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.

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.

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)] .

6.1 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

8.2 Lactation

8.3 Females and Males of Reproductive Potential

Confirm that the patient has a negative pregnancy test within the 24 hours before ExEm Foam administration [see Dosage and Administration (2.1) and Use in Specific Populations (8.1)].

8.4 Pediatric Use

The safety and effectiveness of ExEm Foam have not been established in pediatric patients.

12.1 Mechanism of Action

ExEm Foam (air polymer-type A) intrauterine foam is formed by mixing the clear Gel [polymer-type A (hydroxyethyl cellulose), glycerin, and purified water] with air and Sterile Purified Water, creating an echogenic contrast agent. When visualized with ultrasound, the foam appears echogenic or bright within the fallopian tubes and peritoneal cavity.

12.2 Pharmacodynamics

ExEm Foam has no known pharmacological activity.

12.3 Pharmacokinetics

Assuming that a full 10 mL of ExEm Foam is used, and all glycerol is absorbed, the normal fasting endogenous glycerol plasma levels would not be affected. No literature data is found on absorption of hydroxyethyl cellulose (HEC) from the female reproductive tract and peritoneum. HEC is poorly permeable across GI epithelial mucosa; therefore, HEC is expected to exhibit very low permeability after administration and to produce negligible HEC systemic exposure.

The metabolism and excretion of HEC are not known.

Supplied

ExEm Foam is supplied as a single-dose kit, NDC 73254-310-01. Each kit contains:

• Syringe A: One sterile syringe containing 5 mL of clear Gel [polymer-type A (hydroxyethyl cellulose), glycerin and purified water
• Syringe B: One sterile syringe containing 5 mL of Sterile Purified Water
• One sterile Combifix Adaptor (coupling device)

Storage and Handling

Store the kit and components at controlled room temperature between 20° to 25°C (68° to 77°F); [see USP Controlled Room Temperature]; excursions permitted at 15° to 30°C (59° to 86°F). Do not store in refrigerator. Do not freeze.

Risk for Post-Procedure Gynecologic Infections

Patients should be counseled regarding the risk of post-procedure gynecologic infections. Instruct patients to report to their healthcare provider any continued pelvic and abdominal pain, significant vaginal discharge and/or fever post-procedure [see Warnings and Precautions (5.2) and Adverse Reactions (6.2)] .

Abdominal and Pelvic Pain

Inform patients of the potential for transient abdominal and pelvic pain during and after ExEm Foam sonohysterosalpingography [see Adverse Reactions (6.1)]