WARNING: RISKS ASSOCIATED WITH INTRATHECAL ADMINISTRATION OF OMNIPAQUE INJECTION 140 mg IODINE/mL and 350 mg IODINE/ml
Use only the OMNIPAQUE iodine concentrations and presentations recommended for intrathecal procedure. Intrathecal administration of OMNIPAQUE of a wrong iodine concentration, even if inadvertent, may cause death, convulsions, seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema.

INDICATIONS:

OMNIPAQUE is indicated for intrathecal procedures for:

• Myelography and computerized tomography myelography (lumbar, thoracic, cervical, total columnar) in adults and pediatric patients aged 2 weeks and older
• CT cisternography in adults and pediatric patients aged 2 weeks and older

OMNIPAQUE is indicated for intra-arterial procedures for:

• Cardiac ventriculography in adults and pediatric patients
• Aortography including studies of aorta and its branches in adults and pediatric patients
• Selective coronary arteriography in adults
• Cerebral arteriography in adults
• Peripheral arteriography in adults
• Intra-arterial digital subtraction angiography (IA-DSA) of the head, neck, abdominal, renal, and peripheral vessels in adults
• Pulmonary angiography in pediatric patients

OMNIPAQUE is indicated for intravenous procedures for:

• Excretory urography in adults and pediatric patients
• CT of the head and body in adults and pediatric patients
• Peripheral venography (phlebography) in adults
• Intravenous digital subtraction angiography (IV-DSA) of the head, neck, abdominal, renal, and peripheral vessels in adults

OMNIPAQUE is indicated for oral or rectal procedures for:

• Radiographic examination of the gastrointestinal tract in adults and pediatric patients
• CT of the abdomen and pelvis in conjunction with intravenous administration of OMNIPAQUE in adults and pediatric patients

OMNIPAQUE is indicated for intraarticular procedures for:

• Arthrography in adults

  OMNIPAQUE is indicated for body cavity procedures for:

• Endoscopic retrograde pancreatography and cholangiopancreatography in adults
• Herniography in adults
• Hysterosalpingography in adults
• Voiding cystourethrography in pediatric patients

Specific dosage forms, concentrations and presentations of OMNIPAQUE are recommended for each type of imaging procedure.  See dosing and administration in the prescribing information.

CONTRAINDICATIONS:

OMNIPAQUE for hysterosalpingography is contraindicated during pregnancy or suspected pregnancy, menstruation or when menstruation is imminent, within 6 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.

WARNINGS AND PRECAUTIONS:

Risks Associated with Intrathecal Administration of OMNIPAQUE injection 140 mg iodine/mL and 350mg iodine/ml:  Use only the iodine concentrations and presentations recommended for intrathecal procedures. See Boxed Warning

Risks Associated with Parenteral Administration of OMNIPAQUE Oral Solution:  Use for oral use only. Adverse reactions such as hemolysis may occur if OMNIPAQUE is administered intravenously or intraarterially due to low osmolality.

Hypersensitivity Reactions: OMNIPAQUE can cause life-threating or fatal hypersensitivity reactions including anaphylaxis. Most severe reactions develop shortly after the start of the injection (within 1 to 3 minutes), but delayed reactions can also occur. There is an increased risk in patients with a history of a previous reaction to contrast agent and known allergic disorders or other hypersensitivities.  Premedication with antihistamines or corticosteroids does not prevent serious life-threatening reactions but may reduce both incidence and severity.

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 lowest dose in patients with renal impairment.  Adequately hydrate patients prior to administration and do not use laxatives, diuretics, or preparatory dehydration prior to OMNIPAQUE administration.

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 the injection or 5-10 minutes later, with cardiovascular disease as the main aggravating factor. Use the lowest dose necessary in patient with congestive heart failure and have resuscitation equipment and trained personnel available.

