HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
LIPIODOL safely and effectively. See full prescribing
information for LIPIODOL.
LIPIODOL® (Ethiodized Oil) Injection
Initial U.S. Approval: 1954
WARNING: FOR INTRALYMPHATIC, INTRAUTERINEAND SELECTIVE HEPATIC INTRA-ARTERIAL USE
ONLY
See Full Prescribing Information for complete Boxed Warning.
Pulmonary and cerebral embolism can result from inadvertent
intravascular injection or intravasation of Lipiodol. Inject
Lipiodol slowly with radiologic monitoring; do not exceed
recommended dose (5.1).
_______________RECENT MAJOR CHANGES______________
Warnings and Precautions, Thyroid Dysfunction (5.4)
6/2020---------------------- INDICATIONS AND USAGE --------------------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) (1)------------------ DOSAGE AND ADMINISTRATION ---------------Use a disposable syringe to draw and inject Lipiodol. (2)•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.
------------------ DOSAGE FORMS AND STRENGTHS ------------Each mL of Lipiodol contains 480 mg Iodine organically combinedwith ethyl esters of fatty acids of poppy seed oil. (3)------------------------- CONTRAINDICATIONS -----------------------Hypersensitivity to Lipiodol, hyperthyroidism, traumatic injuries,
recent hemorrhage or bleeding. (4)•Lipiodol Hysterosalpingography is contraindicated in:pregnancy, acute pelvic inflammatory disease, marked cervicalerosion, endocervicitis and intrauterine bleeding, in the immediatepre-or postmenstrual phase, or within 30 days of curettage orconization.
•
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, orradiation therapy to the examined area.
•
Lipiodol Selective Hepatic Intra-arterial Injection iscontraindicated in: the presence of dilated bile ducts unlessexternal biliary drainage was performed before injection.
----------------- WARNINGS AND PRECAUTIONS ----------------• Pulmonary and cerebral embolism: avoid use in patients withseverely impaired lung function, cardiorespiratory failure or rightsided cardiac overload (5.1)• Hypersensitivity reactions: avoid use in patients with a history ofsensitivity 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)------------------------ ADVERSE REACTIONS -----------------------Adverse reactions caused by Lipiodol include hypersensitivity
reactions, pulmonary embolism, pulmonary dysfunction, exacerbationof liver disease, procedural complications, abdominal pain, fever,nausea, vomiting, and thyroid dysfunction. (6.2)
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------------------------DRUG INTERACTIONS-------------------------Lipiodol may interfere with thyroid function testing and with radioactive
iodine uptake by the thyroid tissue during diagnostic or therapeutic
procedures. (7.1)-----------------USE IN SPECIFIC POPULATIONS------------------• Pregnancy: Consider thyroid function testing in pregnant
women and their infants if exposed to Lipiodol either before or
during pregnancy, if clinically indicated (8.1)• Lactation: Consider thyroid function testing in a breastfed
infant whose mother was exposed to Lipiodol or, if clinicallyindicated (8.2)
See 17 for PATIENT COUNSELING INFORMATION
Revised: 6/2020
6

FULL PRESCRIBING INFORMATION: CONTENTS*
1
INDICATIONS AND USAGE
2
DOSAGE AND ADMINISTRATION
2.1
Dosing Guidelines
2.2
Drug Handling
3
DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS5WARNINGS AND PRECAUTIONS
5.1
Pulmonary and Cerebral Embolism
5.2
Hypersensitivity Reactions
5.3
Exacerbation of Chronic Liver Disease
5.4
Thyroid Dysfunction

7

8Page 1 of 7

ADVERSE REACTIONS
6.2
Postmarketing Experience
DRUG INTERACTIONS
7.1
Interference with Iodine-Based Diagnostic Tests andIodine-Based Radiotherapy
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
8.2
Lactation
8.3
Female and Males of Reproductive Potential
8.4
Pediatric Use
8.5
Geriatric Use
8.6
Renal Impairment

10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics

12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the fullprescribing information are not listed.
______________________________________________________________________________________________________________
FULL PRESCRIBING INFORMATIONWARNING: FOR INTRALYMPHATIC, INTRAUTERINE AND SELECTIVE HEPATIC INTRA-ARTERIAL USE ONLY
Pulmonary and cerebral embolism can result from inadvertent intravascular injection or intravasation of Lipiodol.
Inject Lipiodol slowly with radiologic monitoring; do not exceed recommended dose (5.1).
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)2

DOSAGE AND ADMINISTRATION

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 thevolume of the uterine cavity, usually not exceeding 15 mL. A 24-hour image can be obtained if, after slow peritoneal spillage, theevaluation 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 tominimize 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 isevident. Limit the dose to only the quantity required for adequate visualization. The total dose of Lipiodol administered should
not exceed 20 mL.
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2.2 Drug Handling
Inspect Lipiodol visually for particulate matter and discoloration before administration. Do not use the solution if particulate matter ispresent 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.
3

DOSAGE FORMS AND STRENGTHS

Each milliliter of Lipiodol contains 480 mg/mL of Iodine organically combined with ethyl esters of fatty acids of poppy seed oil.
4

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, or within 30 days of curettage or conization. [seeUse 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.
5

WARNINGS AND PRECAUTIONS

5.1 Pulmonary 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 distresssyndrome and fatalities. Embolization of Lipiodol to brain and other major organs may occur. Avoid use of Lipiodol in patients withseverely 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 theprocedure when Lipiodol becomes visible in the thoracic duct or lymphatic obstruction is observed.
5.2 Hypersensitivity 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 otheriodinated 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 afteradministration. Observe patients for signs and symptoms of hypersensitivity reactions during and for at least 30 minutes following Lipiodol
administration.
5.3 Exacerbation of Chronic Liver Disease
Lipiodol hepatic intra-arterial administration can exacerbate the following conditions: portal hypertension and cause variceal bleeds due toobstruction 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.

