Norgestrel + Ethinyl Estradiol + Ferrous Fumarate

Approved Indication

• Contraception: Indicated for the prevention of pregnancy in women who choose to use oral contraceptives as a method of birth control.

Important Off-Label Uses

• Menstrual Regulation: Used to regulate irregular menstrual cycles.
• Dysmenorrhea: Reduces the severity and duration of menstrual pain.
• Acne Treatment: Some combinations are approved to treat moderate acne vulgaris in women who desire contraception.
• Endometriosis (off-label): Used off-label to reduce pain and bleeding associated with mild to moderate endometriosis.

Typical tablet composition (per active tablet):

• Norgestrel: 0.3 mg (progestin)
• Ethinyl Estradiol: 0.03 mg (estrogen)

Placebo/Reminder Tablets:

• Each inactive tablet contains Ferrous Fumarate 75 mg (provides ~25 mg elemental iron) — no contraceptive effect; included to maintain daily dosing habit and supply iron during withdrawal bleeding.

Note: Exact composition may vary slightly by brand. Always verify the specific product labeling.

Typical Oral Regimen

• Active Phase: Take one active tablet daily for 21 consecutive days at the same time each day.
• Reminder Phase: Follow with 7 ferrous fumarate tablets taken daily to allow withdrawal bleeding.
• Cycle: Each pack = 28 tablets (21 active + 7 inert).

Initiation

• First-Day Start: Begin on the first day of menstrual bleeding.
• Sunday Start: Alternatively, begin on the first Sunday after menstruation starts.
• Use backup contraception for the first 7 days if starting later than day 1.

Missed Dose

• One missed active tablet: Take as soon as remembered; take next at regular time.
• Two or more missed active tablets: Take last missed tablet ASAP, continue pack, use backup contraception for 7 days; follow detailed pack instructions.

Pediatrics

• Approved for post-menarcheal females only.

Elderly

• Not indicated in postmenopausal women.

Hepatic Impairment

• Contraindicated in significant hepatic disease or liver tumors.

Renal Impairment

• No dose adjustment specified, but use with caution.

Administration Note

• Tablets should be swallowed whole with or without food. Consistent daily timing is critical for contraceptive reliability.

This combined oral contraceptive contains a synthetic progestin (Norgestrel) and a synthetic estrogen (Ethinyl Estradiol) which work together to suppress ovulation by inhibiting the mid-cycle surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) via negative feedback on the hypothalamic-pituitary-ovarian axis. They also thicken cervical mucus to impede sperm penetration and alter the endometrial lining, reducing the chance of implantation. The Ferrous Fumarate does not affect contraceptive efficacy but supplies iron to help replenish iron stores lost during menstruation.

Absorption

• Ethinyl Estradiol and Norgestrel are well absorbed; Ethinyl Estradiol undergoes significant first-pass metabolism (~40–50% bioavailability).

Distribution

• Highly protein-bound: Ethinyl Estradiol binds to albumin and SHBG; Norgestrel binds primarily to SHBG and albumin.

Metabolism

• Ethinyl Estradiol is extensively metabolized via hepatic CYP3A4; Norgestrel also undergoes hepatic metabolism to active and inactive metabolites.

Excretion

• Metabolites excreted in urine and feces.
• Terminal half-life: Ethinyl Estradiol ~13–27 hours; Norgestrel ~24 hours.

Pregnancy                            

• FDA Pregnancy Category X: Contraindicated — do not use if pregnancy is confirmed or suspected.

Lactation

• Small amounts of hormones may pass into breast milk and may reduce milk production. Use caution; progestin-only contraception is preferred in breastfeeding mothers, especially during the first 6 weeks postpartum.

• Class: Combined Oral Contraceptive (COC)
• Subclass: Monophasic combination with iron supplement

• Known or suspected pregnancy
• Current or history of thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism)
• Cerebrovascular or coronary artery disease
• Known or suspected breast carcinoma or other estrogen/progestin-sensitive malignancies
• Undiagnosed abnormal genital bleeding
• Active liver disease or hepatic tumors
• Hypersensitivity to any component of the product

• Thromboembolic Risk: Increased risk of venous and arterial thromboembolism, especially in smokers over 35.
• Hypertension: May elevate blood pressure — monitor periodically.
• Hepatic Tumors: Rare reports of benign liver tumors; avoid in significant liver disease.
• Cancer Risk: Slight increased risk of cervical and possibly breast cancer with long-term use.
• Visual Changes: Discontinue if unexplained vision loss, proptosis, or retinal vascular thrombosis occurs.
• Gallbladder Disease: May increase risk of gallbladder stones or disease.
• Mood Changes: Monitor for severe depression or mood swings.

Common (by system):

• GI: Nausea, vomiting
• CNS: Headache, mood swings, dizziness
• Breast: Tenderness, enlargement
• Reproductive: Breakthrough bleeding, spotting, amenorrhea

Serious/Rare:

• Venous thromboembolism (DVT, PE)
• Stroke, myocardial infarction
• Hypertension
• Hepatic adenomas
• Gallbladder disease
• Retinal vascular thrombosis

Timing:

• Nausea and breast tenderness often resolve after first 2–3 cycles.
• Irregular bleeding is more common in early cycles.

• CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin): May reduce contraceptive effectiveness — backup contraception required.
• Antibiotics (e.g., rifampin): Known to reduce hormone levels.
• HIV Protease Inhibitors and NNRTIs: May alter plasma hormone levels; may require alternative contraception.
• St. John’s Wort: Induces CYP3A4, may decrease contraceptive effect.
• Lamotrigine: Ethinyl Estradiol may lower lamotrigine levels, increasing seizure risk.

• FDA and CDC emphasize risk of thrombosis and highlight that COCs are contraindicated in smokers >35 years old.
• WHO Medical Eligibility Criteria updated: care should be individualized, especially in high-risk groups.
• Current practice encourages patient counseling on non-hormonal alternatives when appropriate.

• Store at 20°C to 25°C (68°F–77°F); excursions permitted to 15°C–30°C (59°F–86°F).
• Protect from moisture and direct light.
• Keep in original blister until use.
• Keep out of reach of children.