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|Omnipaque Omnipaque Injection |
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Rx ONLY Omnipaque DescriptionIohexol, N,N´ - Bis(2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl)-acetamido]-2,4,6-triiodo-isophthalamide, is a nonionic, water-soluble radiographic contrast medium with a molecular weight of 821.14 (iodine content 46.36%). In aqueous solution each triiodinated molecule remains undissociated.The chemical structure is:  Omnipaque is provided as a sterile, pyrogen-free, colorless to pale-yellow solution, in the following iodine concentrations: 140, 180, 240, 300, and 350 mgI/mL. Omnipaque 140 contains 302 mg of iohexol equivalent to 140 mg of organic iodine per mL; Omnipaque 180 contains 388 mg of iohexol equivalent to 180 mg of organic iodine per mL; Omnipaque 240 contains 518 mg of iohexol equivalent to 240 mg of organic iodine per mL; Omnipaque 300 contains 647 mg of iohexol equivalent to 300 mg of organic iodine per mL; and Omnipaque 350 contains 755 mg of iohexol equivalent to 350 mg of organic iodine per mL. Each milliliter of iohexol solution contains 1.21 mg tromethamine and 0.1 mg edetate calcium disodium with the pH adjusted between 6.8 and 7.7 with hydrochloric acid or sodium hydroxide. All solutions are sterilized by autoclaving and contain no preservatives. Unused portions must be discarded. Iohexol solution is sensitive to light and therefore should be protected from exposure. The available concentrations have the following physical properties:
Omnipaque 140, Omnipaque 180, Omnipaque 240, Omnipaque 300, and Omnipaque 350 have osmolalities from approximately 1.1 to 3.0 times that of plasma (285 mOsm/kg water) or cerebrospinal fluid (301 mOsm/kg water) as shown in the above table and are hypertonic under conditions of use. SECTION ICLINICAL PHARMACOLOGY—IntrathecalIohexol is absorbed from cerebrospinal fluid (CSF) into the bloodstream and is eliminated by renal excretion. No significant metabolism, deiodination, or biotransformation occurs. In five adult patients receiving 16 to 18 milliliters of iohexol (180 mgI/mL) by lumbar intrathecal injection, approximately 88 (73.1-98.2) percent of the injected dose was excreted in the urine within the first 24 hours after administration. The renal and body clearances were 99 (47-137) milliliters per minute and 109 (52-138) milliliters per minute. The mean maximal plasma concentration was 119 (72-177) micrograms of iohexol per milliliter and occurred after 3.8 (2-6) hours. The volume of distribution was 557 (350-849) milliliters per kilogram. In one patient with a large spinal cord tumor, excretion was delayed (67 percent of the dose appeared in the urine within the first 24 hours) with no difference in the total overall recovery in the urine after 48 hours. The delay in excretion appeared to be related to a decrease in the rate of transfer of iohexol from the cerebrospinal fluid to the blood (plasma maximal concentration was approximately 30 micrograms/mL). The initial concentration and volume of the medium, in conjunction with appropriate patient manipulation and the volume of CSF into which the medium is placed, will determine the extent of the diagnostic contrast that can be achieved. Following intrathecal injection in conventional radiography, Omnipaque 180, Omnipaque 240, and Omnipaque 300 will continue to provide good diagnostic contrast for at least 30 minutes. Slow diffusion of iohexol takes place throughout the CSF with subsequent absorption into the bloodstream. Once in the systemic circulation, iohexol displays little tendency to bind to serum or plasma proteins. At approximately 1 hour following injection, contrast of diagnostic quality will no longer be available for conventional myelography. If computerized tomographic (CT) myelography is to follow, consideration should be given to a delay of several hours to allow the degree of contrast to decrease. After administration into the lumbar subarachnoid space, computerized tomography shows the presence of contrast medium in the thoracic region in about 1 hour, in the cervical region in about 2 hours, and in the basal cisterns in 3 to 4 hours. In patients with renal impairment, depending on the degree of impairment, prolonged plasma iohexol levels may be anticipated due to decreased renal elimination. INDICATIONS AND USAGE—IntrathecalOmnipaque 180, Omnipaque 240, and Omnipaque 300 are indicated for intrathecal administration in adults including myelography (lumbar, thoracic, cervical, total columnar) and in contrast enhancement for computerized tomography (myelography, cisternography, ventriculography). Omnipaque 180 is indicated for intrathecal administration in children including myelography (lumbar, thoracic, cervical, total columnar) and in contrast enhancement for computerized tomography (myelography, cisternography). CONTRAINDICATIONS—IntrathecalOmnipaque should not be administered to patients with a known hypersensitivity to iohexol. Myelography should not be performed in the presence of significant local or systemic infection where bacteremia is likely. Intrathecal administration of corticosteroids with Omnipaque is contraindicated. Because of the possibility of overdosage, immediate repeat myelography in the event of technical failure is contraindicated (see DOSAGE AND ADMINISTRATION). WARNINGS—GeneralSEVERE ADVERSE EVENTS—INADVERTENT INTRATHECAL ADMINISTRATIONSerious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use. These serious adverse reactions include: death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to insure that Omnipaque 140 and 350 are not administered intrathecally. (All other concentrations of Omnipaque are