CYCRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYCRIN (CYCRIN).
Medroxyprogesterone acetate is a progestin that inhibits gonadotropin secretion, suppressing ovulation and inducing a withdrawal bleeding in an estrogen-primed endometrium. It exerts its effects via binding to progesterone receptors, leading to endometrial transformation and inhibition of endometrial proliferation.
| Metabolism | Hepatic metabolism via hydroxylation and conjugation; primarily metabolized by CYP3A4. |
| Excretion | Primarily renal (50-60% as sulfate and glucuronide conjugates), with approximately 30% fecal elimination. |
| Half-life | Terminal elimination half-life ranges from 12 to 24 hours, supporting once-daily dosing for continuous hormone replacement. |
| Protein binding | 90-97% bound to serum albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Approximately 2.5 L/kg, indicating extensive distribution into tissues including breast and uterine tissue. |
| Bioavailability | Oral bioavailability of micronized progesterone is less than 10% due to extensive first-pass metabolism; for CYCRIN (medroxyprogesterone acetate), oral bioavailability is approximately 100% due to minimal first-pass effect. |
| Onset of Action | Oral: clinical effects (e.g., withdrawal bleeding) occur within 2-3 days after course completion. |
| Duration of Action | Duration of action is 2-3 days after last dose, sufficient for cyclic withdrawal bleeding in hormone therapy. |
2.5 mg to 10 mg orally once daily for 5 to 10 days per cycle.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). Use with caution in mild to moderate impairment. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor for adverse effects such as fluid retention and thromboembolism. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYCRIN (CYCRIN).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Potential for adverse effects in infant; use with caution, generally avoided. |
| Teratogenic Risk | First trimester: Increased risk of congenital anomalies including cardiovascular and neural tube defects; use contraindicated. Second and third trimesters: Associated with genitourinary tract abnormalities, masculinization of female fetuses; avoid use. |
| Fetal Monitoring |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Known hypersensitivity to medroxyprogesterone acetate or any component","Known or suspected pregnancy","Undiagnosed vaginal bleeding","Known or suspected breast cancer","Active thrombophlebitis or thromboembolic disorders","History of thrombophlebitis or thromboembolic disorders associated with progestin use","Markedly impaired liver function"]
| Precautions | ["Thrombotic disorders (history or risk of thrombophlebitis, pulmonary embolism, cerebrovascular disease)","Use caution in patients with hepatic impairment","May cause fluid retention","May impair glucose tolerance","May increase risk of breast cancer (long-term use)","Use caution in patients with depression history","Not for use during pregnancy"] |
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| Monitor for thromboembolic events, fluid retention, glucose intolerance, blood pressure; fetal monitoring for growth and development. |
| Fertility Effects | May suppress ovulation, impair spermatogenesis; reversible upon discontinuation. |