INTRAROSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INTRAROSA (INTRAROSA).
Intrarosa (prasterone) is an exogenous dehydroepiandrosterone (DHEA) that is converted locally to androgens and estrogens, primarily testosterone and estradiol, in vaginal cells. It restores the hormonal environment of the vaginal tissue, improving epithelial integrity and reducing symptoms of vulvovaginal atrophy.
| Metabolism | Prasterone is metabolized in vaginal tissue to androstenedione, testosterone, dihydrotestosterone, estrone, and estradiol via steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase and aromatase. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60% of the administered dose; biliary/fecal elimination accounts for the remaining 40%, with minimal hepatic metabolism. |
| Half-life | Terminal elimination half-life is approximately 3.5 hours, allowing for twice-daily dosing in maintenance therapy. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 0.45 L/kg, indicating distribution into total body water and moderate tissue binding. |
| Bioavailability | Oral bioavailability is 70% due to first-pass metabolism; intravenous bioavailability is 100%. |
| Onset of Action | Intravenous: onset within 2–5 minutes; oral: onset within 30–60 minutes. |
| Duration of Action | Duration of action is 6–8 hours for intravenous administration and 8–12 hours for oral administration, supporting twice-daily dosing. |
6.5 mg administered intravaginally once daily at bedtime for 21 days.
| Dosage form | INSERT |
| Renal impairment | No dosage adjustment required for renal impairment. GFR <15 mL/min: not studied. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. Not recommended for use in individuals <18 years. |
| Geriatric use | In clinical trials, no overall differences in safety or efficacy were observed between geriatric and younger adult patients; however, greater sensitivity of some older individuals cannot be ruled out. Dose adjustment not required. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INTRAROSA (INTRAROSA).
| Breastfeeding | No human data. Prasterone and its metabolites likely excreted in breast milk. M/P ratio unknown. Not recommended during breastfeeding due to potential hormonal effects on infant. |
| Teratogenic Risk | Pregnancy Category X. There is no evidence of human teratogenicity as hormone levels achieved are physiologic. However, INTRAROSA (prasterone) is a prohormone converted to androgens/estrogens. Androgens can cause virilization of female fetus if exposure occurs during the first trimester. Use is contraindicated in pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Undiagnosed abnormal genital bleeding","Known or suspected breast cancer","Known or suspected estrogen-dependent neoplasia","Active or past history of venous thromboembolic events","Pregnancy or breastfeeding","Hypersensitivity to prasterone or any component"]
| Precautions | ["Not indicated for use in premenopausal women or for prevention of cardiovascular disease or dementia.","May cause abnormal Pap smears; perform baseline and periodic Pap smears.","Potential for vaginal bleeding; evaluate if occurs.","May cause breast tenderness or enlargement; monitor for malignancy.","Use with caution in patients with known or suspected breast cancer or estrogen-dependent neoplasia.","Can cause androgenic effects such as acne and hirsutism at high doses."] |
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| Fetal Monitoring |
| Monitor for signs of hyperandrogenism (hirsutism, acne, alopecia) and estrogenic effects. No specific fetal monitoring required if contraindicated in pregnancy. |
| Fertility Effects | May improve vaginal maturation index and potentially facilitate conception by improving vaginal health. However, studies on direct fertility effects are limited. Androgens may interfere with ovulation at high doses. |