INTRAROSA

1 Dosing Considerations No dose adjustment is required in these situations:  elderly women (> 65 years of age).  in case of hepatic or renal impairment. The pharmacokinetics of prasterone have not been studied in these patients. 2 Recommended Dose and Dosage Adjustment  Intrarosa® is administered intravaginally with the use of the provided applicator or with fingers.

 One vaginal ovule is administered once a day at bedtime.  Once treatment has been initiated, women should be re-evaluated periodically, preferably every 6 months or as clinically appropriate, to determine if treatment is still necessary.

 Intrarosa® is not indicated for pediatric use. 4 Administration Intrarosa® can be placed into the vagina with the use of the provided applicator: 1. Using an applicator, administer one vaginal ovule once a day at bedtime. 2. Place the vaginal ovule into the vagina as far as it can comfortably go without force.

3. Press the plunger to release the ovule. 4. Withdraw the applicator, disassemble, and rinse the two pieces for 30 seconds under running water before wiping with a paper towel or the like and reassemble. 5. Discard the applicator after one week of usage.

6. Two extra applicators are provided, if necessary. Intrarosa® can be placed into the vagina with fingers: 1. The vaginal ovule should be placed into the vagina as far as it can comfortably go without force. 5 Missed Dose If a dose is forgotten, it should be taken as soon as the woman remembers.

However, if the next dose is due in less than 8 hours, the woman should skip the missed vaginal ovule. Do not use two vaginal ovules to make up for a forgotten dose.

5 mg prasterone). 2 Clinical Trial Adverse Drug Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The safety data for Intrarosa® were obtained from one single-center and four multicenter, randomized, double blind, placebo-controlled PK/efficacy studies and one uncontrolled, 52-week open-label safety study.

5 mg of prasterone, including 435 women treated daily for one year. 4% for placebo. 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings Laboratory Parameters - Hematology, serum chemistry and urinalysis parameters displayed no clinically significant changes from baseline to the final assessment (up to 12 weeks), and values generally remained within the normal adult female ranges.

Serum Prasterone and Related Steroid Levels - Following intravaginal administration of prasterone, serum steroid levels did not increase beyond the normal upper limits for postmenopausal women. Endometrial Biopsies - A total of 882 women had an end-of-study endometrial biopsy in clinical trials ERC-210 (12 weeks), ERC-230 (52 weeks), ERC-231 (12 weeks) and ERC-234 (12 weeks; reduced dosing regimen).

6% (817) of subjects. Cervical Cytology - According to study protocol, participants were to have a normal Pap smear and normal mammography at study entrance. 1%) were reported. The 11 cases of abnormal Pap smear at week 52 included 10 cases of atypical squamous cells of unknown significance (ASCUS) and 1 case of low grade squamous intraepithelial lesion (LSIL).

General Estrogen is a metabolite of prasterone. Use of exogenous estrogen is contraindicated in women with a known history of breast cancer. Intrarosa® has not been studied in women with a history of breast cancer. INTRAROSA® (prasterone vaginal ovules) Page 6 of 17  Women should undergo regular gynecological and breast exams according to current Canadian guidelines.

 Women with vaginal infection should be treated with appropriate antimicrobial therapy before starting treatment with Intrarosa®.  The melting of the hard fat, associated with increased vaginal secretions, may result in vaginal discharge.

1 Pregnant Women Intrarosa® is only indicated in postmenopausal women. There are no data on the use of Intrarosa® in pregnant women. No studies in animals were performed with regard to reproductive toxicity. 2 Breast-feeding Intrarosa® is not indicated during breast-feeding.

It is unknown if the drug is excreted in human milk. 3 Pediatrics Pediatrics (< 16 years of age): Intrarosa® is indicated only in postmenopausal women, therefore safety and effectiveness have not been examined in pediatric patients.

2% of participants in the 52-week open-label clinical trial were over age 65. Use as recommended.

 Intrarosa® is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

 Intrarosa® is contraindicated in women with undiagnosed abnormal genital bleeding. Any postmenopausal woman with undiagnosed, persistent, or recurring genital bleeding should be adequately evaluated to determine the cause before considering initiating treatment with Intrarosa®.