ESTROSTEP FE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ESTROSTEP FE (ESTROSTEP FE).
Combination estrogen-progestin contraceptive: ethinyl estradiol suppresses gonadotropin release via negative feedback on hypothalamic-pituitary axis; norethindrone acetate produces progestational effects including endometrial transformation and cervical mucus thickening, inhibiting sperm penetration and implantation.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes sulfation and glucuronidation. Norethindrone acetate: hydrolyzed to norethindrone, then metabolized by reduction and glucuronidation. |
| Excretion | Renal: ~40% as metabolites; fecal: ~30% (biliary); remainder as conjugates. |
| Half-life | Ethinyl estradiol: 13-27 hours (terminal); norethindrone acetate: 5-14 hours. Clinical context: Steady-state reached within 7-10 days. |
| Protein binding | Ethinyl estradiol: 97-98% bound to albumin and SHBG; norethindrone acetate: 91-95% bound to albumin and SHBG. |
| Volume of Distribution | Ethinyl estradiol: 2.3-3.6 L/kg; norethindrone acetate: 1.5-2.5 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: Ethinyl estradiol ~45% (first-pass metabolism); norethindrone acetate ~64%. |
| Onset of Action | Oral: contraceptive effect begins after 7 days of continuous dosing. |
| Duration of Action | Contraceptive effect persists for 24 hours with daily dosing; missed dose guidelines recommend backup contraception. |
One tablet daily orally, each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 20 mcg (24 active tablets) followed by ferrous fumarate 75 mg tablets (4 placebo tablets).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment is recommended for patients with mild to moderate renal impairment. Use is contraindicated in patients with severely impaired renal function (GFR <30 mL/min/1.73 m²) due to potential for fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in patients with acute or chronic hepatic dysfunction (Child-Pugh class B or C). For mild hepatic impairment (Child-Pugh class A), use with caution and monitor liver function; no specific dose adjustment guidelines are established. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients below 16 years of age. Post-pubertal adolescents may be dosed as adults, with careful consideration of risks (e.g., bone density). |
| Geriatric use | Not indicated for use in women over 65 years due to lack of efficacy and safety data, and increased risk of cardiovascular and thrombotic events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ESTROSTEP FE (ESTROSTEP FE).
| Breastfeeding | Excreted in breast milk in small amounts (estrogen M/P ratio ~0.2, progestin M/P ratio ~0.6). May reduce milk quantity and quality. Use caution; generally not recommended. No adverse effects reported in infants at typical doses. |
| Teratogenic Risk | Category X. Estrostep FE (norethindrone acetate/ethinyl estradiol/ferrous fumarate) is contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects from sex hormones. Second/third trimester: feminization of male fetus, potential for urogenital malformations, and long-term reproductive tract effects. Postnatal: possible increased risk of childhood cancers. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and smoking intensity (especially >35 years). Women >35 years who smoke should not use this product.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease, known or suspected breast carcinoma, endometrial carcinoma or other estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, cholestatic jaundice of pregnancy or jaundice with prior pill use, hepatic adenoma or carcinoma, pregnancy, hypersensitivity to any component.
| Precautions | Thromboembolic disorders, cardiovascular disease (MI, stroke), hypertension, gallbladder disease, hepatic neoplasia, lipid effects, glucose intolerance, headache, breakthrough bleeding, depression, contact lens intolerance, fluid retention, hereditary angioedema. |
Loading safety data…
| Fetal Monitoring | Monitor for pregnancy if considering use; urine HCG before initiation. Inadvertent use during pregnancy: ultrasound for fetal anatomy. No routine monitoring required if used as directed. |
| Fertility Effects | Suppresses ovulation via gonadotropin inhibition. After discontinuation, return to fertility may be delayed by 1-2 cycles but no permanent effect. No known impact on oocyte quality or long-term fertility. |