BREVICON 28-DAY
Clinical safety rating
cautionComprehensive clinical and safety monograph for BREVICON 28-DAY (BREVICON 28-DAY).
Combination oral contraceptive; ethinyl estradiol and norethindrone suppress gonadotropin secretion (FSH and LH) via negative feedback, inhibiting ovulation. Additionally, alters cervical mucus consistency and endometrial lining to impede sperm penetration and implantation.
| Metabolism | Hepatic; ethinyl estradiol metabolized primarily via CYP3A4; norethindrone metabolized via reduction and conjugation (sulfation and glucuronidation). |
| Excretion | Renal: ~40% as metabolites and unchanged drug; fecal/biliary: ~60% as metabolites |
| Half-life | Norethindrone: 8-11 hours; Ethinyl estradiol: 13-27 hours; half-life for ethinyl estradiol allows once-daily dosing |
| Protein binding | Norethindrone: ~61% bound to albumin and SHBG; Ethinyl estradiol: ~97% bound to albumin |
| Volume of Distribution | Norethindrone: 4 L/kg; Ethinyl estradiol: 2-4 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: ~64% for norethindrone; ~40% for ethinyl estradiol due to first-pass metabolism |
| Onset of Action | Oral: 7 days of continuous use to achieve contraceptive effect; immediate use if started on day 1 of menses |
| Duration of Action | 24 hours; requires daily dosing; missed pill reduces efficacy |
| Molecular Weight | Ethinyl estradiol: 296.40 Da; Norethindrone: 298.42 Da |
One tablet (0.5 mg norethindrone and 35 mcg ethinyl estradiol) orally once daily for 28 days (21 active tablets followed by 7 inert tablets).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <30 mL/min) or dialysis, use is not recommended due to potential fluid retention and hypertension. |
| Liver impairment | Contraindicated in acute hepatic disease, cholestatic jaundice of pregnancy or prior oral contraceptive use, or severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use is not recommended unless benefits outweigh risks; close monitoring of hepatic function advised. |
| Pediatric use | Safety and efficacy in postmenarchal adolescents are established. Dosing is the same as adults: one tablet orally once daily for 28 days. Use before menarche is not indicated. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dosing adjustments are provided for elderly patients as the drug is not intended for this population. |
| 1st trimester | Data suggest low risk; however, ethinyl estradiol and norethindrone are not recommended for use during pregnancy due to potential adverse effects on fetal development. Use only if clearly needed. |
| 2nd trimester | Avoid use during pregnancy; prolonged exposure to sex hormones may be associated with genital abnormalities in female fetuses. |
| 3rd trimester | Avoid use; estrogens can inhibit lactation and may cause neonatal withdrawal symptoms if used near term. |
Clinical note
Comprehensive clinical and safety monograph for BREVICON 28-DAY (BREVICON 28-DAY).
| Placental transfer | Both ethinyl estradiol and norethindrone cross the placenta; norethindrone demonstrates significant transfer. |
| Breastfeeding | Small amounts of ethinyl estradiol and norethindrone are excreted in breast milk. Use caution; may reduce milk production and affect infant bilirubin metabolism. Consider risks versus benefits. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category X. Estrogen/progestin combination contraceptives are contraindicated in pregnancy due to risk of fetal harm, including cardiovascular and limb defects, particularly in the first trimester. Use in second and third trimesters is associated with increased risk of fetal genital tract abnormalities and other adverse outcomes. |
| Fetal Monitoring | Pregnancy test prior to initiation. Monitor for signs of pregnancy monthly. If pregnancy occurs, discontinue immediately and evaluate for ectopic pregnancy. No specific fetal monitoring required if drug is stopped upon pregnancy diagnosis. |
| Fertility Effects | Suppresses ovulation through inhibition of gonadotropins. After discontinuation, normal ovulation and fertility typically return, but a delay in return to fertility may occur in some women. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from oral contraceptive use. Risk increases with age (especially in women over 35 years) and with number of cigarettes smoked. Women who use oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
PregnancyCurrent or past history of thromboembolic disordersCerebrovascular diseaseCoronary artery diseaseKnown or suspected breast cancerUndiagnosed abnormal genital bleedingCholestatic jaundice of pregnancy or jaundice with prior pill useActive liver disease or hepatic adenomasHypersensitivity to any component
| Precautions | Increased risk of thromboembolic events (especially in smokers, obese, or hypertension), myocardial infarction, stroke, hepatic neoplasia, gallbladder disease, hypertension, and carbohydrate/lipid metabolism effects. Should be discontinued if jaundice, visual disturbances, or migraine occur. May decrease bone density in long-term use. |
| Food/Dietary | Grapefruit juice may increase ethinyl estradiol levels; avoid excessive consumption. No other significant food interactions. |
| Clinical Pearls | Breakthrough bleeding is common in first 3 cycles; counsel patients to continue dosing. Efficacy may be reduced with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort). If vomiting occurs within 3-4 hours of dose, use backup contraception. Consistent timing of daily dose reduces pregnancy risk. |
| Patient Advice | Take one tablet daily at the same time, even if you don't have sex that day. · Use back-up contraception (e.g., condoms) if you miss a pill or start late. · Breakthrough spotting may occur, especially in the first few months; do not stop taking your pills. · Smoking increases risk of serious cardiovascular side effects, especially if over 35 years old. · Check pill package for inactive (placebo) pills in the last week. |
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