AYGESTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AYGESTIN (AYGESTIN).
Progestin that suppresses gonadotropin secretion, inhibits ovulation, and induces endometrial changes by binding to progesterone receptors.
| Metabolism | Primarily hepatic metabolism via reduction and conjugation; CYP3A4 involved in hydroxylation. |
| Excretion | Approximately 50-80% renal as metabolites, 10-20% fecal; less than 1% unchanged. |
| Half-life | Terminal half-life 5-12 hours; clinical context: requires twice-daily dosing for consistent serum levels. |
| Protein binding | Approximately 90% bound, primarily to albumin and SHBG. |
| Volume of Distribution | Approximately 0.6 L/kg; indicates extensive distribution into tissues. |
| Bioavailability | Oral bioavailability 60-75% due to first-pass metabolism. |
| Onset of Action | Oral: endometrial effects within hours to days; maximum effect on secretory transformation of endometrium after 10-14 days of continuous therapy. |
| Duration of Action | Duration of action after single dose ~24 hours; clinical note: continuous daily dosing required for therapeutic effect in endometriosis or contraception. |
5 mg orally once daily for secondary amenorrhea; 5 mg orally once daily from day 5 to day 25 of menstrual cycle for abnormal uterine bleeding.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines available; use with caution in significant renal impairment. |
| Liver impairment | Contraindicated in severe hepatic dysfunction (Child-Pugh class C). No specific dose adjustments for mild to moderate impairment; use with caution. |
| Pediatric use | Safety and efficacy not established for pediatric populations; not recommended. |
| Geriatric use | No specific dose adjustments; use with caution due to potential increased sensitivity and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AYGESTIN (AYGESTIN).
| Breastfeeding | Excreted in breast milk in small amounts. M/P ratio not established. Potential for adverse effects in nursing infants including jaundice and breast enlargement. Use with caution, weighing benefits against risks. |
| Teratogenic Risk | First trimester: Increased risk of congenital anomalies including cardiovascular and limb defects. Second and third trimesters: Potential for urogenital abnormalities, masculinization of female fetuses, and other adverse effects such as altered sexual development. Use is contraindicated in pregnancy. |
■ FDA Black Box Warning
Not recommended during pregnancy as progestins may cause fetal harm.
| Serious Effects |
["Known or suspected pregnancy","Undiagnosed vaginal bleeding","Known or suspected breast cancer","Active thrombophlebitis or thromboembolic disorders","History of thromboembolic disorders","Liver dysfunction or disease"]
| Precautions | ["Discontinue if thrombotic disorders occur","Monitor for fluid retention","May cause glucose intolerance","Use with caution in conditions aggravated by fluid retention (e.g., asthma, migraine, cardiac or renal dysfunction)","Breakthrough bleeding may occur"] |
| Food/Dietary | No specific food interactions. Grapefruit juice may increase norethindrone levels; avoid excessive consumption. |
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| Fetal Monitoring |
| Monitor maternal liver function, blood pressure, and signs of thromboembolism. Fetal monitoring for growth and development if inadvertent use during pregnancy. |
| Fertility Effects | May impair fertility through inhibition of ovulation and alteration of endometrial receptivity. Effects are reversible upon discontinuation. |
| Clinical Pearls | AYGESTIN (norethindrone acetate) is a progestin used for secondary amenorrhea and abnormal uterine bleeding. It should not be used as a contraceptive. Initiate at lowest effective dose. Monitor for thromboembolic events, especially in patients with risk factors. Discontinue if jaundice, migraine, or visual disturbances occur. Consider pregnancy test before starting treatment. |
| Patient Advice | Take once daily at the same time each day, with or without food. · Missed dose: take as soon as remembered; if almost time for next dose, skip missed dose and resume regular schedule. Do not double dose. · Report unusual vaginal bleeding, severe headache, vision changes, leg pain or swelling, chest pain, or shortness of breath immediately. · Not for use during pregnancy; use effective non-hormonal contraception if needed. · May cause nausea, breast tenderness, or mood changes; report if persistent. |