approved for intrathecal administration.) If grossly bloody CSF is encountered, the possible benefits of a myelographic procedure should be considered in terms of the risk to the patient. Caution is advised in patients with a history of epilepsy, severe cardiovascular disease, chronic alcoholism, or multiple sclerosis. Elderly patients may present a greater risk following myelography. The need for the procedure in these patients should be evaluated carefully. Special attention must be paid to dose and concentration of the medium, hydration, and technique used. Patients who are receiving anticonvulsants should be maintained on this therapy. Should a seizure occur, intravenous diazepam or phenobarbital sodium is recommended. In patients with a history of seizure activity who are not on anticonvulsant therapy, premedication with barbiturates should be considered. Prophylactic anticonvulsant treatment with barbiturates should be considered in patients with evidence of inadvertent intracranial entry of a large or concentrated bolus of the contrast medium since there may be an increased risk of seizure in such cases. Drugs which lower the seizure threshold, especially phenothiazine derivatives, including those used for their antihistamine properties, are not recommended for use with Omnipaque. Others include MAO inhibitors, tricyclic antidepressants, CNS stimulants, and psychoactive drugs described as analeptics, major tranquilizers, or antipsychotic drugs. While the contributory role of these medications has not been established, the use of such drugs should be based on physician evaluation of potential benefits and potential risks. Physicians have discontinued these agents at least 48 hours before and for at least 24 hours postprocedure. Care is required in patient management to prevent inadvertent intracranial entry of a large dose or concentrated bolus of the medium. Also, effort should be directed to avoid rapid dispersion of the medium causing inadvertent rise to intracranial levels (eg, by active patient movement). Direct intracisternal or ventricular administration for standard radiography (not CT) is not recommended. In most reported cases of major motor seizures with nonionic myelographic media, one or more of the following factors were present. Therefore avoid:
PRECAUTIONS—GeneralDiagnostic procedures which involve the use of radiopaque diagnostic agents should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed. Appropriate facilities should be available for coping with any complication of the procedure, as well as for emergency treatment of severe reactions to the contrast agent itself. After parenteral administration of a radiopaque agent, competent personnel and emergency facilities should be available for at least 30 to 60 minutes since severe delayed reactions have occurred. (See ADVERSE REACTIONS.) Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with advanced vascular disease, diabetic patients, and in susceptible nondiabetic patients (often elderly with preexisting renal disease). Dehydration in these patients seems to be enhanced by the osmotic diuretic action of contrast agents. Patients should be well hydrated prior to and following administration of any contrast medium, including iohexol. The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid, cardiovascular or central nervous system reactions, should always be considered (see ADVERSE REACTIONS.) Therefore, it is of utmost importance that a course of action be carefully planned in advance for the immediate treatment of serious reactions, and that adequate and appropriate facilities and personnel be readily available in case of any reaction. The possibility of an idiosyncratic reaction in susceptible patients should always be considered (see ADVERSE REACTIONS). The susceptible population includes, but is not limited to, patients with a history of a previous reaction to contrast media, patients with a known sensitivity to iodine per se, and patients with a known clinical hypersensitivity: bronchial asthma, hay fever, and food allergies. The occurrence of severe idiosyncratic reactions has prompted the use of several pretesting methods. However, pretesting cannot be relied upon to predict severe reactions and may itself be hazardous for the patient. It is suggested that a thorough medical history with emphasis on allergy and hypersensitivity, prior to the injection of any contrast media, may be more accurate than pretesting in predicting potential adverse reactions. A positive history of allergies or hypersensitivity does not arbitrarily contraindicate the use of a contrast agent where a diagnostic procedure is thought essential, but caution should be exercised (see ADVERSE REACTIONS). Premedication with antihistamines or corticosteroids to avoid or minimize possible allergic reactions in such patients should be considered. Recent reports indicate that such pretreatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity. In patients with severe renal insufficiency or failure, compensatory biliary excretion of the drug is anticipated to occur, with a slow clearance into the bile. Patients with hepatorenal insufficiency should not be examined unless the possibility of benefit clearly outweighs the additional risk. Administration of contrast media should be performed by qualified personnel familiar with the procedure and appropriate patient management (see PATIENT MANAGEMENT). Sterile technique must be used with any spinal puncture. When Omnipaque is to be injected using plastic disposable syringes, the contrast medium should be drawn into the syringe and used immediately. If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents. Parenteral products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is present, do not use. Repeat Procedures: If in the clinical judgment of the physician sequential or repeat examinations are required, a suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY). Information for Patients (or if applicable, children)Patients receiving injectable radiopaque diagnostic agents should be instructed to:
Drugs which lower seizure threshold, especially phenothiazine derivatives including those used for their antihistaminic or antinauseant properties, are not recommended for use with Omnipaque. Others include monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, CNS stimulants, psychoactive drugs described as analeptics, major tranquilizers, or antipsychotic drugs. Such medications should be discontinued at least 48 hours before myelography, should not be used for the control of nausea or vomiting during or after myelography, and should not be resumed for at least 24 hours postprocedure. In nonelective procedures in patients on these drugs, consider prophylactic use of anticonvulsants. Carcinogenesis, Mutagenesis, Impairment of FertilityNo long-term animal studies have been performed to evaluate carcinogenic potential, mutagenesis, or whether Omnipaque can affect fertility in men or women. Pregnancy Category BReproduction studies have been performed in rats and rabbits with up to 100 times the recommended human dose. No evidence of impaired fertility or harm to the fetus has been demonstrated due to Omnipaque. There are, however, no studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing MothersIt is not known to what extent iohexol is excreted in human milk. However, many injectable contrast agents are excreted unchanged in human milk. Although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast media are administered to nursing women. Bottle feedings may be substituted for breast feedings for 24 hours following administration of Omnipaque. Pediatric UsePediatric patients at higher risk of experiencing adverse events during contrast medium administration may include those having asthma, a sensitivity to medication and/or allergens, congestive heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age. ADVERSE REACTIONS—IntrathecalThe most frequently reported adverse reactions with Omnipaque are headache, mild to moderate pain including backache, neckache and stiffness, nausea, and vomiting. These reactions usually occur 1 to 10 hours after injection, and almost all occur within 24 hours. They are usually mild to moderate in degree, lasting for a few hours, and usually disappearing within 24 hours. Rarely, headaches may be severe or persist for days. Headache is often accompanied by nausea and vomiting and tends to be more frequent and persistent in patients not optimally hydrated. Transient alterations in vital signs may occur and their significance must be assessed on an individual basis. Those reactions reported in clinical studies with Omnipaque are listed below in decreasing order of occurrence, based on clinical studies of 1531 patients. Headaches: The most frequently occurring adverse reaction following myelography has been headache, with an incidence of approximately 18%. Headache may be caused by either a direct effect of the contrast medium or by CSF leakage at the dural puncture site. However, in managing the patient, it is considered more important to minimize intracranial entry of contrast medium by postural management than attempting to control possible CSF leakage (see PATIENT MANAGEMENT). Pain: Mild to moderate pain including backache, neckache and stiffness, and neuralgia occurred following injection with an incidence of about 8%. Nausea and Vomiting: Nausea was reported with an incidence of about 6%, and vomiting about 3% (see PATIENT MANAGEMENT). Maintaining normal hydration is very important. The use of phenothiazine antinauseants is not recommended. (See WARNINGS—General.) Reassurance to the patient that the nausea will clear usually is all that is required. Dizziness: Transient dizziness was reported in about 2% of the patients. Other Reactions: Other reactions occurring with an individual incidence of less than 0.1% included: feeling of heaviness, hypotension, hypertonia, sensation of heat, sweating, vertigo, loss of appetite, drowsiness, hypertension, photophobia, tinnitus, neuralgia, paresthesia, difficulty in micturition, and neurological changes. All were transient and mild with no clinical sequelae. PediatricsIn controlled clinical trials involving 152 patients for pediatric myelography by lumbar puncture, adverse events following the use of Omnipaque 180 were generally less frequent than with adults. Headache: 9% Other Reactions: Other reactions occurring with an individual incidence of less than 0.7% included: fever, hives, stomachache, visual hallucination, and neurological changes. All were transient and mild with no clinical sequelae. General Adverse Reactions to Contrast MediaPhysicians should remain alert for the occurrence of adverse effects in addition to those discussed above, particularly the following reactions which have been reported in the literature for other nonionic, water-soluble myelographic media, and rarely with iohexol. These have included, but are not limited to, convulsion, aseptic and bacterial meningitis, and CNS and other neurological disturbances. An aseptic meningitis syndrome has been reported rarely (less than 0.01%). It was usually preceded by pronounced headaches, nausea and vomiting. Onset usually occurred about 12 to 18 hours postprocedure. Prominent features were meningismus, fever, sometimes with oculomotor signs and mental confusion. Lumbar puncture revealed a high white