Omnipaque Dailymed

Adverse Reactions: Intravasculargeneral

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.

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 uled under that indication.

Pediatrics

In controlled clinical trials involving 391 patients for pediatric angiocardiography and urography, adverse reactions following the use of OMNIPAQUE 300 and OMNIPAQUE 350 were generally not more 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 Media

Physicians should remain alert for the occurrence of adverse effects in addition to those discussed above.

The following reactions have been reported after administration of - intravascular iodinated contrast media. Reactions due to technique: hematomas and ecchymoses. Hemodynamic reactions: vein cramp and thrombophlebitis following intravenous injection. Cardiovascular reactions: cardiac arrhythmias, reflex tachycardia, chest pain, cyanosis, hypertension, hypotension, peripheral vasodilatation, shock, and cardiac arrest. Renal reactions: transient proteinuria, oliguria or anuria. Endocrine reactions: hyperthyroidism, hypothyroidism. Skin and Subcutaneous Tissue Disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticaria, skin discoloration) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)]. Allergic reactions: asthmatic attacks, nasal and conjunctival symptoms, dermal reactions such as urticaria with or without pruritus, as well as pleomorphic rashes, sneezing and lacrimation, anaphylactic reactions and anaphylactic shock. Fatalities have occurred, due to this or unknown causes. Signs and symptoms related to the respiratory system: pulmonary or laryngeal edema, bronchospasm, dyspnea; or to the nervous system: restlessness, tremors, convulsions. Other reactions: flushing, pain, warmth, metallic taste, nausea, vomiting, anxiety, headache, confusion, pallor, weakness, sweating, localized areas of edema, especially facial cramps, neutropenia, and dizziness. Immediate or delayed rigors can occur, sometimes accompanied by hyperpyrexia. Infrequently, "iodism" (salivary gland swelling) from organic iodinated compounds appears two days after exposure and subsides by the sixth day.

In general, the reactions which are known to occur upon parenteral administration of iodinated contrast agents are possible with any nonionic agent. Severe, life-threatening, fatal anaphylactoid shock has been reported. Reported incidences of death range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 (0.01 percent). Most deaths occur during injection or 5 to 10 minutes later; the main feature being cardiac arrest with cardiovascular disease as the main aggravating factor.

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 are 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.

Regardless of the contrast agent employed, the overall estimated incidence of serious adverse reactions is higher with angiocardiography than with other procedures. Cardiac decompensation, serious arrhythmias, angina pectoris, or myocardial ischemia or infarction may occur during angiocardiography and left ventriculography. Immediately following intravascular injection of contrast medium, a transient sensation of mild warmth is not unusual. Warmth is less frequent with OMNIPAQUE than with ionic media. (see ADVERSE REACTIONS: Intravascular—General)

Overdosage

Overdosage may occur. The adverse effects of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular systems. The symptoms included: cyanosis, bradycardia, acidosis, pulmonary hemorrhage, convulsions, coma, and cardiac arrest. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy.

The intravenous LD₅₀ values of OMNIPAQUE (in grams of iodine per kilogram body weight) are 24.2 in mice and 15.0 in rats.

Dosage And Administration General

As with all radiopaque contrast agents, the lowest dose of OMNIPAQUE necessary to obtain adequate visualization should be used. A lower dose may reduce the possibility of an adverse reaction. Most procedures do not require use of either the maximum volume or the highest concentration of OMNIPAQUE. The combination of volume and concentration of OMNIPAQUE to be used should be carefully individualized accounting for factors such as age, body weight, size of the vessel and the rate of blood flow within the vessel. Other factors such as anticipated pathology, degree and extent of opacification required, structure(s) or area to be examined, disease processes affecting the patient, and equipment and technique to be employed should be considered.

Sterile technique must be used in all vascular injections involving contrast media.

Refer to DIRECTIONS FOR PROPER USE OF OMNIPAQUE PHARMACY BULK PACKAGE section for instructions.

If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents.

It may be desirable that solutions of radiopaque diagnostic agents be used at body temperature when injected.

Parenteral products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Solutions of OMNIPAQUE should be used only if clear and within the normal colorless to pale yellow range. If particulate matter or discoloration is present, do not use.

Individual Indications And Usage

ANGIOCARDIOGRAPHY

PharmacologyHemodynamic Changes

OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in adults for angiocardiography (ventriculography, aortic root injections, and selective coronary arteriography). OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in pediatric patients for angiocardiography (ventriculography, pulmonary arteriography, and venography, and studies of the collateral arteries).

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in pediatric patients pediatric patients for angiocardiography (ventriculography).

