ExEm Foam

1 INDICATIONS AND USAGE ExEm ® Foam is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. ExEm ® Foam is an ultrasound contrast agent indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. ( 1 )

2 DOSAGE AND ADMINISTRATION Confirm the patient is not pregnant prior to ExEm Foam administrations ( 2.1 ) Recommended dose is 2 mL to 3 mL of ExEm Foam by intrauterine infusion using a 5-Fr or larger catheter. Dose may be repeated in 2 mL to 3 mL increments, as needed, to achieve visualization of the fallopian tubes. Maximum total dose is 10 mL ( 2.2 ) See Full Prescribing Information for preparation and administration instructions. ( 2.3 ) 2.1 Important Pre-Administration Information To ensure that the patient is not pregnant prior to ExEm Foam administration [see Contraindications (4) and Warnings and Precautions (5.1) ]: Confirm that the patient has a negative pregnancy test within the 24 hours before ExEm Foam administration . Confirm the patient is in the pre-ovulatory phase of her menstrual cycle (cycle days 6 through 11). 2.2 Recommended Dosage The recommended initial dose of ExEm Foam is 2 mL to 3 mL by intrauterine infusion using a 5-Fr or larger catheter with luer connection. The dose may be repeated in increments of 2 mL to 3 mL, as needed, to achieve visualization of the fallopian tubes. Maximum total dose is 10 mL. 2.3 Preparation and Administration The ExEm Foam kit includes the following components: Syringe A containing 5 mL clear Gel [polymer type A (hydroxyethyl cellulose), glycerin and purified water] Syringe B containing 5 mL Sterile Purified Water Combifix Adapter (coupling device) Preparation Examine the package and do not use if package has been previously opened or damaged. Ensure the kit is at room temperature. Handle products following aseptic practices (e.g. sterile gloves). Generate foam by mixing Syringe A (Gel) with Syringe B (Sterile Purified Water) included in the package as described in Figure 1. Infuse foam within 5 minutes of reconstitution. FIGURE 1: Reconstitution of ExEm Foam Unscrew and discard the caps from each syringe when ready to prepare the foam. Push and screw Syringe A to one end of the Combifix Adapter. Push and screw Syringe B to the other end of the Combifix Adapter. Make sure these syringes are attached tightly to avoid loss of liquid when mixing. Push the plunger of one syringe vigorously to transfer, and begin mixing the contents from one syringe to the other syringe. Repeat this process at least 10 times. The reconstituted foam is completely milky white (opaque) in color After mixing, transfer all of the foam into one syringe, then disconnect the adapter and other syringe. Approximately 10 mL of ExEm Foam is created by mixing Syringe A of clear Gel with Syringe B of Sterile Purified Water. Infuse within 5 minutes of mixing to ensure adequate imaging. Figure Figure Administration Administer through a 5-Fr or larger catheter with luer connection only. If there is resistance when infusing foam use a larger catheter. Do not infuse forcefully. Infuse 1 mL of foam to confirm proper placement of the catheter tip in the cervix and access to the uterine cavity. Slowly infuse 2 mL to 3 mL of the foam at a time to avoid patient discomfort. Discard unused portion after use. 2.4 Imaging Guidance Conduct transvaginal ultrasound imaging in accordance with ultrasound manufacturer recommendations. ExEm Foam in the fallopian tube will appear as an echogenic line along the length of the tube on the image. A fallopian tube is classified as patent if ExEm Foam is observed to pass from the tube and spill into the peritoneal cavity. The tube will appear as a thin, bright line. A fallopian tube is classified as occluded if ExEm Foam is not observed to pass from the tube and spill into the peritoneal cavity. As secondary findings, (1) there may be no bright line due to no flow into the fallopian tube, or (2) the tubal lumen may appear distended and contrast flow might be observed only in the intramural or isthmic part of the tube.

4 CONTRAINDICATIONS ExEm Foam is contraindicated for use in: Pregnancy [see Warnings and Precautions (5.1) ] . Patients with known or suspected lower genital tract inflammation or infection [see Warnings and Precautions (5.2) ]. Patients who have had a gynecologic procedure within the last 30 days [see Warnings and Precautions (5.2) ]. Patients with vaginal bleeding Due to the risk of intravasation of ExEm Foam as a result of exposure of the endometrial vessels during bleeding, and Due to the potential risk of endometriosis as a result of seeding the peritoneum with endometrial tissue. Patients with known or suspected reproductive tract neoplasia due to the risk of peritoneal spread of neoplasm . ExEm Foam is contraindicated in: Pregnancy ( 4 ) Patients with known or suspected lower genital tract inflammation or infection ( 4 ) Patients who have had a gynecologic procedure within the last 30 days ( 4 ) Patients with vaginal bleeding ( 4 ) Patient with known or suspected reproductive tract neoplasia. ( 4 )

5 WARNINGS AND PRECAUTIONS Risk for fetal harm: Confirm that the patient has a negative pregnancy test within the 24 hours before ExEm Foam administration and confirm that the patient is in the pre-ovulatory phase of her menstrual cycle (cycle days 6 through 11). ( 4 , 5.1 ) Risk for Post-Procedure Gynecologic Infections: Do not use in contraindicated situations even if the patient is receiving antimicrobial therapy. ( 4 , 5.2 ) 5.1 Risk for Fetal Harm ExEm Foam is contraindicated for use in pregnancy due to the potential risk of fetal harm from an intrauterine procedure. To ensure that the patient is not pregnant prior to ExEm Foam administration, confirm that the patient has a negative pregnancy test within the 24 hours before ExEm Foam administration and confirm that the patient is in the pre-ovulatory phase of her menstrual cycle (cycle days 6 through 11) [see Contraindications (4) ]. 5.2 Risk for Post-Procedure Gynecologic Infections There is a risk of post-procedure gynecological infections when ExEm Foam is used in sonohysterosalpingography. ExEm Foam is contraindicated for use in patients with known or suspected genital tract inflammation or infections (e.g. including pelvic inflammatory disease (PID) or suspected sexually transmitted disease) even if the patient is receiving antimicrobial therapy. ExEm Foam is contraindicated in patients who have had a gynecologic procedure within the past 30 days (e.g. curettage or conization) due to the risk of post-procedure infections [see Contraindications (4) and Adverse Reactions (6.2) ] .

6 ADVERSE REACTIONS Common adverse reactions are: pelvic and abdominal pain; vasovagal reactions and associated symptoms such as nausea and faintness; and post-procedure spotting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ExEm Foam Inc. at 1-844-963-EXEM (1-844-963-3936) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice. The common adverse reactions associated with ExEm Foam when used as indicated in sonohysterosalpingography are: pelvic and abdominal pain; vasovagal reactions and associated symptoms such as nausea and faintness; and post-procedure spotting. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of (air polymer-type A) intrauterine foam outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gynecologic Infections: pelvic inflammatory disease, salpingitis, and tubo-ovarian abscess

8.1 Pregnancy Risk Summary ExEm Foam is contraindicated for use in pregnancy due to the potential risk to the fetus from an intrauterine procedure [see Contraindications (4) and Warnings and Precautions (5.1) ] . There are no available data on the use of ExEm Foam in pregnant women. Animal reproduction studies have not been conducted with ExEm Foam.