Iohexol (Systemic)


VA CLASSIFICATION
Primary: DX101

Commonly used brand name(s): Omnipaque 140; Omnipaque 180; Omnipaque 210; Omnipaque 240; Omnipaque 300; Omnipaque 350.

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



Category:

Note: Iohexol is a nonionic radiopaque contrast agent. {01} {02}



Diagnostic aid, radiopaque (central nervous system disorders)—

Diagnostic aid, radiopaque (cerebrospinal fluid disorders)—

Diagnostic aid, radiopaque (cardiac disease)—

Diagnostic aid, radiopaque (vascular disease)—

Diagnostic aid, radiopaque (urinary tract disorders)—

Diagnostic aid, radiopaque (peritoneal disorders)—

Diagnostic aid, radiopaque contrast enhancer in computed tomography—

Diagnostic aid, radiopaque contrast enhancer adjunct in computed tomography—

Diagnostic aid, radiopaque (biliary tract disorders)—

Diagnostic aid, radiopaque (joint disease)—

Diagnostic aid, radiopaque (gastrointestinal tract disorders)—

Indications

Accepted

Intrathecal
Myelography (lumbar, thoracic, cervical, total columnar)—Iohexol is indicated in adults and children for lumbar, thoracic, cervical, and total columnar myelography (standard or computed tomographic) to determine the presence of abnormalities in the spinal column, spinal canal, and the central nervous system (CNS). {01} {02} {31} {33} {34} {49} {50} {52}

Intravascular
Angiocardiography—Iohexol is indicated in angiocardiography (selective coronary arteriography or ventriculography) to visualize lesions or malformations of the heart and obstructions or anomalies of the major thoracic vessels. {01} {02} {34} {38}

Angiography
Aortography
Arteriography or
Venography—Iohexol is indicated in aortography (aortic arch, ascending aorta, abdominal aorta and branches), arteriography (cerebral or peripheral), and in peripheral venography (phlebography) to visualize specific regions of the vascular system and blood flow in such areas to help in the diagnosis and evaluation of neoplasms (known or suspected) or vascular diseases (congenital or acquired) that may cause changes in normal vascular anatomy or physiology. Also, it is indicated in adults for intra-arterial and intravenous digital subtraction angiography of head, neck, abdominal, renal, and peripheral vessels. {01} {02} {34} {52}
—In cerebral arteriography, iohexol is indicated to determine the presence and extent of certain neoplasms (e.g., gliomas, pituitary adenomas, metastatic lesions) and non-neoplastic lesions, such as cerebral infarctions, arteriovenous malformations, and aneurysms.
—In venography, it is used mainly for deep venous thrombosis. {01} {34} {50}

Urography, excretory—Iohexol is indicated for excretion urography to evaluate abnormalities of the urinary tract such as urinary tract obstructions. {01} {02} {34}

Herniography1—Iohexol is indicated in herniography in adults. {01}

Brain imaging, computed tomographic—Iohexol is indicated for enhancement of computed tomographic images (CT of the brain) to determine the presence and extent of neoplasms or other lesions such as cerebral infarction or infection. {01} {34} {50}

Body imaging, computed tomographic—Iohexol is indicated for enhancement of computed tomographic images (CT of the body) to detect and evaluate lesions in the liver, pancreas, kidneys, aorta, mediastinum, pelvis, abdominal cavity, and retroperitoneal space. {01} {34}

Intraductal
Pancreatography, endoscopic retrograde1and
Cholangiopancreatography, endoscopic retrograde1—Iohexol is indicated in adults in endoscopic retrograde pancreatography and endoscopic retrograde cholangiopancreatography for visualization of all portions of the biliary tree. {01}

Intrasynovial
Arthrography—Iohexol is indicated for arthrography in the diagnosis of post-traumatic or degenerative joint diseases or synovial rupture, for visualization of communicating bursae or cysts, and in meniscography. {01} {30} {34} {52}

Oral
Abdominal imaging, computed tomographic, adjunct1—Diluted iohexol administered orally is indicated for use in contrast enhanced computed tomography of the abdomen (CT of the abdomen) in conjunction with intravenous iohexol. {01} {74}

Radiography, gastrointestinal1—Undiluted iohexol is indicated for oral pass-through examination of the gastrointestinal tract. {01} {74}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    821.14


Osmolality
    Low. The osmolality of the injection with iodine concentrations of 140, 180, 210, 240, 300, and 350 mg per mL is 322, 408, 460, 520, 672, and 844 mOsmol per kg of water, respectively {01}

Note: Iohexol injection is hypertonic as compared to plasma and cerebrospinal fluid (approximately 285 and 301 mOsmol per kg of water, respectively). {01}


Mechanism of action/Effect:

Organic iodine compounds block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine {53}. 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 intrathecal administration into the subarachnoid space, diffusion of iohexol in the CSF allows the visualization of the subarachnoid spaces of the head and spinal canal. After intravascular administration, iohexol makes opaque those vessels in its path of flow, allowing visualization of the internal structures until significant hemodilution occurs. {01} {02} {50}

