MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. The iodine atoms in iohexol provide attenuation of X-rays in direct proportion to the concentration of iohexol. Since concentration changes over time, iohexol provides time-dependent image contrast which may assist in visualizing body structures.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term animal studies have not been performed with iohexol to evaluate carcinogenic potential. Iohexol was not genotoxic in series of studies, including the Ames test, the mouse lymphoma TK locus forward mutation assay, and mouse micronucleus assay. Iohexol did not impair the fertility of male or female rats when repeatedly administered at intravenous dosages up to g iodine/kg.

OVERDOSAGE SECTION.

10 OVERDOSAGE. 10.1 Intravascular Administration. The adverse effects of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular systems. The symptoms included: cyanosis, bradycardia, acidosis, pulmonary hemorrhage, convulsions, coma, and cardiac arrest. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy. Iohexol displays low affinity for serum or plasma proteins and is poorly bound to serum albumin and can be dialyzed.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 140 mgI/mL Bottle Label. NDC 0407-1401-5250 mLOMNIPAQUE(TM) (iohexol) Injection140 mgI/mLNOT FOR INTRATHECAL USEin +PLUSPAK(TM) (polymer bottle). PRINCIPAL DISPLAY PANEL 140 mgI/mL Bottle Label.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Lactation: lactating woman may pump and discard breast milk for 10 hours after OMNIPAQUE administration. (8.2). Lactation: lactating woman may pump and discard breast milk for 10 hours after OMNIPAQUE administration. (8.2). 8.1 Pregnancy. Risk SummaryHysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [see Contraindications (4)]. There are no data with iohexol use in pregnant women to inform any drug-associated risks. Iohexol crosses the placenta and reaches fetal tissues in small amounts (see Data). In animal reproduction studies, no developmental toxicity occurred with intravenous iohexol administration to rats and rabbits at doses up to 0.4 (rat) and 0.5 (rabbit) times the maximum recommended human intravenous dose (see Data ).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.. Data. Human DataLiterature reports show that intravenously administered iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth.. Animal DataIohexol was neither embryotoxic nor teratogenic in either rats or rabbits at the following dose levels tested: 1.0, 2.0, 4.0 iodine/kg in rats, administered intravenously to groups of 25 dams once daily during days through 15 of pregnancy; 0.3, 1.0, 2.5 iodine/kg in rabbits, administered intravenously to groups of 18 rabbits dosed once day during days through 18 of pregnancy.. 8.2 Lactation. Risk SummaryPublished literature reports that breast feeding after intravenous iohexol administration to the mother would result in the infant receiving an oral dose of approximately 0.7% of the maternal intravenous dose; however, lactation studies have not been conducted with oral, intrathecal, or intracavity administration of iohexol. There is no information on the effects of the drug on the breastfed infant or on milk production. Iodinated contrast agents are excreted unchanged in human milk in very low amounts with poor absorption from the gastrointestinal tract of breastfed infant. Exposure to iohexol to breastfed infant can be minimized by temporary discontinuation of breastfeeding (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for OMNIPAQUE and any potential adverse effects on the breastfed infant from OMNIPAQUE or from the underlying maternal condition.. Clinical Considerations Interruption of breastfeeding after exposure to iodinated contrast agents is not necessary because the potential exposure of the breastfed infant to iodine is small. However, lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hours (approximately elimination half-lives) after OMNIPAQUE administration to minimize drug exposure to breastfed infant.. 8.4 Pediatric Use. Intrathecal UseThe safety and effectiveness of OMNIPAQUE 180 have been established in pediatric patients weeks to 17 years of age for myelography (lumbar, thoracic, cervical, total columnar) and for CT (myelography, cisternography). Use of OMNIPAQUE 180 is supported by controlled clinical studies in adults for myelography, in addition to clinical studies in pediatric patients undergoing myelography. The safety and effectiveness of OMNIPAQUE 180 have not been established for intrathecal use in patient pediatric patients less than weeks of age. The safety and effectiveness of OMNIPAQUE 240 and 300 have not been established in pediatric patients for myelography (lumbar, thoracic, cervical, total columnar) and for CT (myelography, cisternography, or ventriculography).. Intravascular Use. Angiocardiography (Ventriculography, Pulmonary Arteriography, Venography, and Studies of the Collateral Arteries) and Aortography The safety and effectiveness of OMNIPAQUE 300 have been established in pediatric patients from birth to 17 years of age for angiocardiography (ventriculography) and of OMNIPAQUE 350 in pediatric patients from birth to 17 years of age for angiocardiography (ventriculography, pulmonary arteriography, venography, and studies of the collateral arteries) and aortography. Use of OMNIPAQUE 300 and 350 is supported by controlled clinical studies in adults for angiocardiography and aortography, in addition to controlled clinical studies in pediatric patients undergoing angiocardiography, including aortography. The safety and effectiveness of OMNIPAQUE 300 have not been established in pediatric patients for aortography.. Intra-arterial Digital Subtraction Angiography, Intravenous Digital Subtraction Angiography, Cerebral Arteriography, or Peripheral Arteriography and VenographyThe safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for intra-arterial digital subtraction angiography, intravenous digital subtraction angiography, cerebral arteriography, or peripheral arteriography and venography.. CT of the Head and BodyThe safety and effectiveness of OMNIPAQUE 240 and 300 have been established in pediatric patients from birth to 17 years of age for CT imaging of the head and body. Use of OMNIPAQUE 240 and 300 is supported by controlled clinical studies in adults for head and body CT, in addition to clinical studies in pediatric patients undergoing head CT and in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. The safety and effectiveness of OMNIPAQUE 350 have not been established in pediatric patients for CT imaging of the head and body.. UrographyThe safety and effectiveness of OMNIPQUE 300 have been established in pediatric patients from birth to 17 years of age for urography. Use of OMNIPAQUE 300 is supported by controlled clinical studies in adults for urography, in addition to controlled clinical studies in pediatric patients undergoing urography and clinical safety data in pediatric patients down to birth. Oral or Rectal Use. Undiluted OMNIPAQUE InjectionThe safety and effectiveness of OMNIPAQUE 180, 240, and 300 administered orally and rectally have been established in pediatric patients, from birth to 17 years of age for examination of the GI tract. Use of OMNIPAQUE 180, 240, and 300 administered orally and rectally is supported by controlled studies in adults for examination of the GI tract, in addition to clinical studies in pediatric patients undergoing examination of the GI tract.. Oral Use in Conjunction with Intravenous Use. Diluted OMNIPAQUE InjectionThe safety and effectiveness of OMNIPAQUE injection diluted to concentrations from to 21 mg iodine/mL administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen have been established in pediatric patients from birth to 17 years of age. Use is supported by clinical trials in adults, in addition to clinical studies in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. OMNIPAQUE Oral SolutionThe safety and effectiveness of OMNIPAQUE oral solution and 12 administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen in pediatric patients have been established in pediatric patients from birth to 17 years of age. Use is supported by the data establishing safety and effectiveness for OMNIPAQUE injection diluted and administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen in pediatric patients.. Intraarticular UseThe safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for arthrography.. Body Cavity UseOMNIPAQUE 240, 300, 350 diluted to concentrations from 50 mg iodine/mL to 100 mg iodine/mL is indicated for use in pediatric patients from birth to 17 years of age for voiding cystourethrography (VCU). The use for voiding cystourethrography is supported by clinical studies in 51 pediatric patients undergoing VCU. The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for ERCP, herniography, or hysterosalpingography.In general, the frequency of adverse reactions in pediatric patients was similar to that seen in adults [see Adverse Reactions (6.1)]. Pediatric patients at higher risk of experiencing adverse events during contrast-medium administration may include those having asthma, sensitivity to medication and/or allergens, congestive heart failure, serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to pediatric patients, including infants. Some patients were treated for hypothyroidism [see Adverse Reactions (6.2)].. 8.5 Geriatric Use. In clinical studies of OMNIPAQUE for CT, 52/299 (17%) of patients were 70 and over. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity Reactions: Life-threatening or fatal reactions can occur. Always have emergency equipment and trained personnel available. (5.3)Contrast Induced Acute Kidney Injury: Acute injury including renal failure can occur. Minimize dose and maintain adequate hydration to minimize risk. (5.4)Cardiovascular Reactions: Hemodynamic disturbances including shock and cardiac arrest may occur during or after administration. (5.5). Hypersensitivity Reactions: Life-threatening or fatal reactions can occur. Always have emergency equipment and trained personnel available. (5.3). Contrast Induced Acute Kidney Injury: Acute injury including renal failure can occur. Minimize dose and maintain adequate hydration to minimize risk. (5.4). Cardiovascular Reactions: Hemodynamic disturbances including shock and cardiac arrest may occur during or after administration. (5.5). 5.1 Risks Associated with Inadvertent Intrathecal Administration. OMNIPAQUE injection 140 and 350 are contraindicated for intrathecal use [see Contraindications (4) and Dosage and Administration (2.1) ]. Inadvertent intrathecal administration can cause death, convulsions/seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema.. 5.2 Risks Associated with Inadvertent Parenteral Administration. OMNIPAQUE oral solution and 12 are contraindicated for parenteral administration [see Contraindications (4) and Dosage and Administration (2.1)]. Adverse reactions such as hemolysis may occur if administered intravascularly. Do not administer OMNIPAQUE oral solution and 12 parenterally.. 5.3 Hypersensitivity Reactions. OMNIPAQUE can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock. Most severe reactions develop shortly after the start of the injection (within minutes), but reactions can occur up to hours later. There is an increased risk in patients with history of previous reaction to contrast agent, and known allergies (i.e., bronchial asthma, drug, or food allergies) or other hypersensitivities. Premedication with antihistamines or corticosteroids does not prevent serious life-threatening reactions, but may reduce both their incidence and severity.Obtain history of allergy, hypersensitivity, or hypersensitivity reactions to iodinated contrast agents and always have emergency resuscitation equipment and trained personnel available prior to OMNIPAQUE administration. Monitor all patients for hypersensitivity reactions.. 5.4 Contrast Induced Acute Kidney Injury. Acute kidney injury, including renal failure, may occur after parenteral administration of OMNIPAQUE. Risk factors include: pre-existing renal impairment, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma paraproteinaceous diseases, repetitive and/or large doses of an iodinated contrast agent.Use the lowest necessary dose of OMNIPAQUE in patients with renal impairment. Adequately hydrate patients prior to and following parenteral administration of OMNIPAQUE. Do not use laxatives, diuretics, or preparatory dehydration prior to OMNIPAQUE administration.. 5.5 Cardiovascular Adverse Reactions. Life-threatening or fatal cardiovascular reactions including hypotension, shock, cardiac arrest have occurred with the parenteral administration of OMNIPAQUE. Most deaths occur during injection or five to ten minutes later, with cardiovascular disease as the main aggravating factor. Cardiac decompensation, serious arrhythmias, and myocardial ischemia or infarction can occur during coronary arteriography and ventriculography.Based upon clinical literature reported deaths from the administration of iodinated contrast agents range from 6.6 per million (0.00066%) to in 10,000 (0.01%). Use the lowest necessary dose of OMNIPAQUE in patients with congestive heart failure and always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions.. 5.6 Thromboembolic Events. AngiocardiographySerious, rarely fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiocardiography procedures with both ionic and nonionic contrast media. During these procedures, increased thrombosis and activation of the complement system occurs. Risk factors for thromboembolic events include: length of procedure, catheter and syringe material, underlying disease state, and concomitant medications.To minimize thromboembolic events, use meticulous angiographic techniques, and minimize the length of the procedure. Avoid blood remaining in contact with syringes containing iodinated contrast agents, which increases the risk of clotting. Avoid angiocardiography in patients with homocystinuria because of the risk of inducing thrombosis and embolism.. 5.7 Extravasation and Injection Site Reactions Extravasation of OMNIPAQUE during intravascular injection may cause tissue necrosis and/or compartment syndrome, particularly in patients with severe arterial or venous disease. Ensure intravascular placement of catheters prior to injection. Monitor patients for extravasation and advise patients to seek medical care for progression of symptoms.. 5.8 Thyroid Storm in Patients with Hyperthyroidism Thyroid storm has occurred after the intravascular use of iodinated contrast agents in patients with hyperthyroidism, or with an autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of OMNIPAQUE.. 5.9 Hypertensive Crisis in Patients with Pheochromocytoma Hypertensive crisis has occurred after the use of iodinated contrast agents in patient with pheochromocytoma. Monitor patients when administering OMNIPAQUE intravascularly if pheochromocytoma or catecholamine-secreting paragangliomas are suspected. Inject the minimum amount of contrast necessary, assess the blood pressure throughout the procedure, and have measures for treatment of hypertensive crisis readily available.. 5.10 Sickle Cell Crisis in Patients with Sickle Cell Disease. Iodinated contrast agents when administered intravascularly may promote sickling in individuals who are homozygous for sickle cell disease. Hydrate patients prior to and following OMNIPAQUE administration and use OMNIPAQUE only if the necessary imaging information cannot be obtained with alternative imaging modalities.. 5.11 Severe Cutaneous Adverse Reactions. Severe cutaneous adverse reactions (SCAR) may develop from hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agents; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering OMNIPAQUE to patients with history of severe cutaneous adverse reaction to OMNIPAQUE.