cell count, high protein content often with a low glucose level and with absence of organisms. The condition usually started to clear spontaneously about 10 hours after onset, with complete recovery over 2 to 3 days. Allergy or Idiosyncrasy: Chills, fever, profuse diaphoresis, pruritus, urticaria, nasal congestion, dyspnea, and a case of Guillain-Barre syndrome. CNS Irritation: Mild and transitory perceptual aberrations such as hallucinations, depersonalization, amnesia, hostility, amblyopia, diplopia, photophobia, psychosis, insomnia, anxiety, depression, hyperesthesia, visual or auditory or speech disturbances, confusion and disorientation. In addition, malaise, weakness, convulsion, EEG changes, meningismus, hyperreflexia or areflexia, hypertonia or flaccidity, hemiplegia, paralysis, quadriplegia, restlessness, tremor, echoacousia, echolalia, asterixis, cerebral hemorrhage, and dysphasia have occurred. Profound mental disturbances have also rarely been reported. They have usually consisted of various forms and degrees of aphasia, mental confusion, or disorientation. The onset is usually at 8 to 10 hours and lasts for about 24 hours, without aftereffects. However, occasionally they have been manifest as apprehension, agitation, or progressive withdrawal in several instances to the point of somnolence, stupor, and coma. In a few cases these have been accompanied by transitory hearing loss or other auditory symptoms and visual disturbances (believed subjective or delusional), including unilateral or bilateral loss of vision which may last for hours. In one case, persistent cortical loss of vision has been reported in association with convulsions. Ventricular block has been reported; amnesia of varying degrees may be present for the reaction event. Rarely, persistent though transitory weakness in the leg or ocular muscles has been reported. Peripheral neuropathies have been rare and transitory. They include sensory and/or motor or nerve root disturbances, myelitis, persistent leg muscle pain or weakness, 6th nerve palsy, or cauda equina syndrome. Muscle cramps, fasciculation or myoclonia, spinal convulsion, or spasticity is unusual and has responded promptly to a small intravenous dose of diazepam. In general, the reactions which are known to occur upon parenteral administration of iodinated contrast agents are possible with any nonionic agent. Approximately 95 percent of adverse reactions accompanying the use of water-soluble contrast agents are mild to moderate in degree. However, severe, life-threatening, anaphylactoid and fatal reactions, mostly of cardiovascular origin and central nervous system origin, have occurred. Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and idiosyncratic reactions. Chemotoxic reactions result from the physicochemical properties of the contrast media, the dose, and speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by the contrast medium are included in this category. Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40 years old. Idiosyncratic reactions may or may not be dependent on the amount of dose injected, the speed of injection, and the radiographic procedure. Idiosyncratic reactions are subdivided into minor, intermediate, and severe. The minor reactions are self-limited and of short duration; the severe reactions are life-threatening and treatment is urgent and mandatory. The reported incidence of adverse reactions to contrast media in patients with a history of allergy is twice that of the general population. Patients with a history of previous reactions to a contrast medium are three times more susceptible than other patients. However, sensitivity to contrast media does not appear to increase with repeated examinations. Most adverse reactions to injectable contrast media appear within 1 to 3 minutes after the start of injection, but delayed reactions may occur. OVERDOSAGEClinical consequences of overdosage with Omnipaque have not been reported. However, based on experience with other nonionic myelographic media, physicians should be alert to a potential increase in frequency and severity of CNS-mediated reactions. Even use of a recommended dose can produce effects tantamount to overdosage, if incorrect management of the patient during or immediately following the procedure permits inadvertent early intracranial entry of a large portion of the medium. The intracisternal LD50 value of Omnipaque (in grams of iodine per kilogram body weight) is greater than 2.0 in mice. DOSAGE AND ADMINISTRATION — IntrathecalThe volume and concentration of Omnipaque 180, Omnipaque 240, or Omnipaque 300 to be administered will depend on the degree and extent of contrast required in the area(s) under examination and on the equipment and technique employed. Omnipaque 180 at a concentration of 180 mgI/mL, Omnipaque 240 at a concentration of 240 mgI/mL, or Omnipaque 300 at a concentration of 300 mgI/mL is recommended for the examination of the lumbar, thoracic, and cervical regions in adults by lumbar or direct cervical injection and is slightly hypertonic to CSF. Omnipaque 180 at a concentration of 180 mgI/mL recommended for the examination of the lumbar, thoracic, and cervical regions in children by lumbar injection and is slightly hypertonic to CSF. A total dose of 3060 mg iodine or a concentration of 300 mgI/mL should not be exceeded in adults and a total dose of 2700 mg iodine or a concentration of 180 mgI/mL should not be exceeded in children in a single myelographic examination. This is based on clinical trial evaluation to date. As in all diagnostic procedures, the minimum volume and dose to produce adequate visualization should be used. Most procedures do not require either maximum dose or concentration. Anesthesia is not necessary. Premedication sedatives or tranquilizers are usually not needed (see PRECAUTIONS). Patients should be well hydrated prior to and following contrast administration. Seizure-prone patients should be maintained on anticonvulsant medication. Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many other drugs; therefore, concurrent drugs should not be physically admixed with contrast agents. Rate of Injection: To avoid excessive mixing with CSF and consequent dilution of contrast, injection should be made slowly over 1 to 2 minutes. Depending on the estimated volume of contrast medium which may be required for the procedure a small amount of CSF may be removed to minimize distention of the subarachnoid spaces. The lumbar or cervical puncture needle may be removed immediately following injection since it is not necessary to remove Omnipaque after injection into the subarachnoid space. Adults: The usual recommended total doses for use in lumbar, thoracic, cervical, and total columnar myelography in adults are 1.2 gI to 3.06 gI as follows:
Pediatrics: The usual recommended total doses for lumbar, thoracic, cervical, and/or total columnar myelography by lumbar puncture in children are 0.36 gI to 2.94 gI (see table below). Actual volumes administered depend largely on patient age and the following guidelines are recommended.
Withdrawal of contrast agents from their containers should be accomplished under aseptic conditions with sterile syringes. Spinal puncture must always be performed under sterile conditions. Parenteral products should be inspected visually for particulate matter or discoloration prior to administration. If particulate matter or discoloration is present, do not use. Repeat Procedures: If in the clinical judgment of the physician sequential or repeat examinations are required, a suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body. An interval of at least 48 hours should be allowed before repeat examination; however, whenever possible, 5 to 7 days is recommended. PATIENT MANAGEMENT—IntrathecalSuggestions for Usual Patient ManagementGood patient management should be exercised at all times to minimize the potential for procedurally related complications. Preprocedure
During Procedure
Postprocedure
Alternative Postprocedure Method
HOW SUPPLIEDOmnipaque 180 Omnipaque 240 Omnipaque 300 Storage: Protect vials of Omnipaque from strong daylight and direct exposure to sunlight. Do not freeze. Omnipaque should be stored at controlled room temperature, 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. SECTION IICLINICAL PHARMACOLOGY—IntravascularFollowing intravascular injection, iohexol is distributed in the extracellular fluid compartment and is excreted unchanged by glomerular filtration. It will opacify those vessels in the path of flow of the contrast medium permitting radiographic visualization of the internal structures until significant hemodilution occurs. Approximately 90% or more of the injected dose is excreted within the first 24 hours, with the peak urine concentrations occurring in the first hour after administration. Plasma and urine iohexol levels indicate that the iohexol body clearance is due primarily to renal clearance. An increase in the dose from 500 mgI/kg to 1500 mgI/kg does not significantly alter the clearance of the drug. The following pharmacokinetic values were observed following the intravenous administration of iohexol (between 500 mgI/kg to 1500 mgI/kg) to 16 adult human subjects: renal clearance—120 (86-162) mL/min; total body clearance—131 (98-165) mL/min; and volume of distribution—165 (108-219) mL/kg. Renal accumulation is sufficiently rapid that the period of maximal opacification of the renal passages may begin as early as 1 minute after intravenous injection. Urograms become apparent in about 1 to 3 minutes with optimal contrast occurring between 5 to 15 minutes. In nephropathic conditions, particularly when excretory capacity has been altered, the rate of excretion may vary unpredictably, and opacification may be delayed after injection. Severe renal impairment may result in a lack of diagnostic opacification of the collecting system and, depending on the degree of renal impairment, prolonged plasma iohexol levels may be anticipated. In these patients, as well as in infants with immature kidneys, the route of excretion through the gallbladder and into the small intestine may increase. Iohexol displays a low affinity for serum or plasma proteins and is poorly bound to serum albumin. No significant metabolism, deiodination or biotransformation occurs. Omnipaque probably crosses the placental barrier in humans by simple diffusion. It is not known to what extent iohexol is excreted in human milk. Animal studies indicate that iohexol does not cross an intact blood-brain barrier to any significant extent following intravascular administration. Omnipaque enhances computed tomographic imaging through augmentation of radiographic efficiency. The degree of density enhancement is directly related to the iodine content in an administered dose; peak iodine blood levels occur immediately following rapid intravenous injection. Blood levels fall rapidly within 5 to 10 minutes and the vascular compartment half-life is approximately 20 minutes. This can be accounted for by the dilution in the vascular and extravascular fluid compartments which causes an initial sharp fall in plasma concentration. Equilibration with the extracellular compartments is reached in about ten minutes; thereafter, the fall becomes exponential. The pharmacokinetics of iohexol in both normal and abnormal tissue have been shown to be variable. Contrast enhancement appears to be