Distribution:

Intrathecal—Diffuses upward through the CSF; penetrates into nerve root sleeves, nerve rootlets, and narrow areas of the subarachnoid space. Also, enters extracellular fluid of the brain tissue and pial surface of cerebral and cerebellar tissue adjacent to subarachnoid areas. In patients with normal CSF dynamics, it is eliminated from CSF into the blood within several hours. {01} {34} {52}

Intravascular—Rapidly distributed throughout extracellular fluid following intravenous administration. No significant deposition in tissues. Does not cross blood-brain barrier, but accumulates within the interstitial tissues of malignant tumors of the brain due to the break in the blood-brain barrier caused by the tumor. {01} {02} {34} {52}

Protein binding:

Very low. {14}

Half-life:


Elimination:

Intrathecal: 3.4 hours (mean). {52}

Intravascular: Approximately 2 hours (with normal renal function). {02} {34} {52}



Time to peak opacification:


Standard myelography:

Immediate and for up to 30 minutes. {34} {52}



CT myelography {52}:

Thoracic region: 1 hour.

Cervical region: 2 hours.

Basal cisterns: 3 to 4 hours.

Ventricles and sulci: 5 to 6 hours.



Arteriography:

Immediate.



Urography:

5 to 15 minutes. {52}


Peak serum concentration:

Intrathecal—2 to 6 hours. {52}

Intravascular—Immediate, but concentration falls rapidly as iohexol is distributed throughout the extravascular compartment. {52}

Elimination:
    Intrathecal—Primarily renal, mainly by glomerular filtration (88% of dose eliminated unchanged within 24 hours). {52}
    Intravascular—Primarily renal, mainly by glomerular filtration (80 to 90% of dose eliminated unchanged in 24 hours). {52}
    Intraductal or intrasynovial—Absorbed into the surrounding tissue and eliminated by the kidneys and bowel, as for intravascular administration. {01}
    Oral—Only 0.1 to 0.5% of the administered dose is excreted by the kidneys; renal elimination may increase in the presence of bowel perforation or obstruction. {01}

Note: In patients with impaired renal function, the elimination of iohexol is prolonged depending upon the degree of impairment, thus, resulting in prolonged plasma iohexol levels. Excretion through the gallbladder and into the small intestine may increase. {01} {34} {52}



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to iodine or other iodinated contrast media may be sensitive to iohexol also. {52}

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of iohexol have not been performed. {68}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. However, other organically bound iodine–containing preparations administered near term by intra-amniotic injection have caused hypothyroidism in some neonates. {04}

Also, elective contrast radiography of the abdomen is usually not recommended during pregnancy because of the risks to the fetus from radiation exposure {01}.

Reproduction studies in rats and rabbits have not shown that iohexol, administered in doses up to 100 times the human dose, impairs fertility or causes harm to the fetus. {01} {34} {52}

FDA Pregnancy Category B. {01} {68}

Breast-feeding

Although it is not known to what extent iohexol is distributed into breast milk, breast-feeding is not recommended for at least 24 hours following administration of iohexol. {01} {68}

Pediatrics

Appropriate studies on the relationship of age to the effects of iohexol have not been performed in pediatric patients. However, it is known that pediatric patients, especially those with asthma, allergies, congestive heart failure, or serum creatinine greater than 1.5 mg per dL or those less than 12 months of age, exhibit an increased risk of having severe adverse side effects to radiopaque contrast media. {01} {34} {50}

Dehydration and/or the risk of renal failure may be exacerbated by iohexol in infants and young children, especially those with polyuria, oliguria, diabetes, or pre-existing dehydration; adequate hydration is recommended before and following intravascular administration of iohexol. {01} {34} {50}


Geriatrics


Diagnostic studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of iohexol in the elderly. However, elderly patients are more likely to have age-related renal function impairment, which may require lower dosage in patients receiving iohexol. {26} {28}

Dehydration and/or the risk of renal failure may be exacerbated by iohexol in geriatric patients, especially those with polyuria, oliguria, diabetes, or pre-existing dehydration; adequate hydration is recommended before and following administration of iohexol. {34}

The elderly may be more sensitive to the effects of iohexol on thyroid function. Iodine-induced thyrotoxicosis may occur 4 to 12 weeks following contrast radiography. Thyroid function monitoring may be needed in geriatric patients. {75} {80}

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):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antidepressants, tricyclic or
CNS stimulation–producing medications (See Appendix II ) or
Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline or
» Phenothiazines or
» Trimeprazine    (although not specifically reported for iohexol, concurrent use of phenothiazines with intrathecal administration of metrizamide, another nonionic contrast agent, has been associated with occurrence of seizures because of lowered seizure threshold effect of these medications; until more conclusive evidence is available medications that lower the seizure threshold should be discontinued for at least 48 hours before and 24 hours after myelography {01} {34} {49} {50} {52})


