SEASONALE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEASONALE (SEASONALE).
Seasonale is a combination oral contraceptive containing ethinyl estradiol and levonorgestrel. It suppresses gonadotropin release, inhibiting ovulation, and alters cervical mucus to reduce sperm penetration and endometrial lining to reduce implantation.
| Metabolism | Ethinyl estradiol is metabolized primarily by CYP3A4; levonorgestrel is metabolized by CYP3A4 and other enzymes. |
| Excretion | Renal excretion of metabolites (approximately 50-60% as glucuronide and sulfate conjugates of ethinyl estradiol and levonorgestrel) and fecal elimination (approximately 40-50%). |
| Half-life | Ethinyl estradiol: terminal half-life 13-27 hours (mean 17 hours); levonorgestrel: terminal half-life 11-45 hours (mean 25 hours). Clinical context: Supports once-daily dosing; steady-state achieved within 5-10 days. |
| Protein binding | Ethinyl estradiol: 98% bound to albumin; levonorgestrel: 97-99% bound to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Ethinyl estradiol: 2.5-4.5 L/kg; levonorgestrel: 1.5-2.5 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability: Ethinyl estradiol 38-48% (first-pass metabolism); levonorgestrel 90-100% (minimal first-pass). |
| Onset of Action | Oral administration: Estrogen/progestin effects begin within 1-2 hours; contraceptive efficacy requires 7 days of continuous dosing during first cycle. |
| Duration of Action | Contraceptive effect persists for 24 hours with daily dosing; extended regimen (91 days) reduces withdrawal bleeds. Upon discontinuation, return to fertility may be delayed but typically occurs within 1-3 months. |
One tablet (0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel) orally once daily for 84 consecutive days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment provided; use with caution in patients with renal impairment due to potential fluid retention. |
| Liver impairment | Contraindicated in patients with hepatic impairment or active liver disease; no adjustment recommended due to contraindication. |
| Pediatric use | Not indicated for use in pediatric patients before menarche; post-menarche same as adult dosing. |
| Geriatric use | Not indicated for use in postmenopausal women; no specific geriatric dosing available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEASONALE (SEASONALE).
| Breastfeeding | Excreted in breast milk in small amounts; estrogen and progestin may reduce milk production and composition. M/P ratio not available. Use only if benefits outweigh risks; consider alternative contraception. |
| Teratogenic Risk | Use during pregnancy is contraindicated. First trimester: Associated with congenital anomalies including cardiovascular defects and limb reduction defects. Second and third trimesters: Risk of feminization of male fetus, hepatic adenoma, and adverse pregnancy outcomes. No trimester is safe. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. This risk increases with age and with heavy smoking (≥15 cigarettes per day) and is quite marked in women over 35 years of age. Women who use combination oral contraceptives 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 cancer","Carcinoma of the endometrium or other known or suspected 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","Heavy smoking (≥15 cigarettes/day) and age ≥35"]
| Precautions | ["Increased risk of thromboembolic events, especially in smokers over 35","Risk of myocardial infarction and stroke","Hepatic neoplasia","Gallbladder disease","Hypertension","Carbohydrate and lipid effects","Headache and migraine","Uterine bleeding irregularities","Depression","Contact lens intolerance"] |
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| Fetal Monitoring |
| Monitor blood pressure, glucose tolerance, and liver function. Fetal ultrasound for anomaly detection if inadvertent exposure occurs. Assess for signs of thromboembolism. |
| Fertility Effects | Suppresses ovulation via negative feedback on gonadotropins. Reversible upon discontinuation; no long-term impairment of fertility. May delay return to fertility after cessation. |