DAYSEE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DAYSEE (DAYSEE).
DAYSEE (estradiol/norethindrone acetate) is a combination hormonal contraceptive that suppresses gonadotropins (FSH and LH) via negative feedback of estrogen and progestin, thereby inhibiting ovulation. Norethindrone also increases cervical mucus viscosity and induces endometrial atrophy.
| Metabolism | Estradiol is metabolized primarily via hydroxylation (CYP1A2, CYP3A4) and conjugation to glucuronides and sulfates. Norethindrone is metabolized via reduction and conjugation (CYP3A4). |
| Excretion | Renal 70% (metabolites), biliary/fecal 30% (parent drug and metabolites). No active drug excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 18-36 hours), supporting once-daily dosing for steady state within 5 days. |
| Protein binding | 99% bound to albumin (secondary to alpha-1-acid glycoprotein). |
| Volume of Distribution | 10-15 L/kg (large distribution into tissues, including pancreas and liver). |
| Bioavailability | Oral: 75% (high; food reduces rate but not extent). |
| Onset of Action | Oral: 30-60 minutes for measurable serum levels; clinical effect (glucose lowering) begins within 2-4 hours. |
| Duration of Action | Duration of glucose lowering effect is 24 hours, consistent with once-daily dosing; maximal effect seen after 4-8 weeks of therapy. |
One active tablet (norgestimate 0.18 mg/ethinyl estradiol 0.025 mg) orally once daily for 21 days, followed by 7 days of placebo. Each cycle: 7 days placebo, then 21 days active.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment provided. Use with caution in patients with renal impairment; monitor for fluid retention and hypertension. |
| Liver impairment | Contraindicated in patients with impaired liver function or active liver disease. No specific dose adjustment recommended. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults. |
| Geriatric use | Not indicated for postmenopausal women; no relevant use in geriatric population. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DAYSEE (DAYSEE).
| Breastfeeding | Compatible with breastfeeding. Progestin-only pills do not suppress lactation. Levonorgestrel is excreted in breast milk in small amounts; estimated infant dose <1% of maternal weight-adjusted dose. M/P ratio not available. |
| Teratogenic Risk | Daysee (progestin-only pill) has a low teratogenic risk. First trimester: no increased risk of major malformations. Second and third trimesters: no known adverse fetal effects. No association with congenital anomalies. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. This risk increases with age (>35 years) and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Known or suspected pregnancy.","Current or history of thrombophlebitis or venous thromboembolic disorders.","Cerebrovascular or coronary artery disease.","Known or suspected breast carcinoma.","Carcinoma of the endometrium or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding.","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use.","Hepatic adenoma or carcinoma, or active liver disease.","Tobacco use in women ≥35 years."]
| Precautions | ["Thrombotic disorders: venous thromboembolism, arterial thromboembolism (e.g., stroke, MI), especially in smokers ≥35 years.","Hepatic disease: discontinue if jaundice occurs; may cause cholestatic jaundice.","Hypertension: monitor blood pressure; discontinue if significant hypertension develops.","Gallbladder disease: increased risk of gallstones.","Carbohydrate/lipid metabolism: monitor in women with diabetes or hypertriglyceridemia.","Headache: evaluate if new or worsening migraine; discontinue if neurological signs.","Uterine bleeding: irregular bleeding may occur; rule out pregnancy.","Depression: monitor; discontinue if severe.","Hereditary angioedema: may exacerbate.","Ocular effects: discontinue if vision loss or proptosis."] |
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| No specific monitoring required beyond routine prenatal care. Use caution in patients with hepatic impairment or history of ectopic pregnancy. |
| Fertility Effects | No long-term effects on fertility. Normal menstrual cycles and ovulation typically resume within 1-2 months after discontinuation. Does not cause infertility. |
| Food/Dietary | No specific food restrictions. Grapefruit juice may increase ethinyl estradiol levels; avoid large amounts. Consistent consumption of St. John's wort, certain antiepileptics (e.g., phenytoin), and rifampin can reduce contraceptive efficacy. |
| Clinical Pearls | Daysee (ethinyl estradiol/levonorgestrel) is a combined oral contraceptive (COC) with a 91-day extended cycle regimen (84 active pills, 7 placebo). It reduces the frequency of withdrawal bleeds to 4 per year. Efficacy may be reduced if active pills are missed within the first 7 days of a new cycle. Use backup contraception if vomiting or diarrhea occurs within 3-4 hours of taking a pill. |
| Patient Advice | Take one pill daily at the same time; missing pills increases pregnancy risk. · You will have fewer periods (about 4 per year) while on Daysee. · Use a backup method (e.g., condoms) if you miss a pill or have severe GI upset. · Do not smoke while on this medication; smoking increases risk of serious cardiovascular side effects. · Inform your doctor if you experience severe headaches, chest pain, or leg swelling. |