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. OMNIPAQUE (iohexol) injection is nonionic, x-ray or radiographic contrast medium for intrathecal, intravenous, oral, rectal and body cavity use. OMNIPAQUE oral solution is for oral use only.OMNIPAQUE injection and OMNIPAQUE oral solution are both provided as sterile, pyrogen-free and gluten-free solutions. OMNIPAQUE injection and OMNIPAQUE oral solution are colorless to pale yellow solutions. The chemical name of iohexol is Bis(2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl)-acetamido]-2,4,6- triiodoisophthalamide with molecular weight of 821.14 (iodine content 46.36%). Iohexol has the following structural formula:OMNIPAQUE injection is available in five strengths: OMNIPAQUE 140 mg iodine/mL (302 mg of iohexol/mL): Each mL contains 140 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumOMNIPAQUE 180 mg iodine/mL (388 mg of iohexol/mL): Each mL contains 180 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumOMNIPAQUE 240 mg iodine/mL (518 mg of iohexol/mL): Each mL contains 240 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumOMNIPAQUE 300 mg iodine/mL (647 mg of iohexol/mL): Each mL contains 300 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumOMNIPAQUE 350 mg iodine/mL (755 mg of iohexol/mL): Each mL contains 350 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumOMNIPAQUE oral solution is available in two strengths:OMNIPAQUE oral solution mg iodine/mL (19 mg of iohexol/mL): Each mL contains mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumOMNIPAQUE oral solution 12 mg iodine/mL (26 mg of iohexol/mL): Each mL contains 12 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodiumThe pH is adjusted between 6.8 and 7.7 with hydrochloric acid or sodium hydroxide. OMNIPAQUE injection and OMNIPAQUE oral solution are sterilized by autoclaving and contain no preservatives.. OMNIPAQUE 140 mg iodine/mL (302 mg of iohexol/mL): Each mL contains 140 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. OMNIPAQUE 180 mg iodine/mL (388 mg of iohexol/mL): Each mL contains 180 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. OMNIPAQUE 240 mg iodine/mL (518 mg of iohexol/mL): Each mL contains 240 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. OMNIPAQUE 300 mg iodine/mL (647 mg of iohexol/mL): Each mL contains 300 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. OMNIPAQUE 350 mg iodine/mL (755 mg of iohexol/mL): Each mL contains 350 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. OMNIPAQUE oral solution mg iodine/mL (19 mg of iohexol/mL): Each mL contains mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. OMNIPAQUE oral solution 12 mg iodine/mL (26 mg of iohexol/mL): Each mL contains 12 mg organically bound iodine, 1.21 mg tromethamine and 0.1 mg edetate calcium disodium. 11.2 Physical Characteristics. OMNIPAQUE injection and OMNIPAQUE oral solution have the following physical properties:PresentationConcentration(mg iodine/mL)OsmolalityBy vapor-pressure osmometry. (mOsmol/kg water)Absolute Viscosity(cP)Specific Gravity20C37C37COMNIPAQUE 1401403222.31.51.164OMNIPAQUE 1801804083.12.01.209OMNIPAQUE 2402405205.83.41.280OMNIPAQUE 30030067211.86.31.349OMNIPAQUE 35035084420.410.41.406OMNIPAQUE oral solution 99381.10.81.011OMNIPAQUE oral solution 1212451.10.81.014OMNIPAQUE 140, OMNIPAQUE 180, OMNIPAQUE 240, OMNIPAQUE 300, and OMNIPAQUE 350 have osmolalities from approximately 1.1 to 3.0 times that of plasma (285 mOsmol/kg water) or cerebrospinal fluid (301 mOsmol/kg water) as shown in the above table and are hypertonic under conditions of use.OMNIPAQUE oral solution and OMNIPAQUE oral solution 12 are hypotonic under conditions of use (see table above).. Chemical Structure.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following clinically significant adverse reactions are described elsewhere in the labeling:Risks Associated with Inadvertent Intrathecal Administration [see Warnings and Precautions (5.1)]Risks Associated with Inadvertent Parenteral Administration [see Warnings and Precautions (5.2)]Hypersensitivity Reactions [see Warnings and Precautions (5.3)]Contrast Induced Kidney Injury [see Warnings and Precautions (5.4)]Cardiovascular Adverse Reactions [see Warnings and Precautions (5.5)]Thromboembolic Events see Warnings and Precautions (5.6) Severe Cutaneous Reactions [see Warnings and Precautions (5.11)]. Risks Associated with Inadvertent Intrathecal Administration [see Warnings and Precautions (5.1)]. Risks Associated with Inadvertent Parenteral Administration [see Warnings and Precautions (5.2)]. Hypersensitivity Reactions [see Warnings and Precautions (5.3)]. Contrast Induced Kidney Injury [see Warnings and Precautions (5.4)]. Cardiovascular Adverse Reactions [see Warnings and Precautions (5.5)]. Thromboembolic Events see Warnings and Precautions (5.6) . Severe Cutaneous Reactions [see Warnings and Precautions (5.11)]. Most common adverse reactions (incidence >= 1.0%) in adult patients after OMNIPAQUE administration. (6.1) Intrathecal: Headaches, Pain including backache, neckache, stiffness and neuralgia, nausea, vomiting and dizzinessIntravascular: Pain, vision abnormalities (including blurred vision and photomas), headache, taste perversion, arrhythmias including premature ventricular contractions (PVCs) and premature atrial contractions (PACs), angina/chest pain, nauseaOral: Diarrhea, nausea, vomiting, abdominal pain, flatulence, headacheBody Cavity: Pain, swelling and heat sensationPost-marketing adverse reactions (6.2): Hypersensitivity and manifestations like rash, pruritus, urticaria, and dyspnea, in addition chest pain, and swelling.To report SUSPECTED ADVERSE REACTIONS, contact GE Healthcare at 1-800-654-0118 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. Intrathecal: Headaches, Pain including backache, neckache, stiffness and neuralgia, nausea, vomiting and dizziness. Intravascular: Pain, vision abnormalities (including blurred vision and photomas), headache, taste perversion, arrhythmias including premature ventricular contractions (PVCs) and premature atrial contractions (PACs), angina/chest pain, nausea. Oral: Diarrhea, nausea, vomiting, abdominal pain, flatulence, headache. Body Cavity: Pain, swelling and heat sensation. 6.1Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.. Intrathecal Administration. AdultsTABLE 23 ADVERSE REACTIONS INTRATHECAL ADMINISTRATIONIn controlled clinical studies involving 1531 patients using OMNIPAQUE the following adverse reactions were reported:System Organ ClassAdverse ReactionIncidenceNervous SystemHeadaches18%Musculoskeletal and Connective TissuePain including backache, neckache, stiffness and neuralgia8%Gastrointestinal SystemNausea6%Vomiting3%Nervous SystemDizziness2%Other ReactionsFeeling of heaviness, hypotension, hypertonia, sensation of heat, sweating, vertigo, loss of appetite, drowsiness, hypertension, photophobia, tinnitus, neuralgia, paresthesia, difficulty in micturition, and neurological changes<0.1%. Pediatric PatientsTABLE 24 ADVERSE REACTIONS INTRATHECAL ADMINISTRATIONIn clinical studies involving 152 patients for pediatric myelography by lumbar puncture, adverse events following the use of OMNIPAQUE 180 were generally similar to those reported in adults.ProcedureSystem Organ ClassAdverse ReactionIncidenceMyelography by Lumbar PunctureNervous SystemHeadache9%Gastrointestinal SystemVomiting6%Musculoskeletal and Connective TissueBackache1.3%Other Reactions All were transient and mild with no clinical sequelae. Fever<0.7%HivesStomachacheVisual HallucinationNeurological Changes. Intravascular AdministrationImmediately following intravascular injection of contrast medium, transient sensation of mild warmth is not unusual. Warmth is less frequent with OMNIPAQUE than with ionic contrast media.. AdultsIn controlled clinical studies involving 1485 patients, the following adverse reactions occurred (Table 25).TABLE 25 ADVERSE REACTIONS INTRAVASCULAR ADMINISTRATIONSystem Organ ClassAdverse ReactionIncidenceCardiovascular SystemArrhythmias including PVCs and PACs (2%),2%Hypotension0.7%Others including cardiac failure, asystole, bradycardia, tachycardia, and vasovagal reaction<= 0.3%Nervous SystemVertigo (including dizziness and lightheadedness)0.5%Pain3%Vision Abnormalities (including blurred vision and photomas)2%Taste Perversion1%Other ReactionsAnxiety, fever, motor and speech dysfunction, convulsion, paresthesia, somnolence, stiff neck, hemiparesis, syncope, shivering, transient ischemic attack, cerebral infarction, and nystagmusIndividual incidence of 0.3% or lessRespiratory SystemDyspnea, rhinitis, coughing, and laryngitisIndividual incidence of 0.2% or lessGastrointestinal SystemNausea2%Vomiting0.7%Others including diarrhea, dyspepsia, cramp, and dry mouthIndividual incidence of less than 0.1%.Skin and Subcutaneous TissuesUrticaria0.3%Purpura0.1%Abscess0.1%Pruritus0.1%. Pediatric PatientsIn controlled clinical studies involving 391 patients for pediatric angiocardiography, urography, and CT head imaging, adverse reactions following the use of OMNIPAQUE 240, 300, and 350 were generally similar in quality and frequency to those reported in adults (Table 26).TABLE 26 ADVERSE REACTIONS INTRAVASCULAR ADMINISTRATIONSystem Organ ClassAdverse ReactionIncidenceCardiovascular SystemVentricular Tachycardia0.5%2:1 Heart Block0.5%Hypertension0.3%Anemia0.3%General Disorders and Administration Site ConditionsPain0.8%Fever0.5%Nervous SystemConvulsion0.3%Taste Abnormality0.5%Respiratory SystemCongestion0.3%Apnea0.3%Gastrointestinal SystemNausea1%Vomiting2%Endocrine SystemHypoglycemia0.3%Skin and Subcutaneous TissueRash0.3%. Oral Administration for Examination of the Gastrointestinal Tract. AdultsNausea, vomiting, and diarrhea have been most frequently reported following orally administered undiluted OMNIPAQUE for radiographic examination of the gastrointestinal tract. In controlled clinical studies involving 54 adult patients for oral radiographic examination of the gastrointestinal tract using undiluted OMNIPAQUE 350 the following adverse reactions were reported (Table 27).TABLE 27 ADVERSE REACTIONS ORAL ADMINISTRATION OF UNDILUTED OMNIPAQUE 350System Organ ClassAdverse ReactionIncidenceGastrointestinal SystemDiarrhea42%Nausea15%Vomiting11%Abdominal Pain7%Flatulence2%Nervous SystemHeadache2%. Pediatrics Patients (Oral and Rectal Administration)In clinical studies involving 58 pediatric patients, the adverse reactions were found to mostly affect the gastrointestinal system with diarrhea (36%), vomiting (9%), nausea (5%) and abdominal pain (2%). However, fever (5%), hypotension (2%) and urticaria (2%) were also reported.. Oral Administration for CT of the Abdomen in Conjunction with Intravenous Administration. AdultsIn controlled clinical study involving 44 adult patients receiving oral administration of diluted OMNIPAQUE (4-9 mg iodine/mL) in conjunction with intravenously injected OMNIPAQUE 300 for CT examination of the abdomen, adverse reactions were limited to single report of vomiting.. Pediatric PatientsIn clinical studies involving 69 pediatric patients receiving oral administration of diluted OMNIPAQUE (9-29 mg iodine/mL) in conjunction with intravenously administered OMNIPAQUE 240 and OMNIPAQUE 300 for CT examination of the abdomen, adverse reactions were limited to single report of vomiting (1.4%).. Body Cavity Use. Adults Arthrography: In controlled clinical studies involving 285 adult patients for various body cavity examinations using OMNIPAQUE 240, 300 and 350, the most frequent adverse reactions were administration site reactions: pain 26% and swelling 22%, were exclusively reported for arthrography and were generally related to the procedure rather than the contrast medium. Patients also experienced heat (7%). All other adverse reaction occurred at rate less than or equal to 1%. Pediatric PatientsNo adverse reactions associated with the use of OMNIPAQUE for VCU procedures were reported in 51 pediatric patients studied.. 6.2Post-marketing Experience. The following additional reactions listed by indication have been identified during post-approval use of OMNIPAQUE. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.. GeneralImmune System Disorders: Hypersensitivity reactions, anaphylactic or anaphylactoid reactions, anaphylactic or anaphylactoid shock including life-threatening or fatal anaphylaxis.General Disorders and Administration Site Conditions: Pyrexia, chills, pain and discomfort, asthenia, administration site conditions including extravasation.. Intrathecal AdministrationNervous System Disorders: Meningism, aseptic meningitis, seizures or status epilepticus, disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia.Musculoskeletal and Connective Tissue Disorders: Pain, muscle spasms or spasticity.Psychiatric Disorders: Confusional state, agitation, anxiety.Eye Disorders: Transient visual impairment including cortical blindness.Renal Reactions: Acute kidney injury.. Intravascular AdministrationCardiovascular Disorders: Severe cardiac complications (including cardiac arrest, cardiopulmonary arrest), shock, peripheral vasodilatation, palpitations, vasospasm including spasm of coronary arteries, myocardial infarction, syncope, cyanosis, pallor, flushing, chest pain.Hemodynamic Reactions: Vasospasm and thrombophlebitis following intravenous injection.Blood and Lymphatic System Disorders: Neutropenia. Nervous System Disorders: Disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia.Psychiatric Disorders: Confusional state, agitation.Eye Disorders: Eye irritation or itchiness, periorbital edema, ocular or conjunctival hyperemia, lacrimation.Renal Reactions: Acute kidney injury, toxic nephropathy (CIN), transient proteinuria, oliguria or anuria, increased serum creatinine.Gastrointestinal Disorders: Abdominal pain, pancreatitis aggravated, salivary gland enlargement.Endocrine Reactions: Hyperthyroidism. Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to adult and pediatric patients, including infants. Some patients were treated for hypothyroidism.Respiratory; Thoracic, and Mediastinal Disorders: Respiratory distress, respiratory failure, pulmonary edema, bronchospasm, laryngospasm, throat irritation, throat tightness, laryngeal edema, wheezing, chest discomfort, asthmatic attack.Skin and Subcutaneous Tissue Disorders: Contrast media reactions range from mild (e.g. pleomorphic rashes, drug eruption, erythema and skin discoloration, blisters, hyperhidrosis, angioedema, localized areas of edema) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), bullous or exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)].. Oral AdministrationGastrointestinal Disorders: Dysphagia, abdominal pain.. Body Cavity AdministrationGastrointestinal Disorders: Pancreatitis.Musculoskeletal and Connective Tissue Disorders: Arthritis (arthrography).Hysterosalpingography: Injection of OMNIPAQUE for hysterosalpingography is associated with immediate, transient pain. Monitor injection pressure and volume instilled to minimize pain and to avoid disruptive distention of the uterus and fallopian tubes. Fluoroscopic monitoring is recommended. Nervous system: Pain (49%), somnolence and fever each with an individual incidence of 3%. Gastrointestinal system: Nausea (3%).

