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Iodixanol (Systemic)


VA CLASSIFICATION
Primary: DX101

Commonly used brand name(s): Visipaque 270; Visipaque 320.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid, radiopaque (cardiac disease)—

Diagnostic aid, radiopaque (peripheral vascular disorders)—

Diagnostic aid, radiopaque (urinary tract disorders) —

Diagnostic aid, radiopaque contrast enhancer in computed tomography—

Diagnostic aid, radiopaque (brain disorders)—
Note: Iodixanol is a dimeric nonionic radiopaque contrast agent {01}.



Indications

Accepted

Angiocardiography—Iodixanol is indicated in angiocardiography (left ventriculography and selective coronary arteriography) for the evaluation of coronary arteries and left ventricle {01}.

Angiography
Aortography
Arteriography or
Venography—Iodixanol by intra-arterial injection is indicated in arteriography for the evaluation of the peripheral arteries, major visceral arterial branches, and arterial lesions of the brain; and in aortography to visualize the aorta {01}. Also, it is indicated for visceral intra-arterial digital subtraction angiography {01}. Iodixanol is indicated by intravenous injection in venography for the evaluation of the peripheral venous system {01}.

Urography, excretory—Iodixanol is indicated in excretory urography to evaluate renal function {01}.

Brain imaging, computed tomographic—Iodixanol is indicated for enhancement of computed tomographic images of the brain (CT of the brain) {01}.

Body imaging, computed tomographic—Iodixanol is indicated for enhancement of computed tomographic images of the body (CT of the body) {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    1550.2 {01}


Osmolality
    Low. The osmolality of the injections with iodine concentrations of 270 and 320 mg per mL is 290 milliosmoles (mOsmol) per kg of water {01}.

Mechanism of action/Effect:

Organic iodine compounds attenuate x-rays as they pass through the body, thereby allowing the body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. The degree of opacity produced by these compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. After intravascular administration, iodixanol makes opaque those internal structures in its path of flow, allowing their visualization until significant hemodilution and elimination occur {01}.

Distribution:

Volume of distribution—0.26 L per kg of body weight {01}.

Protein binding:

None {01}.

Half-life:


Elimination:

Approximately 123 (± 8) minutes (in men) {01}.


Note: In patients with significantly impaired renal function (mean creatinine clearance rate, 9.91 [± 3.58] mL per minute), the plasma half-life is increased to 23 hours.



Time to peak opacification

Immediate; 15 to 120 seconds after bolus injection {01}.

Renal parenchyma (calyces and pelves)—1 to 3 minutes, with optimum contrast within 5 to 15 minutes {01}.

Peak serum concentration:

Immediate, but concentration falls rapidly within 5 to 10 minutes as iodixanol is distributed throughout the vascular and extravascular compartments {01}.

Elimination:
    Renal—Approximately 97% of dose is eliminated unchanged within 24 hours {01}.
    Fecal—Less than 2% of dose is excreted within 5 days after injection {01}.
    In dialysis—Iodixanol is dialyzable {01}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to iodine or other iodinated contrast media may be sensitive to iodixanol also {01}.

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate the carcinogenic potential of iodixanol have not been performed {01}. Iodixanol demonstrated no mutagenic effects in the Ames test, the CHO/HGPRT assay, a chromosome aberration assay in CHO cells, and an in vivo mouse micronucleus test {01}.

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

Reproduction studies in rats and rabbits have not shown that iodixanol causes harm to the fetus when administered in doses up to 0.2 times (in rats) and 0.4 times (in rabbits) the maximum recommended dose for a 50-kg human {01}.

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known whether iodixanol is distributed into breast milk {01}. However, the manufacturer recommends that consideration be given to temporarily discontinue breast-feeding following the administration of iodixanol {01}.

Pediatrics

Safety and efficacy have not been established {01}.


Geriatrics


Approximately one-half of the patients in clinical trials with iodixanol were 60 years of age or older {01}. These studies did not demonstrate geriatrics-specific problems that would limit the usefulness of iodixanol in the elderly {01}.

