Radiographic Contrast Agent

Lipiodol

Approved 31 Mar 1954Intralymphatic, IntrauterineOil

Indications

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)

Contraindications

Lipiodol is contraindicated in patients with hypersensitivity to Lipiodol, hyperthyroidism, traumatic injuries, recent hemorrhage or bleeding. Hysterosalpingography Lipiodol hysterosalpingography is contraindicated in pregnancy, acute pelvic inflammatory disease, marked cervical erosion, endocervicitis and intrauterine bleeding, in the immediate pre-or postmenstrual phase, and within 30 days of curettage or conization or patients with known or suspected reproductive tract neoplasia due to the risk of peritoneal spread of neoplasm. [see Use in Specific Populations ( 8.1 ) . ] Lymphography Lipiodol Lymphography is contraindicated in patients with a right to left cardiac shunt, advanced pulmonary disease, tissue trauma or hemorrhage advanced neoplastic disease with expected lymphatic obstruction, previous surgery interrupting the lymphatic system, radiation therapy to the examined area.

Selective Hepatic Intra-arterial Use Patients with HCC Lipiodol use is contraindicated in areas of the liver where the bile ducts are dilated unless external biliary drainage was performed before injection. Hypersensitivity to Lipiodol, hyperthyroidism, traumatic injuries, recent hemorrhage or bleeding. Lipiodol Hysterosalpingography is contraindicated in: pregnancy, acute pelvic inflammatory disease, marked cervical erosion, endocervicitis and intrauterine bleeding, in the immediate pre-or postmenstrual phase, and within 30 days of curettage or conization or patients with known or suspected reproductive tract neoplasia due to the risk of peritoneal spread of neoplasm.

Lipiodol Lymphography is contraindicated in: right to left cardiac shunt, advanced pulmonary disease, tissue trauma or hemorrhage, advanced neoplastic disease with expected lymphatic obstruction, previous surgery interrupting the lymphatic system, or radiation therapy to the examined area. Lipiodol Selective Hepatic Intra-arterial Injection is contraindicated in: the presence of dilated bile ducts unless external biliary drainage was performed before injection.

Indications

Contraindications

Warnings and precautions

Pulmonary and cerebral embolism: avoid use in patients with severely impaired lung function, cardiorespiratory failure or right-sided cardiac overload ( 5.1 ) Hypersensitivity reactions: avoid use in patients with a history of sensitivity to other iodinated contrast agents, bronchial asthma or allergic disorders because of an increased risk of a hypersensitivity reaction to Lipiodol ( 5.2 ) Exacerbation of chronic liver disease ( 5.3 ) Thyroid dysfunction ( 5.4 )

5.1Pulmonary and Cerebral Embolism

Pulmonary embolism may occur immediately or after a few hours to days from inadvertent systemic vascular injection or intravasation of Lipiodol and cause decreased pulmonary diffusing capacity and pulmonary blood flow, pulmonary infarction, acute respiratory distress syndrome and fatalities. Embolization of Lipiodol to brain and other major organs may occur. Avoid use of Lipiodol in patients with severely impaired lung function, cardiorespiratory failure, or right–sided cardiac overload.

Perform radiological monitoring during the Lipiodol injection. Do not exceed the recommended maximum dose and rate of injection of Lipiodol. During lymphography to minimize the risk of pulmonary embolism obtain radiographic confirmation of intralymphatic (rather than venous) injection, and terminate the procedure when Lipiodol becomes visible in the thoracic duct or lymphatic obstruction is observed.

5.2Hypersensitivity Reactions Anaphylactoid

and anaphylactic reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Lipiodol administration. Avoid use in patients with a history of sensitivity to other iodinated contrast agents, bronchial asthma or allergic disorders because of an increased risk of a hypersensitivity reaction to Lipiodol. Administer Lipiodol only in situations where trained personnel and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in resuscitation; ensure continuous medical monitoring and maintain an intravenous access line.

Most hypersensitivity reactions to Lipiodol occur within half an hour after administration. Delayed reactions can occur up to several days after administration. Observe patients for signs and symptoms of hypersensitivity reactions during and for at least 30 minutes following Lipiodol administration.

