LO LOESTRIN FE
Clinical safety rating
cautionComprehensive clinical and safety monograph for LO LOESTRIN FE (LO LOESTRIN FE).
Combination of ethinyl estradiol and norethindrone acetate suppresses gonadotropin-releasing hormone (GnRH) from the hypothalamus, reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary, thereby inhibiting ovulation. The progestin component thickens cervical mucus, impeding sperm penetration, and alters endometrial receptivity. Ferrous fumarate provides supplemental iron.
| Metabolism | Ethinyl estradiol is metabolized primarily via CYP3A4, with hydroxylation and conjugation pathways. Norethindrone acetate is rapidly hydrolyzed to norethindrone, which is metabolized via reduction and conjugation. Ferrous fumarate is absorbed and utilized for hemoglobin synthesis. |
| Excretion | Renal (primarily as glucuronide conjugates of norethindrone and ethinyl estradiol): ~40% norethindrone metabolites, ~30% ethinyl estradiol metabolites; Fecal: ~30% norethindrone metabolites, ~40% ethinyl estradiol metabolites. |
| Half-life | Norethindrone: ~8 hours (range 5–12 h); Ethinyl estradiol: ~14 hours (range 10–20 h). Terminal half-life supports once-daily dosing with steady-state reached within 7–14 days. |
| Protein binding | Norethindrone: ~61% bound (primarily to albumin and SHBG); Ethinyl estradiol: ~97–98% bound (primarily to albumin, with ~1–2% free). |
| Volume of Distribution | Norethindrone: ~4 L/kg; Ethinyl estradiol: ~3–4 L/kg. Indicates extensive tissue distribution consistent with lipophilic steroids. |
| Bioavailability | Norethindrone: ~64% (oral); Ethinyl estradiol: ~45% (oral) due to first-pass metabolism, with high interindividual variability. |
| Onset of Action | Oral: Contraceptive effect requires 7 consecutive days of active tablets; initial suppression of ovulation begins within first cycle. Peak plasma concentrations: norethindrone ~1–2 h, ethinyl estradiol ~1.5–2 h post-dose. |
| Duration of Action | Contraceptive effect persists for 22 days of active therapy; 2 days of placebo with withdrawal bleed; 6 days of iron supplements. Duration of action is drug-dependent and supports daily dosing schedule. |
| Molecular Weight | 364.5 |
One tablet orally once daily. Each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 10 mcg (24 active tablets) followed by ferrous fumarate 75 mg (2 inactive tablets).
| Dosage form | TABLET |
| Renal impairment | No specific dosage adjustment required for renal impairment. Use with caution in patients with renal dysfunction due to potential fluid retention. |
| Liver impairment | Contraindicated in patients with hepatic impairment, including acute or chronic liver disease, hepatic adenomas, or impaired liver function. No adjustment guidelines available; do not use. |
| Pediatric use | Not indicated for use before menarche. For post-menarchal adolescents, same dosing as adults: one tablet orally once daily. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dosing adjustments for elderly patients as the drug is not used in this population. |
| 1st trimester | Use not recommended due to risk of oral clefts and congenital heart defects; combination hormonal contraceptives are contraindicated in pregnancy. |
| 2nd trimester | Use not recommended; may increase risk of preterm birth and low birth weight. |
| 3rd trimester | Use not recommended; may cause fetal harm including masculinization of female genitalia with high doses of progestins. |
Clinical note
Comprehensive clinical and safety monograph for LO LOESTRIN FE (LO LOESTRIN FE).
| Placental transfer | Hormones cross the placenta; degree depends on specific progestin and estrogen components. |
| Breastfeeding | Estrogen in combination OCs may reduce milk production and quality; progestin-only contraception preferred. Small amounts of hormones excreted in milk, but no adverse effects reported in infants with appropriate doses. |
| Lactation Rating | L3 (Moderately Safe) - Use with caution; not first-line in breastfeeding. |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnant women due to risk of fetal harm, including cardiovascular defects and neural tube defects. Use during first trimester associated with oral clefts; second and third trimester use may lead to fetal hyperbilirubinemia and jaundice. |
| Fetal Monitoring | Monitor blood pressure, liver function, and signs of thromboembolism. Assess for pregnancy status before initiation; rule out pregnancy before continuation. Consider fetal monitoring during third trimester if used inadvertently. |
| Fertility Effects | Normal fertility returns upon discontinuation; no permanent negative impact. May cause transient delay in ovulation resumption after cessation. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
Pregnancy or suspected pregnancyCurrent or history of thromboembolic disordersCerebrovascular or coronary artery diseaseKnown or suspected breast cancerUndiagnosed abnormal uterine bleedingHepatic tumors or acute liver diseaseKnown hypersensitivity to components
| Precautions | Increased risk of venous thromboembolism (VTE), myocardial infarction, and stroke, especially in smokers and women with hypertension or migraines, Adverse effects on bone density and potential for fractures with long-term use, Hepatic adenoma or hepatocellular carcinoma risk, Gallbladder disease, Glucose intolerance and insulin resistance, Elevated blood pressure, Cholestatic jaundice, Ocular lesions (e.g., retinal thrombosis), Depression, Iron overload in patients with hemochromatosis or chronic hemolytic anemia (due to ferrous fumarate) |
| Food/Dietary | No specific food interactions are known for Lo Loestrin Fe. However, grapefruit juice may increase ethinyl estradiol levels, potentially increasing side effects; it is prudent to advise against excessive grapefruit juice consumption. Iron tablets should be taken with food to reduce gastrointestinal upset; calcium-rich foods or supplements may decrease iron absorption, so separate iron intake from high-calcium meals by at least 2 hours. |
| Clinical Pearls | Lo Loestrin Fe contains norethindrone acetate and ethinyl estradiol (1 mg/10 mcg) as the active hormonal pills, with a low iron (75 mg ferrous fumarate) supplement during the placebo week. It is the lowest-dose combination oral contraceptive available, which may minimize estrogen-related side effects. The regimen is 24 active pills, 2 placebo pills, then 2 iron pills, for a 28-day cycle. Spotting and breakthrough bleeding are common, especially in the first few cycles. It is indicated for contraception and not for emergency contraception. The iron tablets do not replace iron deficiency treatment. Contraindicated in patients with a history of thromboembolic disorders, liver disease, or known/suspected pregnancy. |
| Patient Advice | Take one pill daily at the same time each day, preferably after the evening meal. · The first 24 pills are light blue (hormonal), the next 2 are white (placebo), and the last 2 are brown (iron tablets). · If you miss a dose: take it as soon as remembered, and if more than 12 hours late, use backup contraception for 7 days. · Common side effects: spotting, nausea, breast tenderness, and mood changes; these often improve after 3 months. · If you experience severe abdominal or chest pain, headache, or vision changes, seek medical attention. · Iron pills do not treat anemia; they only supplement daily iron needs. · Report any jaundice, depression, or high blood pressure to your healthcare provider. · Use an additional non-hormonal method if starting for the first time after the 5th day of your period. |
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