greatest immediately after bolus administration (15 seconds to 120 seconds). Thus, greatest enhancement may be detected by a series of consecutive two-to-three second scans performed within 30 to 90 seconds after injection (ie, dynamic computed tomographic imaging). Utilization of a continuous scanning technique (ie, dynamic CT scanning) may improve enhancement and diagnostic assessment of tumor and other lesions such as abscess, occasionally revealing unsuspected or more extensive disease. For example, a cyst may be distinguished from a vascularized solid lesion when precontrast and enhanced scans are compared; the nonperfused mass shows unchanged x-ray absorption (CT number). A vascularized lesion is characterized by an increase in CT number in the few minutes after a bolus of intravascular contrast agent; it may be malignant, benign, or normal tissue, but would probably not be a cyst, hematoma, or other nonvascular lesion. Because unenhanced scanning may provide adequate diagnostic information in the individual patient, the decision to employ contrast enhancement, which may be associated with risk and increased radiation exposure, should be based upon a careful evaluation of clinical, other radiological, and unenhanced CT findings. CT SCANNING OF THE HEADIn contrast enhanced computed tomographic head imaging, Omnipaque does not accumulate in normal brain tissue due to the presence of the normal blood-brain barrier. The increase in x-ray absorption in normal brain is due to the presence of contrast agent within the blood pool. A break in the blood-brain barrier such as occurs in malignant tumors of the brain allows for the accumulation of contrast medium within the interstitial tissue of the tumor. Adjacent normal brain tissue does not contain the contrast medium. Maximum contrast enhancement in tissue frequently occurs after peak blood iodine levels are reached. A delay in maximum contrast enhancement can occur. Diagnostic contrast enhanced images of the brain have been obtained up to 1 hour after intravenous bolus administration. This delay suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing medium within the lesion and outside the blood pool, although the mechanism by which this occurs is not clear. The radiographic enhancement of nontumoral lesions, such as arteriovenous malformations and aneurysms, is probably dependent on the iodine content of the circulating blood pool. In patients where the blood-brain barrier is known or suspected to be disrupted, the use of any radiographic contrast medium must be assessed on an individual risk to benefit basis. However, compared to ionic media, nonionic media are less toxic to the central nervous system. CT SCANNING OF THE BODYIn contrast enhanced computed tomographic body imaging (nonneural tissue), Omnipaque diffuses rapidly from the vascular into the extravascular space. Increase in x-ray absorption is related to blood flow, concentration of the contrast medium, and extraction of the contrast medium by interstitial tissue of tumors since no barrier exists. Contrast enhancement is thus due to the relative differences in extravascular diffusion between normal and abnormal tissue, quite different from that in the brain. INDICATIONS AND USAGE, GENERAL—IntravascularOmnipaque 350 is indicated in adults for angiocardiography (ventriculography, selective coronary arteriography), aortography including studies of the aortic root, aortic arch, ascending aorta, abdominal aorta and its branches, contrast enhancement for computed tomographic head and body imaging, intravenous digital subtraction angiography of the head, neck, abdominal, renal and peripheral vessels, peripheral arteriography, and excretory urography. Omnipaque 350 is indicated in children for angiocardiography (ventriculography, pulmonary arteriography, and venography; studies of the collateral arteries and aortography, including the aortic root, aortic arch, ascending and descending aorta). Omnipaque 300 is indicated in adults for aortography including studies of the aortic arch, abdominal aorta and its branches, contrast enhancement for computed tomographic head and body imaging, cerebral arteriography, peripheral venography (phlebography), and excretory urography. Omnipaque 300 is indicated in children for angiocardiography (ventriculography), excretory urography, and contrast enhancement for computed tomographic head imaging. Omnipaque 240 is indicated in adults for contrast enhancement for computed tomographic head imaging and peripheral venography (phlebography). Omnipaque 140 is indicated in adults for intra-arterial digital subtraction angiography of the head, neck, abdominal, renal and peripheral vessels. Omnipaque 240 is indicated in children for contrast enhancement for computed tomographic head imaging. CONTRAINDICATIONSOmnipaque should not be administered to patients with a known hypersensitivity to iohexol. WARNINGS—GeneralNonionic iodinated contrast media inhibit blood coagulation, in vitro, less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes containing nonionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications, may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to guidewire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinized saline solutions and minimizing the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting. Omnipaque should be used with extreme care in patients with severe functional disturbances of the liver and kidneys, severe thyrotoxicosis, or myelomatosis. Diabetics with a serum creatinine level above 3 mg/dL should not be examined unless the possible benefits of the examination clearly outweigh the additional risk. Omnipaque is not recommended for use in patients