LOW-OGESTREL-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOW-OGESTREL-28 (LOW-OGESTREL-28).
Combination oral contraceptive: ethinyl estradiol and norgestrel inhibit ovulation via suppression of gonadotropins (LH, FSH); increase viscosity of cervical mucus, impairing sperm penetration; alter endometrial structure, reducing implantation likelihood.
| Metabolism | Ethinyl estradiol: metabolized via CYP3A4, undergoes first-pass metabolism, conjugates with sulfate and glucuronide. Norgestrel: primarily metabolized via reduction, hydroxylation, and conjugation; CYP3A4 involved. |
| Excretion | Renal 50-60% as metabolites, fecal 40-50% via biliary elimination. Ethinyl estradiol undergoes enterohepatic recirculation. |
| Half-life | Norgestrel: ~45 hours (terminal). Ethinyl estradiol: ~13 hours (terminal). Steady-state achieved within 5-7 days. |
| Protein binding | Norgestrel: 97-99% bound to SHBG and albumin. Ethinyl estradiol: 98% bound to albumin. |
| Volume of Distribution | Norgestrel: 3-4 L/kg (extensive tissue distribution). Ethinyl estradiol: 3-5 L/kg. |
| Bioavailability | Norgestrel: ~90% oral (first-pass metabolism minimal). Ethinyl estradiol: ~45% oral (extensive first-pass metabolism). |
| Onset of Action | Oral: 7 days of continuous dosing required for full contraceptive effect; ovulation inhibition begins after first dose. |
| Duration of Action | Contraceptive protection lasts 24 hours with daily dosing; missed pills reduce efficacy. Withdrawal bleed occurs during placebo week. |
One tablet (norgestrel 0.3 mg/ethinyl estradiol 30 mcg) orally once daily at the same time each day for 28 days, with 21 active tablets followed by 7 inactive tablets.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Insufficient data for severe impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Contraindicated in severe hepatic disease or liver tumors (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution and monitor liver function; no specific dose adjustment established. |
| Pediatric use | Not indicated for premenarchal patients. Postmenarchal adolescents: same as adult dose (one tablet daily) after menarche. |
| Geriatric use | Not indicated for postmenopausal women due to lack of contraceptive need and potential increased risks of thrombosis, cardiovascular events, and malignancies. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOW-OGESTREL-28 (LOW-OGESTREL-28).
| Breastfeeding | Excreted in breast milk in small amounts; estimated M/P ratio approximately 0.5-0.8 for progestins. May reduce milk production and quality. Use with caution and only if clearly needed. Monitor infant for jaundice, weight gain, and hormonal effects. |
| Teratogenic Risk | First trimester: Low risk of major malformations; no evidence of increased risk of neural tube defects. Second and third trimesters: Possible increased risk of liver tumors and jaundice; may cause fetal harm if administered during pregnancy due to hormonal effects. Post-marketing reports of external genitalia anomalies in male and female fetuses exposed to progestins. Not recommended for use during pregnancy. Discontinue if pregnancy occurs. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day) and is significant in women over 35. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; history of DVT or PE; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; endometrial carcinoma or other estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; cholestatic jaundice of pregnancy or jaundice with prior pill use; hepatic adenoma or carcinoma; known or suspected pregnancy; hypersensitivity to any component.
| Precautions | Thrombotic events (e.g., DVT, PE, stroke, MI); hepatic neoplasia; elevated blood pressure; gallbladder disease; carbohydrate and lipid metabolism effects; headache; uterine bleeding irregularities; ectopic pregnancy risk; reduced efficacy with hepatic impairment; monitoring for hypertension, hyperlipidemia, and glucose intolerance. |
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| Fetal Monitoring | Monitor blood pressure, liver function, glucose tolerance, and lipid profile. Rule out pregnancy before initiating therapy. Perform pregnancy test if pregnancy is suspected. Monitor for signs of thromboembolism. For fetal monitoring, consider ultrasound if prolonged use during gestation. |
| Fertility Effects | Suppresses ovulation; fertility returns rapidly after discontinuation. No permanent adverse effects on fertility. Approved for oral contraception. |