AVIANE-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVIANE-21 (AVIANE-21).
Combination estrogen-progestin contraceptive; inhibits gonadotropin secretion, suppressing ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial receptivity.
| Metabolism | Ethinyl estradiol: primarily CYP3A4; levonorgestrel: reduction, conjugation (glucuronidation), and hydroxylation; partially enterohepatic recirculation. |
| Excretion | Renal (primarily as metabolites, ~60%), fecal (~40%), with less than 10% excreted unchanged as ethinyl estradiol and levonorgestrel. |
| Half-life | Levonorgestrel: terminal half-life 27.7 ± 7.2 hours; ethinyl estradiol: terminal half-life 15.4 ± 8.4 hours. Steady-state achieved within 7–14 days. |
| Protein binding | Levonorgestrel: 98–99% bound to sex hormone-binding globulin (SHBG) and albumin; ethinyl estradiol: ~98% bound to albumin, induces SHBG synthesis. |
| Volume of Distribution | Levonorgestrel: 1.5 ± 0.5 L/kg; ethinyl estradiol: 2.3–4.3 L/kg (reports vary). High Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: levonorgestrel ~100% (no first-pass metabolism significant); ethinyl estradiol ~45% due to first-pass metabolism (range 38–49%). |
| Onset of Action | Oral: contraceptive effect requires 7 days of continuous dosing for full suppression of ovulation; peak plasma levels of levonorgestrel reached 1–3 hours, ethinyl estradiol 1–2 hours. |
| Duration of Action | Daily dosing required; contraceptive protection persists for 24 hours per dose; if one active pill is missed, backup contraception needed for 7 days. |
| Molecular Weight | Ethinylestradiol: 296.4 Da; Levonorgestrel: 312.4 Da |
One tablet orally once daily for 21 consecutive days, followed by 7 drug-free days. Each tablet contains levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Severe renal impairment (GFR <30 mL/min) is contraindicated due to potential fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in Child-Pugh class B or C (moderate to severe hepatic impairment). For mild impairment (Child-Pugh A), no dose adjustment is recommended but use with caution. |
| Pediatric use | Not indicated for use before menarche. For adolescent females post-menarche, dosing is same as adult: one tablet daily for 21 days, followed by 7 days off. |
| Geriatric use | Not indicated for use after menopause. Contraindicated in postmenopausal women due to increased risk of cardiovascular events and thromboembolism. |
| 1st trimester | Contraindicated due to risk of fetal malformations (oral clefts, cardiac defects) associated with hormonal contraceptives. |
| 2nd trimester | Contraindicated; may cause fetal harm including masculinization of female fetuses from progestin component. |
| 3rd trimester | Contraindicated; risk of adverse effects on fetal development and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for AVIANE-21 (AVIANE-21).
| Placental transfer | Steroid hormones cross the placenta; ethinylestradiol and levonorgestrel are transferred to fetal circulation. |
| Breastfeeding | Excreted in human milk; may reduce milk production and composition; use alternative contraception during breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events; women over 35 who smoke should not use this product.
| Serious Effects |
Known or suspected pregnancyBreast cancer or estrogen-sensitive neoplasiaActive liver disease or hepatic adenomaHistory of thromboembolic disorders or thrombophiliaUncontrolled hypertensionSmoking over 35 years of ageMigraine with focal neurological symptoms
| Precautions | Increased risk of thromboembolism, stroke, myocardial infarction, Hepatic neoplasia risk, Gallbladder disease, Hypertension, Carbohydrate/lipid metabolic effects, Ocular lesions (e.g., retinal thrombosis), Headache exacerbation, Breakthrough bleeding/amenorrhea |
| Food/Dietary | Grapefruit juice may increase ethinyl estradiol levels, but effect is usually minimal; no strict avoidance is required. No other significant food interactions. St. John's wort (herbal supplement) reduces contraceptive efficacy and should be avoided. A high-fat meal may slightly increase desogestrel absorption but is not clinically significant. |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | First trimester: major malformations (cardiac, limb reduction) ~1-2% above baseline. Second/third trimester: potential androgenization of female fetus (labioscrotal fusion, clitoromegaly). Postnatal: subtle neurodevelopmental effects reported. |
| Fetal Monitoring | Maternal: BP every visit, liver enzymes if cholestasis suspected, glucose tolerance test at 24-28 weeks. Fetal: ultrasound for anatomy at 18-20 weeks, growth scans every 4 weeks from 24 weeks. |
| Fertility Effects | No adverse effect on fertility; used as oral contraceptive to prevent pregnancy. Discontinuation may allow rapid return of ovulation. |
| Clinical Pearls | AVIANE-21 is a combination oral contraceptive containing ethinyl estradiol and desogestrel. The progestin desogestrel is a third-generation progestin with lower androgenic activity, which may be beneficial for acne and hirsutism. However, it carries a slightly higher risk of venous thromboembolism compared to second-generation progestins like levonorgestrel. Ensure no contraindications such as smoking over age 35, hypertension, migraine with aura, or history of DVT. Advise consistent timing; missed pills increase pregnancy risk. Drug interactions include rifampin, certain anticonvulsants, and St. John's wort, which reduce efficacy. Consider non-oral backup if vomiting or severe diarrhea occurs within 4 hours of dosing. |
| Patient Advice | Take one tablet daily at the same time each day, even if you are not sexually active. · If you miss a pill, follow the package instructions: if you miss 1 pill, take it as soon as you remember, then take the next pill at your regular time (may take 2 pills in one day). If you miss 2 or more pills, use a backup contraception method (e.g., condoms) for at least 7 days. · Contact your healthcare provider immediately if you experience sudden severe headache, chest pain, leg pain/swelling, vision changes, or jaundice. · AVIANE-21 does not protect against HIV or other sexually transmitted infections. · Inform your doctor of all medications and supplements you take, including over-the-counter products and herbal remedies. · Avoid smoking while taking this medication, especially if you are over 35 years old, as it increases the risk of serious cardiovascular side effects. · If you have vomiting or severe diarrhea within 4 hours of taking a pill, consider it a missed dose and follow the missed pill instructions. |