BOXED WARNING SECTION.

WARNING: RISKS WITH INADVERTENT INTRATHECAL ADMINISTRATIONOMNIPAQUE injection, 140 and 350 mg iodine/mL. See full prescribing information for complete boxed warning. Inadvertent intrathecal administration may cause death, convulsions/seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema (4, 5.1). WARNING: RISKS WITH INADVERTENT INTRATHECAL ADMINISTRATION OF OMNIPAQUE injection 140 and 350 mg iodine/mL. See full prescribing information for complete boxed warning.Inadvertent intrathecal administration may cause death, convulsions/seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema (4, 5.1).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term animal studies have not been performed with iohexol to evaluate carcinogenic potential. Iohexol was not genotoxic in series of studies, including the Ames test, the mouse lymphoma TK locus forward mutation assay, and mouse micronucleus assay. Iohexol did not impair the fertility of male or female rats when repeatedly administered at intravenous dosages up to g iodine/kg.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. The iodine atoms in iohexol provide attenuation of X-rays in direct proportion to the concentration of iohexol. Since concentration changes over time, iohexol provides time-dependent image contrast which may assist in visualizing body structures. 12.2 Pharmacodynamics. Intrathecal Administration The initial concentration and volume of the contrast medium, in conjunction with patient manipulation and the volume of cerebrospinal fluid (CSF) into which the contrast medium is placed, will determine the extent of the contrast that can be achieved. Following intrathecal injection in conventional radiography, OMNIPAQUE 180, 240, and 300 will continue to provide contrast for at least 30 minutes. Slow diffusion of iohexol takes place throughout the CSF with subsequent absorption into the bloodstream. At approximately hour following injection, contrast will no longer be sufficient for conventional myelography.After administration into the lumbar subarachnoid space, computerized tomography shows the presence of contrast medium in the thoracic region in about hour, in the cervical region in about hours, and in the basal cisterns in to hours.. Intravascular AdministrationFollowing intravascular administration of OMNIPAQUE, the degree of contrast enhancement is directly related to the iodine concentration of an administered dose; peak iodine blood concentrations occur immediately (15 seconds to 120 seconds) following rapid intravenous injection. The time to maximum contrast enhancement can vary, depending on the organ, from the time that peak blood iodine concentrations are reached to one hour after intravenous bolus administration. When delay between peak blood iodine concentrations and peak contrast is present, it suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing agent within the lesion and outside the blood pool. Oral Administration Orally administered OMNIPAQUE produces visualization of the gastrointestinal tract. Less than 1% of orally administered iohexol is recovered in the urine, suggesting minimal amounts are absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction.. Intraarticular AdministrationVisualization of the joint spaces can be accomplished by direct injection of contrast medium. For intraarticular cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation.. Body Cavity AdministrationFor most body cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation. Examinations of the uterus (hysterosalpingography) and bladder (voiding cystourethrography) involve the almost immediate drainage of contrast medium from the cavity upon conclusion of the radiographic procedure.. 12.3 Pharmacokinetics. Following the intravenous administration of iohexol (between 500 mg iodine/kg to 1500 mg iodine/kg) to 16 adult human subjects, apparent first-order terminal elimination half-life was 12.6 hrs and total body clearance was 131 (98-165) mL/min. Clearance was not dose dependent.. AbsorptionAs evidenced by the amount recovered in urine, <1% of orally administered iohexol is absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction.. DistributionIn 16 adult subjects (receiving between 500 mg iodine/kg to 1500 mg iodine/kg intravenous iohexol) the plasma volume of distribution was165 (108-219) mL/kg.In five adult patients receiving 16 mL to 18 mL of OMNIPAQUE (180 mg iodine/mL) by lumbar intrathecal injection the plasma volume of distribution was 559 (350-849) mL/kg.. Elimination. MetabolismNo significant metabolism, deiodination or biotransformation occurs.. ExcretionFollowing intravascular or intrathecal administration, iohexol is excreted unchanged by glomerular filtration. Approximately 90% of the intravenously injected iohexol dose is excreted within the first 24 hours. Following intravascular administration, peak urine concentration occurs in the first hour after injection.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. OMNIPAQUE 140 and OMNIPAQUE 350 are contraindicated for intrathecal use [see Warnings and Precautions (5.1)]OMNIPAQUE oral solution and 12 are contraindicated for parenteral administration [see Warnings and Precautions (5.2)] OMNIPAQUE body cavity 240 and 300 for hysterosalpingography is contraindicated during pregnancy or suspected pregnancy, menstruation or when menstruation is imminent, within months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract including the external genitalia, and when reproductive tract neoplasia is known or suspected because of the risk of peritoneal spread of neoplasm.. OMNIPAQUE 140 and OMNIPAQUE 350 are contraindicated for intrathecal use [see Warnings and Precautions (5.1)]. OMNIPAQUE oral solution and 12 are contraindicated for parenteral administration [see Warnings and Precautions (5.2)] OMNIPAQUE body cavity 240 and 300 for hysterosalpingography is contraindicated during pregnancy or suspected pregnancy, menstruation or when menstruation is imminent, within months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract including the external genitalia, and when reproductive tract neoplasia is known or suspected because of the risk of peritoneal spread of neoplasm.. OMNIPAQUE injection 140 and 350 are contraindicated for Intrathecal use 4 OMNIPAQUE oral solution and 12 are contraindicated for parenteral use 4 OMNIPAQUE body cavity 240 and 300 for hysterosalpingography is contraindicated during pregnancy (or suspected pregnancy), menstruation (or when menstruation is imminent), within months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract, including the external genitalia, and when reproductive tract neoplasia is known or suspected. (4) OMNIPAQUE injection 140 and 350 are contraindicated for Intrathecal use 4 . OMNIPAQUE oral solution and 12 are contraindicated for parenteral use 4 . OMNIPAQUE body cavity 240 and 300 for hysterosalpingography is contraindicated during pregnancy (or suspected pregnancy), menstruation (or when menstruation is imminent), within months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract, including the external genitalia, and when reproductive tract neoplasia is known or suspected. (4).

