Visipaque

>10%

Discomfort at injection site (<30%)

1-10%

Angina pectorin (<2%)

Chest pain (<2%)

Headache (<3%)

Migraine (<3%)

Vertigo (<2%)

Parethesia (1%)

Pruritus (2%)

Skin rash (<2%)

Erythema (<2%)

Dysguesia (4%)

Postmarketing Reports

Cardiovascular Disorders: Cardiac arrest, palpitations, spasms of coronary arteries, hypertension, and flushing

Endocrine Disorders: 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; hypoglycemia, hyperthyroidism

Eye Disorders: Transient visual impairment including cortical blindness, diplopia, and blurred vision

Gastrointestinal Disorders: Abdominal pain, pancreatitis, salivary gland enlargement

General Disorders and Administration Site Conditions: Chills, pyrexia, pain and discomfort, administration site reactions including extravasation

Immune System Disorders: Hypersensitivity reactions, anaphylactic shock including, life-threatening or fatal anaphylaxis

Nervous System Disorders: Tremor (transient), coma, disturbance in consciousness, transient contrast-induced encephalopathy caused by extravasation of contrast media (including amnesia, hallucination, paralysis, paresis, transient speech disorder, aphasia, dysarthria)

Psychiatric Disorders: Anxiety, agitation

Respiratory, Thoracic, and Mediastinal Disorders: Cough, sneezing, throat irritation or tightness, laryngeal edema, pharyngeal edema, bronchospasm

Skin and subcutaneous tissue disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticaria, and skin discoloration) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)]

Iodixanol is injected into a vein through an IV. A healthcare provider will give you this injection just before your radiologic test.

You may be given medication to prevent certain side effects while you are receiving iodixanol.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when iodixanol is injected.

Drink extra fluids before and after your radiologic test. Iodixanol can cause you to get dehydrated, which can lead to dangerous effects on your kidneys. Follow your doctor's instructions about the types and amount of fluids you should drink before and after your test.

Older adults may need special care to avoid becoming dehydrated. Your kidney function may need to be checked after you have received iodixanol.

Iodixanol can interfere with certain medical tests for up to 16 days after you are treated with this medicine. Tell any doctor who treats you that you have recently received iodixanol.

Iodixanol can make radioactive iodine less effective in people with thyroid cancer. This effect can last for up to 8 weeks after you receive iodixanol. Tell your doctor if you are scheduled to be treated with radioactive iodine I-131 or I-123.

Get emergency medical help if you have signs of an allergic reaction: hives; wheezing, difficult breathing; swelling of your face, lips, tongue, or throat.

In rare cases, iodixanol may cause a severe drug reaction that can affect many parts of the body. This type of reaction can start several weeks after you begin using this medicine. Seek medical treatment if you have new or worsening symptoms of fever, facial swelling, a red or blistering skin rash, flu symptoms, swollen glands, feeling weak or tired, severe tingling or numbness, upper stomach pain, loss of appetite, jaundice (yellowing of the skin or eyes), weight loss, pain or burning when you urinate, lower back pain, swelling in your legs or feet, cough, chest pain, or trouble breathing.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• swelling, rapid weight gain, little or no urinating;

• wheezing or trouble breathing;

• a seizure (convulsions);

• thyroid symptoms--extreme tired feeling, dry skin, joint pain or stiffness, muscle pain or weakness, hoarse voice, feeling more sensitive to cold temperatures, weight gain;

• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

• signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood; or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• pain or warm feeling when the medicine is injected;

• dizziness, spinning sensation;

• numbness or tingly feeling;

• vision changes;

• sleep problems (insomnia);

• headache, migraine;

• chest pain;

• nausea, vomiting, diarrhea;

• agitation, anxiety, nervousness;

• skin rash, itching; or

• changes in your sense of taste or smell.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all your current medicines, especially:

• metformin (Glucophage, Glucovance, Actoplus Met, PrandiMet, Avandamet, Kombiglyze, Janumet, Kazano, Invokamet, Jentadueto, Xigduo, Synjardy, Metaglip, and others).

This list is not complete. Other drugs may interact with iodixanol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

A doctor or other trained health professional will give you this medicine in a hospital. This medicine is given through a needle placed in an artery or a vein.