Beta-adrenergic blocking agents    (concurrent intravascular administration of iohexol with beta-adrenergic blocking agents may increase the risk of moderate to severe anaphylactoid reaction; also, hypotensive effects may be exacerbated; discontinuation of the beta-adrenergic blocking agent may be advisable before administration of contrast media in patients with other risk factors {34} {35} {49} {52} {54} {55} {56} {71} {80})


Cholecystographic agents, oral    (may increase the risk of renal toxicity when closely followed by intravascular iohexol, especially in patients with hepatic function impairment {34} {52})


Hypotension-producing medications, other (See Appendix II )    (the risk of severe hypotension may be increased if iohexol is given concurrently with other medications that produce hypotension {49})


Interleukin-2    (incidence of delayed reactions to intravenous contrast media [e.g., hypersensitivity, fever, skin rash, flu-like symptoms, joint pain, flushing, pruritus, emesis, hypotension, dizziness occurring more than 1 hour after administration] may be increased in patients who have received interleukin-2; some symptoms may resemble a ``recall'' reaction to interleukin-2; supportive medical treatment may be necessary if symptoms are significant; delaying contrast media administration until 6 weeks after administration of interleukin-2 may reduce incidence of these reactions {57} {58} {59} {60} {61} {62})


Nephrotoxic medications, other (See Appendix II )    (concurrent intrathecal or intravascular administration of iohexol with other nephrotoxic medications may increase the potential for nephrotoxicity {49})


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
Blood pool imaging    (intravascular administration of iohexol decreases technetium Tc 99m–labeling of red blood cells, which may impair blood pool imaging {49})


Leukocyte counts and
Red cell counts    (may be temporarily decreased {34})


Prothrombin time (PT) and
Thromboplastin time    (may be increased with iohexol since in vitro studies with animal blood have shown other nonionic contrast media to slightly inhibit all stages of coagulation {45} {49})


Skeletal imaging    (intravenous administration of iohexol immediately after administration of Tc 99m medronate, technetium Tc 99m oxidronate, technetium Tc 99m pyrophosphate, and technetium Tc 99m [pyro- and trimeta-] phosphates may cause renal and hepatic uptake of these technetium Tc 99m–labeled agents {49} {63})


Thyroid function determinations and
Thyroid imaging    (intravascular or intrathecal administration of iohexol may alter serum protein–bound iodine [PBI] concentrations and radioactive iodine or pertechnetate ion uptake for up to 2 weeks; thyroid test should be performed prior to administration of iohexol. Other thyroid function tests not based on measurement of iodine, such as resin triiodothyronine uptake, may not be affected {01} {34} {52} {75})


Urinalysis    (iohexol may interfere with some chemical determinations made on urine, such as protein and specific gravity; urine should be collected prior to or at least 2 days after intravenous administration of iohexol {46} {47})

With physiology/laboratory test values
Creatinine, serum    (concentration may be increased with iohexol {28} {45} {49})


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 {01} {34} {50}

For all procedures (especially those requiring intrathecal or intravascular administration):
Allergic reaction (anaphylaxis) to penicillins or to skin allergens, previous    (although the risk of anaphylactoid reaction may be less with iohexol than with high-osmolality contrast agents, caution is recommended when administering iohexol to patients who have had a previous reaction to penicillins or to skin allergens {51} {52} {54} {55} {64} {71} {80})


Allergies or asthma, history of    (although the risk of idiosyncratic response or anaphylactoid reaction may be less with iohexol than with high-osmolality contrast agents, caution is recommended when administering iohexol to patients with a history of allergies or asthma {43} {51} {52} {54} {55} {64} {71} {80})


» Dehydration, especially associated with pre-existing renal disease, advanced vascular disease, or diabetes mellitus, or in pediatric and elderly patients    (osmotic diuretic action of iohexol may exacerbate dehydration and increase risk of acute renal failure {51} {52} {65})


Renal function impairment, severe    (elimination of iohexol may be delayed; although the risk of contrast-induced nephrotoxicity in the presence of renal insufficiency [serum creatinine ³ 132.6 micromoles/L] may be less with iohexol than with high-osmolality contrast agents, caution is recommended {26} {27} {28} {34} {66} {69} {80})


» Sensitivity to iodinated contrast media    (increased risk of anaphylactoid reaction in patients with history of prior reactions to contrast media {01} {35})


For intrathecal use {01}:
Alcoholism, chronic    (increased risk of side effects because of existing brain or liver damage {49})


Bleeding, subarachnoid    (increased risk of meningeal irritation or arachnoiditis {01} {52})


Epilepsy, history of    (myelographic procedure may increase risk of seizures {49})


Infection, local or systemic, significant{52}
Multiple sclerosis{49}
For intravascular use {01}:
Hyperthyroidism    (administration of iohexol may precipitate thyroid storm)


