Omnipaque

SECTION I - INTRATHECAL

Iohexol 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.

SECTION II - INTRAVASCULAR

Following 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 Head

In 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 Body

In 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.

SECTION III - ORAL/BODY CAVITY USE

For most body cavities, the injected iohexol is absorbed into the surrounding tissue and eliminated by the kidneys and bowel as previously described in SECTION II, CLINICAL PHARMACOLOGY—Intravascular. Examinations of the uterus (hysterosalpingography) and bladder (voiding cystourethrography) involve the almost immediate drainage of contrast medium from the cavity upon conclusion of the radiographic procedure.

Orally administered iohexol is very poorly absorbed from the normal gastrointestinal tract. Only 0.1 to 0.5 percent of the oral dose was excreted by the kidneys. This amount may increase in the presence of bowel perforation or bowel obstruction. Iohexol is well tolerated and readily absorbed if leakage into the peritoneal cavity occurs.

Visualization of the joint spaces, uterus, fallopian tubes, peritoneal herniations, pancreatic and bile ducts, and bladder can be accomplished by direct injection of contrast medium into the region to be studied. The use of appropriate iodine concentrations assures diagnostic density. Orally administered OMNIPAQUE produces good visualization of the gastrointestinal tract. OMNIPAQUE is particularly useful when barium sulfate is contraindicated as in patients with suspected bowel perforation or those where aspiration of contrast medium is a possibility.

All products:

• Tell all of your health care providers that you take Omnipaque. This includes your doctors, nurses, pharmacists, and dentists.
• Very bad and sometimes deadly allergic reactions have rarely happened. Talk with your doctor.
• Your blood work may need to be checked. Talk with your doctor.
• Thyroid problems have happened after use of this medicine. Some people had to be treated for these thyroid problems. Talk with the doctor.
• A very bad and sometimes deadly reaction has happened with Omnipaque. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• If you have sickle cell disease, talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• If you are 65 or older, use Omnipaque with care. You could have more side effects.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Injection:

• Blood clots have happened with Omnipaque when used with some heart procedures. Sometimes, blood clots may cause heart attack and stroke, which may be deadly. Talk with the doctor.

Injection (if given into the spine):

• This medicine may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking this medicine.