GE Healthcare Receives FDA Indication Approval for Visipaque™ (iodixanol) Injection for use with coronary CT angiography

Chalfont St. Giles, UK: – Broadening its range of diagnostic options for clinicians and their patients, GE Healthcare announced that it has received an indication approval from the U.S. Food and Drug Administration (FDA) for its imaging agent Visipaque™ (iodixanol) Injection.

Visipaque 320 mg Iodine/mL is an iso-osmolar agent that is now approved for use in coronary computed tomography angiography (CCTA) to assist in the diagnostic evaluation of adult and pediatric patients 12 years of age or older with suspected coronary artery disease in the United States.

The new CCTA indication allows healthcare practitioners to image the coronary arteries of patients with suspected coronary artery disease (CAD), offering a non-invasive approach to diagnosis.

Traditionally, radiologists and cardiologists have utilized Invasive Coronary Angiography (ICA) procedures to diagnose potential CAD in patients, which can be costly and result in longer patient hospital stays. With Visipaque’s CCTA label extension, healthcare practitioners now have an FDA-approved contrast agent in CCTA procedures that can be performed as an outpatient procedure when evaluating patients with suspected CAD.

According to Matt Budoff, Professor of Medicine at UCLA, “Coronary heart disease is a major cause of death in the United States. We are excited about the label extension of Visipaque™ as the first FDA approved iodinated contrast media for use in CCTA.

Having an approved contrast agent for CCTA may facilitate the use of CCTA as a gatekeeper to ICA in patients with mild to moderate coronary artery disease, sparing patients from a more invasive procedure and long recovery times.”

“Technology to image the coronary artery has improved dramatically over the past decade and we are delighted to complement these developments with an extension to the approved use of Visipaque,” said Emmanuel Ligner, General Manager of GE Healthcare’s Core Imaging business.

“GE Healthcare is focused on continued innovation and investment in our contrast media portfolio to deliver a range of options for our customers and their patients, and we believe the CCTA label extension is an excellent development for patient care. "

Label extension approval for VISIPAQUE 320 mg Iodine/mL for CCTA was evaluated in two prospective, multicenter clinical studies in a total of 1,106 adult patients. Data from the two studies showed that Visipaque™ has a 99% negative predictive value in the diagnosis of CAD (study 1: sensitivity (76-89%), specificity (84-89%); study 2: sensitivity (95%), specificity (87%)).

Visipaque’s label extension further enhances GE Healthcare’s cardiology portfolio , joining, Myoview, Adreview, and the recently announced distribution rights for Rapiscan outside the US and Canada.

INDICATIONS AND USAGE

Intra-arterial Procedures

Adult and pediatric patients 12 years of age and older

• (270 and 320 mg Iodine/mL) intra-arterial digital subtraction angiography (IA-DSA).


• (320 mg Iodine/mL) angiocardiography (left ventriculography and selective coronary arteriography), peripheral arteriography, visceral arteriography, and cerebral arteriography.

Pediatric patients less than 12 years of age

• (320 mg Iodine/mL) angiocardiography, cerebral arteriography, and visceral arteriography.

Intravenous Procedures

Adult and pediatric patients 12 years of age and older

• (270 mg Iodine/mL) CT imaging of the head and body, excretory urography, and peripheral venography.


• (320 mg Iodine/mL) CT imaging of the head and body, excretory urography, and coronary computed tomography angiography (CCTA) to assist in the diagnostic evaluation of patients with suspected coronary artery disease.

Pediatric patients less than 12 years of age

• (270 mg Iodine/mL) CT imaging of the head and body and excretory urography.

Boxed Warning and Important Risk and Safety Information About Visipaque

WARNING: NOT FOR INTRATHECAL USE 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.

CONTRAINDICATIONS: Visipaque Injection is contraindicated for intrathecal use.

WARNINGS AND PRECAUTIONS:

Hypersensitivity Reactions: Visipaque can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Most severe reactions develop shortly after the start of the injection, but reactions can occur up to hours later. Obtain a history of allergy, hypersensitivity, or hypersensitivity reactions to iodinated contrast agents and always have emergency resuscitation equipment and trained personnel available prior to Visipaque administration. Monitor all patients for hypersensitivity reactions.

Contrast Induced Acute Kidney Injury: Acute kidney injury, including renal failure, may occur after Visipaque administration. Use the lowest necessary dose of Visipaque in patients with renal impairment. Adequately hydrate patients prior to and following Visipaque administration. Do not use laxatives, diuretics, or preparatory dehydration prior to Visipaque administration.

Cardiovascular Adverse Reactions: Life-threatening or fatal cardiovascular reactions including hypotension, shock, 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 and always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions.

Thromboembolic Events: Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiocardiography procedures with both ionic and nonionic contrast media. Use meticulous angiographic techniques, and minimize the length of the procedure. Avoid blood remaining in contact with syringes containing iodinated contrast agents. Avoid angiocardiography in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

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. Monitor patients for extravasation and advise patients to seek medical care for progression of symptoms.

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 Visipaque.

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 Visipaque 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 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. Hydrate patients prior to and following Visipaque administration and use Visipaque only if the necessary imaging information cannot be obtained with alternative imaging modalities.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR) may develop from 1 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 Visipaque to patients with a history of a severe cutaneous adverse reaction 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, CHF, 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.

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. As Visipaque is substantially excreted by the kidney, the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Lactation: There are no data on the presence of iodixanol in human milk, the effects on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Visipaque and any potential adverse effects on the breastfed infant from Visipaque or from the underlying maternal condition. 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, a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hours after Visipaque administration in order to minimize drug exposure to a breast fed infant.

ADVERSE REACTIONS: Serious, life-threatening, and fatal reactions, mostly of CV origin, have been associated with the administration of iodine-containing contrast agents, including Visipaque Injection. Most deaths occur during injection or five to 10 minutes later. Rare reports of anaphylaxis have been documented during postmarketing surveillance. As with other contrast agencys, Visipaque is often associated with sensations of discomfort, warmth, or pain. The reported incidence of adverse reactions to contrast agents in patients with a history of allergy is twice that of the general population. Patients with a history of a previous reaction to CM are three times more susceptible than other patients.

DRUG INTERACTIONS:

Metformin: In patients with renal impairment, metformin can cause lactic acidosis. Iodinated contrast agents appear to increase the risk of metformin induced lactic acidosis, possibly as a result of worsening renal function. Stop metformin at the time of, or prior to, Visipaque administration in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a 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 Iodine: Administration 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 Agents: The 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 Visipaque to patients taking beta-blockers.

Oral Cholecystographic Contrast Agents: Renal toxicity has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by intravascular iodinated contrast agents. Postpone the administration of Visipaque in patients who have recently received an oral cholecystographic contrast agent.

OVERDOSAGE: The adverse effects of CM overdose may be life-threatening, affecting mainly the pulmonary and CV systems.

Prior to Visipaque administration, please read the Full Prescribing Information.