» Pheochromocytoma    (use of iohexol may precipitate severe hypertension; amount of iohexol injected should be kept to a minimum and blood pressure should be monitored during the procedure; also, pretreatment with the alpha-adrenergic blocking agent phentolamine is recommended {49} {51})


Sickle cell disease    (iohexol may promote sickling in patients who are homozygous for sickle cell disease; however, sickling potential of iohexol is less than that of high-osmolality ionic agents {49})


For angiocardiography:
Angina, unstable    (increased risk of a severe cardiac reaction {71})


Cardiac failure, incipient    (fluid overload, pressure changes, and expansion of blood volume may aggravate condition {01} {68})


Pulmonary hypertension, severe    (hypervolemic effect of iohexol may further increase pulmonary artery and venous pressures due to an increase in cardiac output and a rise in left ventricular end-diastolic and left atrial pressures {01} {49} {50})


For cerebral arteriography:
Arteriosclerosis, advanced or
Cardiac decompensation or
Cerebral embolism, recent or
Hypertension, severe or
Migraine or
Senility or
Thrombosis, recent    (increased risk of vessel occlusion {01} {52} {68})


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


For peripheral arteriography:
» Buerger's disease    (procedure may induce severe arterial or venous spasm {68})


» Ischemia, severe, associated with ascending infection{68}
For excretory urography:
» Anuria or
» Diabetes mellitus    (administration of iohexol may increase risk of acute renal failure {01} {68})


For arthrography:
» Infection in or near joint to be examined    (procedure may increase risk of complications)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For intravascular use
Blood pressure determinations    (may be required during examination, especially in patients with known or suspected pheochromocytoma or hemodynamic compromise or instability {53})


Thyroid function determinations    (iodine-induced thyrotoxicosis may occur 4 to 12 weeks following contrast radiography in geriatric patients; thyroid function monitoring may be needed {75})




Side/Adverse Effects

Note: Adverse effects may vary directly with the concentration of the agent, the amount and technique used, and the underlying pathology. Increases in osmolality, volume, concentration, viscosity, and rate of administration of the solution may increase the incidence and severity of adverse effects. {01} {02} {25} {26} {51}
Most of the adverse effects are usually self-limited and of short duration. {32} {51}
Overall incidence of adverse effects with nonionic contrast agents, such as iohexol, has been reported to be less than with ionic contrast agents. {02} {10} {12} {25} {27} {51} {71} {77} {79}
Nonionic contrast media, such as iohexol, have been reported to produce fewer and less severe alterations in cardiac hemodynamics and electrocardiograms than standard ionic contrast agents during cardiac angiography. {11} {12} {13} {25} {38} {71} {77}
Low-osmolality contrast agents, such as iohexol, are reported to cause less heat and pain on injection than high-osmolality agents, such as diatrizoates and iothalamate. {02} {06} {34} {77}
Thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with non-ionic contrast media; however, these events appear to be technique-related. {01} {09} {34} {50} {76} {78}
Headaches following intrathecal administration of iohexol may be more frequent and persistent in patients not adequately hydrated. {01}
Dehydration may be exacerbated by the osmotic diuretic action of the hypertonic contrast solutions of iohexol, in some cases resulting in a shock-like state, following intravascular administration of iohexol in geriatric, azotemic, and dehydrated or debilitated patients. {34} {68}
Transient global amnesia has been reported in 2 patients after cerebral angiography, in which 20 mL of iohexol (containing the equivalent of 240 mg of iodine per mL) was administered into the ascending aorta. {72}

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 rare
With all procedures
    
Pseudo-allergic reaction (skin rash or hives; stuffy nose; swelling of face or skin; swelling of the tongue; wheezing, tightness in chest or troubled breathing{22}{23}{24}{25}{49}{50}{71}{73}{79})
Note: Pseudo-allergic reactions are usually transient. However, they may be initial manifestations of more severe anaphylactoid reactions. The anaphylactoid reaction may progress to respiratory arrest and vasomotor collapse if appropriate treatment is not administered. {55}



With intrathecal or intravascular administration
    
Bronchospasm or pulmonary edema (severe wheezing or troubled breathing{36}{39})
    
severe hypotension (unusual tiredness or weakness{38}{39}{71})

With intravascular administration
    
Cardiotoxic effects, with ventricular tachycardia or fibrillation (fast or irregular heartbeat{01}{39}{40}{71})
    
seizures{01}
Note: In angiocardiography, bradyarrhythmias occur far less commonly with low-osmolality contrast agents than with high-osmolality agents. For iohexol, bradycardia has been reported with an incidence of 1%. {01} {68} {71} {79}






Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
With intrathecal or intravascular administration {01} {31} {32} {33}
    
Mild to moderate headache
    
mild to moderate nausea and vomiting{52}
Note: Headache, nausea, and vomiting may occur 1 to 10 hours after intrathecal injection and last for a few hours, usually disappearing within 24 hours; or, less frequently after intravascular injection, may occur immediately and last for a few minutes. {52}



