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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Breastfeeding | Levonorgestrel and ethinyl estradiol are excreted in breast milk in small amounts; M/P ratio not well defined. Hormonal contraceptives may reduce milk production and quality. Ferrous fumarate is excreted in minimal amounts and is considered safe. Use in breastfeeding is generally not recommended due to hormonal effects. |
| Teratogenic Risk |
■ 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 |
["Known or suspected pregnancy","Current or past venous thromboembolism","Cerebrovascular or coronary artery disease","Uncontrolled hypertension (BP >160/100 mmHg)","Diabetes with vascular involvement","Headaches with focal neurological symptoms (e.g., migraine with aura)","Breast cancer or other estrogen- or progestin-sensitive neoplasia","Liver tumors (benign or malignant) or active liver disease","Undiagnosed abnormal uterine bleeding","Cigarette smoking in women over 35","Major surgery with prolonged immobilization","Breastfeeding (within first 6 weeks postpartum) unless deemed appropriate"]
| 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…
| 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. |