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. The concentration and volume required will depend on the indication, size and condition of the patient, and the equipment and imaging technique used. For CT of the head and body, OMNIPAQUE may be used with an automated contrast injection system or contrast media management system cleared for use with OMNIPAQUE. See full prescribing information for complete dosing information (2).. 2.1Important Dosage and Administration Instructions. OMNIPAQUE 140, 180, 240, 300 and 350 are indicated for intravascular, oral, rectal, intraarticular, and body cavity administration. OMNIPAQUE 180, 240, and 300 are indicated for intrathecal administration [see Boxed Warning, Contraindications (4), Warnings and Precautions (5.1)]. Use sterile technique for all handling and administration of OMNIPAQUE for intravascular, intrathecal, intraarticular, and body cavity administration.OMNIPAQUE oral solution and 12 are indicated for oral use only see Contraindications (4) and Warnings and Precautions (5.2) ]. Do not use if tamper-evident ring is broken or missing.OMNIPAQUE injection may be administered at either body (37C, 98.6F) or room temperature (20 to 25C, 68 to 77F). Inspect OMNIPAQUE injection for particulate matter or discoloration before administration, whenever solution and container permit. Do not administer if OMNIPAQUE injection contains particulate matter or is discolored.Do not mix OMNIPAQUE injection with, or inject in intravenous lines containing, other drugs or total nutritional admixtures.Use the lowest dose necessary to obtain adequate visualization.Individualize the volume, strength, and rate of administration of OMNIPAQUE injection. Consider factors such as age, body weight, vessel size, blood flow rate within the vessel, anticipated pathology, degree and extent of opacification required, structures or area to be examined, disease processes affecting the patient, and equipment and technique to be employed.Avoid extravasation when administering OMNIPAQUE injection intravascularly, especially in patients with severe arterial or venous disease [see Warnings and Precautions (5.6)]. Hydrate patients before and after intravascular administration of OMNIPAQUE injection [see Warnings and Precautions (5.4)]. Each bottle of OMNIPAQUE injection and oral solution is intended for one procedure only. Discard any unused portion.. OMNIPAQUE 140, 180, 240, 300 and 350 are indicated for intravascular, oral, rectal, intraarticular, and body cavity administration. OMNIPAQUE 180, 240, and 300 are indicated for intrathecal administration [see Boxed Warning, Contraindications (4), Warnings and Precautions (5.1)]. Use sterile technique for all handling and administration of OMNIPAQUE for intravascular, intrathecal, intraarticular, and body cavity administration.. OMNIPAQUE oral solution and 12 are indicated for oral use only see Contraindications (4) and Warnings and Precautions (5.2) ]. Do not use if tamper-evident ring is broken or missing.. OMNIPAQUE injection may be administered at either body (37C, 98.6F) or room temperature (20 to 25C, 68 to 77F). Inspect OMNIPAQUE injection for particulate matter or discoloration before administration, whenever solution and container permit. Do not administer if OMNIPAQUE injection contains particulate matter or is discolored.. Do not mix OMNIPAQUE injection with, or inject in intravenous lines containing, other drugs or total nutritional admixtures.. Use the lowest dose necessary to obtain adequate visualization.. Individualize the volume, strength, and rate of administration of OMNIPAQUE injection. Consider factors such as age, body weight, vessel size, blood flow rate within the vessel, anticipated pathology, degree and extent of opacification required, structures or area to be examined, disease processes affecting the patient, and equipment and technique to be employed.. Avoid extravasation when administering OMNIPAQUE injection intravascularly, especially in patients with severe arterial or venous disease [see Warnings and Precautions (5.6)]. Hydrate patients before and after intravascular administration of OMNIPAQUE injection [see Warnings and Precautions (5.4)]. Each bottle of OMNIPAQUE injection and oral solution is intended for one procedure only. Discard any unused portion.. 2.2Intrathecal Dosage and Administration. Rate of injection: Injection should be made slowly over to minutesRepeat procedures: If sequential or repeat examinations are required, suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body; at least 48 hours should be allowed before repeat examination; however, whenever possible, days to days is recommended.If computerized tomographic (CT) myelography follows myelography, delay imaging several hours to allow the degree of contrast to decrease.TABLE - INTRATHECAL ADULTSThe usual recommended total doses for use in lumbar, thoracic, cervical, and total columnar myelography in adults are 1,200 mg iodine to 3,100 mg iodine (see below).STUDY TYPEINJECTION TYPECONCENTRATION(mg iodine/mL)VOLUME(mL) total dose of 3,100 mg iodine or concentration of 300 mg iodine/mL should not be exceeded in adults.LUMBAR MYELOGRAPHYLUMBAROMNIPAQUE 180OMNIPAQUE 24010 to 177 to 12.5THORACIC MYELOGRAPHYLUMBARCERVICALOMNIPAQUE 240OMNIPAQUE 3006 to 12.56 to 10CERVICAL MYELOGRAPHYLUMBAROMNIPAQUE 240OMNIPAQUE 3006 to 12.56 to 10CERVICAL MYELOGRAPHYC1-2OMNIPAQUE 180OMNIPAQUE 240OMNIPAQUE 3007 to 106 to 12.54 to 10TOTAL COLUMNAR MYELOGRAPHYLUMBAROMNIPAQUE 240OMNIPAQUE 3006 to 12.56 to 10TABLE - INTRATHECAL PEDIATRICSThe usual recommended total doses for lumbar, thoracic, cervical, and/or total columnar myelography by lumbar puncture in children are 360 mg iodine to 2700 mg iodine (see below). Actual volumes administered depend largely on patient age and the following guidelines are recommended.AGESTUDY TYPEINJECTION TYPECONCENTRATION(mg iodine/mL)VOLUME(mL)A total dose of 2,700 mg iodine or concentration of 180 mg iodine/mL should not be exceeded in single myelographic examination in pediatrics.0 up to mos.LUMBAR, THORACIC, CERVICAL AND/OR TOTAL COLUMNAR MYELOGRAPHYLUMBAR PUNCTUREOMNIPAQUE 1802 to 43 up to 36 mos.OMNIPAQUE 1804 to 83 up to yrs.OMNIPAQUE 1805 to 107 up to 13 yrs.OMNIPAQUE 1805 to 1213 to 18 yrs.OMNIPAQUE 1806 to 15. Rate of injection: Injection should be made slowly over to minutes. Repeat procedures: If sequential or repeat examinations are required, suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body; at least 48 hours should be allowed before repeat examination; however, whenever possible, days to days is recommended.. If computerized tomographic (CT) myelography follows myelography, delay imaging several hours to allow the degree of contrast to decrease.. 2.3Intravascular Dosage and Administration. Intra-arterial ProceduresTABLE ANGIOCARDIOGRAPHIC PROCEDURESPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 350VENTRICULOGRAPHYThe recommended single dose is 40 mL (Range of 30 mL to 60 mL) May be combined with selective coronary arteriographySELECTIVE CORONARY ARTERIOGRAPHYThe recommended single dose is mL (Range of mL to 14 mL)Doses may be repeated as necessary.Maximum volume with multiple injections should not exceed 250 mL.PediatricsOMNIPAQUE 300VENTRICULOGRAPHYThe recommended single dose is 1.75 mL/kg (Range of 1.5 mL/kg to mL/kg) May be repeated as necessaryMaximum dose with multiple injections should not exceed mL/kg up to total volume of 291 mL.OMNIPAQUE 350VENTRICULOGRAPHYRecommended single dose is 1.25 mL/kg (Range of mL/kg to 1.5 mL/kg). May be repeated as necessary Maximum dose with multiple injections should not exceed mL/kg up to total volume of 250 mL. PULMONARY ANGIOGRAPHY (PULMONARY ARTERIOGRAPHY AND/OR PULMONARY VENOGRAPHY) The recommended single dose is mL/kg.TABLE AORTOGRAPHYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 300 and 350AORTOGRAPHY AND SELECTIVE VISCERAL ARTERIOGRAPHYThe recommended single dose is: 50 mL to 80 mL for the aorta (aortic arch, ascending aorta)30 mL to 60 mL for abdominal aorta and its branches (celiac, mesenteric, hepatic and splenic arteries)5 mL to 15 mL for renal arteriesInjections may be repeated if indicated, but the total volume should not exceed: 290 mL of OMNIPAQUE 300250 mL of OMNIPAQUE 350 OMNIPAQUE 350AORTIC ROOT AND ARCH STUDY WHEN USED ALONEThe recommended single dose is 50 mL (Range of 20 mL to 75 mL)PediatricsOMNIPAQUE 350AORTOGRAPHY (AORTIC ROOT, AORTIC ARCH, AND DESCENDING AORTA)The recommended single dose is mL/kg. May be repeated as necessaryMaximum dose should not exceed mL/kg up to total volume of 250 mL.TABLE CEREBRAL ARTERIOGRAPHYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 300Single dose for cerebral arteriography is as follows: Common carotid artery (6 mL to 12 mL)Internal carotid artery (8 mL to 10 mL)External carotid artery (6 mL to mL)Vertebral artery (6 mL to 10 mL) TABLE INTRA-ARTERIAL DIGITAL SUBTRACTION ANGIOGRAPHY HEAD, NECK, ABDOMINAL, RENAL AND PERIPHERAL VESSELSPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)Mechanical or hand injection can be used to administer one or more bolus intra-arterial injections of OMNIPAQUE 140.AdultsOMNIPAQUE 140ARTERIESVOLUME/INJECTION (mL)RATE OF INJECTION(mL/sec)Aorta20 to 458 to 20Carotid5 to 103 to 6Femoral9 to 203 to 6Vertebral4 to 102 to 8Renal6 to 123 to 6Other branches of aorta (includes subclavian, axillary, innominate and iliac)8 to 253 to 10TABLE PERIPHERAL ARTERIOGRAPHYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 300 and 350The recommended dose for use in peripheral angiography is as follows:Aortofemoral runoffs: 30 mL to 90 mL of OMNIPAQUE 30020 mL to 70 mL of OMNIPAQUE 350Selective arteriograms: 10 mL to 60 mL of OMNIPAQUE 30010 mL to 30 mL of OMNIPAQUE 350 The recommended single dose is 40 mL (Range of 30 mL to 60 mL) May be combined with selective coronary arteriography. The recommended single dose is mL (Range of mL to 14 mL). May be repeated as necessary. May be repeated as necessary. 