SEASONIQUE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEASONIQUE (SEASONIQUE).
Combination of ethinyl estradiol (estrogen) and levonorgestrel (progestin) that inhibits ovulation by suppressing gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH); increases cervical mucus viscosity and alters endometrial receptivity.
| Metabolism | Primarily hepatic via CYP3A4; ethinyl estradiol undergoes first-pass metabolism and is conjugated; levonorgestrel is metabolized by hydroxylation and reduction. |
| Excretion | Renal: approximately 60% (as glucuronide and sulfate conjugates); Fecal: approximately 40% (as metabolites, with enterohepatic recycling). |
| Half-life | Ethinyl estradiol: approximately 15.9 hours (range 9-28 hours); Levonorgestrel: approximately 24.4 hours (range 12-48 hours). Terminal elimination half-life accounts for steady-state attainment within 5-7 days. |
| Protein binding | Ethinyl estradiol: 97-98% bound to serum albumin; Levonorgestrel: 97.5-99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Ethinyl estradiol: approximately 2.5 L/kg; Levonorgestrel: approximately 1.8 L/kg. Indicates extensive tissue distribution with binding to estrogen and progesterone receptors. |
| Bioavailability | Ethinyl estradiol: oral bioavailability approximately 45% (range 38-49%) due to first-pass metabolism; Levonorgestrel: oral bioavailability nearly 100%. |
| Onset of Action | Oral: contraceptive effect requires 7 days of continuous dosing to inhibit ovulation; for emergency contraception (if applicable), onset within 24 hours if taken immediately after unprotected intercourse. |
| Duration of Action | Oral: 24-hour dosing interval; contraceptive protection persists as long as daily dosing is maintained; after discontinuation, ovulation may resume within 1–3 months. |
One tablet daily orally: 84 days of ethinyl estradiol 0.02 mg / levonorgestrel 0.1 mg (active), followed by 7 days of ethinyl estradiol 0.01 mg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | Contraindicated in acute hepatic disease, jaundice, or hepatocellular carcinoma. Child-Pugh Class A: no adjustment; Class B or C: avoid use due to impaired hormone metabolism. |
| Pediatric use | Not indicated for use in patients before menarche. For post-menarche adolescents: same as adult dosing (one tablet daily). |
| Geriatric use | Not indicated for use in postmenopausal women; no dosing guidelines available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEASONIQUE (SEASONIQUE).
| Breastfeeding | Small amounts of ethinyl estradiol and levonorgestrel are excreted in breast milk. M/P ratio not established. May reduce milk production and composition, particularly in early postpartum. Use lactation-compatible contraception; avoid during breastfeeding if possible, especially in first 6 months. |
| Teratogenic Risk | Seasonique (levonorgestrel/ethinyl estradiol) is contraindicated in pregnancy. First trimester: No increased risk of major birth defects from inadvertent use, but continuation is not recommended. Second and third trimesters: Known risk of fetal harm including masculinization of female fetuses from progestins, though low-dose formulations have minimal documented effects. No adequate well-controlled studies. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. The risk increases with age (especially in women over 35) and with the number of cigarettes smoked. Do not use in women over 35 who smoke.
| Serious Effects |
["Known or suspected pregnancy","Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Endometrial cancer or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Hepatic adenoma or carcinoma","Acute or chronic liver disease with abnormal function","Hypersensitivity to any component","Smoking in women over 35","Migraine with aura in women over 35","Severe hypertension (uncontrolled or >160/100 mmHg)","Diabetes with vascular involvement"]
| Precautions | ["Thromboembolic disorders (venous and arterial)","Cardiovascular disease risk, especially in smokers over 35","Hepatic neoplasia","Gallbladder disease","Hypertension","Glucose intolerance","Depression","Carbohydrate and lipid metabolism effects","Chloasma (mask of pregnancy)","Fluid retention","Hereditary angioedema","Ocular lesions (retinal thrombosis)"] |
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| Fetal Monitoring | If inadvertently used during pregnancy: monitor fetal development with ultrasound. No specific fetal monitoring required post-exposure. Routine prenatal care. In postpartum: monitor for thromboembolic events if resumed early. |
| Fertility Effects | Returns to baseline fertility after discontinuation. No permanent effect on fertility. Transient delay in return to ovulation may occur. |