with anuria. Radiopaque contrast agents are potentially hazardous in patients with multiple myeloma or other paraproteinemia, particularly in those with therapeutically resistant anuria. Although neither the contrast agent nor dehydration has separately proven to be the cause of anuria in myeloma, it has been speculated that the combination of both may be causative factors. The risk in myelomatous patients is not a contraindication; however, special precautions are necessary. Partial dehydration in the preparation of these patients prior to injection is not recommended since this may predispose the patient to precipitation of the myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing the effect. Myeloma, which occurs most commonly in persons over age 40, should be considered before instituting intravascular administration of contrast agents. Ionic contrast media, when injected intravenously or intra-arterially, may promote sickling in individuals who are homozygous for sickle cell disease. Administration of radiopaque materials to patients known or suspected of having pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The patient"s blood pressure should be assessed throughout the procedure and measures for the treatment of hypertensive crisis should be readily available. Reports of thyroid storm following the use of iodinated, ionic radiopaque contrast media in patients with hyperthyroidism or with an autonomously functioning thyroid nodule suggest that this additional risk be evaluated in such patients before use of any contrast medium. Urography should be performed with caution in patients with severely impaired renal function and patients with combined renal and hepatic disease. PRECAUTIONS—GeneralDiagnostic procedures which involve the use of radiopaque diagnostic agents should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed. Appropriate facilities should be available for coping with any complication of the procedure, as well as for emergency treatment of severe reactions to the contrast agent itself. After parenteral administration of a radiopaque agent, competent personnel and emergency facilities should be available for at least 30 to 60 minutes since severe delayed reactions have occurred (see ADVERSE REACTIONS: Intravascular–General). Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with advanced vascular disease, diabetic patients, and in susceptible nondiabetic patients (often elderly with preexisting renal disease), infants and small children. Dehydration in these patients seems to be enhanced by the osmotic diuretic action of urographic agents. It is believed that overnight fluid restriction prior to excretory urography generally does not provide better visualization in normal patients. Patients should be well hydrated prior to and following administration of any contrast medium, including iohexol. Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible nondiabetic patients (often elderly with preexisting renal disease) following excretory urography. Therefore, careful consideration of the potential risks should be given before performing this radiographic procedure in these patients. Immediately following surgery, excretory urography should be used with caution in renal transplant recipients. The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid or cardiovascular reactions, should always be considered (see ADVERSE REACTIONS: Intravascular—General). It is of utmost importance that a course of action be carefully planned in advance for immediate treatment of serious reactions, and that adequate and appropriate personnel be readily available in case of any reaction. The possibility of an idiosyncratic reaction in susceptible patients should always be considered (see ADVERSE REACTIONS: Intravascular—General). The susceptible population includes, but is not limited to, patients with a history of a previous reaction to contrast media, patients with a known sensitivity to iodine per se, and patients with a known clinical hypersensitivity: bronchial asthma, hay fever, and food allergies. The occurrence of severe idiosyncratic reactions has prompted the use of several pretesting methods. However, pretesting cannot be relied upon to predict severe reactions and may itself be hazardous for the patient. It is suggested that a thorough medical history with emphasis on allergy and hypersensitivity, prior to the injection of any contrast media, may be more accurate than pretesting in predicting potential adverse reactions. A positive history of allergies or hypersensitivity does not arbitrarily contraindicate the use of a contrast agent where a diagnostic procedure is thought essential, but caution should be exercised (see ADVERSE REACTIONS: Intravascular—General). Premedication with antihistamines or corticosteroids to avoid or minimize possible allergic reactions in such patients should be considered and administered using separate syringes. Recent reports indicate that such pretreatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity. Even though the osmolality of Omnipaque is low compared to diatrizoate- or iothalamate-based ionic agents of comparable iodine concentration, the potential transitory increase in the circulatory osmotic load in patients with congestive heart failure requires caution during injection. These patients should be observed for several hours following the procedure to detect delayed hemodynamic disturbances. General anesthesia may be indicated in the performance of some procedures in selected adult patients; however, a higher incidence of adverse reactions has been reported in these patients, and may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia which can reduce