Dehydration and/or the risk of renal failure may be exacerbated by iodixanol in geriatric patients, especially those with advanced vascular disease, age-related renal function impairment, or pre-existing dehydration; adequate hydration is recommended before and following the administration of iodixanol {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Cholecystographic agents, oral    (may increase the risk of renal toxicity when closely followed by intravascular iodixanol, especially in patients with hepatic function impairment {01})


General anesthesia    (a greater number of adverse effects have been reported in patients who have undergone general anesthesia, in part due to the patient's inability to identify symptoms or due to the hypotensive effects of anesthesia, which can prolong the exposure to iodixanol {01})


Diagnostic interference
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With other diagnostic test results
Thyroid function determinations    (intravascular administration of iodixanol may alter serum protein–bound iodine [PBI] concentrations for up to 16 days; thyroid test should be performed prior to administration of iodixanol. Other thyroid function tests not based on measurement of iodine, such as resin triiodothyronine uptake, may not be affected {01})


Urinalysis    (iodixanol may interfere with some chemical determinations made on urine, such as protein and specific gravity {01})

With physiology/laboratory test values
Platelet aggregation and activation    (may be decreased with iodixanol {01})


Thrombin generation time    (may be increased with iodixanol since in vitro studies with human blood and serum have shown iodixanol to slightly inhibit coagulation {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist

For all procedures:
Allergies or asthma, history of    (risk of idiosyncratic response or anaphylactoid reaction; caution is recommended when administering iodixanol to patients with a history of allergies or asthma {01})


» Dehydration, especially associated with pre-existing renal disease, advanced vascular disease, congestive heart disease, diabetes mellitus, or in elderly patients    (osmotic diuretic action of iodixanol may exacerbate dehydration and increase risk of acute renal failure {01})


Hyperthyroidism    (administration of iodixanol may precipitate thyroid storm {01})


Immunodeficiency or autoimmune disorders    (nonspecific mediator release may increase risk of idiosyncratic response or anaphylactoid reaction {01})


» Pheochromocytoma    (use of iodixanol may precipitate severe hypertension; amount of iodixanol should be kept to a minimum and blood pressure should be monitored during the procedure {01})


Renal function impairment, severe    (elimination of iodixanol may be delayed; may cause disruption of the blood-brain barrier, leading to accumulation of iodixanol in the brain {01})


» Sensitivity to iodinated contrast media    (increased risk of anaphylactoid reaction in patients with history of prior reactions to contrast media {01})


Sickle cell disease    (iodixanol may promote sickling in patients who are homozygous for sickle cell disease {01})


For angiocardiography
Pulmonary emphysema, chronic    (caution should be used in patients with this condition {01})


For angiography
Homocystinuria    (procedure may increase risk of thrombosis and embolism {01})


For venography
Infection, local or
Ischemia, severe or
Phlebitis or
Thrombosis or
Venous system obstruction    (caution should be used in patients with these conditions {01})




Side/Adverse Effects

Note: Most of the adverse effects occur soon after the administration of contrast media and are usually self-limiting and of short duration. However, some adverse effects may be delayed or may be long-lasting {01}.
Iodixanol is reported to cause heat and pain on injection at a rate similar to other low-osmolality contrast agents {01}.
Thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with nonionic contrast media; however, these events appear to be related to the administration technique {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Cardiovascular effects, including angina pectoris{01} (chest pain), arrythmias{01} (irregular heartbeat), hypotension{01} (lightheadedness; unusual tiredness or weakness), and syncope{01} (fainting)
    
central nervous system (CNS) effects, including paresthesia{01} (tingling or burning sensation)
    
edema{01}
    
pseudoallergic reaction{01} (skin rash or hives; stuffy nose; troubled breathing)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Diarrhea{01}
    
dizziness{01}
    
headache{01}
    
nausea{01}
    
vomiting{01}





Overdose

Treatment of overdose
Treatment of iodixanol overdose is symptomatic and supportive {01}.

Iodixanol can be dialyzed {01}.


Patient Consultation
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use

Action in the body
Injection into vein or artery; visualization of radiopacity in heart, blood vessels, brain, urinary tract, and other organs possible with x-rays

Before having this test
»   Conditions affecting use, especially:
Sensitivity to iodine or other iodinated contrast media





Breast-feeding—Temporary discontinuation should be considered





Use in the elderly—Possible exacerbation of dehydration
Other medical problems, especially dehydration and pheochromocytoma

Preparation for this test
Adequate intake of fluids to prevent dehydration

Special preparatory instructions may be given; patient should inquire in advance

Precautions after having this test
Possible interference with future thyroid tests


Side/adverse effects
Signs of potential side effects, especially cardiovascular effects, CNS effects, edema, and pseudoallergic reaction, which may occur immediately or within minutes of administration


General Dosing Information
Manufacturer's package insert or other appropriate literature should be consulted for specific techniques and procedures for the administration of contrast media.

Sensitivity test doses are not usually recommended since severe or fatal reactions to contrast media are not predictable from a patient's history or a sensitivity test. On some occasions, severe or fatal reactions have occurred with a test dose or with a full dose in patients who did not react to the test dose {01}.

Pretreatment with corticosteroids and/or antihistamines may minimize the incidence and severity of reactions in patients with a history of severe reaction to contrast media or with other high-risk conditions (e.g., asthma or history of allergies, positive allergy history to skin allergens or penicillins, dehydration, history of seizures, pheochromocytoma) {01}.