50 mL to 80 mL for the aorta (aortic arch, ascending aorta). 30 mL to 60 mL for abdominal aorta and its branches (celiac, mesenteric, hepatic and splenic arteries). mL to 15 mL for renal arteries. 290 mL of OMNIPAQUE 300. 250 mL of OMNIPAQUE 350. May be repeated as necessary. Common carotid artery (6 mL to 12 mL). Internal carotid artery (8 mL to 10 mL). External carotid artery (6 mL to mL). Vertebral artery (6 mL to 10 mL). 30 mL to 90 mL of OMNIPAQUE 300. 20 mL to 70 mL of OMNIPAQUE 350. 10 mL to 60 mL of OMNIPAQUE 300. 10 mL to 30 mL of OMNIPAQUE 350. Intravenous ProceduresTABLE PERIPHERAL VENOGRAPHY (PHLEBOGRAPHY)PATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 240 and 300The recommended dose (per leg) is: 20 mL to 150 mL of OMNIPAQUE 24040 mL to 100 mL of OMNIPAQUE 300 TABLE EXCRETORY UROGRAPHYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 300 and 350The recommended dose is: 0.6 mL/kg to 1.2 mL/kg body weight PediatricsOMNIPAQUE 300Dose ranging from 0.5 mL/kg to mL/kg of body weight: The usual dose for children is mL/kg to 1.5 mL/kg.The total administered dose should not exceed mL/kg. TABLE 10 DIGITAL SUBTRACTION ANGIOGRAPHY HEAD, NECK, ABDOMINAL, RENAL AND PERIPHERAL VESSELSPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)RATE OF INJECTION(mL/sec)AdultsOMNIPAQUE 350The usual dose for the intravenous digital technique is 30 mL to 50 mL.Frequently three or more doses may be required, up to total volume not to exceed 250 mL7.5 mL/second to 30 mL/second using pressure injectorTABLE 11 CT SCANNING OF THE HEAD AND BODYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUMEOMNIPAQUE may be used with an automated contrast injection system or contrast management system cleared for use with OMNIPAQUE [see Dosage and Administration (2.8)]. See device labeling for device indications, additional information, and instructions for use. (mL)AdultsOMNIPAQUE 240, 300 and 350Head and body imaging by rapid injectionCT Imaging Head:70 mL to 150 mL of OMNIPAQUE 30080 mL of OMNIPAQUE 350CT Imaging Body:50 mL to 200 mL of OMNIPAQUE 30060 mL to 100 mL of OMNIPAQUE 350Head imaging by infusionCT Imaging Head:120 mL to 250 mL of OMNIPAQUE 240PediatricsOMNIPAQUE 240 and 300 CT Imaging Head and Body: mL/kg to mL/kg (with maximum 3 mL/kg)Maximum single dose 116 mL. 20 mL to 150 mL of OMNIPAQUE 240. 40 mL to 100 mL of OMNIPAQUE 300. 0.6 mL/kg to 1.2 mL/kg body weight. The usual dose for children is mL/kg to 1.5 mL/kg.. The total administered dose should not exceed mL/kg.. 70 mL to 150 mL of OMNIPAQUE 300. 80 mL of OMNIPAQUE 350. 50 mL to 200 mL of OMNIPAQUE 300. 60 mL to 100 mL of OMNIPAQUE 350. 120 mL to 250 mL of OMNIPAQUE 240. mL/kg to mL/kg (with maximum 3 mL/kg). Maximum single dose 116 mL. 2.4Oral or Rectal Dosage and Administration. Oral and Rectal Administration Undiluted OMNIPAQUE Injection for Radiographic Examination of the Gastrointestinal (GI) TractTABLE 12 DOSING FOR RADIOGRAPHIC EXAMINATION OF THE GI TRACTPATIENT POPULATIONCONCENTRATION(mg iodine/mL)ORAL VOLUME(mL)RECTAL VOLUMEWhen given rectally, larger volumes may be used. (mL)AdultsOMNIPAQUE 350The recommended dose is 50 mL to 100 mL-PediatricsOMNIPAQUE 180, 240 and 300The recommended dose is mL to 100 mLThe recommended dose is mL to 100 mL Less than months oldOMNIPAQUE 1805 mL to 30 mL- Three months to yearsOMNIPAQUE 180, 240 and 300Up to 60 mL- Four years to 10 yearsOMNIPAQUE 180, 240 and 300Up to 80 mL- Greater than 10 yearsUp to 100 mL- 2.5Oral Dosage and Administration in Conjunction with Intravenous Administration. See Table 16 for concurrent intravenous dosing.. Oral Administration of Diluted OMNIPAQUE Injection in Conjunction with Intravenous Administration of OMNIPAQUE Injection for CT of the AbdomenTABLE 13 DOSING OF DILUTEDDilutions of OMNIPAQUE should be prepared just prior to use and any unused portion discarded after the procedure. OMNIPAQUE INJECTION FOR ORAL ADMINISTRATIONPATIENT POPULATIONORAL CONCENTRATION(mg iodine/mL)ORAL VOLUME(mL)ADMINISTRATION INSTRUCTIONSAdultsOMNIPAQUE 240, 300 and 350 DILUTED to to 12 mg iodine/mL (See Table 14 below) Recommended oral dose is: 500 mL to 1,000 mL Smaller administered volumes can be given if the iodine concentration in final diluted product is increased (See Table 14 below) The oral dosage may be given all at once or over period of up to 45 minutes if there is difficulty in consuming the required volume.PediatricsOMNIPAQUE 240, 300 and 350 DILUTED to to 21 mg iodine/mL (See Table 14 below) Recommended oral dose is: 180 mL to 750 mLDo not exceed an oral dose of grams iodine for patients less than years old.Do not exceed an oral dose of 10 grams iodine for patients to 18 years old.Smaller administered volumes can be given if the iodine concentration in final diluted product is increased (See Table 14 below) The oral dosage may be given all at once or over period of up to 45 minutes if there is difficulty in consuming the required volume.TABLE 14 PROCEDURE FOR PREPARATION OF DILUTED OMNIPAQUE INJECTION FOR ORAL ADMINISTRATIONOMNIPAQUE to be mixed with liquid such as water, carbonated beverage, milk, infant formula, or juice to achieve one liter of oral contrast agent.Final Iodine Concentration of Diluted Contrast Agent(mg iodine/mL)OMNIPAQUE 240OMNIPAQUE 300OMNIPAQUE 350Volume of Contrast Agent (mL)Volume of Liquid (mL)Volume of Contrast Agent (mL)Volume of Liquid (mL)Volume of Contrast Agent (mL)Volume of Liquid (mL)6259752098017983938962309702697412509504096035965156393750950439571875925609405294821889127093060940. 500 mL to 1,000 mL. 180 mL to 750 mL. Oral Administration of OMNIPAQUE Oral Solution in Conjunction with Intravenous Administration of OMNIPAQUE Injection for CT of the AbdomenTABLE 15 DOSING AND ADMINISTRATION OF OMNIPAQUE ORAL SOLUTIONPATIENT POPULATIONORAL CONCENTRATION(mg iodine/mL)ORAL VOLUME(mL)ADMINISTRATION INSTRUCTIONSAdultsOMNIPAQUE oral solution and 12The recommended oral dose is: 500 mL to 1,000 mL The oral dosage may be given all at once or over period of up to 45 minutes if there is difficulty in consuming the required volume.PediatricsOMNIPAQUE oral solution and 12The recommended oral dose is: 180 mL to 750 mLDo not exceed an oral dose of grams iodine for patients less than years old.Do not exceed an oral dose of 10 grams iodine for patients to 18 years old.The oral dosage may be given all at once or over period of up to 45 minutes if there is difficulty in consuming the required volume.TABLE 16 INTRAVENOUS ADMINISTRATION OF OMNIPAQUE INJECTION FOR CT OF THE ABDOMEN IN CONJUNCTION WITH ORALLY ADMINISTERED DILUTED OMNIPAQUE INJECTION OR OMNIPAQUE ORAL SOLUTION PATIENT POPULATIONINTRAVENOUS CONCENTRATION(mg iodine/mL)INTRAVENOUS VOLUMEOMNIPAQUE may be used with an automated contrast injection system or contrast management system cleared for use with OMNIPAQUE [see Dosage and Administration (2.8)]. See device labeling for device indications, additional information, and instructions for use. (mL)ADMINISTRATION INSTRUCTIONSAdultsOMNIPAQUE 300The recommended dose is: 100 mL to 150 mL Administer up to 40 minutes AFTER consumption of the oral dosePediatricsOMNIPAQUE 240 and 300The recommended dose is: mL/kg with range of mL/kg to mL/kg (maximum mL/kg) Administer up to 60 minutes AFTER consumption of the oral dose. 500 mL to 1,000 mL. 180 mL to 750 mL. 100 mL to 150 mL. mL/kg with range of mL/kg to mL/kg (maximum mL/kg). 