Drink extra fluids so you will pass more urine while you or your child are receiving this medicine. This may help prevent kidney problems.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

PHARMACY BULK PACKAGE–NOT FOR DIRECT INFUSION

NOT FOR INTRATHECAL USE

Visipaque (iodixanol) Injection was administered to 1244 adult patients. The comparators administered to 861 adult patients included low osmolar nonionic, and high and low osmolar ionic contrast media. Approximately one-half (590) of the Visipaque patients were 60 years of age or older; the mean age was 56 years (range 18-90). Of the 1244 patients, 806 (65%) were male and 438 (35%) were female. The racial distribution was: Caucasian-85%, Black-12%, Oriental <1%, and other or unknown-3%. The demographic information for the pool of patients who received a comparison contrast agent was similar.

There were 1235 patients given Visipaque and 855 patients given other contrast agents were evaluated for efficacy. Efficacy assessment was based on quality of the radiographic diagnostic visualization (i.e., either excellent, good, poor, or none) and on the ability to make a diagnosis (i.e., either confirmed a previous diagnosis, found normal, or diagnosed new findings). Results were compared to those of active controls (ioxaglate, iohexol, iopromide, and meglumine-sodium diatrizoate) at concentrations which were similar to those of Visipaque Injection.

INTRA-ARTERIAL ADMINISTRATION

Angiocardiography, cerebral arteriography, peripheral arteriography, and visceral arteriography were studied with either one or both concentrations of Visipaque Injection (270 mgI/mL or 320 mgI/mL). In these intra-arterial studies, diagnostic visualization ratings were good or excellent in 100% of the patients and a radiologic diagnosis was made in all (100%) of the patients given Visipaque Injection. In additional intra-arterial studies, overall quality of diagnostic visualization was rated optimal in the majority of patients and a radiologic diagnosis was made in all (100%) of the patients administered Visipaque Injection. Results were compared to those of active controls (ioxaglate, iohexol, iopromide). The number of patients studied in each indication is provided below.

Angiocardiography was evaluated in two randomized, double-blind clinical trials in 101 adult patients given Visipaque Injection 320 mgI/mL and 97 given iohexol 350 mgI/mL. Seven additional angiocardiography studies were performed in 217 adult patients given Visipaque Injection 320 mgI/mL, 37 given iohexol 350 mgI/mL, 40 given meglumine-sodium diatrizoate 370 mgI/mL, and 96 given ioxaglate 320 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given Visipaque; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Cerebral arteriography was evaluated in two randomized, double-blind clinical trials in 51 adult patients given Visipaque Injection 320 mgI/mL and 48 given iohexol 300 mgI/mL. Two additional cerebral arteriography studies were performed in 15 adult patients given Visipaque Injection 270 mgI/mL, 40 patients given Visipaque Injection 320 mgI/mL, and 40 patients given ioxaglate 320 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given Visipaque a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Peripheral arteriography was evaluated in two randomized, double-blind clinical trials in 49 adult patients given Visipaque Injection 320 mgI/mL, 25 given iohexol 350 mgI/mL, and 25 given ioxaglate 320 mgI/mL. Four additional peripheral arteriography studies were performed in 41 adult patients given Visipaque Injection 270 mgI/mL, 85 patients given Visipaque Injection 320 mgI/mL, 37 given iohexol 300 mgI/mL, and 47 given iopromide 300 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given Visipaque; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Visceral arteriography was evaluated in two randomized, double-blind clinical trials in 55 adult patients given Visipaque Injection 320 mgI/mL, 26 given iohexol 350 mgI/mL, and 25 given ioxaglate 320 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given Visipaque; a radiologic diagnosis was made in the majority of the patients. The results were similar to iohexol. Confirmation of the radiologic findings by other diagnostic methods was not obtained. The risk added to renal arteriography by giving Visipaque could not be analyzed.

Similar studies with digital subtraction angiography (DSA) were completed with comparable findings noted in cerebral arteriography, peripheral arteriography, and visceral arteriography. Studies have not been conducted to determine the lowest effective concentration.

INTRAVENOUS ADMINISTRATION

Excretory urography, contrast-enhanced computed tomography (CECT) of the head, CECT of the body, and peripheral venography were studied with either one or both Visipaque Injection concentrations (270 mgI/mL or 320 mgI/mL). In these intravenous studies, diagnostic visualization ratings were good or excellent in 96-100% of the patients and a radiologic diagnosis was made in all (100%) of the patients given Visipaque Injection. Results were compared to those of the active control. The number of patients studied in each indication is provided below.

