Ethiodized Oil

1 INDICATIONS AND USAGE Lipiodol is an oil-based radio-opaque contrast agent indicated for: hysterosalpingography in adults lymphography in adult and pediatric patients selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma (HCC) Lipiodol is an oil-based radiopaque contrast agent indicated for: hysterosalpingography in adults lymphography in adult and pediatric patients selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma (HCC)

2 DOSAGE AND ADMINISTRATION Use a disposable syringe to draw and inject Lipiodol. Hysterosalpingography Inject increments of 2 mL of Lipiodol into the endometrial cavity until tubal patency is determined; stop the injection if the patient develops excessive discomfort. Inject with radiologic monitoring. Lymphography Inject Lipiodol into a lymphatic vessel with radiologic monitoring. Adults: unilateral lymphography of the upper extremities: 2 to 4 mL unilateral lymphography of the lower extremities: 6 to 8 mL penile lymphography: 2 to 3 mL cervical lymphography: 1 to 2 mL Pediatric patients: Inject a minimum of 1 mL to a maximum of 6 mL according to the anatomical area to be visualized. Do not exceed 0.25 mL/kg. Selective Hepatic Intra-arterial Use Inject 1.5 to 15 mL of Lipiodol slowly under continuous radiologic monitoring. Do not exceed 20 mL total dosage. 2.1 Dosing Guidelines Draw Lipiodol into a disposable syringe. Use the smallest possible amount of Lipiodol according to the anatomical area to be visualized. Hysterosalpingography Using aseptic technique inject Lipiodol into the endometrial cavity with fluoroscopic control. Inject increments of 2 mL of Lipiodol until tubal patency is determined; stop the injection if patient develops excessive discomfort. The total volume to be injected depends on the volume of the uterine cavity, usually not exceeding 15 mL. A 24-hour image can be obtained if, after slow peritoneal spillage, the evaluation of adhesions is needed. Perform the procedure during the follicular phase of the menstrual cycle. Before using Lipiodol exclude the presence of these conditions: pregnancy, uterine bleeding and endocervicitis, acute pelvic inflammatory disease, the immediate pre-or postmenstrual phase or within 30 days of curettage or conization. [see Contraindications ( 4 ) & Pregnancy ( 8.1 ) ]. Lymphography Inject Lipiodol into a lymphatic vessel under radiologic guidance to prevent inadvertent venous administration or intravasation. Adults: unilateral lymphography of the upper extremities 2 to 4 mL unilateral lymphography of the lower extremities 6 to 8 mL penile lymphography 2 to 3 mL cervical lymphography 1 to 2 mL Pediatric patients: Inject a minimum of 1 mL to a maximum of 6 mL according to the anatomical area to be visualized. Do not exceed 0.25 mL/kg. The following method is recommended for lymphography of the upper or lower extremities. Start the injection of Lipiodol into a lymphatic channel at a rate not to exceed 0.2 mL per minute. Inject the total dose of Lipiodol in no less than 1.25 hours. Use frequent radiologic monitoring to determine the appropriate injection rate and to follow the progress of Lipiodol within the lymphatics. Interrupt the injection if the patient experiences pain. Terminate the injection if lymphatic blockage is present to minimize introduction of Lipiodol into the venous circulation via lymphovenous channels. Terminate the injection as soon as Lipiodol is radiographically evident in the thoracic duct to minimize entry of Lipiodol into the subclavian vein and pulmonary embolization. Obtain immediate post-injection images. Re-image at 24 or 48 hours to evaluate nodal architecture. Selective Hepatic Intra-arterial Injection Determine the dose depending on the tumor size, local blood flow in the liver and in the tumor(s). Inject from 1.5 to 15 mL slowly under continuous radiologic monitoring. Stop the injection when stagnation or reflux is evident. Limit the dose to only the quantity required for adequate visualization. The total dose of Lipiodol administered should not exceed 20 mL. 2.2 Drug Handling Inspect Lipiodol visually for particulate matter and discoloration before administration. Do not use the solution if particulate matter is present or if the container appears damaged. Lipiodol is a clear, pale yellow to amber colored oil; do not use if the color has darkened. Draw Lipiodol into a disposable syringe and use promptly. Discard any unused portion of Lipiodol.

6 ADVERSE REACTIONS Adverse reactions caused by Lipiodol include hypersensitivity reactions, pulmonary embolism, pulmonary dysfunction, exacerbation of liver disease, procedural complications, abdominal pain, fever, nausea, vomiting, and thyroid dysfunction. To report SUSPECTED ADVERSE REACTIONS, contact GUERBET LLC at 1-877-729-6679 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.2 Postmarketing Experience The following adverse reactions (Table 1) have been identified during post approval use of Lipiodol. 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. The following adverse reactions are described in more detail in other sections of the prescribing information: Pulmonary and cerebral embolism [see Warnings and Precautions ( 5.1 ) ] Hypersensitivity reactions [see Warnings and Precautions ( 5.2 ) ] Exacerbation of chronic liver disease [see Warnings and Precautions ( 5.3 ) ] Thyroid dysfunction [see Warnings and Precautions ( 5.4 ) ]. Thyroid dysfunction in the mother and the infant of a subsequent pregnancy [See Use in Specific Populations ( 8.1 )] Table 1: Adverse Reactions in the Postmarketing Experience System Organ Class Adverse Reaction Eye disorders retinal vein thrombosis General disorders and administration site conditions fever, pain, granuloma Immune system disorders hypersensitivity, anaphylactic reaction, anaphylactoid reaction, cardiovascular reactions Nervous system disorders cerebral embolism Respiratory, thoracic and mediastinal disorders pulmonary embolism, dyspnea, cough, acute respiratory distress syndrome Urinary system disorders renal insufficiency Hysterosalpingography Abdominal pain, foreign body reactions, exacerbation of pelvic inflammatory disease, salpingitis or pelvic peritonitis have been reported after the examination in case of latent infection. Lymphography Lymphangitis, thrombophlebitis, edema or exacerbation of preexisting lymphedema, dyspnea and cough, iodism (headache, soreness of mouth and pharynx, coryza and skin rash), allergic dermatitis, lipogranuloma, delayed healing at the site of incision. Selective Hepatic Intra-arterial Injection Abdominal pain, nausea, and vomiting are the most common reactions; other reactions include hepatic vein thrombosis, hepatic ischemia, liver enzymes abnormalities, transitory decrease in liver function, liver decompensation and renal insufficiency. Procedural risks include vascular complications and infections.

12.3 Pharmacokinetics Following intra-arterial administration of Lipiodol, ethiodized oil retained in normal hepatic parenchyma is phagocytized by the Kupffer cells of the liver and washed out via the hepatic lymphatic system in about 2 to 4 weeks. In HCC, retention in the liver tumor is prolonged, allowing re-imaging of the tumor for four weeks or longer.