2.6Intraarticular Dosage and Administration. TABLE 17 ARTHROGRAPHYPATIENT POPULATIONLOCATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)DOUBLE CONTRAST/SINGLE CONTRASTAdultsKneePassive or active manipulation is used to disperse the medium throughout the joint space. OMNIPAQUE 2405 to 15Lower volumes recommended for double-contrast examinations; higher volumes recommended for single-contrast examinations.OMNIPAQUE 3005 to 15OMNIPAQUE 3505 to 10AdultsShoulder OMNIPAQUE 2403OMNIPAQUE 30010AdultsTemporomandibular OMNIPAQUE 3000.5 to 1. 2.7Body Cavity Dosage and Administration. Body Cavity Administration Undiluted OMNIPAQUE InjectionTABLE 18 ENDOSCOPIC RETROGRADE PANCREATOGRAPHY (ERP) ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ECRP)PATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 24010 mL to 50 mL but may vary depending on individual anatomy and/or disease state.TABLE 19 HYSTEROSALPINGOGRAPHYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 240 and 30015 mL to 20 mL but may vary depending on individual anatomy and/or disease state.TABLE 20 HERNIOGRAPHYPATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)AdultsOMNIPAQUE 24050 mL but may vary depending on individual anatomy and/or disease state.. Body Cavity Administration Diluted OMNIPAQUE Injection TABLE 21 VOIDING CYSTOURETHROGRAPHY (VCU) (CAN BE PERFORMED IN CONJUNCTION WITH EXCRETORY UROGRAPHY)PATIENT POPULATIONCONCENTRATION(mg iodine/mL)VOLUME(mL)PediatricsThe concentration may vary depending upon the patients size and age and with the technique and equipment used.OMNIPAQUE injection may be diluted with Sterile Water for Injection. (See Table 22 below). OMNIPAQUE injection may be diluted, utilizing aseptic technique, with Sterile Water for Injection to concentration of 50 mg iodine/mL to 100 mg iodine/mL for voiding cystourethrography.Range: 50 mL to 300 mL of DILUTED OMNIPAQUE at concentration of 100 mg iodine/mL50 mL to 600 mL of DILUTED OMNIPAQUE at concentration of 50 mg iodine/mL. TABLE 22 PROCEDURE FOR PREPARATION OF DILUTEDDilutions of OMNIPAQUE should be prepared just prior to use and any unused portion discarded after the procedure. OMNIPAQUE INJECTION FOR VCUFinal Iodine Concentration of Diluted Contrast Agent(mg iodine/mL)Volume of OMNIPAQUE 240(mL)Volume of Sterile Water for Injection(mL)Volume of OMNIPAQUE 300(mL)Volume of Sterile Water for Injection (mL)Volume of OMNIPAQUE 350(mL)Volume of Sterile Water for Injection (mL)1001001401002001002509016723328980200275338702433304006030040048350380500600. 50 mL to 300 mL of DILUTED OMNIPAQUE at concentration of 100 mg iodine/mL. 50 mL to 600 mL of DILUTED OMNIPAQUE at concentration of 50 mg iodine/mL.. 2.8Instructions for Use with an Automated Contrast Injection System or Contrast Management System for CT of the Head and Body. OMNIPAQUE may be used with an automated contrast injection system cleared for use with contrast media. See above Important Dosage and Administration Instructions for OMNIPAQUE (2.1).See device labeling for information on device indications, instructions for use, and techniques to help assure safe use. OMNIPAQUE 300 mg iodine/mL and 350 mg iodine/mL in 150 mL bottles may be used with contrast media management system cleared for use with OMNIPAQUE 300 mg iodine/mL and 350 mg iodine/mL in 150 mL bottles. See device labeling for information on device indications, instructions for use, and techniques to help assure safe use.Use sterile technique for penetrating the container closure of OMNIPAQUE 300 and 350 and transferring OMNIPAQUE solution. The container closure may be penetrated only one time with suitable sterile component of the contrast media management system cleared for use with OMNIPAQUE 300 and 350 in 150 mL bottles.Once the OMNIPAQUE 300 and 350 Injection is punctured, do not remove the bottle from the work area during the entire period of use.Maximum use time is hours after initial puncture.Each bottle is for one procedure only. Discard unused portion. OMNIPAQUE may be used with an automated contrast injection system cleared for use with contrast media. See above Important Dosage and Administration Instructions for OMNIPAQUE (2.1).See device labeling for information on device indications, instructions for use, and techniques to help assure safe use. See above Important Dosage and Administration Instructions for OMNIPAQUE (2.1).. See device labeling for information on device indications, instructions for use, and techniques to help assure safe use.. OMNIPAQUE 300 mg iodine/mL and 350 mg iodine/mL in 150 mL bottles may be used with contrast media management system cleared for use with OMNIPAQUE 300 mg iodine/mL and 350 mg iodine/mL in 150 mL bottles. See device labeling for information on device indications, instructions for use, and techniques to help assure safe use.Use sterile technique for penetrating the container closure of OMNIPAQUE 300 and 350 and transferring OMNIPAQUE solution. The container closure may be penetrated only one time with suitable sterile component of the contrast media management system cleared for use with OMNIPAQUE 300 and 350 in 150 mL bottles.Once the OMNIPAQUE 300 and 350 Injection is punctured, do not remove the bottle from the work area during the entire period of use.Maximum use time is hours after initial puncture.Each bottle is for one procedure only. Discard unused portion. See device labeling for information on device indications, instructions for use, and techniques to help assure safe use.. Use sterile technique for penetrating the container closure of OMNIPAQUE 300 and 350 and transferring OMNIPAQUE solution. The container closure may be penetrated only one time with suitable sterile component of the contrast media management system cleared for use with OMNIPAQUE 300 and 350 in 150 mL bottles.. Once the OMNIPAQUE 300 and 350 Injection is punctured, do not remove the bottle from the work area during the entire period of use.. Maximum use time is hours after initial puncture.. Each bottle is for one procedure only. Discard unused portion.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. OMNIPAQUE Injection140 mg of iodine per mL (302 mg of iohexol/mL) in +PlusPak(TM) polymer bottles180 mg of iodine per mL (388 mg of iohexol/mL) in glass vials240 mg of iodine per mL (518 mg of iohexol/mL), 300 mg of iodine per mL (647 mg of iohexol/mL) and 350 mg of iodine per mL (755 mg of iohexol/mL) in glass vials and bottles and +PlusPak(TM) polymer bottlesOMNIPAQUE Oral Solution9 mg of iodine per mL (19 mg of iohexol/mL) and 12 mg of iodine per mL (26 mg of iohexol/mL) in +PlusPak(TM) polymer bottles. 140 mg of iodine per mL (302 mg of iohexol/mL) in +PlusPak(TM) polymer bottles. 180 mg of iodine per mL (388 mg of iohexol/mL) in glass vials. 240 mg of iodine per mL (518 mg of iohexol/mL), 300 mg of iodine per mL (647 mg of iohexol/mL) and 350 mg of iodine per mL (755 mg of iohexol/mL) in glass vials and bottles and +PlusPak(TM) polymer bottles. mg of iodine per mL (19 mg of iohexol/mL) and 12 mg of iodine per mL (26 mg of iohexol/mL) in +PlusPak(TM) polymer bottles. OMNIPAQUE (iohexol) Injection and Oral SolutionSterile, pyrogen-free, gluten-free, colorless to pale yellow solution containing the nonionic, water-soluble x-ray contrast medium iohexol, and available in the following strengths and formats: OMNIPAQUE (iohexol) Injection140 mg of organically bound iodine per mL (302 mg iohexol/mL) Available in +PLUSPAK(TM) (polymer bottle) 180 mg of organically bound iodine per mL (388 mg iohexol/mL) Available in glass vials 240 mg of organically bound iodine per mL (518 mg iohexol/mL)300 mg of organically bound iodine per mL (647 mg iohexol/mL)350 mg of organically bound iodine per mL (755 mg iohexol/mL) Available in glass vials and bottles and +PLUSPAK(TM) polymer bottles. 140 mg of organically bound iodine per mL (302 mg iohexol/mL) Available in +PLUSPAK(TM) (polymer bottle) Available in +PLUSPAK(TM) (polymer bottle). 180 mg of organically bound iodine per mL (388 mg iohexol/mL) Available in glass vials Available in glass vials. 240 mg of organically bound iodine per mL (518 mg iohexol/mL). 300 mg of organically bound iodine per mL (647 mg iohexol/mL). 350 mg of organically bound iodine per mL (755 mg iohexol/mL) Available in glass vials and bottles and +PLUSPAK(TM) polymer bottles. Available in glass vials and bottles and +PLUSPAK(TM) polymer bottles.. OMNIPAQUE Oral Solution9 mg of organically bound iodine per mL (19 mg iohexol/mL)12 mg of organically bound iodine per mL (26 mg iohexol/mL) Available in +PLUSPAK(TM) polymer bottles. 9 mg of organically bound iodine per mL (19 mg iohexol/mL). 12 mg of organically bound iodine per mL (26 mg iohexol/mL) Available in +PLUSPAK(TM) polymer bottles. Available in +PLUSPAK(TM) polymer bottles.