Thromboembolic Events: Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiocardiography procedures with iodinated contrast agents. Risk factors for thromboembolic events include: length of procedure, catheter and syringe material, underlying disease state, and concomitant medications. Use meticulous angiographic techniques and minimize length of procedures to minimize events. Avoid blood remaining in contact with syringes containing OMNIPAQUE and avoid angiocardiography in patients with homocystinuria.

Extravasation and Injection Site Reactions: Extravasation of OMNIPAQUE during intravenous or intra-arterial injection may cause tissue necrosis and/or compartment syndrome, particularly in patients with severe arterial or venous disease. Ensure correct placement and monitor patients for extravasation.

Thyroid Storm in Patients with Hyperthyroidism: Thyroid storm has occurred after the intravenous or intra-arterial use of iodinated contrast agents in patients with hyperthyroidism, or with an autonomously functioning thyroid nodule. Evaluate the risk in these patients before use of OMNIPAQUE.

Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age: Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media.

Hypertensive Crisis in Patients with Pheochromocytoma: Hypertensive crisis has occurred after the use of iodinated contrast agents in patients with pheochromocytoma.  Monitor patients when administering OMNIPAQUE intravenously or intra-arterially. Use the minimum amount of contrast necessary and monitor blood pressure throughout the procedure.

Sickle Cell Crisis in Patients with Sickle Cell Disease: Iodinated contrast agents when administered intravenously or intra-arterially may promote sickling in individuals who have sickle cell disease. Hydrate patient prior to and following OMNIPAQUE administration and use OMNIPAQUE only if the necessary imaging cannot be obtained with alternative imaging modalities.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions may develop from 1 hour to several weeks after intravenous or intra-arterial contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms. Reaction severity may increase and time to onset my decrease with repeat administration of contrast agents. Prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering to patients with a history of severe cutaneous reactions.

Interference with Laboratory Test: OMNIPAQUE can interfere with protein-bound iodine test.

Increased Risk of Seizures with Intrathecal Procedures: Focal and generalized motor seizures have been reported after intrathecal use of iodinated contrast agents. Use of medications that may lower the seizure threshold should be carefully evaluated. Consider discontinuing these agents at least 48 hours before and at least 24 hours following intrathecal administration of OMNIPAQUE.

Most Common Adverse Reactions

Intrathecal Administration: In clinical trials ≥1% of 1,531 adult patients included: headaches, pain (including backache, neckache, stiffness, and neuralgia), nausea, vomiting and dizziness. In clinical trials ≥1% of 152 pediatric patients included headache, vomiting and backache.

Intra-arterial or Intravenous Administration: In clinical trials ≥1% of 1,485 adult patients included arrhythmias (including PVCs and PACs), pain, vision abnormalities (including blurred vision and photomas), taste perversion and nausea. In clinical trials ≥1% of 391 pediatric patients included vomiting and nausea.

Oral or Rectal Administration for Examination of the Gastrointestinal Tract: In clinical trials ≥1% of 54 adult patients included diarrhea, nausea, vomiting, abdominal pain, flatulence and headache. In clinical trials of 58 pediatric patients included diarrhea, vomiting, nausea, abdominal pain, fever, urticaria and hypotension.

Intraarticular Administration: In clinical trials ≥1% of 285 adult patients included administration site pain, swelling and heat.

Body Cavity Use: No new adverse reactions were associated with the use of OMNIPAQUE in 51 pediatric patients.

Drug-Drug Interactions:

In patients with renal impairment, metformin can cause lactic acidosis.

OMNIPAQUE may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post OMNIPAQUE.

Pregnancy and Lactation:

There are no data with iohexol use in pregnant women. Published literature report intravenously iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth.

Published 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. Lactating women may consider pumping and discarding breast milk for 10 hours after OMNIPAQUE administration to minimize drug exposure to the breastfed infant.

Prior to Omnipaque administration, please read the full Prescribing Information, including Boxed Warning, for Omnipaque.

To report SUSPECTED ADVERSE REACTIONS, contact GE HealthCare at 800 654 0118 (option 2, then option 1), or the FDA at 800 FDA 1088 or www.fda.gov/medwatch.

