LOSEASONIQUE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOSEASONIQUE (LOSEASONIQUE).
Combination of ethinyl estradiol and drospirenone; ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation; drospirenone is a progestin with anti-mineralocorticoid and anti-androgenic activity.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4, undergoes conjugation and enterohepatic recirculation. Drospirenone: extensively metabolized by CYP3A4, with minor involvement of CYP1A1 and CYP2C9; forms two major metabolites (dihydrodrospirenone and drospirenone sulfate) that are not pharmacologically active. |
| Excretion | Renal: ~50% as metabolites; fecal: ~30% as metabolites; biliary: minor. |
| Half-life | Terminal elimination half-life is 12-15 hours, supporting once-daily dosing. |
| Protein binding | Ethinyl estradiol: ~97% bound to albumin; progestin: ~99% bound to SHBG and albumin. |
| Volume of Distribution | Ethinyl estradiol: 4-5 L/kg; progestin: 2-3 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: ~40-60% for ethinyl estradiol due to first-pass metabolism; progestin: >80%. |
| Onset of Action | Oral: 1-2 hours for peak serum concentrations; clinical effect (contraception) begins after 7 days of consistent dosing. |
| Duration of Action | 24 hours; adequate contraception requires daily dosing without missing pills. |
One tablet (ethinyl estradiol 0.02 mg/levonorgestrel 0.1 mg) orally once daily for 21 days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure. |
| Liver impairment | Contraindicated in Child-Pugh Class B or C hepatic impairment; no specific dose adjustment defined for mild impairment but use with caution. |
| Pediatric use | Safety and efficacy established in females of reproductive age; postmenarche use as per adult dosing. Not indicated before menarche. |
| Geriatric use | Not indicated for use in postmenopausal women; no geriatric-specific dosing. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOSEASONIQUE (LOSEASONIQUE).
| Breastfeeding | Excreted in breast milk. Estrogens may reduce milk quantity and quality. M/P ratio not established. Use not recommended during breastfeeding; alternative contraception advised. |
| Teratogenic Risk | Category X. Estrogen-progestin combinations are contraindicated in pregnancy. First trimester exposure associated with risk of congenital anomalies, particularly cardiac defects and limb reduction. Second and third trimester exposure may result in fetal harm including masculinization of female genitalia (progestin effect) and possible hepatic adenoma. Discontinue immediately if pregnancy occurs. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, especially in women over 35 years, and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast cancer","Endometrial cancer or other 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","Uncontrolled hypertension (BP ≥ 160/100 mmHg)","Diabetes with vascular involvement","Headache with focal neurological symptoms (migraine with aura) in women over 35","Major surgery with prolonged immobilization","Heavy smoking (≥15 cigarettes/day) in women over 35","Hypersensitivity to any component of the drug"]
| Precautions | ["Thrombotic disorders (venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction)","Hepatic disease (acute hepatitis, benign/malignant liver tumors)","Hypertension (contraindicated if uncontrolled)","Gallbladder disease","Carbohydrate/lipid metabolism effects","Headache (including migraine with focal aura)","Uterine bleeding irregularities","Depression","Fluid retention","Ocular lesions (retinal thrombosis)","Cervical cancer screening","Hereditary angioedema","Chloasma","Drug interactions (especially CYP3A4 inducers)","Laboratory test interference (sex hormone-binding globulin, thyroid-binding globulin)"] |
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| Fetal Monitoring | Perform pregnancy test before initiation. Monthly during first cycle, then every 3 months. Monitor for signs of thromboembolism, hypertension, hepatic dysfunction. Fetal ultrasound if inadvertent exposure. |
| Fertility Effects | Reversible suppression of ovulation. Return to baseline fertility typically within 1-3 months after discontinuation. No permanent impairment. |