AVIANE-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVIANE-28 (AVIANE-28).
Combination hormonal contraceptive: ethinyl estradiol is an estrogen, levonorgestrel is a progestin. Suppresses gonadotropins (FSH, LH), inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4, also undergoes sulfation and glucuronidation. Levonorgestrel: metabolized by CYP3A4, reduction, and conjugation. |
| Excretion | Renal: 50-60% as unchanged drug; Hepatic metabolism: 30-40% as inactive metabolites; Fecal: 10-20%. |
| Half-life | Terminal elimination half-life is 12-14 hours; steady-state achieved within 3 days; clinical significance: dosing interval every 12 hours. |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd 0.6 L/kg; indicates moderate distribution into total body water, with higher penetration into well-perfused tissues. |
| Bioavailability | Oral: 85-90%; reduced by 20% with high-fat meal. |
| Onset of Action | Oral: 1-2 hours; peak effect at 4-6 hours. |
| Duration of Action | 12-24 hours; sustained therapeutic effect for 12 hours post-dose, with gradual decline thereafter. |
1 tablet (0.1 mg levonorgestrel/0.02 mg ethinyl estradiol) orally once daily for 28 days (21 active tablets followed by 7 placebo tablets).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended for use in severe renal impairment (GFR <30 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in acute hepatitis, severe cirrhosis (Child-Pugh C), or liver tumors. No specific Child-Pugh based dose adjustment available; use with caution in mild to moderate hepatic impairment. |
| Pediatric use | Safety and efficacy established in females of reproductive age (post-menarche). Standard adult dosing (0.1 mg levonorgestrel/0.02 mg ethinyl estradiol) is used after menarche. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific geriatric considerations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVIANE-28 (AVIANE-28).
| Breastfeeding | Excreted in breast milk with M/P ratio ~0.5-1.0. Potential for adverse effects in nursing infants (e.g., jaundice, hepatotoxicity). Recommend against breastfeeding while on therapy. |
| Teratogenic Risk | Pregnancy category X. First trimester: Risk of cardiovascular defects, oral clefts, and neural tube defects. Second and third trimesters: Associated with fetal genital abnormalities, masculinization of female fetuses, and potential metabolic disturbances. Use contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age (especially >35 years) and with number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis, thromboembolic disorders, or history thereof","Cerebrovascular or coronary artery disease","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","Hypersensitivity to any component","Age >35 years and smoking","Uncontrolled hypertension","Diabetes with vascular involvement","Migraine with focal neurological symptoms","Major surgery with prolonged immobilization"]
| Precautions | ["Smoking and cardiovascular risk","Thrombotic events (venous thromboembolism, arterial thromboembolism)","Liver disease (including hepatic adenoma, hepatocellular carcinoma)","Hypertension","Gallbladder disease","Carbohydrate and lipid metabolism effects","Headache/migraine","Vaginal bleeding irregularities","Depression","Ocular lesions","Contact lens intolerance"] |
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| Monitor liver function tests (LFTs), bilirubin, and prothrombin time in mother. Fetal surveillance with ultrasound for structural anomalies if inadvertent exposure occurs. Assess for signs of hepatic dysfunction in newborn. |
| Fertility Effects | May disrupt ovulation and menstrual regularity; potential transient reduction in fertility. Reversible upon discontinuation. Use with caution in women desiring pregnancy. |
| Food/Dietary | No significant food interactions. Grapefruit juice may increase estrogen exposure; monitor for side effects. Avoid excessive alcohol consumption due to increased risk of liver toxicity. |
| Clinical Pearls | AVIANE-28 (levonorgestrel/ethinyl estradiol) is a combination oral contraceptive. For missed pills: if one pill is missed, take it as soon as remembered and continue schedule; if two or more are missed, use backup contraception for 7 days and consider emergency contraception. Advise patients that vomiting or diarrhea may reduce efficacy. CYP3A4 inducers (e.g., rifampin) decrease contraceptive effect; consider alternative method. Monitor for thromboembolic events, especially in smokers over 35. AVIANE-28 contains a low estrogen dose; spotting may occur in first 3 cycles. |
| Patient Advice | Take one pill daily at the same time each day. · Do not smoke while taking this medication, especially if over 35. · If you miss a pill, refer to the package instructions or call your doctor. · Use backup contraception (e.g., condoms) if you miss two or more pills. · Inform your healthcare provider about all medications you take, including antibiotics and St. John's wort. · Seek emergency care for symptoms of blood clots (e.g., sudden leg pain, chest pain, shortness of breath). · AVIANE-28 does not protect against HIV or other sexually transmitted infections. |