CONTRAINDICATION: Visipaque injection is contraindicated for intrathecal use.

WARNINGS AND PRECAUTIONS:
• Hypersensitivity Reactions: Life-threatening or fatal reactions can occur. Most severe reactions develop shortly after the start of the injection, but reactions can occur up to hours later. Always have emergency equipment and trained personnel available.
• Contrast Induced Acute Kidney Injury: Acute injury including renal failure can occur. Minimize dose and maintain adequate hydration to minimize risk.
• Cardiovascular Reactions: Life-threatening or fatal cardiovascular reactions, including hypotension, shock, and cardiac arrest have occurred with the use of Visipaque. Most deaths occur during injection or five to ten minutes later, with cardiovascular disease as the main aggravating factor. Use the lowest necessary dose of Visipaque in patients with congestive heart failure.
• Thromboembolic Events: Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiocardiography procedures with both ionic and nonionic contrast agents.
• Extravasation and Injection Site Reactions: Extravasation of Visipaque 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.
• 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.
• Hypertensive Crisis in Patients With Pheochromocytoma: Hypertensive crisis has occurred after the use of iodinated contrast agents in patients with pheochromocytoma. Inject the minimum amount of contrast necessary, assess the blood pressure throughout the procedure, and have measures for treatment of a hypertensive crisis readily available.
• 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.
• Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCARs) may develop from one 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). Avoid administering Visipaque to patients with a history of a SCAR to Visipaque.
• Pediatric Use: Pediatric patients at high risk of adverse reactions during and after administration of contrast agents include those with asthma, hypersensitivity to other medication and/or allergens, cyanotic and acyanotic heart disease, chronic heart failure, or a serum creatinine >1.5 mg/dL. Patients with immature renal function or dehydration may be at increased risk due to prolonged elimination of iodinated contrast agents. Thyroid dysfunction in pediatric patients 0 to 3 Years of Age: Monitor these patients for thyroid function abnormalities and treat as clinically needed.
• Geriatric Use: While no overall differences in safety or effectiveness were observed in patients >65 years, greater sensitivity regarding some older individuals cannot be ruled out.

ADVERSE REACTIONS:
• Serious, life-threatening, and fatal reactions, mostly of cardiovascular origin, have been associated with the administration of iodine-containing contrast agents, including Visipaque Injection. 
• Most common adverse reactions (incidence greater than 0.5%) in adult patients after Visipaque injection: Discomfort, warmth, pain; Cardiovascular: angina. Gastrointestinal: diarrhea, nausea, vomiting. Nervous System: agitation, anxiety, insomnia, nervousness, dizziness, headache, migraine, unusual skin sensations, sensory disturbance, fainting, sensation of spinning. Skin: itchy rash, severe itching, hives. Special Senses: Smell, taste, and vision alteration. Pediatric patients experienced similar adverse reactions.

Product Indications

Intra-Arterial Procedures
Adult and pediatric patients 12 years of age and older: Intra-arterial digital subtraction angiography (270 and 320 mg iodine/mL); angiocardiography (left ventriculography and selective coronary arteriography), peripheral arteriography, visceral arteriography, and cerebral arteriography (320 mg iodine/mL). Pediatric patients less than 12 years of age: Angiocardiography, cerebral arteriography, and visceral arteriography (320 mg iodine/mL)

Intravenous Procedures
Adult and pediatric patients 12 years of age and older: Computed tomography (CT) imaging of the head and body (270 and 320 mg iodine/mL); excretory urography (270 and 320 mg iodine/mL); peripheral venography (270 mg iodine/mL); coronary computed tomography angiography (CCTA) to assist in the diagnostic evaluation of patients with suspected  artery disease (320 mg iodine/mL). Pediatric patients less than 12 years of age: CT imaging of the head and body (270 mg iodine/mL); excretory urography (270 mgiodine/mL)

Please see full Prescribing Information for Visipaque and full Prescribing Information for Visipaque Bulk Package.

