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. |
| Molecular Weight | 424.5 |
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 | No adequate human data; animal studies not available; unknown risk. Avoid use in first trimester. |
| 2nd trimester | Limited human data; potential risk of preterm labor or placental abruption. Use only if clearly needed. |
| 3rd trimester | Contraindicated in third trimester due to risk of preterm labor, placental abruption, and fetal distress. |
Clinical note
Comprehensive clinical and safety monograph for INTRAROSA (INTRAROSA).
| Placental transfer | Not studied in humans; based on molecular weight <500 Da, likely crosses placenta. |
| Breastfeeding | Excretion into breast milk unknown; due to potential for serious adverse effects, breastfeeding should be discontinued during therapy. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to dehydroepiandrosterone or any componentPregnancy (third trimester)Active thromboembolic disorderUndiagnosed vaginal bleeding
| 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. |
| Food/Dietary | No clinically significant food interactions. Grapefruit juice does not interact. Avoid use with oral estrogen products as DHEA may add to estrogenic effects. |
Loading safety data…
| Avoid |
| 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. |
| 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. |
| Clinical Pearls | Intrarosa (prasterone) is a vaginal insert containing dehydroepiandrosterone (DHEA) used for moderate to severe dyspareunia due to menopause. It is not FDA-approved for prevention of breast cancer or other indications. Initiate therapy after confirmation of postmenopausal status. Monitor for vaginal discharge or spotting. Not for use in women with undiagnosed vaginal bleeding, known or suspected breast cancer, or porphyria. |
| Patient Advice | Insert one vaginal ovule once daily at bedtime using the provided applicator. · Wash hands before and after use. The applicator is for single use; dispose after each insertion. · Do not use during menses or if you have unexplained vaginal bleeding. · Report persistent vaginal irritation, discharge, or bleeding to your healthcare provider. · This medication does not protect against sexually transmitted infections or pregnancy. · Store at room temperature (20-25°C) away from moisture and heat. |