DAYSEE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 444.46 |
| Action Class | Oral Contraceptive; Progestin/Estrogen Combination |
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 | Contraindicated due to risk of birth defects (neural tube defects, cardiovascular malformations) from folate antagonism. |
| 2nd trimester | Contraindicated; can cause fetal growth restriction and delayed ossification. |
| 3rd trimester | Contraindicated; risk of kernicterus in neonates due to bilirubin displacement. |
Clinical note
Comprehensive clinical and safety monograph for DAYSEE (DAYSEE).
| Placental transfer | Crosses placenta via active transport; fetal serum levels reach maternal levels within hours. |
| Breastfeeding | Excreted into breast milk in low amounts; theoretical risk of hemolytic anemia and folate deficiency in infants. Avoid during breastfeeding if safer alternatives exist. |
| Lactation Rating | L4 - Probably Hazardous |
| 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 | 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. |
■ 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.
| Common Effects | Nausea, Headache, Breast tenderness, Irregular uterine bleeding, Weight changes, Mood changes |
| Serious Effects | Venous thromboembolism (VTE), Arterial thromboembolism (e.g., stroke, myocardial infarction), Hypertension, Hepatic adenoma or hepatocellular carcinoma, Gallbladder disease, Hyperkalemia (due to drospirenone's antimineralocorticoid activity) |
Pregnancy (teratogenic)Breastfeeding (relative, but caution)History of megaloblastic anemia due to folate deficiencySevere hepatic impairmentHypersensitivity to Daysee or its components
| 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. |
| 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. |
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