After both ventricular and coronary injection, decreases in systolic pressure were less pronounced and returned to baseline values earlier with OMNIPAQUE 350 than with diatrizoate meglumine and diatrizoate sodium injection.

OMNIPAQUE 350 produced less Q-T interval prolongation than seen with diatrizoate meglumine and diatrizoate sodium injection.

In pediatric patients, after injection of all sites, but particularly following ventricular and pulmonary artery injections, decreases in both systolic and diastolic intravascular pressure were significantly less pronounced with OMNIPAQUE 350 than with diatrizoate meglumine and diatrizoate sodium injection. In pediatric patients OMNIPAQUE 350 produced significantly less shortening of the R-R interval than seen with diatrizoate meglumine and diatrizoate sodium injection.

If repeat injections are made in rapid succession, all these changes are likely to be more pronounced. (See DOSAGE AND ADMINISTRATION.)

Precautions

During administration of large doses of OMNIPAQUE 350, continuous monitoring of vital signs is desirable. Caution is advised in the administration of large volumes to patients with incipient heart failure because of the possibility of aggravating the preexisting condition. Hypotension should be corrected promptly since it may induce serious arrhythmias. Special care regarding dosage should be observed in patients with right ventricular failure, pulmonary hypertension, or stenotic pulmonary vascular beds because of the hemodynamic changes which may occur after injection into the right heart outflow tract. (See PRECAUTIONS—General.)

Pediatric 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

Cardiovascular system reactions in angiocardiography included angina (8%), hypotension (2.5%), bradycardia (1%), and tachycardia (1%). (See ADVERSE REACTIONS: Intravascular—General.)

Dosage and Administration

The individual dose or volume is determined by the size of the structure to be visualized, the anticipated degree of hemodilution, and valvular competence. Weight is a minor consideration in adults, but must be considered in infants and young pediatric patients. The volume of each individual injection is a more important consideration than the total dosage used. When large individual volumes are administered, as in ventriculography and aortography, it has been suggested that several minutes be permitted to elapse between each injection to allow for subsidence of possible hemodynamic disturbances.

The recommended single injection volume of OMNIPAQUE 350 for angiocardiographic procedures in adults and the recommended single injection volumes of OMNIPAQUE 350 and OMNIPAQUE 300 for angiographic procedures in pediatric patients are as follows:

Ventriculography

Selective Coronary Arteriography

The usual adult volume for right or left coronary arteriography is 5 mL (range 3 mL to 14 mL) per injection.

Aortic Root and Arch Study When Used Alone

The usual adult single injection volume is 50 mL, with a range of 20 mL to 75 mL.

Pulmonary Angiography

Combined Angiocardiographic Procedures

AORTOGRAPHY AND SELECTIVE VISCERAL ARTERIOGRAPHY

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL and OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL are indicated in adults for use in aortography and selective visceral arteriography including studies of the aortic arch, ascending aorta, and abdominal aorta and its branches (celiac, mesenteric, renal, hepatic and splenic arteries).

OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in pediatric patients for use in aortography including studies of the aortic root, aortic arch, ascending and descending aorta.

Precautions

Under conditions of slowed aortic circulation there is an increased likelihood for aortography to cause muscle spasm. Occasional serious neurologic complications, including paraplegia, have also been reported in patients with aortoiliac obstruction, femoral artery obstruction, abdominal compression, hypotension, hypertension, spinal anesthesia, and injection of vasopressors to increase contrast. In these patients the concentration, volume and number of repeat injections of the medium should be maintained at a minimum with appropriate intervals between injections. The position of the patient and catheter tip should be carefully monitored.

Entry of a large aortic dose into the renal artery may cause, even in the absence of symptoms, albuminuria, hematuria, and an elevated creatinine and urea nitrogen. Rapid and complete return of function usually follows. (See PRECAUTIONS—General.)

Adverse Reactions

See ADVERSE REACTIONS: Intravascular—General, and ADVERSE REACTIONS ANGIOCARDIOGRAPHY.

Dosage and Administration

Adults

The usual adult volume as a single injection is 50 mL to 80 mL for the aorta, 30 mL to 60 mL for major branches including celiac and mesenteric arteries, and 5 mL to 15 mL for renal arteries. Repeated injections may be performed if indicated, but the total volume should not exceed 291 mL of OMNIPAQUE 300 or 250 mL of OMNIPAQUE 350 (87.5 g Iodine).

Pediatrics

The usual single injection dose is 1.0 mL/kg of OMNIPAQUE 350 and should not exceed 5.0 mL/kg up to a total volume of 250 mL of OMNIPAQUE 350.