5.3Exacerbation of Chronic Liver Disease

Lipiodol hepatic intra-arterial administration can exacerbate the following conditions: portal hypertension and cause variceal bleeds due to obstruction of the intrahepatic portal channels by opening a pre sinusoidal anastomosis; hepatic ischemia and cause liver enzyme elevations, fever and abdominal pain; hepatic failure and cause ascites and encephalopathy. Hepatic vein thrombosis, irreversible liver insufficiency and fatalities have been reported.

Procedural risks include vascular complications and infections.

5.4Thyroid Dysfunction

Iodinated contrast media can affect thyroid function because of the iodide content and can cause hyperthyroidism or hypothyroidism. Ethiodized oil may remain in the body for several months, depending on dose administered and route of administration. Keep the dose of Lipiodol as low as possible and consider monitoring thyroid function closely for several months after administration of Lipiodol.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Hysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [see Contraindications ( 4 ) ]. The use of Lipiodol before or during pregnancy may interfere with thyroid function in both the pregnant woman and her fetus and may affect fetal development. There are maternal, fetal, and neonatal clinical considerations for women who are exposed to Lipiodol either before or during pregnancy (see Clinical Considerations).

Rare pregnancy outcomes reported in the post marketing setting with Lipiodol use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects or miscarriage (see Data). Animal reproduction studies have not been conducted using the indicated routes of administration of Lipiodol, it was not embryotoxic or teratogenic in animal studies with oral administration. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Maternal adverse reactions The use of Lipiodol before or during pregnancy may interfere with the thyroid function of the pregnant woman.

Untreated hypothyroidism in pregnancy is associated with adverse perinatal outcomes, such as spontaneous abortion, preeclampsia, preterm birth, abruptio placentae, and fetal death. Consider thyroid function testing during pregnancy if a woman was exposed to Lipiodol either before or during pregnancy or if clinically indicated [see Warnings and Precautions ( 5.4 ) ]. Fetal / Neonatal adverse reactions The use of Lipiodol before or during pregnancy causes iodide transfer across the placenta which may interfere with fetal thyroid function and may affect fetal development.

Untreated hypothyroidism is associated with increased fetal risk of low birth weight, fetal distress, and impaired neuropsychological development. Consider thyroid function testing in infants whose mothers were exposed to Lipiodol before and during pregnancy or if clinically indicated [see Warnings and Precautions ( 5.4 ) ]. Data Human Data In a prospective study, twenty-two euthyroid women with infertility underwent hysterosalpingography, and thyroid stimulating hormone, serum iodine concentration, and urinary iodide/creatine excretion were evaluated at 4, 8, 12, 24 weeks.

Six patients were followed upto12 months. The median value of urinary iodide excretion peaked at four weeks post-procedure and remained elevated at 8, 12, 24 weeks post-procedure compared to pre-procedure. Three patients showed elevated TSH (5 uIU/L) with normal T4 at 4 or 8 weeks after hysterosalpingography. In addition, there are post marketing reports of goiters and hypothyroidism in fetuses and infants whose mothers were exposed to Lipiodol for hysterosalpingography prior to pregnancy.

Animal Data Lipiodol was not embryotoxic or teratogenic in rats after oral administration of up to 250 mg Iodine/kg each day between gestation days 6 to 17, or in rabbits after 4-5 intermittent (once every three days) oral administrations of 12.5 mg Iodine/kg between gestation days 6 to 18. Maternal toxicity was observed in rats at 250 mg Iodine/kg/day.

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

6.2Postmarketing 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.

Lipiodol

Indications

Contraindications

Two medicines in one question?

Lipiodol

Indications

Contraindications

Two medicines in one question?

Warnings and precautions

5.1Pulmonary and Cerebral Embolism

5.2Hypersensitivity Reactions Anaphylactoid

5.3Exacerbation of Chronic Liver Disease

5.4Thyroid Dysfunction

Interactions

7.1Interference with Iodine-Based Diagnostic Tests and Iodine-Based Radiotherapy Following

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.2Postmarketing Experience

Composition

Official product information

At a glance