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5.4 Thyroid 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.
6

ADVERSE REACTIONS

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 relationshipto 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 ClassEye disorders
General disorders and administration site
conditions
Immune system disorders
Nervous system disorders
Respiratory, thoracic and mediastinal disorders
Urinary system disorders

Adverse Reaction
retinal vein thrombosis
fever, pain, granuloma
hypersensitivity, anaphylactic reaction,
anaphylactoid reaction, cardiovascular reactions
cerebral embolism
pulmonary embolism, dyspnea, cough, acuterespiratory distress syndrome
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 ofmouth 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.
7

DRUG INTERACTIONS

7.1 Interference with Iodine-Based Diagnostic Tests and Iodine-Based Radiotherapy
Following Lipiodol administration, ethiodized oil remains in the body for several months. Ethiodized oil interferes with radioactive iodine
uptake by the thyroid for several weeks to months may impair visualization of thyroid scintigraphy and reduce effectiveness of iodine 131
treatment.
8

USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
Pregnancy Category C
Risk Summary
Hysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [seePage 4 of 7

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 settingwith 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 abackground risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk ofmajor 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, andimpaired 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 postprocedure 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.
8.2 Lactation
Risk Summary
Ethiodized oil is present in human milk.
There are no data on the effects of ethiodized oil on the breastfed infant, or effects on milk production, however, the use of Lipiodol may
increase the concentration of iodide in human milk and may interfere with the thyroid function of the breastfed infant. Consider thyroid
function testing in a breastfed infant whose mother was exposed to Lipiodol or if clinically indicated. The developmental and healthbenefits of breastfeeding should be considered along with the mother’s clinical need for Lipiodol and any potential adverse effects on thebreastfed child from Lipiodol or from the underlying maternal condition.
8.3 Females and Males of Reproductive potential
Pregnancy Testing
Confirm that the patient has a negative pregnancy test within 24 hours before Lipiodol administration for hysterosalpingography [seeDosage and Administration (2.1), Contraindications (4)].
8.4 Pediatric Use
For lymphography use a dose of 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. Administer the smallest possible amount of Lipiodol according to the anatomical area to be visualized.
Page 5 of 7

8.5 Geriatric Use
There are no studies conducted in geriatric patients.
8.6 Renal Impairment
Prior to an intra-arterial administration of Lipiodol screen all patients for renal dysfunction by obtaining history and/or laboratory tests.
Consider follow-up renal function assessments for patients with a history of renal dysfunction.
10 OVERDOSAGE
Overdose may lead to respiratory, cardiac or cerebral complications, which can potentially be fatal. Microembolisms to multiple organs
may occur more frequently after overdose. Promptly initiate symptomatic treatment and support of vital functions.
11 DESCRIPTION
Lipiodol, ethiodized oil injection, is a sterile injectable radio-opaque agent. Each milliliter contains 480 mg of Iodine organically combinedwith ethyl esters of fatty acids of poppy seed oil. The precise structure of Lipiodol is unknown.
Lipiodol is a sterile, clear, pale yellow to amber colored oil. Lipiodol has a viscosity of 34 – 70 mPa·s at 20°C, and a density of 1.28 g/cm3
at 20°C.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Lipiodol opacifies vessels and body structures in the path of the flow of the contrast medium, permitting visualization of the internal
structures.
12.2 Pharmacodynamics
Following administration of Lipiodol, the degree of enhancement is directly related to the local iodine content in the body structures to be
imaged.
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.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential, Lipiodol did not demonstrate mutagenic potential
in bacterial reverse mutation assays (in vitro), in a chromosomal aberration test in the mouse lymphoma assay (in vitro) and was negativein an in vivo micronucleus test in rats after intravenous injection of 479 mg I/kg.
16 HOW SUPPLIED/STORAGE AND HANDLING
Lipiodol is supplied in a box of one 10 mL ampoule, NDC 67684-1901-1.
Lipiodol is supplied in a box of one 10 mL vial, NDC 67684-1901-2.
Each vial is closed with a rubber stopper and sealed with an aluminum cap.
Store at controlled room temperature 15°-30°C (59°-86°F) [see USP, Controlled Room Temperature (CRT)].
Protect from light. Remove from carton only upon use.
17 PATIENT COUNSELING INFORMATION
Hypersensitivity Reactions
Advise the patient concerning the risk of hypersensitivity reactions that can occur both during and after Lipiodol administration. Advise
the patient to report any signs or symptoms of hypersensitivity reactions during the procedure and to seek medical attention for signs orPage 6 of 7

symptoms experienced after discharge [see Warnings and Precautions (5.2)].
Thyroid Dysfunction
Advise patients concerning the risk of hyper- or hypothyroidism flowing the use of Lipiodol due to ethiodized oil remaining in the bodyfor several months. Instruct patients to follow up with their physician if they become pregnant or develop any signs of thyroid
dysfunction in the months after administration [see Warnings and Precautions (5.4), Use in Specific Populations (8.1 and 8.3)].

Rx Only
Guerbet LLC
821 Alexander Road, Suite 204
Princeton, New Jersey 08540, USA
For further information or ordering, call
1-877-729-6679
Ampoules manufactured for Guerbet LLC by:
Jubilant HollisterStier General Partnership, Canada
Vials manufactured for Guerbet LLC by: Recipharm Monts, France

Revised 6/2020

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