CEREBRAL ARTERIOGRAPHY

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in adults for use in cerebral arteriography.

The degree of pain and flushing as the result of the use of OMNIPAQUE 300 in cerebral arteriography is less than that seen with comparable injections of many contrast media.

In cerebral arteriography, patients should be appropriately prepared consistent with existing or suspected disease states.

Precautions

Cerebral arteriography should be undertaken with extreme care with special caution in elderly patients, patients in poor clinical condition, advanced arteriosclerosis, severe arterial hypertension, recent cerebral embolism or thrombosis, and cardiac decompensation.

Since the contrast medium is given by rapid injection, the patient should be monitored for possible untoward reactions. (See PRECAUTIONS—General.)

Adverse Reactions

Cerebral arteriography with water-soluble contrast media has been associated with temporary neurologic complications including seizures, drowsiness, transient paresis, and mild disturbances in vision such as photomas of 1-second or less duration.

Central nervous system reactions in cerebral arteriography included photomas (15%), headache (5.5%), and pain (4.5%). (See ADVERSE REACTIONS: Intravascular—General.)

Dosage and Administration

OMNIPAQUE 300 is recommended for cerebral arteriography at the following volumes: common carotid artery (6 mL to 12 mL), internal carotid artery (8 mL to 10 mL), external carotid artery (6 mL to 9 mL), and vertebral artery (6 mL to 10 mL).

DIGITAL SUBTRACTION ANGIOGRAPHY

Intravenous Administration

OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in adults for use in intravenous digital subtraction angiography (I.V.DSA) of the vessels of the head, neck, and abdominal, renal and peripheral vessels.

Arteriograms of diagnostic quality can be obtained following the intravenous administration of contrast media employing digital subtraction and computer imaging enhancement techniques. The intravenous route of administration using these techniques has the advantage of being less invasive than the corresponding selective catheter placement of medium. The dose is administered into a peripheral vein, the superior vena cava or right atrium, usually by mechanical injection although sometimes by rapid manual injection. The technique has been used to visualize the ventricles, aorta and most of its larger branches, including the carotids, cerebrals, vertebrals, renal, celiac, mesenterics, and the major peripheral vessels of the limbs. Radiographic visualization of these structures is possible until significant hemodilution occurs.

OMNIPAQUE 350 can be injected intravenously as a rapid bolus to provide arterial visualization using digital subtraction radiography. Preprocedural medications are not considered necessary. OMNIPAQUE 350 has provided diagnostic arterial radiographs in about 95% of patients. In some cases, poor arterial visualization has been attributed to patient movement. OMNIPAQUE 350 is very well tolerated in the vascular system. Patient discomfort (general sensation of heat and/or pain) following injection is less than with various other contrast media.

Precautions

Since the contrast medium is usually administered mechanically under high pressure, rupture of smaller peripheral veins can occur. It has been suggested that this can be avoided by using an intravenous catheter threaded proximally beyond larger tributaries or, in the case of the antecubital vein, into the superior vena cava. Sometimes the femoral vein is used. (See PRECAUTIONS—General.)

Adverse Reactions

Cardiovascular system reactions in digital arteriography included transient PVCs (16%) and PACs (6.5%). (See ADVERSE REACTIONS: Intravascular—General.)

Dosage and Administration

The usual injection volume of OMNIPAQUE 350 for the intravenous digital technique is 30 mL to 50 mL of a 350 mg Iodine/mL solution. This is administered as a bolus at 7.5 to 30 mL/second using a pressure injector. The volume and rate of injection will depend primarily on the type of equipment and technique used.

Frequently three or more injections may be required, up to a total volume not to exceed 250 mL (87.5 g Iodine).

PERIPHERAL ANGIOGRAPHY

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL or OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in adults for use in peripheral arteriography. OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in adults for use in peripheral venography.

Sedative medication may be employed prior to use. Anesthesia is not considered necessary. Patient discomfort during and immediately following injection is substantially less than that following injection of various other contrast media. Moderate to severe discomfort is very unusual.

Precautions

Pulsation should be present in the artery to be injected. In thromboangiitis obliterans, or ascending infection associated with severe ischemia, angiography should be performed with extreme caution, if at all. (See PRECAUTIONS—General.)

Adverse Reactions

A transient sensation of mild warmth is usual, immediately following injection. This has not interfered with the procedure.

In phlebography the incidence of leg pain was 21%. This usually was mild and lasted a short time after injection. (See ADVERSE REACTIONS: Intravascular—General.)

