CRINONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CRINONE (CRINONE).
Progesterone is a naturally occurring steroid hormone that binds to progesterone receptors, initiating a cascade of events that result in the development of a secretory endometrium, maintenance of pregnancy, and suppression of gonadotropin release. In CRINONE, micronized progesterone is formulated in a bioadhesive gel for vaginal administration, providing sustained local and systemic effects.
| Metabolism | Progesterone is primarily metabolized by the liver via cytochrome P450 enzymes, including CYP2C19 and CYP3A4, to various metabolites such as pregnanolone and allopregnanolone, which are conjugated and excreted in urine and feces. |
| Excretion | Renal (50-60% as metabolites), biliary/fecal (20-30% as metabolites), with less than 5% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 17-28 hours for progesterone and its metabolites; clinical context: supports single daily dosing with Crinone 8%. |
| Protein binding | 96-99% bound primarily to albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Approximately 17-30 L in adults (not typically reported as L/kg); distribution is extensive into tissues, especially reproductive organs. |
| Bioavailability | Vaginal: approximately 100% uterine bioavailability with lower serum levels due to uterine first-pass effect; oral bioavailability is <10% due to extensive first-pass metabolism. |
| Onset of Action | Vaginal: 2-6 hours for endometrial transformation; time to peak serum levels is 2-6 hours post-dose. |
| Duration of Action | Approximately 24 hours for endometrial effects with single daily dosing; sustained progesterone levels allow once-daily administration. |
Intravaginally, 90 mg (one applicatorful of 8% gel) once daily in the morning. In assisted reproductive technology, initiate on the day of oocyte retrieval and continue for up to 12 weeks if pregnancy occurs.
| Dosage form | GEL |
| Renal impairment | No dose adjustment is necessary for renal impairment. However, caution is advised in severe renal impairment due to potential accumulation of excipients. |
| Liver impairment | No specific dose adjustment guidelines exist. Use with caution in moderate to severe hepatic impairment (Child-Pugh B or C) due to reduced progesterone metabolism; monitor for adverse effects. |
| Pediatric use | Not indicated for use in pediatric patients. Safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment required. Use with caution due to potential age-related comorbidities and limited data in women over 65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CRINONE (CRINONE).
| Breastfeeding | Progesterone is excreted into breast milk in small amounts (M/P ratio approximately 0.7). Peak milk concentration occurs 1-2 hours after administration. No adverse effects in breastfed infants have been reported. Use with caution in breastfeeding women, especially if high doses are used. |
| Teratogenic Risk | Progesterone is not associated with increased risk of congenital malformations when used as replacement therapy during pregnancy. However, exogenous progesterone in the first trimester may be associated with a small increase in hypospadias (odds ratio ~1.3), but data are inconsistent. No known risk in second or third trimester. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to progesterone or any component of the formulation","Undiagnosed vaginal bleeding","Known or suspected pregnancy (except for use in ART)","Active or history of thromboembolic disorders (e.g., DVT, PE, stroke)","Known or suspected breast cancer","Severe hepatic impairment or disease","Missed abortion or ectopic pregnancy"]
| Precautions | ["Not to be used during pregnancy except for luteal phase support in ART","Use caution in patients with a history of thromboembolic disorders, cardiac disease, or hepatic impairment","May cause drowsiness or dizziness; caution when driving","Monitor for signs of fluid retention","Use caution in patients with depression history"] |
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| Fetal Monitoring | Monitor maternal blood pressure, glucose levels, and signs of fluid retention. Fetal monitoring includes ultrasound for growth and anatomy if used in early pregnancy. No specific antidote; monitor for signs of thromboembolism. |
| Fertility Effects | Progesterone is essential for luteal phase support and implantation. Infertility patients using Crinone for luteal phase support have normal fertility outcomes. No negative impact on fertility with therapeutic use. |