LEVONORGESTREL AND ETHINYL ESTRADIOL AND FERROUS FUMARATE
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Combination hormonal contraceptive. Ethinyl estradiol and levonorgestrel inhibit gonadotropin release (FSH, LH), suppressing ovulation. Progestin effect: thickens cervical mucus, alters endometrial receptivity. Ferrous fumarate provides iron supplementation during placebo phase.
| Metabolism | Ethinyl estradiol: primarily hepatic via CYP3A4; undergoes sulfation and glucuronidation. Levonorgestrel: hepatic via CYP3A4; reduction and conjugation. Ferrous fumarate: not metabolized; absorbed in duodenum/jejunum. |
| Excretion | Levonorgestrel: ~45% renal, ~32% fecal. Ethinyl estradiol: ~40% renal, ~60% fecal. Ferrous fumarate: iron excreted in feces as unabsorbed; minimal renal. |
| Half-life | Levonorgestrel: ~25 hours, steady-state after 5 days. Ethinyl estradiol: ~13 hours (7–20). Ferrous fumarate: not applicable. |
| Protein binding | Levonorgestrel: ~97.5% to SHBG and albumin. Ethinyl estradiol: ~98% to albumin (primarily). Ferrous fumarate: iron >99% to transferrin. |
| Volume of Distribution | Levonorgestrel: ~1.4 L/kg. Ethinyl estradiol: ~4.3 L/kg. Ferrous fumarate: iron distributed as body iron stores (~0.1 L/kg). |
| Bioavailability | Levonorgestrel: ~100% orally. Ethinyl estradiol: ~40% oral (first-pass). Ferrous fumarate: ~20% of elemental iron absorbed. |
| Onset of Action | Oral: contraceptive effect occurs after 7 days of continuous use if started on day 1 of menses; immediate if started on first day of cycle. |
| Duration of Action | Contraceptive protection lasts 24 hours per pill; daily dosing required. Iron supplementation effect duration not clinically relevant. |
| Molecular Weight | 863.51 |
One tablet (0.15 mg levonorgestrel, 0.03 mg ethinyl estradiol, 75 mg ferrous fumarate) orally once daily at the same time for 21 consecutive days, followed by one ferrous fumarate-only tablet (75 mg) orally once daily for 7 days (28-day cycle).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Use with caution in severe renal impairment (eGFR <30 mL/min) due to potential fluid retention; monitor blood pressure and electrolyte balance. |
| Liver impairment | Contraindicated in Child-Pugh class B or C cirrhosis. For Child-Pugh class A, use with caution; reduce dose or consider alternative contraception if signs of cholestasis or hepatic dysfunction occur. |
| Pediatric use | For post-menarche adolescents: same dosing as adults (one active tablet daily for 21 days, then one ferrous fumarate tablet daily for 7 days). Weight-based adjustments not required. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dose adjustment in elderly patients; however, consider increased risk of thromboembolic events and monitor for adverse effects. |
| 1st trimester | Risk of neural tube defects, congenital heart defects, and oral clefts. Use only if clear need. |
| 2nd trimester | General lack of data; avoid use as risks unknown. |
| 3rd trimester | Avoid use due to potential estrogenic effects on fetus and lactation. |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Placental transfer | Yes, both components cross the placenta. |
| Breastfeeding | Enters breast milk; decreases quantity and quality; use caution, especially in early postpartum. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day) and is significant in women over 35. Women who use COCs should be strongly advised not to smoke.
| Common Effects | osteoporosis prevention |
| Serious Effects |
PregnancyThrombophlebitis or thromboembolic disordersHypersensitivity to componentsUndiagnosed abnormal genital bleedingKnown or suspected breast cancer
| Precautions | Thrombotic Disorders: increased risk of venous thromboembolism, stroke, myocardial infarction; discontinue if thrombotic events occur., Carcinoma: risk of breast cancer diagnosis; cervical cancer risk with HPV., Hepatic Disease: jaundice, cholestasis; discontinue if liver function abnormalities develop., Eye Lesions: retinal thrombosis; discontinue if unexplained vision loss., Carbohydrate Metabolism: impaired glucose tolerance; monitor diabetics., Headache: migraine exacerbation; discontinue if new or recurrent persistent headache., Uterine Bleeding: irregular bleeding common; evaluate if persistent., Gallbladder Disease: possible increased risk., Depression: monitor; discontinue if severe., Iron Overload: caution in hemochromatosis or conditions predisposing to iron accumulation. |
Loading safety data…
| Lactation Rating | L3 |
| Teratogenic Risk | First trimester: Exposure to ethinyl estradiol and levonorgestrel is associated with a low risk of congenital anomalies, but should not be used during pregnancy as it may cause harm. Second and third trimesters: Avoid use; hormonal contraceptives are not indicated in pregnancy. Iron supplementation with ferrous fumarate is generally safe but high doses may be toxic. |
| Fetal Monitoring | Monitor for signs of pregnancy if used inadvertently. In cases of accidental exposure, fetal ultrasound may be considered. No specific monitoring required for ferrous fumarate. |
| Fertility Effects | Levonorgestrel and ethinyl estradiol inhibit ovulation and have contraceptive effects. Fertility returns to baseline upon discontinuation. Ferrous fumarate has no known effect on fertility. |
| Food/Dietary | No significant food interactions with LNG/EE. Ferrous fumarate absorption is enhanced by vitamin C (e.g., citrus fruits) and reduced by calcium supplements, dairy, antacids, and caffeine. Take iron pills on an empty stomach or with orange juice for best absorption; if GI upset occurs, take with a small amount of food. Avoid concurrent ingestion within 2 hours of calcium-rich foods (milk, yogurt, cheese) or antacids. Grapefruit does not interact with LNG/EE, but a theoretical CYP3A4 inhibition is not clinically significant. |
| Clinical Pearls | Levonorgestrel/ethinyl estradiol (LNG/EE) combined with ferrous fumarate is a monophasic oral contraceptive with 21 active pills (0.1 mg LNG/0.02 mg EE) and 7 iron supplement pills (75 mg ferrous fumarate). Use for contraception and dysmenorrhea. The iron component helps prevent iron deficiency in menstruating women. Advise patients to take at same time daily. Missed dose rules: if >3 hours late, take as soon as remembered and use backup contraception for 7 days. Efficacy comparable to other low-dose COCs. Not recommended in BMI >35 kg/m² due to increased VTE risk. Contraindicated with migraine with aura, DVT/PE history, breast cancer, liver disease. |
| Patient Advice | Take one pill daily at the same time, starting on the first day of your period or as directed. · The first 21 pills are active hormones; the last 7 pills are iron supplements to prevent anemia. Do not skip the iron pills. · If you miss a pill during the first 3 weeks, take it as soon as you remember and use backup contraception for 7 days. · Common side effects include nausea, breast tenderness, and breakthrough bleeding. These usually improve within 3 months. · Serious risks include blood clots (leg, lung, stroke, heart attack). Seek emergency if sudden chest pain, leg pain/swelling, or severe headache. · Do not smoke while taking this medication; smoking increases risk of blood clots. · Tell your doctor before starting other medications, as some antibiotics, antifungals, and antiseizure drugs can reduce effectiveness. · There are no restrictions on grapefruit or alcohol consumption with this medication. · Iron tablets may cause dark stools or constipation; this is normal. Take with food to reduce stomach upset. |