PRODUCT INDICATIONS AND USE:

Clariscan™ (gadoterate meglumine) is a prescription gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

CONTRAINDICATIONS
History of clinically important hypersensitivity reactions to Clariscan.

WARNINGS AND PRECAUTIONS

• Risk Associated with Intrathecal Use: Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of Clariscan have not been established with intrathecal use. Clariscan is not approved for intrathecal use.
• Nephrogenic Systemic Fibrosis: GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of Clariscan among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.
• Hypersensitivity Reactions: Anaphylactic and anaphylactoid reactions have been reported with Clariscan, involving cardiovascular, respiratory, and/or cutaneous manifestations. Some patients experienced circulatory collapse and died.
• Before Clariscan administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to Clariscan.
• Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by other organs (e.g. brain, skin, kidney, liver and spleen). While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible.
• Acute Kidney Injury: In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging
• Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of Clariscan. Extravasation into tissues during Clariscan administration may result in tissue irritation

ADVERSE REACTIONS

• In clinical trials, the most frequent adverse reactions that occurred in > 0.2% of patients who received Clariscan included: nausea, headache, injection site pain, injection site coldness and rash.
• Serious adverse reactions in the postmarketing experience have been reported with Clariscan. Serious adverse reactions include but are not limited to arrhythmia, cardiac arrest, respiratory arrest, pharyngeal edema, laryngospasm, bronchospasm, coma, convulsion, and acute pancreatitis with onset within 48 hours post GBCA administration.

USE IN SPECIFIC POPULATIONS

• Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. Use only if imaging is essential during pregnancy and cannot be delayed
• Lactation: There are no data on the presence of gadoterate in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk.
• Pediatric Use:The safety of Clariscan has not been established in preterm neonates. No dosage adjustment according to age is necessary in pediatric patients.
• Geriatric Use: The use of Clariscan in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. No age-related dosage adjustment is necessary.
• Renal Impairment: No Clariscan dosage adjustment is recommended for patients with renal impairment.

To report SUSPECTED ADVERSE REACTIONS, contact GE HealthCare at 1-800-654-0118 or by email at gpv.drugsafety@gehealthcare.com  or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Please see CLARISCAN full Prescribing Information, including the Medication Guide, for additional important safety information.

PRODUCT INDICATIONS AND USE:

OMNISCAN is a gadolinium-based contrast agent for diagnostic magnetic resonance imaging (MRI) indicated for intravenous use to:

• Visualize lesions with abnormal vascularity in the brain, spine, and associated tissues 
• Facilitate the visualization of lesions with abnormal vascularity within the thoracic, abdominal, pelvic cavities, and the retroperitoneal space

CONTRAINDICATIONS

•     Patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m²) or acute kidney injury •       Patients with prior hypersensitivity to OMNISCAN

WARNINGS AND PRECAUTIONS

• Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of OMNISCAN have not been established with intrathecal use. OMNISCAN is not approved for intrathecal use
• GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of OMNISCAN among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. 
• Anaphylactoid and other serious hypersensitivity reactions including fatal reactions have occurred particularly in patients with history of allergy or drug reactions. Monitor patients closely for need of emergency cardiorespiratory support
• Gadolinium is retained for months or years in brain, bone, and other organs 
• Acute renal failure has occurred in patients with preexisting renal insufficiency. Use the lowest necessary dose of OMNISCAN and evaluate renal function in these patients

ADVERSE REACTIONS

• The most frequent adverse reactions (≤ 3%) observed during OMNISCAN adult clinical studies were nausea, headache, and dizziness.
• Serious or life-threatening reactions include: cardiac failure, arrhythmia and myocardial infarction

USE IN SPECIFIC POPULATIONS

Pregnancy: Use only if imaging is essential during pregnancy and cannot be delayed

To report SUSPECTED ADVERSE REACTIONS, contact GE HealthCare at 1-800-654-0118 or by email at gpv.drugsafety@gehealthcare.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.