With intrathecal administration
    
Backache
    
dizziness
    
meningeal irritation (stiffness of neck{01}{31}{32}{33})

With intrasynovial administration
    
Joint pain or exacerbation of existing pain{01}{68}
    
swelling at joint{01}{68}

With intraductal administration
    
Pain{01}{68}
Note: Pain may be associated with injection pressure and volume injected. {01} {68}



With oral administration
    
Mild, transient diarrhea{68}


Incidence less frequent or rare
With intrathecal or intravascular administration
    
Mild unusual feeling of warmth{01}

With intrathecal administration
    
CNS effects (severe headache; ringing or buzzing in ears; unusual tiredness or weakness)
    
difficult urination
    
drowsiness
    
increased sensitivity of eyes to light
    
increased sweating
    
loss of appetite{68}

With intravascular administration
    
Blurred vision or other changes in vision
    
drowsiness or lightheadedness
    
metallic taste
    
pain or burning at injection site{68}

With oral administration
    
Moderate diarrhea
    
nausea and vomiting{68}






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopaque Agents (Diagnostic).

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

Description of use

Action in the body:
Injection into spinal canal; visualization of radiopacity in head and spinal cord possible with x-rays

Injection into vein or artery; visualization of radiopacity in heart, blood vessels, and urinary tract possible with x-rays

Direct injection into region to be studied; visualization of joint spaces, peritoneal herniations, pancreatic and bile ducts

Oral administration; visualization of the gastrointestinal tract

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

Pregnancy—Risk to the fetus from radiation exposure; may cause hypothyroidism in neonate





Breast-feeding—Breast-feeding not recommended for 24 hours afterwards





Use in children—Increased risk of severe adverse reactions, especially in children with other medical problems; possible exacerbation of dehydration






Use in the elderly—Possible exacerbation of dehydration; increased risk of thyrotoxicosis
Other medications, especially phenothiazines, tricyclic antidepressants, and trimeprazine (with intrathecal use)
Other medical problems, especially anuria, dehydration, diabetes mellitus, and pheochromocytoma

Preparation for this test
Adequate intake of fluids to prevent dehydration

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

With intrathecal use
Normal diet up to 2 hours before procedure; moderate amounts of {05} clear liquids may be permitted up to time of procedure

Precautions after having this test
Possible interference with future thyroid tests

With intrathecal use
Avoiding movement during and for several hours after administration

Keeping head position as instructed during and after examination


Side/adverse effects
Signs of possible side effects, especially pseudo-allergic reaction and cardiac or pulmonary problems that 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. {53} {55} {68}

Pretreatment with corticosteroids and/or antihistamines may minimize the incidence and severity of reactions in patients with a history of severe reactions 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). In some studies, the additional use of ephedrine has been shown to be beneficial in preventing anaphylactoid reactions (except in patients with a history of hypertension or cardiovascular disease). When the use of a contrast agent is being considered, the following protocols are recommended: {01} {15} {16} {17} {18} {19} {20} {21} {22} {49} {50} {51} {53} {55} {65} {69} {71} For high-risk patients

   • Use of a high-osmolality contrast agent plus pretreatment with a corticosteroid (oral prednisone 50 mg administered 13 hours, 7 hours, and 1 hour before procedure) and antihistamine (intramuscular, intravenous, or oral diphenhydramine, 50 mg administered 1 hour prior to procedure) or
   • Use of a low-osmolality contrast agent if pretreatment is not feasible or
   • Use of a low-osmolality contrast agent plus corticosteroid pretreatment.
For low-risk patients

   • Use of a high-osmolality contrast agent or
   • Use of a high-osmolality contrast agent and corticosteroid pretreatment.
Adequate hydration is recommended for all patients before and after the examination. Intravenous or oral intake of fluids may continue up to time of administration of iohexol. {01}

During and for at least 30 to 60 minutes after intravascular injection of iohexol, and for at least 12 hours (up to 24 hours in some cases) after intrathecal administration, the patient should be observed for possible severe reactions; competent personnel and emergency facilities should be available during this period. {01} {51}

Dosage and concentration of iodine (as iohexol injection) are dependent upon the degree and extent of contrast needed in the areas under examination and on the equipment and technique used. {68}

For intrathecal use
Pretreatment with barbiturates may be used in patients who have a history of seizures but are not on anticonvulsant therapy. Patients who are on anticonvulsant therapy should continue receiving their medication when receiving iohexol. {01} {34}

A normal diet may be ingested up to 2 hours prior to the administration of iohexol. {01}

If inadvertent intracranial entry of a large or concentrated bolus of iohexol occurs, treatment with anticonvulsants may be used to minimize the risk of seizures. {01} {52} {68}

Direct intracisternal or ventricular administration of iohexol for standard radiography is not recommended. {01}

During and for several hours after the procedure the patient must remain inactive to minimize high cephalad dispersion of iohexol. {34}

Information on patient management and positioning during and after procedure is included in the manufacturer's package insert. {01}