Excretory urography was evaluated in one uncontrolled, unblinded clinical trial in 40 patients, 20 given Visipaque Injection 270 mgI/mL and 20 given Visipaque Injection 320 mgI/mL, and in two randomized, double-blind clinical trials in 50 adult patients given Visipaque Injection 270 mgI/mL, 50 patients given Visipaque Injection 320 mgI/mL, and 50 patients given iohexol 300 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given Visipaque; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active control. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

CECT of the head was evaluated in two randomized, double-blind clinical trials in 49 adult patients given Visipaque Injection 270 mgI/mL, in 50 patients given Visipaque Injection 320 mgI/mL, and in 49 patients given iohexol 300 mgI/mL. CECT of the body was evaluated in three randomized, double-blind clinical trials in 104 adult patients given Visipaque Injection 270 mgI/mL, in 109 patients given Visipaque Injection 320 mgI/mL, and in 101 patients given iohexol 300 mgI/mL. In both CECT of the head and body, visualization ratings were good or excellent in 100% of the patients given Visipaque; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Peripheral venography was evaluated in two randomized, double-blind clinical trials in 46 adult patients given Visipaque Injection 270 mgI/mL and in 50 patients given iohexol 300 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given Visipaque; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active control. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Visipaque (iodixanol) injection was administered to 1244 patients. The comparators administered to 861 patients included low osmolar nonionic, and high and low osmolar ionic contrast media. For complete demographics, see CLINICAL TRIALS section.

Serious, life-threatening and fatal reactions have been associated with the administration of iodine-containing contrast media, including Visipaque Injection. In clinical trials, 3/1244 patients given Visipaque Injection and 1/861 patients given a comparator died within 5 days or later after drug administration. Also, 7/1244 patients given Visipaque Injection and 8/861 given a comparator had serious adverse events. Rare reports of anaphylaxis have been documented during postmarket surveillance.

As with other contrast agents, Visipaque is often associated with sensations of discomfort, warmth or pain. In a subgroup of 1259 patients, for whom data are available; similar percentages of patients (30%) who received Visipaque or a comparator had application site discomfort, pain, warmth or cold. Visipaque had a trend toward fewer patient reports of moderate or severe pain or warmth; however, whether or not this related to the dose, rate of administration, site of injection or concentration has not been determined.

The following table of incidence of events is based upon blinded, controlled clinical trials with Visipaque Injection in controlled clinical studies in which Visipaque (1244 patients) was compared with low osmolar nonionic (iohexol, iopromide), a low osmolar ionic (ioxaglate), and a high osmolar ionic (diatrizoate) contrast agents. This listing includes all reported adverse events regardless of attribution. Adverse events (AEs) are listed by body system and in decreasing order of occurrence greater than 0.5% in the Visipaque group.

As the table shows, one or more adverse events were recorded in 248 of 1244 (20%) patients during the clinical trials, with the administration of Visipaque Injection or within the defined duration of the study follow-up period (24 to 72 hours). In intravenous and intra-arterial procedures, the incidence and type adverse reaction was similar to those of the studied nonionic comparators (iohexol). In a 757 patient subgroup for which data are available, women reported more adverse events 83/299 (27.8%) than men 77/458 (16.2%). Women reported more chest pain (9/299 or 3%) than men (4/458 or 0.8%).

The following selected adverse events were reported in ≤0.5% of the 1244 patients in controlled clinical trials who received Visipaque Injection.

Body as a WholeGeneral Disorders: back pain, fatigue, malaise.

Cardiovascular Disorders: arrhythmias, cardiac failure, conduction abnormalities, hypotension, myocardial infarction.

Nervous System: cerebral vascular disorder, convulsions, hypoesthesia, stupor, confusion.

Gastrointestinal System Disorders: dyspepsia.

Hypersensitivity Disorders: pharyngeal edema.

Respiratory System Disorders: asthma, bronchitis, dyspnea, pulmonary edema, rhinitis.

Renal System Disorders: abnormal renal function, acute renal failure, hematuria.

Peripheral Vascular Disorders: flushing, peripheral ischemia.

Skin and Appendage Disorders: hematoma, increased sweating.

Special Senses, Other Disorders: tinnitus.

Vision Disorders: abnormal vision.

Additional adverse events reported in other clinical studies and in foreign postmarketing surveillance and foreign clinical trials with the use of Visipaque Injection are: anaphylactic reactions, anaphylactoid reactions, hypoglycemia, amnesia, cardiac arrest, hypertension, dyskinesia, hemorrhage not otherwise specified, polymyalgia rheumatica, pulmonary embolism, respiratory depression, and cortical blindness.

The adverse effects of overdosage of any contrast agent may be life-threatening and affect mainly the pulmonary and cardiovascular systems. Treatment of an overdosage is directed toward the support of all vital functions and prompt institution of symptomatic therapy. Visipaque Injection does not bind to plasma or serum protein and can be dialyzed.