Dosage and Administration

The volume required will depend on the size, flow rate, and disease state of the injected vessel and on the size and condition of the patient, as well as the imaging technique used. The dosage recommended for use in peripheral angiography is as follows:

Aortofemoral runoffs:	20 mL to 70 mL of OMNIPAQUE 350 (350 mg Iodine/mL)
	30 mL to 90 mL of OMNIPAQUE 300 (300 mg Iodine/mL)
Selective arteriograms:(femoral/iliac)	10 mL to 30 mL of OMNIPAQUE 350 (350 mg Iodine/mL)10 mL to 60 mL of OMNIPAQUE 300 (300 mg Iodine/mL)
Venography (per leg):	40 mL to 100 mL of OMNIPAQUE 300 (300 mg Iodine/mL)

EXCRETORY UROGRAPHY

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL or OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated for use in adults in excretory urography to provide diagnostic contrast of the urinary tract.

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in pediatric patients for excretory urography. (See Section III for information on voiding cystourethrography.)

For pharmacokinetics of excretion in adults, see CLINICAL PHARMACOLOGY—Intravascular.

Precautions

Preparatory dehydration is not recommended in the elderly, pediatric patients, diabetic or azotemic patients, or in patients with suspected myelomatosis.

Pediatric 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.

Since there is a possibility of temporary suppression of urine formation, it is recommended that a suitable interval elapse before excretory urography is repeated, especially in patients with unilateral or bilateral reduction in renal function. (See PRECAUTIONS—General.)

Adverse Reactions

See ADVERSE REACTIONS: Intravascular—General.

Dosage and Administration

Adults

OMNIPAQUE 300 and OMNIPAQUE 350 at dosages from 200 mg Iodine/kg body weight to 350 mg Iodine/kg body weight have produced diagnostic opacification of the excretory system in patients with normal renal function.

Pediatrics

Section Iii

Clinical Pharmacologyorai/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.

Indications And Usage, Generaloral/body Cavity Use

OMNIPAQUE 300 and OMNIPAQUE 350 have osmolalities from approximately 2.4 to 3 times that of plasma (285 mOsm/kg water) and are hypertonic under conditions of use.

Adults

OMNIPAQUE 350 is indicated in adults for arthrography and oral pass-thru examination of the gastrointestinal tract.

OMNIPAQUE 300 is indicated in adults for arthrography and hysterosalpingography. OMNIPAQUE diluted to concentrations from 6 mg Iodine/mL to 9 mg Iodine/mL administered orally in conjunction with OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL administered intravenously is indicated in adults for contrast enhanced computed tomography of the abdomen.

Pediatric Patients

OMNIPAQUE 300 is indicated in pediatric patients for examination of the gastrointestinal tract.

OMNIPAQUE diluted to concentrations from 50 mg Iodine/mL to 100 mg Iodine/mL is indicated in pediatric patients for voiding cystourethrography.

OMNIPAQUE diluted to concentrations from 9 mg Iodine/mL to 21 mg Iodine/mL administered orally in conjunction with OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL administered intravenously are indicated in pediatric patients for use in contrast enhanced computed tomography of the abdomen.

Contraindications

OMNIPAQUE should not be administered to patients with a known hypersensitivity to iohexol.

Warningsgeneral

See SECTION II, WARNINGS—General.

Precautionsgeneral

See SECTION II, PRECAUTIONS—General.

Orally administered hypertonic contrast media draw fluid into the intestines which, if severe enough, could result in hypovolemia. Likewise, in pediatric patients, the occurrence of diarrhea may result in hypovolemia. Plasma fluid loss may be sufficient to cause a shock- like state which, if untreated, could be dangerous. This is especially pertinent to the elderly, cachectic patients of any age as well as infants and small pediatric patients.

Adverse Reactions: Oral/body Cavity Usegeneral

Body Cavities

In controlled clinical trials involving 285 adult patients for various body cavity examinations using OMNIPAQUE 300 and 350, the following adverse reactions were reported.

Cardiovascular System Incidence > 1%: None Incidence ≤ 1%: Hypertension

Nervous System

Incidence > 1%: Pain (26%)

Incidence ≤ 1%: Headache, somnolence, fever, muscle weakness, burning, unwell feeling, tremors, lightheadedness, syncope

Respiratory System

None

Gastrointestinal System

Incidence > 1%: None

Incidence ≤ 1%: Flatulence, diarrhea, nausea, vomiting, abdominal pressure

Skin and Appendages

Incidence > 1%: Swelling (22%), heat (7%)

Incidence ≤ 1%: Hematoma at injection site

The most frequent reactions, pain and swelling, were almost exclusively reported after arthrography and were generally related to the procedure rather than the contrast medium.

Gastrointestinal reactions were almost exclusively reported after oral pass-thru examinations.

