian axis modulation.
Induction of endometrial alterations leading to decreased implantation likelihood.
Minimal androgenic and estrogenic effects due to selective receptor activity.
Consistent systemic exposure with once-daily oral administration.
Rapid onset of action within 48 hours of commencing treatment.
Low-dose hormonal contraceptive effect suitable for estrogen-sensitive populations.
Absence of estrogen-related thromboembolic risk observed in combination contraceptives.
Maintenance of contraceptive efficacy despite minor metabolic variations.
Reduction in menstrual bleeding intensity and frequency in some users.
Preservation of lactation performance during breastfeeding.
Minimal impact on lipid metabolism compared to combined pills.
Limited disruption of coagulation parameters.

Therapeutic Or Clinical Uses

Primary prevention of pregnancy in women desiring contraception.
Suitable contraceptive option for women who cannot take estrogen-containing products due to contraindications.
Contraceptive choice for breastfeeding mothers without adverse effects on lactation or infant health.
Over-the-counter availability facilitates wider access to effective birth control.
Management of menstrual irregularities related to progestin-only contraceptive use.
Alternative to combined oral contraceptives in patients with hypertension or thromboembolic risk factors.
Use in women with increased sensitivity or allergy to estrogen components.
Contraception in smokers over age 35, where estrogen use is contraindicated.
Emergency contraception is not indicated; used strictly for ongoing pregnancy prevention.
Supports reproductive autonomy without requirement for prescription or medical visits.
May be considered for extended or continuous contraceptive regimens under medical supervision.
Regional and national contraceptive guidelines endorse progestin-only pills for specific indications.
Appropriate for patients on enzyme-inducing medications if supplemented with barrier protection.
Can be integrated into multi-modal family planning services.
May reduce risk of ovarian cyst formation through suppression of ovulation in some users.

Side Or Adverse Effects

Alterations in menstrual bleeding patterns including irregular spotting and breakthrough bleeding.
Headache and migraine exacerbation in susceptible individuals.
Dizziness and lightheadedness episodes.
Nausea and occasional gastrointestinal discomfort following ingestion.
Increased appetite potentially leading to minimal weight changes.
Abdominal cramps, bloating, and pelvic discomfort.
Fatigue and somnolence reported rarely.
Vaginal discharge changes including increased secretions.
Breast tenderness and backache discomfort.
Nervousness and mood fluctuations in some cases.
Acne flare-ups due to hormonal effects on sebaceous glands.
Rare allergic reactions including rash, urticaria, or angioedema related to inactive ingredients such as tartrazine dye.
Potential development of ovarian cysts, generally benign and asymptomatic but occasionally causing pain or requiring surgical intervention.
Risk of ectopic pregnancy if contraceptive failure occurs.
Possible rare liver function disturbances manifesting as jaundice.

Precautions

Discontinue if pregnancy is suspected or confirmed.
Not suitable for women with current or past breast cancer.
Evaluate unexplained vaginal bleeding prior to initiation to exclude malignancy or infection.
Use additional barrier contraception when doses are missed or taken late by more than three hours.
Consult healthcare provider if taking medications known to induce hepatic enzymes including phenytoin, carbamazepine, rifampin, or herbal supplements such as St. John's Wort.
Advise on risk of ectopic pregnancy symptoms such as unilateral lower abdominal pain or irregular bleeding.
Monitor patients for liver abnormalities; discontinue if jaundice or severe hepatic dysfunction develops.
Do not use simultaneously with other hormonal contraceptives or intrauterine devices.
Counsel patients on the need for consistent daily dosing at the same time to maintain contraceptive efficacy.
Advise that Opill does not protect against HIV/AIDS or other sexually transmitted infections; continue barrier protection for STI prevention.
Screen women with history of hormone-sensitive cancers prior to use.
Recommend pregnancy testing if menstrual irregularities persist beyond two cycles without tablets being missed.
Educate about possible changes in menstrual bleeding patterns and initial irregularities.
Careful consideration in patients with history of thromboembolic disorders despite absence of estrogen component.
Regular healthcare follow-up is advisable to assess efficacy and tolerance.

