LOESTRIN FE 1/20
Clinical safety rating
cautionComprehensive clinical and safety monograph for LOESTRIN FE 1/20 (LOESTRIN FE 1/20).
Combination oral contraceptive consisting of ethinyl estradiol and norethindrone acetate. Inhibits gonadotropin secretion (FSH, LH) via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing ovulation. Increases cervical mucus viscosity and alters endometrial structure, impeding sperm penetration and implantation.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes sulfation and glucuronidation. Norethindrone: metabolized primarily by reduction and conjugation (CYP3A4 minor role). Both undergo enterohepatic recycling. |
| Excretion | Norethindrone: 50-60% renal (as metabolites), 20-30% fecal. Ethinyl estradiol: 40-50% renal (as glucuronide conjugates), 30-40% fecal (as sulfate conjugates). |
| Half-life | Norethindrone: 6-9 hours (terminal). Ethinyl estradiol: 13-27 hours (terminal, mean 16 hours). Steady-state reached within 5-7 days. |
| Protein binding | Norethindrone: ~97% bound (mainly SHBG, also albumin). Ethinyl estradiol: ~98% bound (albumin, induces SHBG synthesis). |
| Volume of Distribution | Norethindrone: 2-5 L/kg. Ethinyl estradiol: 2-4 L/kg (increased water solubility vs estradiol). |
| Bioavailability | Norethindrone: 50-80% (oral). Ethinyl estradiol: 40-60% (oral, due to first-pass conjugation). |
| Onset of Action | Oral: Contraceptive effect requires 7 days of continuous dosing for full suppression of ovulation. |
| Duration of Action | 24 hours after daily dosing; maintains suppression of gonadotropins and endometrial changes. Missed dose increases ovulation risk. |
| Molecular Weight | 296.4 |
One tablet (norethindrone acetate 1 mg and ethinyl estradiol 20 mcg) orally once daily for 21 consecutive days, followed by one ferrous fumarate tablet (75 mg) orally once daily for 7 days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe impairment (CrCl <30 mL/min); contraindicated in acute renal disease. |
| Liver impairment | Contraindicated in Child-Pugh class C. Use with caution in Child-Pugh class A or B; may increase risk of fluid retention and impaired metabolism. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents: same dosing as adults (21 days active, 7 days ferrous fumarate). |
| Geriatric use | Not indicated for use after menopause. If prescribed in perimenopause, use lowest effective dose due to increased risk of thromboembolic events and cardiovascular disease. |
| 1st trimester | Contraindicated. Estrogen-progestin combination contraceptives are not indicated during pregnancy. While inadvertent use in very early pregnancy does not appear to increase risk of birth defects, they should be discontinued when pregnancy is confirmed. |
| 2nd trimester | Contraindicated. Not indicated during pregnancy; use only if clearly needed and no alternative. No well-controlled studies in pregnant women. |
| 3rd trimester | Contraindicated. Risk of adverse fetal/neonatal effects; avoid use. |
Clinical note
Comprehensive clinical and safety monograph for LOESTRIN FE 1/20 (LOESTRIN FE 1/20).
| Placental transfer | Steroid hormones (ethinyl estradiol, norethindrone) cross the placenta; significant transfer occurs, but exact degree not well quantified. Ethinyl estradiol: molecular weight 296.4 Da; norethindrone: 298.4 Da. |
| Breastfeeding | Small amounts of contraceptive steroids and/or metabolites are excreted in breast milk. Estrogen-containing contraceptives may reduce milk production and affect milk composition; use during breastfeeding not recommended until weaning or at least 6 months postpartum when milk supply is well established. Progestin-only methods preferred. |
| Lactation Rating | L3 (Moderately Safe) - Generally avoid unless alternative not available; potential for reduced milk supply. |
| Teratogenic Risk | First trimester: Combination hormonal contraceptives are not associated with an increased risk of major birth defects when inadvertently taken. Second and third trimesters: No known risk of fetal abnormalities; however, use during pregnancy is not indicated. Postnatal: No evidence of long-term adverse effects from inadvertent exposure. |
| Fetal Monitoring | No specific fetal monitoring required if inadvertently used during pregnancy. In women of reproductive age, exclude pregnancy before initiation. Monitor blood pressure annually. No routine maternal labs required beyond standard contraceptive follow-up. |
| Fertility Effects | Does not permanently impair fertility. Rapid return to baseline fecundity after discontinuation. No long-term delay in conception. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially women >35 years) and number of cigarettes smoked. Women >35 and who smoke should not use this product.
| Serious Effects |
Pregnancy or suspected pregnancyHistory of or current thrombophlebitis or thromboembolic disordersCerebrovascular or coronary artery diseaseKnown or suspected breast carcinomaUndiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasiaBenign or malignant liver tumor (active or history)Hepatic adenoma or carcinoma (active or history)Jaundice or impaired liver function (acute or chronic)Hypersensitivity to any componentSmoking >15 cigarettes/day and age ≥35 years
| Precautions | Increased risk of thromboembolic disorders (e.g., DVT, PE, stroke, MI), Cerebrovascular disease, Carcinoma of the breast and reproductive organs, Liver disease (hepatic adenoma, hepatocellular carcinoma), Elevated blood pressure, Gallbladder disease, Carbohydrate/lipid metabolic effects, Hereditary angioedema, Chloasma, Ocular lesions (retinal thrombosis), Depression, Reduced efficacy with concomitant enzyme inducers |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase estrogen levels. No other significant food restrictions. The iron in the placebo tablets is best absorbed when taken with vitamin C (e.g., orange juice) but can be taken with food to reduce GI upset. |
| Clinical Pearls | Loestrin Fe 1/20 contains norethindrone acetate 1 mg, ethinyl estradiol 20 mcg, and ferrous fumarate (iron) as a placebo. The low estrogen dose (20 mcg) may increase breakthrough bleeding risk, especially in early cycles. Iron supplementation (75 mg ferrous fumarate) in the placebo phase helps maintain iron stores, which is beneficial for women with heavy menstrual bleeding. The progestin norethindrone acetate has mild androgenic activity, which may benefit libido but can worsen acne or hirsutism in susceptible women. Advise patients that the brown tablets (placebo) contain iron and should not be skipped. Contraindicated in patients with clotting disorders, migraines with aura (especially if age >35), smokers >35, history of breast cancer, or hepatic tumors. |
| Patient Advice | Take one tablet daily at the same time each day. The first 24 white tablets are active hormones; the last 4 brown tablets are iron pills. · You may experience spotting or breakthrough bleeding, especially in the first few months. Do not skip pills. · This pill does not protect against HIV or other STIs. Use condoms for prevention. · If you miss a white pill, take it as soon as remembered and continue the pack. If you miss 2 or more, use backup contraception for 7 days. · The brown tablets contain iron; do not stop taking them even if you have bleeding. · Common side effects include nausea, breast tenderness, headache, and mood changes. Report severe leg pain, chest pain, or vision changes immediately. · Smoking while on this pill increases risk of blood clots, especially if over 35 years old. |
Loading safety data…