cardiac output and increase the duration of exposure to the contrast agent. Angiography should be avoided whenever possible in patients with homocystinuria, because of the risk of inducing thrombosis and embolism. In angiographic procedures, the possibility of dislodging plaques or damaging or perforating the vessel wall should be borne in mind during the catheter manipulations and contrast medium injection. Test injections to ensure proper catheter placement are recommended. Selective coronary arteriography should be performed only in those patients in whom the expected benefits outweigh the potential risk. The inherent risks of angiocardiography in patients with chronic pulmonary emphysema must be weighed against the necessity for performing this procedure. When Omnipaque is to be injected using plastic disposable syringes, the contrast medium should be drawn into the syringe and used immediately. If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents. Parenteral products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is present, do not use. Information for PatientsPatients receiving injectable radiopaque diagnostic agents should be instructed to:
If iodine-containing isotopes are to be administered for the diagnosis of thyroid disease, the iodine-binding capacity of thyroid tissue may be reduced for up to 2 weeks after contrast medium administration. Thyroid function tests which do not depend on iodine estimation, eg, T3 resin uptake or direct thyroxine assays, are not affected. Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many other drugs; therefore, no other pharmaceuticals should be admixed with contrast agents. Carcinogenesis, Mutagenesis, Impairment of FertilityNo long-term animal studies have been performed to evaluate carcinogenic potential, mutagenesis, or whether Omnipaque can affect fertility in men or women. Pregnancy Category BReproduction studies have been performed in rats and rabbits with up to 100 times the recommended human dose. No evidence of impaired fertility or harm to the fetus has been demonstrated due to Omnipaque. There are, however, no studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing MothersIt is not known to what extent iohexol is excreted in human milk. However, many injectable contrast agents are excreted unchanged in human milk. Although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast media are administered to nursing women. Bottle feedings may be substituted for breast feedings for 24 hours following administration of Omnipaque. Pediatric UsePediatric patients at higher risk of experiencing adverse events during contrast medium administration may include those having asthma, a sensitivity to medication and/or allergens, congestive heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age. ADVERSE REACTIONS: Intravascular—GeneralAdverse reactions following the use of Omnipaque 140, Omnipaque 240, Omnipaque 300, and Omnipaque 350 are usually of mild to moderate severity. However, serious, life-threatening and fatal reactions, mostly of cardiovascular origin, have been associated with the administration of iodine-containing contrast media, including Omnipaque. The injection of contrast media is frequently associated with the sensation of warmth and pain, especially in peripheral angiography; pain and warmth are less frequent and less severe with Omnipaque than with many contrast media. Cardiovascular System: Arrhythmias including PVCs and PACs (2%), angina/chest pain (1%), and hypotension (0.7%). Others including cardiac failure, asystole, bradycardia, tachycardia, and vasovagal reaction were reported with an individual incidence of 0.3% or less. In controlled clinical trials involving 1485 patients, one fatality occurred. A cause and effect relationship between this death and iohexol has not been established. Nervous System: Vertigo (including dizziness and lightheadedness) (0.5%), pain (3%), vision abnormalities (including blurred vision and photomas) (2%), headache (2%), and taste perversion (1%). Others including anxiety, fever, motor and speech dysfunction, convulsion, paresthesia, somnolence, stiff neck, hemiparesis, syncope, shivering, transient ischemic attack, cerebral infarction, and nystagmus were reported, with an individual incidence of 0.3% or less. Respiratory System: Dyspnea, rhinitis, coughing, and laryngitis, with an individual incidence of 0.2% or less. Gastrointestinal System: Nausea (2%) and vomiting (0.7%). Others including diarrhea, dyspepsia, cramp, and dry mouth were reported, with an individual incidence of less than 0.1%. Skin and Appendages: Urticaria (0.3%), purpura (0.1%), abscess (0.1%), and pruritus (0.1%). Individual adverse reactions which occurred to a significantly greater extent for a specific procedure are listed under that indication. PediatricsIn controlled clinical trials involving 391 patients for pediatric angiocardiography, urography, and contrast enhanced computed tomographic head imaging, adverse reactions following the use of Omnipaque 240, Omnipaque 300, and Omnipaque 350 were generally less frequent than with adults. Cardiovascular System: Ventricular tachycardia (0.5%), 2:1 heart block (0.5%), hypertension (0.3%), and anemia (0.3%). Nervous System: Pain (0.8%), fever (0.5%), taste abnormality (0.5%), and convulsion (0.3%). Respiratory System: Congestion (0.3%) and apnea (0.3%). Gastrointestinal System: Nausea (1%), hypoglycemia (0.3%), and vomiting (2%). Skin and Appendages: Rash (0.3%). General Adverse Reactions to Contrast MediaPhysicians should remain alert for the occurrence of adverse effects in addition to those discussed above. The following reactions h
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