GYNOREST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GYNOREST (GYNOREST).
Gynorest (dydrogesterone) is a synthetic progestogen that binds to the progesterone receptor with high selectivity, inducing conformational changes that promote transcription of progesterone-responsive genes. It has no androgenic, estrogenic, or corticosteroid activity, and does not inhibit ovulation.
| Metabolism | Extensively metabolized in the liver via reduction and conjugation. The major active metabolite is 20α-dihydrodydrogesterone, formed by the enzyme AKR1C1 (aldo-keto reductase family 1 member C1). Other pathways involve CYP3A4-mediated hydroxylation. |
| Excretion | Renal: 50-80% as metabolites; Fecal: 20-50% as metabolites; Biliary excretion contributes to fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 16-20 hours; supports twice-daily dosing for maintenance of therapeutic levels. |
| Protein binding | 97-99% bound; primarily to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Vd ~ 0.6-0.8 L/kg; indicates extensive distribution into tissues. |
| Bioavailability | Oral: approximately 90-100% due to minimal first-pass metabolism. |
| Onset of Action | Oral: Clinical effect (progestational) appears within 24-48 hours; peak plasma concentrations in 2-4 hours. |
| Duration of Action | Duration of action after discontinuation is 3-5 days; progestational endometrial effects persist for several days. |
100 mg orally twice daily for 5-10 days or 300 mg orally once daily for 6-12 days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (GFR <30 mL/min); use with caution. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). Use with caution in mild to moderate impairment (Child-Pugh A or B); no specific dose adjustment established. |
| Pediatric use | Not indicated for use in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to potential age-related renal and hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GYNOREST (GYNOREST).
| Breastfeeding | Excreted in breast milk in small amounts. M/P ratio not established. Considered compatible with breastfeeding by the American Academy of Pediatrics; however, monitor infant for drowsiness or feeding difficulties due to potential progestogenic effects. |
| Teratogenic Risk | FDA Pregnancy Category B. First trimester: No increased risk of major malformations in human studies, but animal studies show no evidence of teratogenicity. Second and third trimesters: May be used for threatened abortion without demonstrated fetal harm. No known association with congenital anomalies. |
■ FDA Black Box Warning
None
| Serious Effects |
Known or suspected pregnancy (except for threatened miscarriage), undiagnosed vaginal bleeding, known or suspected breast cancer, active thromboembolic disorder (e.g., deep vein thrombosis, pulmonary embolism), severe hepatic disease, known hypersensitivity to dydrogesterone or excipients.
| Precautions | Not for use as a contraceptive. Avoid use in patients with a history of thromboembolic disorders or known hypersensitivity. May cause fluid retention; monitor patients with cardiac or renal impairment. Use with caution in patients with depression, migraine, or epilepsy. Discontinue if jaundice, visual disturbances, or thrombotic events occur. |
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| Fetal Monitoring |
| Monitor maternal blood pressure, serum electrolytes, and renal function during prolonged use. In threatened abortion, assess fetal viability via ultrasound and fetal heart rate monitoring. Observe for signs of thromboembolism due to progestin exposure. |
| Fertility Effects | No known adverse effects on fertility with therapeutic use. May be used to support luteal phase in assisted reproduction. Discontinuation may restore normal ovulatory cycles. In high doses, may inhibit ovulation due to progestogenic negative feedback. |