For intravascular use
Nonionic contrast media, such as iohexol, inhibit blood coagulation in vitro less than ionic contrast media. Blood cell aggregation has been reported when blood remains in contact with syringes containing nonionic contrast media. 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. 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} {09} {34} {78}

During and immediately after administration of iohexol for digital subtraction angiography of neck and head, the patient must remain inactive and avoid swallowing. Otherwise, poor arterial visualization may result. {68}

For treatment of adverse effects
Recommended treatment consists of the following: {01} {35} {41} {42}

   • For major or life-threatening reactions, careful monitoring of vital signs and emergency therapy, including artificial respiration with oxygen, if needed for respiratory depression, and cardiac massage in the event of cardiac arrest.
   • To restore blood pressure, administration of intravenous fluids and/or vasopressors. If hypotension necessitates the use of vasopressors, slow infusion of 0.008 to 0.012 mg per minute of norepinephrine or 0.1 to 0.18 mg per minute of phenylephrine, appropriately diluted. If hypotension is due to increased vagal activity (vasovagal reaction), intravenous administration of 1 mg of atropine, repeated in one to two hours if needed.
   • Other specific treatment may include— {55}

• Diphenhydramine: For minor allergic-like reactions—An antihistamine such as diphenhydramine hydrochloride (except in epileptic patients) may be administered intravenously.


• Epinephrine: For acute allergic-like or anaphylactoid reactions—Slow intravenous infusion of 0.1 mg of epinephrine (1:10,000).For mild to moderate bronchospasm—0.1 to 0.2 mg of epinephrine (1:1000) may be administered subcutaneously, except in hypotension. In extreme emergency, 0.1 mg of epinephrine (1:10,000) may be given slowly by intravenous route, followed by a continuous intravenous infusion at an initial rate of 0.001 mg per minute; the rate may be increased to 0.004 mg per minute if necessary.(Note: Patients on beta-adrenergic blocking agents should not receive epinephrine since they are at risk of unopposed alpha-adrenergic stimulation, which may result in hypertension, reflex bradycardia, and heart-block. In these patients, isoproterenol and norepinephrine are used instead of epinephrine to overcome bronchospasm and hypotension, respectively.)For cardiac arrest—0.1 to 1 mg of epinephrine may be administered by the intravenous route.


• Diazepam or phenobarbital: To control convulsions—5 to 10 mg of diazepam by slow, intravenous administration or phenobarbital sodium may be given intravenously or intramuscularly at a rate not to exceed 30 to 60 mg per minute.



Parenteral Dosage Forms

IOHEXOL INJECTION USP

Usual adult and adolescent dose
Intrathecal—Myelography


Lumbar myelography by lumbar injection:
10 to 17 mL of a solution containing the equivalent of 180 mg of iodine per mL; or 7 to 12.5 mL of a solution containing the equivalent of 240 mg of iodine per mL. {68}



Thoracic myelography by lumbar or cervical injection—:
6 to 12.5 mL of a solution containing the equivalent of 240 mg of iodine per mL; or 6 to 10 mL of a solution containing the equivalent of 300 mg of iodine per mL. {68}



Cervical myelography by lumbar injection—:
6 to 12.5 mL of a solution containing the equivalent of 240 mg of iodine per mL; or 6 to 10 mL of a solution containing the equivalent of 300 mg of iodine per mL. {68}



Cervical myelography by C1/2 puncture—:
7 to 10 mL of a solution containing the equivalent of 180 mg of iodine per mL; 6 to 12.5 mL of a solution containing the equivalent of 240 mg of iodine per mL; or 4 to 10 mL of a solution containing the equivalent of 300 mg of iodine per mL. {68}



Total columnar myelography by lumbar injection—:
6 to 12.5 mL of a solution containing the equivalent of 240 mg of iodine per mL; or 6 to 10 mL of a solution containing the equivalent of 300 mg of iodine per mL. {68} {81}


Note: Injection should be made slowly over a period of 1 to 2 minutes to avoid excessive mixing with cerebrospinal fluid and resultant dilution of iohexol as well as premature cephalad dispersion. {68}
Immediate repeat intrathecal administration is not recommended because of risk of overdose; 48 hours, or preferably 5 to 7 days, should elapse before repeat examination. {68}


Intravascular


Angiocardiography:
Aortic root and arch—Via catheter, 20 to 75 mL of a solution containing the equivalent of 350 mg of iodine per mL as a single dose. {68}

Ventriculography—Via catheter, 30 to 60 mL of a solution containing the equivalent of 350 mg of iodine per mL as a single dose, repeated as needed. {68}

Arteriography, selective coronary—Via catheter, 3 to l4 mL of a solution containing the equivalent of 350 mg of iodine per mL, administered into either artery. {68}



Angiography:
Intra-arterial, by digital subtraction: Intra-arterial, as a solution containing the equivalent of 140 mg of iodine per mL, into the following vessels:

Aorta: 20 to 45 mL injected at a rate of 8 to 20 mL per second. {68}

Carotid: 5 to 10 mL injected at a rate of 3 to 6 mL per second. {68}

Femoral: 9 to 20 mL injected at a rate of 3 to 6 mL per second. {68}

Vertebral: 4 to 10 mL injected at a rate of 2 to 8 mL per second. {68}

Renal: 6 to 12 mL injected at a rate of 3 to 6 mL per second. {68}

Other branches of the aorta: 8 to 25 mL injected at a rate of 3 to 10 mL per second. {68}




Angiography, peripheral:
Arteriography, peripheral—Percutaneous or operative methods, 30 to 90 mL for aortofemoral runoffs, or 10 to 60 mL for selective arteriograms, of a solution containing the equivalent of 300 mg of iodine per mL; or, 20 to 70 mL for aortofemoral runoffs or 10 to 30 mL for selective arteriograms, of a solution containing the equivalent of 350 mg of iodine per mL. {68}

Venography, peripheral—Percutaneous, 20 to 150 mL per leg, of a solution containing the equivalent of 240 mg of iodine per mL; or, 40 to 100 mL per leg, of a solution containing the equivalent of 300 mg of iodine per mL. {68}



Aortography:
Via catheter, as a solution containing the equivalent of 300 mg or 350 mg of iodine per mL, as a single dose, repeated if needed, into the following vessels {68}:

Aorta: 50 to 80 mL.

Major branches of the aorta: 30 to 60 mL.

Renal arteries: 5 to 15 mL.




Arteriography, cerebral:
As a solution containing the equivalent of 300 mg of iodine per mL, by direct injection into the following vessels {01} {50} {68}:

Common carotid artery: 6 to 12 mL.

External carotid artery: 6 to 9 mL.

Internal carotid artery: 8 to 10 mL.

Vertebral artery: 6 to 10 mL.




Arteriography, digital, of the head and neck:
Intravenous, 30 to 50 mL of a solution containing the equivalent of 350 mg of iodine per mL. Three or more injections may be needed. {68}



Urography, excretory:
Intravenous, the equivalent of 200 to 350 mg of iodine per kg of body weight, of a solution containing the equivalent of 300 mg or 350 mg of iodine per mL. {68}



Herniography1:
Intravenous, 50 mL of a solution containing the equivalent of 240 mg of iodine per mL. {68}



CT of the brain:
Intravenous, by infusion, 120 to 250 mL of a solution containing the equivalent of 240 mg of iodine per mL; or, by rapid injection, 70 to 150 mL, of a solution containing the equivalent of 300 mg of iodine per mL; or, by rapid injection, 80 mL of a solution containing the equivalent of 350 mg of iodine per mL. {68}



CT of the body:
Intravenous, by rapid injection or infusion, 50 to 200 mL, of a solution containing the equivalent of 300 mg of iodine per mL; or 60 to 100 mL of a solution containing the equivalent of 350 mg of iodine per mL. {68}


Intraductal


Pancreatography, endoscopic retrograde1and:



Cholangiography, endoscopic retrograde1:
: Via catheter, 10 to 50 mL of a solution containing the equivalent of 240 mg of iodine per mL. {68}


Intrasynovial


Arthrography:
As a solution containing the equivalent of 210 mg of iodine per mL—Intra-articular, 3 mL into the shoulder joint. {01} {68}

As a solution containing the equivalent of 240 mg of iodine per mL—Intra-articular: Knee joint—5 to 15 mL {68}.

Shoulder joint—3 mL {68}.

As a solution containing the equivalent of 300 mg of iodine per mL—Intra-articular: Knee joint—5 to 15 mL {68}.

Shoulder—10 mL {68}.

Temporomandibular—0.5 to 1 mL {68}.

As a solution containing the equivalent of 350 mg of iodine per mL—Intra-articular, 5 to 10 mL into knee joint.



Oral


CT of the abdomen, adjunct1:
500 to 1000 mL of a solution containing the equivalent of 6 to 9 mg of iodine per mL administered orally, in conjunction with the intravenous administration of 100 to 150 mL of a solution containing the equivalent of 300 mg of iodine per mL. {68}

Note: Oral dose should be administered 20 to 40 minutes before the intravenous dose. {01} {68}




Gastrointestinal tract radiographic examination1:
For oral pass-through examination—50 to 100 mL of a solution containing the equivalent of 350 mg of iodine per mL. {68}



Usual adult prescribing limits
Intrathecal—Up to the equivalent of 3.06 grams of iodine.

Intravascular—For multiple or repeat procedures: Up to the equivalent of 87.5 grams of iodine or 250 mL of a solution containing the equivalent of 350 mg of iodine per mL.

Usual pediatric dose
Intrathecal—Myelography: By lumbar injection
As a solution containing the equivalent of 180 mg of iodine per mL {68}:

Children up to 3 months of age—2 to 4 mL.

Children 3 months to 3 years of age—4 to 8 mL.

