LOW-OGESTREL-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOW-OGESTREL-21 (LOW-OGESTREL-21).
Combination oral contraceptive. Suppresses gonadotropin release (FSH and LH) via estrogen (ethinyl estradiol) and progestin (norgestrel), inhibiting ovulation. Also increases cervical mucus viscosity and alters endometrium.
| Metabolism | Hepatic via CYP3A4 isoenzymes (ethinyl estradiol and norgestrel undergo hydroxylation and conjugation). Enterohepatic circulation. |
| Excretion | Ethinyl estradiol and norgestrel are excreted primarily as glucuronide and sulfate conjugates in urine (50-60%) and feces (30-40%). |
| Half-life | Norgestrel: 18-28 hours; ethinyl estradiol: 13-27 hours. Steady-state achieved after 5-7 days. |
| Protein binding | Norgestrel: 93-95% (albumin, SHBG); ethinyl estradiol: 97-98% (albumin). |
| Volume of Distribution | Norgestrel: 3.5-4.5 L/kg; ethinyl estradiol: 2.5-3.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: norgestrel >90%; ethinyl estradiol 40-50% (first-pass metabolism). |
| Onset of Action | Oral: 3-5 hours (peak plasma levels); contraceptive effect requires 7 days of continuous dosing for full suppression of ovulation. |
| Duration of Action | 24 hours (maintains suppression of ovulation with daily dosing); missed pills reduce efficacy. |
One tablet (norgestrel 0.3 mg/ethinyl estradiol 30 mcg) orally once daily for 21 days, followed by 7 pill-free days.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Use is contraindicated in severe renal impairment or acute renal failure due to potential fluid retention. |
| Liver impairment | Contraindicated in acute or chronic hepatic dysfunction, including Child-Pugh class A, B, or C. Do not use. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, use same dosing as adults: one tablet daily for 21 days, then 7 days off. |
| Geriatric use | Not indicated for postmenopausal women. No specific geriatric dosing; contraindicated in women over 35 who smoke, and generally avoided in older women due to increased cardiovascular risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOW-OGESTREL-21 (LOW-OGESTREL-21).
| Breastfeeding | Small amounts of ethinyl estradiol and norgestrel are excreted in human milk. M/P ratio not established. May reduce milk production and composition. Use is generally not recommended during breastfeeding; alternative contraception advised. |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnancy. Fetal risk includes cardiovascular anomalies, neural tube defects, and limb reduction defects if exposed during first trimester. Second and third trimester exposure may cause masculinization of female fetuses due to progestin component. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events (e.g., myocardial infarction, thromboembolism, stroke). Risk increases with age (>35 years) and smoking severity. Women over 35 who smoke should not use this drug.
| Serious Effects |
["Known or suspected pregnancy","Current or history of thrombophlebitis or thromboembolic disorders","Current or history of cerebrovascular or coronary artery disease","Breast cancer or other estrogen-sensitive neoplasia (known or suspected)","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenoma or carcinoma","Known liver impairment","Major surgery with prolonged immobilization","Diabetes mellitus with vascular involvement","Uncontrolled hypertension","Hypertriglyceridemia","Smoking >15 cigarettes/day and age ≥35","Migraine with focal aura at any age"]
| Precautions | ["Thromboembolic disorders (venous and arterial)","Cerebrovascular disease","Myocardial infarction","Hypertension","Hepatic adenoma or carcinoma","Gallbladder disease","Carbohydrate/lipid metabolism effects","Ocular changes (e.g., retinal thrombosis)","Headache/migraine exacerbation","Uterine bleeding irregularities","Fetal development (discontinue if pregnancy suspected)","Depression","Contact lens intolerance","Fluid retention","Breast cancer risk (ongoing surveillance)","Hereditary angioedema"] |
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| Fetal Monitoring |
| Pregnancy test before initiation. Monitor for signs of thromboembolism, hypertension, hepatic dysfunction, and glucose intolerance. No specific fetal monitoring indicated if pregnancy excluded. |
| Fertility Effects | Temporary suppression of ovulation. Rapid return to baseline fertility upon discontinuation. No permanent impairment of reproductive function. |