LO/OVRAL-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LO/OVRAL-28 (LO/OVRAL-28).
Combination of norgestrel, a progestin, and ethinyl estradiol, an estrogen; suppresses gonadotropin secretion (FSH and LH) primarily via progestational activity, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
| Metabolism | Hepatic via CYP3A4 for ethinyl estradiol; norgestrel metabolized via reduction and conjugation. |
| Excretion | Renal (approx. 50% as metabolites, <1% unchanged); biliary/fecal (approx. 50% as metabolites). |
| Half-life | Norgestrel: 20-40 hours; Ethinyl estradiol: 13-27 hours. Steady-state achieved after 3-5 half-lives. |
| Protein binding | Norgestrel: 93-99% (primarily SHBG and albumin); Ethinyl estradiol: 97-98% (primarily albumin and SHBG). |
| Volume of Distribution | Norgestrel: 3.0 L/kg; Ethinyl estradiol: 4.0 L/kg. |
| Bioavailability | Oral: Norgestrel 85-90%; Ethinyl estradiol 38-48% due to first-pass metabolism. |
| Onset of Action | Oral: 7 days of continuous dosing for full contraceptive effect. |
| Duration of Action | 24 hours (requires daily dosing for continuous contraception). |
One tablet orally once daily for 28 days. Each tablet contains 0.3 mg norgestrel and 0.03 mg ethinyl estradiol. Active tablets (21 days) followed by placebo tablets (7 days).
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. However, use with caution in patients with renal dysfunction due to potential fluid retention. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class B or C cirrhosis. For Child-Pugh Class A, use with caution; limited data, but no specific dose adjustment recommended. |
| Pediatric use | Not indicated for use before menarche. For post-menarchal adolescents, the same dosing as adults: one tablet orally daily for 28-day cycles. |
| Geriatric use | Not indicated in postmenopausal women. No geriatric-specific dosing; not for use in elderly due to lack of need for contraception after menopause. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LO/OVRAL-28 (LO/OVRAL-28).
| Breastfeeding | Enters breast milk in small amounts; estrogen and progestin may reduce milk production and composition. M/P ratio not established. Generally avoided during breastfeeding due to theoretical risks; low-dose progestin-only contraception preferred. |
| Teratogenic Risk | First trimester: No known association with major congenital anomalies, but small increased risk of cardiovascular defects and limb reduction defects reported in some studies. Second/third trimesters: Use not recommended due to potential adverse effects on fetal development including virilization of female fetus and hepatic adenoma; contraindicated in known pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and smoking intensity (especially in women over 35). Women should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; history of deep vein thrombosis or pulmonary embolism; 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 disorders (e.g., venous thromboembolism, stroke, myocardial infarction); hepatic neoplasia; hypertension; gallbladder disease; carbohydrate/lipid effects; ocular lesions; breakthrough bleeding; missed periods; ectopic pregnancy risk; lactation; depression. |
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| Fetal Monitoring | Monitor blood pressure, liver function, and signs of thrombotic events due to increased risk in pregnancy. Evaluate for fetal anomalies if inadvertently exposed; no specific fetal testing required unless other risk factors present. |
| Fertility Effects | Suppresses ovulation; return to fertility may be delayed by 1–2 months after discontinuation. Long-term use associated with no permanent impairment of fertility. |