PROGESTASERT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROGESTASERT (PROGESTASERT).
Progesterone released from the intrauterine device (IUD) induces endometrial thinning, thickens cervical mucus, and inhibits sperm motility and penetration, thus preventing implantation.
| Metabolism | Progesterone is primarily metabolized in the liver via reduction and conjugation, including 5α- and 5β-reductase, 3α- and 3β-hydroxysteroid dehydrogenase, and glucuronidation. Main metabolites: pregnanediols and pregnanolones. |
| Excretion | Primarily hepatic metabolism; metabolites excreted in urine (~50-60%) and feces (~40-50%). Less than 1% excreted unchanged in urine. |
| Half-life | Unchanged progesterone: approximately 5 minutes; following intrauterine release, terminal half-life of levonorgestrel is ~8-10 hours. Clinical context: rapid clearance necessitates continuous intrauterine delivery for sustained effect. |
| Protein binding | Levonorgestrel: 98-99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Levonorgestrel: approximately 1.8 L/kg. High Vd indicates extensive tissue distribution, including reproductive organs. |
| Bioavailability | Intrauterine delivery results in direct local exposure with minimal systemic absorption; systemic bioavailability is negligible compared to oral administration. Not applicable for other routes. |
| Onset of Action | Intrauterine device (IUD): contraceptive effect begins within 24 hours of insertion; for emergency contraception, effective if inserted within 5 days of unprotected intercourse. |
| Duration of Action | IUD provides effective contraception for up to 5 years; removal restores fertility promptly. Continuous progestin release maintains endometrial suppression. |
Intrauterine device releasing 65 mcg progesterone per day, inserted into the uterine cavity; replaced annually.
| Dosage form | INSERT, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for renal impairment; pharmacokinetics not significantly altered. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C); use with caution in moderate impairment; no specific dose adjustment data. |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Not indicated for postmenopausal women; avoidance recommended due to age-related uterine changes and lack of efficacy data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROGESTASERT (PROGESTASERT).
| Breastfeeding | Progesterone released from Progestasert is minimally absorbed systemically and unlikely to affect breastfeeding infant. Low levels of progesterone may be present in breast milk but no adverse effects reported. M/P ratio not established; expected to be low due to local action. |
| Teratogenic Risk | Progestasert (progesterone intrauterine device) is not associated with increased risk of congenital malformations when used prior to conception or inadvertently during early pregnancy. However, continued use during pregnancy is contraindicated due to risk of septic abortion, preterm labor, and fetal infection. First trimester: no known teratogenicity from hormone exposure, but device-related risks. Second and third trimesters: device can cause uterine perforation, infection, and adverse fetal outcomes. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Known or suspected pregnancy","Current or recurrent pelvic inflammatory disease (PID)","Postpartum endometritis or infected abortion within past 3 months","Abnormal uterine bleeding of unknown etiology","Known or suspected uterine or cervical neoplasia","Uterine distortion (e.g., fibroids) affecting device placement","Genital actinomycosis","Acute cervicitis or vaginitis (until treated)","Copper allergy (for copper-containing IUDs; not applicable to Progestasert which is hormonal)","Immunocompromised patient (relative)"]
| Precautions | ["Ectopic pregnancy risk: Be alert for pregnancy in users with lower abdominal pain, especially if amenorrheic.","Pelvic infection: Increased risk of PID, especially within first 20 days post-insertion; users with multiple partners are at higher risk.","Embedment or perforation of uterine wall: May occur; use caution in postpartum or lactating patients.","Expulsion: Partial or complete expulsion may occur; check for presence of threads.","Syncope or bradycardia: Can occur during insertion; have resuscitation equipment available."] |
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| Fetal Monitoring | Confirm pregnancy and remove device if pregnancy occurs. Monitor for signs of infection, uterine cramping, or expulsion. Ultrasound may be used to locate device if strings not visible. Monitor fetal growth and amniotic fluid if device retained. |
| Fertility Effects | Progestasert does not impair future fertility. After removal, ovulation and menstrual cycles resume promptly. No long-term effects on ovarian function or fecundity. |