DRUG & OR LABORATORY TEST INTERACTIONS SECTION.

7.2 Drug Laboratory Test Interactions. Effect on Thyroid TestsIf iodine-containing isotopes are to be administered for the diagnosis of thyroid disease, the iodine-binding capacity of thyroid tissue may be reduced for up to weeks after contrast medium administration. Thyroid function tests that do not depend on iodine estimation, e.g., T3 resin uptake or direct thyroxine assays, are not affected.

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. 7.1 Drug-Drug Interactions. MetforminIn patients with renal impairment, metformin can cause lactic acidosis. Iodinated contrast agents appear to increase the risk of metformin-induced lactic acidosis, possibly as result of worsening renal function. Stop metformin at the time of, or prior to, OMNIPAQUE administration in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and reinstitute metformin only after renal function is stable. Radioactive IodineAdministration of iodinated contrast agents may interfere with thyroid uptake of radioactive iodine (I-131 and I-123) and decrease therapeutic and diagnostic efficacy in patients with carcinoma of the thyroid. The decrease in efficacy lasts for 6-8 weeks. Beta-adrenergic Blocking AgentsThe use of beta-adrenergic blocking agents lowers the threshold for and increases the severity of contrast reactions and reduces the responsiveness of treatment of hypersensitivity reactions with epinephrine. Because of the risk of hypersensitivity reactions, use caution when administering OMNIPAQUE to patients taking beta-blockers. Drugs that Lower Seizure ThresholdDrugs that lower seizure threshold, especially phenothiazine derivatives including those used for their antihistaminic or antinauseant properties, are not recommended for use with intrathecal administration of OMNIPAQUE.. CNS Active DrugsDrugs such as monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, CNS stimulants, psychoactive drugs described as analeptics, major tranquilizers, or antipsychotic drugs. Such medications should be discontinued at least 48 hours before myelography, should not be used for the control of nausea or vomiting during or after myelography, and should not be resumed for at least 24 hours post procedure. In non-elective procedures in patients on these drugs, consider prophylactic use of anticonvulsants.. 7.2 Drug Laboratory Test Interactions. Effect on Thyroid TestsIf iodine-containing isotopes are to be administered for the diagnosis of thyroid disease, the iodine-binding capacity of thyroid tissue may be reduced for up to weeks after contrast medium administration. Thyroid function tests that do not depend on iodine estimation, e.g., T3 resin uptake or direct thyroxine assays, are not affected.

GERIATRIC USE SECTION.

8.5 Geriatric Use. In clinical studies of OMNIPAQUE for CT, 52/299 (17%) of patients were 70 and over. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. Volume/ConcentrationConfigurationNDCOMNIPAQUE 140 (140 mg iodine/mL) Boxes of 1050 mL+PLUSPAK(TM) (polymer bottle)0407-1401-52OMNIPAQUE 180 (180 mg iodine/mL) Boxes of 1010 mLGlass Vial0407-1411-1020 mLGlass Vial0407-1411-20OMNIPAQUE 240 (240 mg iodine/mL) Boxes of 1010 mLGlass Vial0407-1412-1020 mLGlass Vial0407-1412-2050 mL+PLUSPAK(TM) (polymer bottle)0407-1412-30100 mL+PLUSPAK(TM) (polymer bottle)0407-1412-33150 mL fill in 200 mL+PLUSPAK(TM) (polymer bottle)0407-1412-34200 mL+PLUSPAK(TM) (polymer bottle)0407-1412-35OMNIPAQUE 300 (300 mg iodine/mL) Boxes of 1010 mLGlass Vial0407-1413-1030 mL fill in 50 mL+PLUSPAK(TM) (polymer bottle)0407-1413-5950 mL+PLUSPAK(TM) (polymer bottle)0407-1413-6175 mL fill in 100 mL+PLUSPAK(TM) (polymer bottle)0407-1413-62100 mL+PLUSPAK(TM) (polymer bottle)0407-1413-63125 mL fill in 150 mLGlass Bottle0407-1413-53125 mL fill in 200 mL+PLUSPAK(TM) (polymer bottle)0407-1413-69150 mL fill in 200 mL+PLUSPAK(TM) (polymer bottle)0407-1413-65200 mL+PLUSPAK(TM) (polymer bottle)0407-1413-66OMNIPAQUE 350 (350 mg iodine/mL) Boxes of 1050 mL+PLUSPAK(TM) (polymer bottle)0407-1414-8975 mL fill in 100 mL+PLUSPAK(TM) (polymer bottle)0407-1414-90100 mL+PLUSPAK(TM) (polymer bottle)0407-1414-91125 mL fill in 150 mLGlass Bottle0407-1414-76125 mL fill in 200 mL+PLUSPAK(TM) (polymer bottle)0407-1414-95150 mL fill in 200 mL+PLUSPAK(TM) (polymer bottle)0407-1414-93200 mL+PLUSPAK(TM) (polymer bottle)0407-1414-94OMNIPAQUE Oral Solution (9 mg iodine/mL) Boxes of 10500 mL+PLUSPAK(TM) (polymer bottle)0407-1415-09OMNIPAQUE Oral Solution 12 (12 mg iodine/mL) Boxes of 10500 mL+PLUSPAK(TM) (polymer bottle)0407-1416-12The container closure system components (bottle, vial, stopper and cap) of OMNIPAQUE injection and OMNIPAQUE oral solution are not made with natural rubber latex.. 16.2 Storage and Handling. Protect OMNIPAQUE glass vials and bottles and +PLUSPAK(TM) polymer bottles from light. Do not freeze. Discard any product that is inadvertently frozen, as freezing may compromise the closure integrity of the immediate container.. OMNIPAQUE Injection 140, 180, 240, 300 and 350 Store at controlled room temperature, 20 to 25C (68 to 77F); excursions permitted to 15 to 30C (59 to 86F) [see USP Controlled Room Temperature]. May be stored in contrast media warmer for up to one month at 36 to 38C (96.8 to 100.4F).. OMNIPAQUE Oral Solution and 12Store between and 30C (32 to 86F).

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. OMNIPAQUE (iohexol) injection is radiographic contrast agent indicated for intrathecal, intravascular, oral, rectal, intraarticular and body cavity use. OMNIPAQUE oral solution is indicated for oral use only in conjunction with OMNIPAQUE injection administered intravenously for computed tomography (CT) of the abdomen (1).. 1.1 Intrathecal Administration. AdultsOMNIPAQUE 180, 240, and 300Myelography (lumbar, thoracic, cervical, total columnar)Computerized Tomography (CT) (myelography, cisternography, ventriculography). Myelography (lumbar, thoracic, cervical, total columnar). Computerized Tomography (CT) (myelography, cisternography, ventriculography). PediatricsOMNIPAQUE 180Myelography (lumbar, thoracic, cervical, total columnar)CT (myelography, cisternography). Myelography (lumbar, thoracic, cervical, total columnar). CT (myelography, cisternography). 1.2 Intravascular Administration. AdultsOMNIPAQUE 140Intra-arterial digital subtraction angiography of the head, neck, abdominal, renal and peripheral vesselsOMNIPAQUE 240CT head imaging Peripheral venography (phlebography)OMNIPAQUE 300Aortography including studies of the aortic arch, abdominal aorta and its branchesCT head and body imagingCerebral arteriographyPeripheral venography (phlebography)Peripheral arteriographyExcretory urographyOMNIPAQUE 350Angiocardiography (ventriculography, selective coronary arteriography)Aortography including studies of the aortic root, aortic arch, ascending aorta, abdominal aorta and its branchesCT head and body imagingIntravenous digital subtraction angiography of the head, neck, abdominal, renal and peripheral vesselsPeripheral arteriographyExcretory urography. Intra-arterial digital subtraction angiography of the head, neck, abdominal, renal and peripheral vessels. CT head imaging Peripheral venography (phlebography). Aortography including studies of the aortic arch, abdominal aorta and its branches. CT head and body imaging. Cerebral arteriography. Peripheral venography (phlebography). Peripheral arteriography. Excretory urography. Angiocardiography (ventriculography, selective coronary arteriography). Aortography including studies of the aortic root, aortic arch, ascending aorta, abdominal aorta and its branches. CT head and body imaging. Intravenous digital subtraction angiography of the head, neck, abdominal, renal and peripheral vessels. Peripheral arteriography. Excretory urography. PediatricsOMNIPAQUE 240CT head and body imagingOMNIPAQUE 300Angiocardiography (ventriculography)Excretory urographyCT head and body imagingOMNIPAQUE 350Angiocardiography (ventriculography, pulmonary arteriography, venography, and studies of the collateral arteries)Aortography including the aortic root, aortic arch, ascending and descending aorta. CT head and body imaging. Angiocardiography (ventriculography). Excretory urography. CT head and body imaging. Angiocardiography (ventriculography, pulmonary arteriography, venography, and studies of the collateral arteries). Aortography including the aortic root, aortic arch, ascending and descending aorta. 1.3 Oral or Rectal Administration. AdultsOMNIPAQUE 350Oral radiographic examination of the gastrointestinal tract. Oral radiographic examination of the gastrointestinal tract. PediatricsOMNIPAQUE 180, 240 and 300Oral and rectal radiographic examination of the gastrointestinal tract. Oral and rectal radiographic examination of the gastrointestinal tract. 1.4 Oral Administration in Conjunction with Intravenous Administration. Diluted OMNIPAQUE Injection. AdultsOMNIPAQUE 240, 300 and 350 diluted and administered orally in conjunction with OMNIPAQUE 300 administered intravenouslyCT of the abdomen. CT of the abdomen. PediatricsOMNIPAQUE 240, 300 and 350 diluted and administered orally in conjunction with OMNIPAQUE 240 or OMNIPAQUE 300 administered intravenouslyCT of the abdomen. CT of the abdomen. OMNIPAQUE Oral Solution. AdultsOMNIPAQUE oral solution and 12 administered orally in conjunction with OMNIPAQUE 300 administered intravenouslyCT of the abdomen. CT of the abdomen. PediatricsOMNIPAQUE oral solution and 12 administered orally in conjunction with OMNIPAQUE 240 or OMNIPAQUE 300 administered intravenouslyCT of the abdomen. CT of the abdomen. 1.5 Intraarticular Administration. AdultsOMNIPAQUE 240, 300, and 350Arthrography. Arthrography. 1.6 Body Cavity Administration. AdultsOMNIPAQUE 240Endoscopic retrograde pancreatography (ERP) and cholangiopancreatography (ERCP)HerniographyHysterosalpingographyOMNIPAQUE 300Hysterosalpingography. Endoscopic retrograde pancreatography (ERP) and cholangiopancreatography (ERCP). Herniography. Hysterosalpingography. Hysterosalpingography. PediatricsOMNIPAQUE 240, 300 and 350 diluted Voiding cystourethrography (VCU). Voiding cystourethrography (VCU).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Hypersensitivity ReactionsAdvise the patient concerning the risk of hypersensitivity reactions that can occur both during and after OMNIPAQUE administration. Advise the patient to report any signs or symptoms of hypersensitivity reactions during the procedure and to seek immediate medical attention for any signs or symptoms experienced after discharge [see Warnings and Precautions (5.3) ]Advise patients to inform their physician if they develop rash after receiving OMNIPAQUE [see Warnings and Precautions (5.11)]. Contrast Induced Acute Kidney InjuryAdvise the patient concerning appropriate hydration to decrease the risk of contrast induced acute kidney injury [see Warnings and Precautions (5.4)].. ExtravasationIf extravasation occurs during injection, advise patients to seek medical care for progression of symptoms [see Warnings and Precautions (5.7)]. LactationAdvise lactating woman that interruption of breastfeeding is not necessary. However, to avoid any exposure, lactating woman may consider pumping and discarding breast milk for 10 hours after OMNIPAQUE administration [see Use in Specific Populations (8.2)].

LACTATION SECTION.