Warnings

Do not use if allergic to norgestrel or inactive ingredients including FD&C Yellow No. 5 (tartrazine), due to risk of hypersensitivity reactions.
Increased risk of ectopic pregnancy if contraceptive failure occurs; urgent medical evaluation recommended for symptoms.
Potential development of ovarian cysts which may cause abdominal pain or require surgery.
Altered bleeding patterns including heavy or prolonged bleeding warrant medical assessment.
Discontinue immediately if signs of liver dysfunction occur, such as jaundice, dark urine, or right upper quadrant pain.
Not effective as emergency contraception; do not use as a morning-after pill.
Missed or delayed doses increase risk of pregnancy; barrier methods should be utilized when doses are missed.
Use with caution in women with a history of cancer, specifically hormone-sensitive tumors.
Monitor for allergic reactions; discontinue and seek emergency help if anaphylaxis or severe rash develops.
Not suitable for concurrent use with other hormonal contraceptives and should not be combined.
May cause dizziness; caution advised when performing activities requiring alertness.
Pregnancy during use requires cessation of drug and medical consultation.
Limited protection against sexually transmitted infections; additional protective measures necessary.
Avoid use with medications that reduce contraceptive effectiveness without consulting a healthcare provider.
Regular medical follow-up is important to monitor safety and contraceptive efficacy.

Contraindication

Known or suspected pregnancy.
Current or history of breast cancer.
Hypersensitivity to norgestrel or any inactive component of Opill, including tartrazine allergy.
Concurrent use with other hormonal contraceptives such as pills, patches, rings, implants, injections, or intrauterine devices.
Undiagnosed abnormal vaginal bleeding until etiology is established.
Active liver disease or impaired liver function.
History of hormone-sensitive malignancies.
Use in emergency contraception setting; Opill is not indicated for postcoital contraception.
Severe allergic reactions to progestins.
Patients unable to adhere to strict daily dosing regimen.
Concomitant use of drugs known to induce metabolism of norgestrel which cannot be substituted or monitored.
Use in patients exhibiting signs of thromboembolic disorders unless benefits outweigh risk; though risk is lower than combined contraceptives.
Known or suspected ectopic pregnancy.
Patients with severe gastrointestinal disorders leading to malabsorption.
Patients allergic to any of the tablet excipients.

Drug Interactions

Enzyme-inducing antiepileptics such as phenytoin and carbamazepine may decrease plasma levels of norgestrel, reducing contraceptive effectiveness.
Rifampin and rifabutin, potent inducers of cytochrome P450 enzymes, reduce norgestrel concentration.
Barbiturates can accelerate metabolism of norgestrel and compromise clinical efficacy.
Efavirenz, an antiretroviral agent, may alter plasma levels and reduce contraceptive reliability.
Bosentan, used to treat pulmonary arterial hypertension, can induce metabolism of norgestrel.
Ulipristal acetate, an emergency contraceptive, may have interactions—use of Opill within 5 days of ulipristal administration requires medical consultation.
Herbal supplements containing St. John's Wort (Hypericum perforatum) induce hepatic enzymes and decrease norgestrel concentrations.
Concomitant use with other hormonal contraceptives can cause additive side effects and complicate dosing.
Potential pharmacodynamic interactions with medications that alter bleeding risk or hormonal balance.
Possible alteration of metabolism in patients on antiretroviral therapy requiring monitoring.
Concomitant use with grapefruit juice is not well studied but may affect cytochrome P450 activity.
Interactions with some antibiotics that alter gastrointestinal flora may indirectly affect absorption.
Use caution when combining with drugs that affect liver function as this may alter norgestrel levels.
Medicines that induce glucuronidation or sulfation pathways may alter drug clearance.
Regular communication with healthcare provider advised when starting or stopping any interacting medication.

Preparations Of The Drug

Opill tablets contain 0.075 mg of norgestrel as the active ingredient.
Inactive ingredients include cellulose, lactose, magnesium stearate, polacrilin potassium, and FD&C Yellow No. 5 (tartrazine).
Available in 28-tablet blister packs for a one-month supply.
Supplied as small, yellow, round oral tablets designed for easy daily ingestion.
Manufactured by Perrigo Company adhering to FDA-approved specifications.
Formulated without estrogen to provide progestin-only contraception.
Packaged for over-the-counter sale, without requiring a prescription in the United States.
Stability requires storage at controlled room temperature between 20° to 25°C (68° to 77°F).
Packaging designed with clear day markers to enhance adherence.
Available for purchase online and through retail pharmacy outlets.
Supplied in tamper-evident, child-resistant packaging.
Lot numbers and expiration dates provided on cartons to ensure quality control.
No known formulations of Opill as extended-release or in combination products.
Over-the-counter access facilitates improved reproductive health autonomy.
Accompanied by patient information leaflets detailing dosing, precautions, and side effects.