LOESTRIN 21 1/20
Clinical safety rating
cautionComprehensive clinical and safety monograph for LOESTRIN 21 1/20 (LOESTRIN 21 1/20).
Combination estrogen-progestin contraceptive; suppresses gonadotropin secretion (FSH, LH) via negative feedback, inhibiting ovulation; increases cervical mucus viscosity and alters endometrial receptivity.
| Metabolism | Ethinyl estradiol is metabolized primarily by CYP3A4; norethindrone is metabolized by CYP3A4 and reduction, conjugation (sulfation and glucuronidation). |
| Excretion | Renal: ~50% (as metabolites, primarily glucuronide conjugates of norethindrone and ethinyl estradiol); Fecal: ~35% (via bile); Urinary recovery of unchanged drug is minimal (<1%). |
| Half-life | Norethindrone: 8-11 hours (terminal half-life; steady-state achieved after 5-10 days); Ethinyl estradiol: 13-27 hours (terminal half-life; significant interindividual variability due to enterohepatic recirculation). |
| Protein binding | Norethindrone: ~61% bound to albumin and SHBG; Ethinyl estradiol: ~97-98% bound to albumin (not to SHBG). |
| Volume of Distribution | Norethindrone: 2-4 L/kg; Ethinyl estradiol: 2-4 L/kg (indicating extensive tissue distribution and high lipophilicity). |
| Bioavailability | Oral: Norethindrone ~64% (due to first-pass metabolism); Ethinyl estradiol ~45% (range 30-60%, with significant first-pass conjugation to sulfate and glucuronide). |
| Onset of Action | Oral: Contraceptive effect requires 7 days of continuous dosing to reliably inhibit ovulation (start on day 1 of menses for immediate effect; if started later, use backup contraception for 7 days). |
| Duration of Action | Oral: 24 hours (once-daily dosing maintains contraceptive efficacy; missed pill increases risk of ovulation, especially if >12 hours late). |
| Molecular Weight | 376.5 |
One tablet orally once daily for 21 days, then 7 days off. Each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 20 mcg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential fluid retention. |
| Liver impairment | Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). For Child-Pugh class A, use with caution; consider alternative contraception. |
| Pediatric use | Not indicated for use before menarche. Post-menarche: same as adult dosing (one tablet daily for 21 days, 7 days off). |
| Geriatric use | Not indicated for postmenopausal women. No specific geriatric dosing studies; use lowest effective dose if considered, but generally avoid due to increased thromboembolic risk. |
| 1st trimester | Not recommended; contains estrogen and progestin; associated with risk of congenital anomalies (e.g., cardiovascular, limb defects) and VACTERL association. |
| 2nd trimester | Not recommended; may increase risk of intrauterine growth restriction and preterm delivery. |
| 3rd trimester | Not recommended; use may cause fetal harm including masculinization of female fetus and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for LOESTRIN 21 1/20 (LOESTRIN 21 1/20).
| Placental transfer | Estrogen and progestin cross the placenta; limited data suggest transfer occurs. |
| Breastfeeding | Small amounts of estrogen and progestin are excreted in breast milk; may reduce milk production and quality; use only if clearly needed and with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnancy. Use during first trimester associated with cardiovascular defects, limb reduction defects, and neural tube defects. Exposure in second and third trimester increases risk of fetal feminization in male fetuses, vaginal adenosis and cervical cancer in female fetuses. No known risk in third trimester for congenital anomalies. |
| Fetal Monitoring | Rule out pregnancy before initiation. Monitor blood pressure, liver function, glucose tolerance, and lipid profile. Urine pregnancy test if pregnancy suspected. Ultrasound for fetal anomalies if accidental exposure during pregnancy. |
| Fertility Effects | Suppresses ovulation, impairs endometrial receptivity. Reversible within 1-3 menstrual cycles after discontinuation. No evidence of long-term fertility reduction. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially >35 years) and with heavy smoking (≥15 cigarettes/day). Women who use COCs should be strongly advised not to smoke.
| Serious Effects |
Known or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected breast cancerCurrent or past history of thrombophlebitis or thromboembolic disordersCerebrovascular or coronary artery diseaseActive liver disease or impaired liver functionKnown or suspected estrogen-dependent neoplasiaHypersensitivity to any component
| Precautions | Increased risk of thromboembolic disorders (e.g., DVT, PE, stroke, MI), Hepatic neoplasia risk, Ocular lesions (e.g., retinal thrombosis), Carbohydrate metabolism alterations, Elevated blood pressure, Gallbladder disease, Depression, Interactions with enzyme-inducing drugs (e.g., rifampin, anticonvulsants) |
| Food/Dietary | No specific food restrictions. Grapefruit juice may increase estrogen levels; consider avoiding large amounts. Alcohol is not contraindicated but may affect liver metabolism. Consult with your healthcare provider. |
| Clinical Pearls | Loestrin 21 1/20 contains norethindrone acetate 1 mg and ethinyl estradiol 20 mcg. It is a low-dose monophasic oral contraceptive. For missed pills, follow standard CDC guidelines: if one pill is missed, take it as soon as remembered; if two or more are missed, consider backup contraception. The 21-day regimen has a 7-day pill-free interval. Patients with breakthrough bleeding should be counseled that this is common in the first few cycles. Use with caution in patients with a history of hypertension, migraine with aura, or thromboembolic disorders. |
| Patient Advice | Take one pill daily at the same time for 21 days, then none for 7 days. · If you miss a pill, take it as soon as you remember. If you miss two or more, use backup contraception (e.g., condoms) for 7 days. · Common side effects include nausea, breast tenderness, and breakthrough bleeding, especially in the first few months. · This medication does not protect against sexually transmitted infections (STIs). · Do not smoke while taking this medication, especially if over age 35, as it increases risk of serious cardiovascular events. · Seek medical attention if you experience severe abdominal pain, chest pain, headache, eye problems, or leg pain/swelling. |
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