8.2 Lactation. Risk SummaryPublished literature reports that breast feeding after intravenous iohexol administration to the mother would result in the infant receiving an oral dose of approximately 0.7% of the maternal intravenous dose; however, lactation studies have not been conducted with oral, intrathecal, or intracavity administration of iohexol. There is no information on the effects of the drug on the breastfed infant or on milk production. Iodinated contrast agents are excreted unchanged in human milk in very low amounts with poor absorption from the gastrointestinal tract of breastfed infant. Exposure to iohexol to breastfed infant can be minimized by temporary discontinuation of breastfeeding (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for OMNIPAQUE and any potential adverse effects on the breastfed infant from OMNIPAQUE or from the underlying maternal condition.. Clinical Considerations Interruption of breastfeeding after exposure to iodinated contrast agents is not necessary because the potential exposure of the breastfed infant to iodine is small. However, lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hours (approximately elimination half-lives) after OMNIPAQUE administration to minimize drug exposure to breastfed infant.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Intrathecal UseThe safety and effectiveness of OMNIPAQUE 180 have been established in pediatric patients weeks to 17 years of age for myelography (lumbar, thoracic, cervical, total columnar) and for CT (myelography, cisternography). Use of OMNIPAQUE 180 is supported by controlled clinical studies in adults for myelography, in addition to clinical studies in pediatric patients undergoing myelography. The safety and effectiveness of OMNIPAQUE 180 have not been established for intrathecal use in patient pediatric patients less than weeks of age. The safety and effectiveness of OMNIPAQUE 240 and 300 have not been established in pediatric patients for myelography (lumbar, thoracic, cervical, total columnar) and for CT (myelography, cisternography, or ventriculography).. Intravascular Use. Angiocardiography (Ventriculography, Pulmonary Arteriography, Venography, and Studies of the Collateral Arteries) and Aortography The safety and effectiveness of OMNIPAQUE 300 have been established in pediatric patients from birth to 17 years of age for angiocardiography (ventriculography) and of OMNIPAQUE 350 in pediatric patients from birth to 17 years of age for angiocardiography (ventriculography, pulmonary arteriography, venography, and studies of the collateral arteries) and aortography. Use of OMNIPAQUE 300 and 350 is supported by controlled clinical studies in adults for angiocardiography and aortography, in addition to controlled clinical studies in pediatric patients undergoing angiocardiography, including aortography. The safety and effectiveness of OMNIPAQUE 300 have not been established in pediatric patients for aortography.. Intra-arterial Digital Subtraction Angiography, Intravenous Digital Subtraction Angiography, Cerebral Arteriography, or Peripheral Arteriography and VenographyThe safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for intra-arterial digital subtraction angiography, intravenous digital subtraction angiography, cerebral arteriography, or peripheral arteriography and venography.. CT of the Head and BodyThe safety and effectiveness of OMNIPAQUE 240 and 300 have been established in pediatric patients from birth to 17 years of age for CT imaging of the head and body. Use of OMNIPAQUE 240 and 300 is supported by controlled clinical studies in adults for head and body CT, in addition to clinical studies in pediatric patients undergoing head CT and in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. The safety and effectiveness of OMNIPAQUE 350 have not been established in pediatric patients for CT imaging of the head and body.. UrographyThe safety and effectiveness of OMNIPQUE 300 have been established in pediatric patients from birth to 17 years of age for urography. Use of OMNIPAQUE 300 is supported by controlled clinical studies in adults for urography, in addition to controlled clinical studies in pediatric patients undergoing urography and clinical safety data in pediatric patients down to birth. Oral or Rectal Use. Undiluted OMNIPAQUE InjectionThe safety and effectiveness of OMNIPAQUE 180, 240, and 300 administered orally and rectally have been established in pediatric patients, from birth to 17 years of age for examination of the GI tract. Use of OMNIPAQUE 180, 240, and 300 administered orally and rectally is supported by controlled studies in adults for examination of the GI tract, in addition to clinical studies in pediatric patients undergoing examination of the GI tract.. Oral Use in Conjunction with Intravenous Use. Diluted OMNIPAQUE InjectionThe safety and effectiveness of OMNIPAQUE injection diluted to concentrations from to 21 mg iodine/mL administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen have been established in pediatric patients from birth to 17 years of age. Use is supported by clinical trials in adults, in addition to clinical studies in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. OMNIPAQUE Oral SolutionThe safety and effectiveness of OMNIPAQUE oral solution and 12 administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen in pediatric patients have been established in pediatric patients from birth to 17 years of age. Use is supported by the data establishing safety and effectiveness for OMNIPAQUE injection diluted and administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen in pediatric patients.. Intraarticular UseThe safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for arthrography.. Body Cavity UseOMNIPAQUE 240, 300, 350 diluted to concentrations from 50 mg iodine/mL to 100 mg iodine/mL is indicated for use in pediatric patients from birth to 17 years of age for voiding cystourethrography (VCU). The use for voiding cystourethrography is supported by clinical studies in 51 pediatric patients undergoing VCU. The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for ERCP, herniography, or hysterosalpingography.In general, the frequency of adverse reactions in pediatric patients was similar to that seen in adults [see Adverse Reactions (6.1)]. Pediatric patients at higher risk of experiencing adverse events during contrast-medium administration may include those having asthma, sensitivity to medication and/or allergens, congestive heart failure, serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to pediatric patients, including infants. Some patients were treated for hypothyroidism [see Adverse Reactions (6.2)].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Intrathecal Administration The initial concentration and volume of the contrast medium, in conjunction with patient manipulation and the volume of cerebrospinal fluid (CSF) into which the contrast medium is placed, will determine the extent of the contrast that can be achieved. Following intrathecal injection in conventional radiography, OMNIPAQUE 180, 240, and 300 will continue to provide contrast for at least 30 minutes. Slow diffusion of iohexol takes place throughout the CSF with subsequent absorption into the bloodstream. At approximately hour following injection, contrast will no longer be sufficient for conventional myelography.After administration into the lumbar subarachnoid space, computerized tomography shows the presence of contrast medium in the thoracic region in about hour, in the cervical region in about hours, and in the basal cisterns in to hours.. Intravascular AdministrationFollowing intravascular administration of OMNIPAQUE, the degree of contrast enhancement is directly related to the iodine concentration of an administered dose; peak iodine blood concentrations occur immediately (15 seconds to 120 seconds) following rapid intravenous injection. The time to maximum contrast enhancement can vary, depending on the organ, from the time that peak blood iodine concentrations are reached to one hour after intravenous bolus administration. When delay between peak blood iodine concentrations and peak contrast is present, it suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing agent within the lesion and outside the blood pool. Oral Administration Orally administered OMNIPAQUE produces visualization of the gastrointestinal tract. Less than 1% of orally administered iohexol is recovered in the urine, suggesting minimal amounts are absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction.. Intraarticular AdministrationVisualization of the joint spaces can be accomplished by direct injection of contrast medium. For intraarticular cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation.. Body Cavity AdministrationFor most body cavities, the injected iohexol is absorbed into the surrounding tissue and subsequently absorbed into systemic circulation. Examinations of the uterus (hysterosalpingography) and bladder (voiding cystourethrography) involve the almost immediate drainage of contrast medium from the cavity upon conclusion of the radiographic procedure.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Following the intravenous administration of iohexol (between 500 mg iodine/kg to 1500 mg iodine/kg) to 16 adult human subjects, apparent first-order terminal elimination half-life was 12.6 hrs and total body clearance was 131 (98-165) mL/min. Clearance was not dose dependent.. AbsorptionAs evidenced by the amount recovered in urine, <1% of orally administered iohexol is absorbed from the normal gastrointestinal tract. This amount may increase in the presence of bowel perforation or bowel obstruction.. DistributionIn 16 adult subjects (receiving between 500 mg iodine/kg to 1500 mg iodine/kg intravenous iohexol) the plasma volume of distribution was165 (108-219) mL/kg.In five adult patients receiving 16 mL to 18 mL of OMNIPAQUE (180 mg iodine/mL) by lumbar intrathecal injection the plasma volume of distribution was 559 (350-849) mL/kg.. Elimination. MetabolismNo significant metabolism, deiodination or biotransformation occurs.. ExcretionFollowing intravascular or intrathecal administration, iohexol is excreted unchanged by glomerular filtration. Approximately 90% of the intravenously injected iohexol dose is excreted within the first 24 hours. Following intravascular administration, peak urine concentration occurs in the first hour after injection.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryHysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [see Contraindications (4)]. There are no data with iohexol use in pregnant women to inform any drug-associated risks. Iohexol crosses the placenta and reaches fetal tissues in small amounts (see Data). In animal reproduction studies, no developmental toxicity occurred with intravenous iohexol administration to rats and rabbits at doses up to 0.4 (rat) and 0.5 (rabbit) times the maximum recommended human intravenous dose (see Data ).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.. Data. Human DataLiterature reports show that intravenously administered iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth.. Animal DataIohexol was neither embryotoxic nor teratogenic in either rats or rabbits at the following dose levels tested: 1.0, 2.0, 4.0 iodine/kg in rats, administered intravenously to groups of 25 dams once daily during days through 15 of pregnancy; 0.3, 1.0, 2.5 iodine/kg in rabbits, administered intravenously to groups of 18 rabbits dosed once day during days through 18 of pregnancy.

RECENT MAJOR CHANGES SECTION.

Contraindications (4)08/2021.

SPL UNCLASSIFIED SECTION.

1.1 Intrathecal Administration. AdultsOMNIPAQUE 180, 240, and 300Myelography (lumbar, thoracic, cervical, total columnar)Computerized Tomography (CT) (myelography, cisternography, ventriculography). Myelography (lumbar, thoracic, cervical, total columnar). Computerized Tomography (CT) (myelography, cisternography, ventriculography). PediatricsOMNIPAQUE 180Myelography (lumbar, thoracic, cervical, total columnar)CT (myelography, cisternography). Myelography (lumbar, thoracic, cervical, total columnar). CT (myelography, cisternography).

STORAGE AND HANDLING SECTION.

16.2 Storage and Handling. Protect OMNIPAQUE glass vials and bottles and +PLUSPAK(TM) polymer bottles from light. Do not freeze. Discard any product that is inadvertently frozen, as freezing may compromise the closure integrity of the immediate container.. OMNIPAQUE Injection 140, 180, 240, 300 and 350 Store at controlled room temperature, 20 to 25C (68 to 77F); excursions permitted to 15 to 30C (59 to 86F) [see USP Controlled Room Temperature]. May be stored in contrast media warmer for up to one month at 36 to 38C (96.8 to 100.4F).. OMNIPAQUE Oral Solution and 12Store between and 30C (32 to 86F).