ALESSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALESSE (ALESSE).
Combination of ethinyl estradiol and levonorgestrel suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus, inhibiting pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby preventing ovulation. Additionally, it thickens cervical mucus, impeding sperm penetration, and alters endometrial receptivity.
| Metabolism | Ethinyl estradiol is primarily metabolized by CYP3A4 and undergoes conjugation (glucuronidation and sulfation). Levonorgestrel is metabolized by CYP3A4 and reduction, with conjugation to glucuronide and sulfate conjugates. |
| Excretion | Renal: ethinyl estradiol (UE2) and levonorgestrel (LNG) metabolites primarily excreted in urine (UE2: ~40% as sulfate and glucuronide conjugates; LNG: ~25% as glucuronides). Fecal/biliary: ~40% (UE2) and ~45% (LNG) eliminated in feces via bile. Unchanged drug excretion is negligible. |
| Half-life | Levonorgestrel: terminal half-life ~17-20 hours (range 11-25 hr). Ethinyl estradiol: biphasic; terminal half-life ~13-27 hours (mean ~17 hr). Clinical context: steady-state achieved within 5-7 days. The half-life supports once-daily dosing with at least 24-hour contraceptive coverage. |
| Protein binding | Levonorgestrel: 97-99% bound to albumin and sex hormone-binding globulin (SHBG). Ethinyl estradiol: 98-99% bound, primarily to albumin (98.5%), with minor binding to SHBG. Free fractions: LNG ~1%, UE2 ~1.0-1.5%. |
| Volume of Distribution | Levonorgestrel: Vd ~1.8 L/kg (range 1.5-2.0 L/kg). Ethinyl estradiol: Vd ~2.5-3.5 L/kg (mean ~2.9 L/kg). Indicates extensive tissue distribution, including target organs (ovaries, endometrium, breast). Not clinically adjusted for obesity. |
| Bioavailability | Oral: levonorgestrel ~95-100% (highly bioavailable). Ethinyl estradiol ~45-55% (first-pass metabolism reduces bioavailability; interindividual variability due to gut wall and hepatic conjugation). Both are prodrugs requiring hydrolysis for activity. |
| Onset of Action | Oral: immediate and consistent suppression of ovulation begins within 2 days if started on day 1 of menstrual cycle. For quick start (any day), additional protection needed for 7 days. Peak serum hormone levels occur 1-2 hours post-dose. |
| Duration of Action | Clinical effect: 24 hours (supports daily dosing). Contraceptive efficacy persists as long as no dose is missed. Missed dose >24 hours increases pregnancy risk. Long-term suppression of ovulation reverses within 1-3 months after discontinuation. |
One tablet (ethinyl estradiol 20 mcg, levonorgestrel 0.1 mg) orally once daily at the same time each day for 21 days, followed by 7 days of placebo. For initiation, start on the first day of menstrual period or first Sunday after onset of menses.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based dose adjustments are recommended; however, use with caution in patients with renal impairment due to potential fluid retention and hypertension. |
| Liver impairment | Contraindicated in patients with severe hepatic disease (Child-Pugh class C) or active liver disease. In mild to moderate impairment (Child-Pugh A or B), use only if benefits outweigh risks; no specific dose reduction guidelines are available. |
| Pediatric use | Approved for postmenarchal adolescents; same dosing as adults: one tablet orally once daily for 21 days followed by 7 days of placebo. No weight-based adjustments are recommended. |
| Geriatric use | Not indicated for use in postmenopausal women; no specific geriatric dosing adjustments are necessary if used off-label, but consider increased risk of thrombotic events in older women. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALESSE (ALESSE).
| Breastfeeding | Excreted in breast milk. Levonorgestrel M/P ratio approximately 0.3–0.4. Small amounts of ethinyl estradiol present. May reduce milk production and quality due to estrogen component. Use only if benefit outweighs risk; consider alternative contraception. American Academy of Pediatrics considers it compatible with nursing. |
| Teratogenic Risk | Pregnancy category X. Use contraindicated in pregnancy. First trimester exposure associated with cardiovascular defects (e.g., VSD), neural tube defects, and cleft lip/palate. Second and third trimester exposure may cause fetal adrenal suppression, hepatic dysfunction, and virilization of female genitalia due to progestin component (levonorgestrel). Increased risk of ectopic pregnancy if conception occurs during use. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. The risk increases with age, particularly in women over 35 years, and with heavy smoking (≥15 cigarettes per day). Women over 35 who smoke should not use this medication.
| Serious Effects |
["Breast cancer (current or history)","Carcinoma of the endometrium or other estrogen-dependent neoplasia","Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Valvular heart disease with complications","Severe hypertension","Diabetes with vascular involvement","Headaches with focal neurological symptoms (e.g., migraine with aura)","Major surgery with prolonged immobilization","Known or suspected pregnancy","Active liver disease or impaired liver function","Undiagnosed abnormal uterine bleeding","Hypersensitivity to any component","Cigarette smoking in women over 35 years of age"]
| Precautions | ["Increased risk of thromboembolic disorders (venous and arterial)","Cigarette smoking increases risk of cardiovascular events, especially in women over 35","Hepatic neoplasia (benign and malignant)","Elevated blood pressure","Gallbladder disease","Carbohydrate and lipid metabolism effects","Headache/migraine","Depression","Uterine bleeding irregularities","Ocular lesions (e.g., retinal thrombosis)","Carcinoma of the breast and reproductive organs (close monitoring in current or history of breast cancer)"] |
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| Fetal Monitoring | Pregnancy test prior to initiation and monthly. For accidental pregnancy, perform ultrasound to rule out ectopic pregnancy and assess fetal development. Monitor fetal growth and anatomy in exposed pregnancies. Maternal liver function tests and blood pressure monitoring due to increased risk of cholestasis and hypertension. |
| Fertility Effects | Reversible suppression of ovulation. Normal fertility returns upon discontinuation. No permanent adverse effects on ovarian reserve or spermatogenesis. May delay return of menses postpartum or post-abortion. |
| Food/Dietary | No specific food restrictions. Grapefruit juice may slightly increase ethinyl estradiol levels but not clinically significant. High-fat meals do not affect absorption. Avoid excessive alcohol as it may impair compliance. |
| Clinical Pearls | ALESSE is a combined oral contraceptive (COC) containing ethinyl estradiol (20 mcg) and levonorgestrel (100 mcg). It is indicated for contraception and treatment of acne vulgaris in women aged ≥14. Monitor for thromboembolic events, especially in smokers >35 years. Assess for contraindications including migraines with aura, hypertension, and history of DVT/PE. Advise use of backup contraception if a pill is missed. Start on first day of menses or first Sunday after onset. Check BP at baseline and annually. Counsel on increased risk of VTE, especially in first year. |
| Patient Advice | Take one pill daily at the same time each day, even if you do not have sex. · Missed pill instructions: if late by <12 hours, take it as soon as remembered and continue schedule. If >12 hours, take missed pill (even if means taking two in one day) and use backup contraception for 7 days. · Possible side effects: nausea, breast tenderness, headache, breakthrough bleeding, especially in first 3 months. · Seek emergency care for signs of blood clot: leg pain/swelling, sudden chest pain, shortness of breath, severe headache, vision changes. · Do not smoke while on ALESSE, especially if over age 35, as it increases risk of serious cardiovascular events. · Inform your healthcare provider of all medications and supplements you take, as some (e.g., rifampin, anticonvulsants, St. John's wort) may reduce effectiveness. |