Children 3 to 7 years of age—5 to 10 mL.

Children 7 to 13 years of age—5 to 12 mL.

Children 13 to 18 years of age—6 to 15 mL.

As a solution containing the equivalent of 210 mg of iodine per mL {68}:

Children up to 3 months of age—2 to 3 mL.

Children 3 months to 3 years of age—3 to 6 mL.

Children 3 to 7 years of age—5 to 8 mL.

Children 7 to 13 years of age—5 to 10 mL.

Children 13 to 18 years of age—6 to 14 mL.


Intravascular


Angiocardiography: Ventriculography:
Via catheter, 1.75 mL per kg of body weight, of a solution containing the equivalent of 300 mg of iodine per mL, up to a total volume of 291 mL; or, 1.25 mL per kg of body weight, of a solution containing the equivalent of 350 mg of iodine per mL, up to a total volume of 250 mL, as a single dose, repeated as needed but not to exceed 5 mL per kg of body weight. {68}



Urography, excretory:
Intravenous, 1 to 1.5 mL per kg of body weight, of a solution containing the equivalent of 300 mg of iodine per mL, not to exceed a total dose of 3 mL per kg of body weight. {68}



CT of the brain:
Intravenous, 1 to 2 mL per kg of body weight, of a solution containing the equivalent of 240 mg or 300 mg of iodine per mL. {01} {68}


Oral


CT of the abdomen, adjunct1:
180 to 750 mL, of a solution containing the equivalent of 9 to 21 mg of iodine per mL, administered orally all at once or over a period of 30 to 45 minutes, in conjunction with the intravenous administration of 1 to 2 mL per kg of body weight of a solution containing the equivalent of 240 or 300 mg of iodine per mL. {68}

Note: Oral dose should be administered 30 to 60 minutes before the intravenous dose. {01}
Total oral dose should not exceed the equivalent of 5 grams of iodine for children up to 3 years of age, the equivalent of 10 grams of iodine for children 3 to 18 years of age. {68}
Total intravenous dose should not exceed 3 mL per kg of body weight. {68}




Gastrointestinal tract radiographic examination1: For oral pass-through examination—:
Dosage must be individualized by physician in proportion to the size of the patient and the nature of the examination. The following guidelines are given for: {73}
A solution containing the equivalent of 180 mg of iodine per mL—Children up to 3 months of age: 5 to 30 mL.

A solution containing the equivalent of 180, 240, or 300 mg of iodine per mL—

Children 3 months to 3 years of age: Up to 60 mL.

Children 4 to 10 years of age: Up to 80 mL.

Children over 10 years of age: Up to 100 mL.




Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients with renal function impairment may be more sensitive to the effects of the usual adult dose; lower doses are recommended.


Strength(s) usually available
U.S.—


302 mg of iohexol with 140 mg of iodine per mL (Rx) [Omnipaque 140]


388.3 mg of iohexol with 180 mg of iodine per mL (Rx) [Omnipaque 180]


453 mg of iohexol with 210 mg of iodine per mL (Rx) [Omnipaque 210]


517.7 mg of iohexol with 240 mg of iodine per mL (Rx) [Omnipaque 240]


647.1 mg of iohexol with 300 mg of iodine per mL (Rx) [Omnipaque 300]


755 mg of iohexol with 350 mg of iodine per mL (Rx) [Omnipaque 350]

Canada—


302 mg of iohexol with 140 mg of iodine per mL (Rx) [Omnipaque 140]


388.3 mg of iohexol with 180 mg of iodine per mL (Rx) [Omnipaque 180]


453 mg of iohexol with 210 mg of iodine per mL (Rx) [Omnipaque 210]


517.7 mg of iohexol with 240 mg of iodine per mL (Rx) [Omnipaque 240]


647.1 mg of iohexol with 300 mg of iodine per mL (Rx) [Omnipaque 300]


755 mg of iohexol with 350 mg of iodine per mL (Rx) [Omnipaque 350]

Note: All formulations above contain 1.21 mg of tromethamine and 0.1 mg of edetate calcium disodium.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing. {70}

Preparation of dosage form:
{68}

Final concentration
of 1 liter of contrast solution
(mg of iodine/mL)
Concentration
of stock solution
of iohexol
(mg of iodine/mL)
Volume of
stock solution
(mL)
Amount of
diluent
(mL)*
6
240
25
975
  300
20
980
  350
17
983
9
240
38
962
  300
30
970
  350
26
974
12
240
50
950
  300
40
960
  350
35
965
15
240
63
937
  300
50
950
  350
43
957
18
240
75
925
  300
60
940
  350
52
948
21
240
88
912
  300
70
930
  350
60
940
* Water, carbonated beverage, milk, or juice may be used as diluent.

Stability:
Iohexol is a clear, colorless to pale yellow solution. Do not use if turbid or discolored. {52} {68}

Any unused portion remaining in the container should be discarded. {52}



Revised: 08/16/1995



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

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