Adequate hydration is recommended for all patients before and after the examination. Intravenous or oral intake of fluids may continue up to the time of administration of iodixanol {01}.

During and for at least 30 to 60 minutes after intravascular injection of iodixanol, the patient should be observed for possible severe reactions; trained personnel and emergency facilities should be available during this period {01}.

Iodixanol should not be administered intrathecally due to possible severe adverse effects including convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, cerebral edema, and death {01}.

Nonionic contrast media, such as iodixanol, inhibit blood coagulation in vitro less than ionic contrast media {01}. Blood cell aggregation has been reported when blood remains in contact with syringes containing nonionic contrast media {01}. Thus, thromboembolic events causing myocardial infarction and stroke, reported during angiographic procedures, may have resulted from aggregation of blood that had come in contact with the contrast agent outside the body {01}. Risk factors for blood cell aggregation should be minimized by performing the procedure in the shortest time possible, using plastic rather than glass syringes, and flushing catheters with heparinized saline solutions. {01}


Parenteral Dosage Forms

IODIXANOL INJECTION

Usual adult dose
Angiocardiography
Intra-arterial, as a solution containing the equivalent of 320 mg of iodine per mL, injected into the following vessels {01}:


• Left coronary artery—range, 3 to 10 mL.


• Right coronary artery—range, 3 to 8 mL.


• Left ventricle—range, 20 to 45 mL.

Angiography
Intra-arterial, by digital subtraction, as a solution containing the equivalent of 270 mg of iodine per mL, injected into the following vessels {01}:


• Renal arteries—range, 10 to 25 mL.


• Aorta—range, 20 to 50 mL.


• Major branches of aorta—range, 5 to 30 mL.
Intra-arterial, as a solution containing the equivalent of 320 mg of iodine per mL, injected into the following vessels {01}:


• Carotid or vertebral arteries—range, 5 to 8 mL.


• Aorta—range, 10 to 50 mL.


• Major branches of aorta—range, 2 to 10 mL.


• Aortofemoral runoffs—range, 6 to 15 mL.


• Peripheral arteries—range, 3 to 15 mL.

Aortography or
Arteriography
Intra-arterial, as a solution containing the equivalent of 320 mg of iodine per mL, injected into the following vessels {01}:


• Carotid arteries—range, 10 to 14 mL.


• Vertebral arteries—range, 10 to 12 mL.


• Renal arteries—range, 8 to 10 mL.


• Aorta—range, 30 to 70 mL.


• Major branches of aorta—range, 10 to 70 mL.


• Aortofemoral runoffs—range, 20 to 90 mL.


• Peripheral arteries—range, 15 to 30 mL.

Venography
Intravenous, 50 to 150 mL per lower extremity of a solution containing the equivalent of 270 mg of iodine per mL {01}.

Urography, excretory
Intravenous, 1 mL per kg of body weight of a solution containing the equivalent of 270 or 320 mg of iodine per mL {01}.

Brain imaging, computed tomography or
Body imaging, computed tomography
Intravenous, by bolus injection, 75 to 150 mL of a solution containing the equivalent of 270 or 320 mg of iodine per mL; or by intravenous infusion, 100 to 150 mL of a solution containing the equivalent of 270 or 320 mg of iodine per mL {01}.


Usual adult prescribing limits
For procedures requiring intra-arterial administration, into the following vessels {01}


• Carotid or vertebral arteries: Up to 175 mL.


• Left coronary artery or


• Right coronary artery or


• Left ventricle: Up to 200 mL.


• Renal arteries or


• Aorta and major branches or


• Aortofemoral runoffs or


• Peripheral arteries: Up to 250 mL.
Venography—Up to 250 mL {01}.
Urography, excretory—Up to 100 mL {01}.
Brain imaging, computed tomography or {01}
Body imaging, computed tomography—Up to 150 mL {01}.

Usual pediatric dose
Safety and efficacy have not been established {01}.

Usual geriatric dose
See Usual adult dose {01}.

Strength(s) usually available
U.S.—


550 mg of iodixanol with 270 mg of iodine per mL (Rx) [Visipaque 270 (0.074 mg calcium chloride dihydrate) (1.87 mg sodium chloride)]


652 mg of iodixanol with 320 mg of iodine per mL (Rx) [Visipaque 320 (0.044 mg calcium chloride dihydrate) (1.11 mg sodium chloride)]

Packaging and storage:
Store between 15 and 30 ºC (59 and 86 ºF), unless otherwise specified by manufacturer. Protect from strong daylight and direct exposure to sunlight. Protect from freezing. {01}



Revised: 10/08/1997



References
  1. Visipaque package insert (Nycomed—US), Rev 4/96, Rec 9/96.
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