For additional information on adverse reactions that may be expected with specific procedures, see INDIVIDUAL INDICATIONS AND USAGE. For information on general adverse reactions to contrast media, see SECTION II, ADVERSE REACTIONS: Intravascular—General.

No adverse reactions associated with the use of OMNIPAQUE for VCU procedures were reported in 51 pediatric patients studied.

Oral Use

See INDIVIDUAL INDICATIONS AND USAGE: Oral Use—Adverse Reactions.

Overdosage

See also SECTION II, OVERDOSAGE.

The recommended dose of OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL for adult oral pass-thru examination of the gastrointestinal tract is 50 mL to 100 mL. In a Phase I study, 150 mL of OMNIPAQUE 350 was administered orally to 11 healthy male subjects. The incidence of diarrhea was 91% (10 of 11) and abdominal cramping was 27% (3 of 11). Despite all of these events being mild and transient the occurrences were more than double that seen at the recommended doses. It is apparent from this finding that larger volumes of hypertonic contrast media, like OMNIPAQUE, increase the osmotic load in the bowel which may result in greater fluid shifts.

Dosage And Administrationgeneral

See SECTION II, DOSAGE AND ADMINISTRATION—General.

Individual Indications And Usage

Oral Use

Adults

OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in adults for use in oral pass-thru examination of the gastrointestinal tract. OMNIPAQUE diluted to concentrations from 6 mg Iodine/mL to 9 mg Iodine/mL administered orally in conjunction with OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL administered intravenously are indicated in adults for use in contrast enhanced computed tomography of the abdomen. Dilute oral plus intravenous OMNIPAQUE may be useful when unenhanced imaging does not provide sufficient delineation between normal loops of the bowel and adjacent organs or areas of suspected pathology.

Pediatric patients

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL administered orally or rectally is indicated in pediatric patients for use in examination of the gastrointestinal tract. OMNIPAQUE diluted to concentrations from 9 mg Iodine/mL to 21 mg Iodine/mL administered orally in conjunction with OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL administered intravenously are indicated in pediatric patients for use in contrast enhanced computed tomography of the abdomen.

Precautions

See PRECAUTIONS—General.

Adverse Reactions

Oral administration of OMNIPAQUE is most often associated with mild, transient diarrhea especially when high concentrations and large volumes are administered. Nausea, vomiting, and moderate diarrhea have also been reported following orally administered OMNIPAQUE, but much less frequently. For CT examinations using dilute oral plus intravenous contrast medium, adverse events are more likely to be associated with the intravenous injection than the hypotonic oral solution. It should be noted that serious or anaphylactoid reactions that may occur with intravascular iodinated media are possible following administration by other routes.

Adults

In controlled clinical trials involving 54 adult patients for oral pass-thru examination of the gastrointestinal tract using OMNIPAQUE 350, the following adverse reactions were reported:

diarrhea (42%), nausea (15%), vomiting (11%), abdominal pain (7%), flatulence (2%), and headache (2%). In controlled clinical studies involving 44 adult patients for dilute oral plus intravenous CT examination of the gastrointestinal tract using OMNIPAQUE 300, adverse reactions were limited to a single report of vomiting (2%).

Pediatric patients

In controlled clinical studies involving 58 pediatric patients for examination of the gastrointestinal tract at a concentration of 300 mg Iodine/mL, the following adverse reactions were reported: diarrhea (36%), vomiting (9%), nausea (5%), fever (5%), hypotension (2%), abdominal pain (2%), and urticaria (2%). In clinical studies an increased frequency and severity of diarrhea was noted with an increase in the administered concentration and dose of the radiocontrast agent. In controlled clinical studies involving 69 pediatric patients for dilute oral plus intravenous CT examination of the gastrointestinal tract using OMNIPAQUE 300, adverse reactions were limited to a single report of vomiting (1.4%).

Dosage and Administration

Adults

The recommended dosage of undiluted OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL for oral pass-thru examination of the gastrointestinal tract in adults is 50 mL to 100 mL depending on the nature of the examination and the size of the patient. The recommended oral dosage of OMNIPAQUE diluted to concentrations of 6 mg Iodine/mL to 9 mg Iodine/mL for contrast enhanced computed tomography of the abdomen in adults is 500 mL to 1000 mL. Smaller administered volumes are needed as the concentration of the final solution is increased (see Table below). In conjunction with dilute oral administration, the recommended dosage of OMNIPAQUE 300 intravenously is 100 mL to 150 mL. The oral dose is administered about 20 to 40 minutes prior to the intravenous dose and image acquisition.

Pediatric Patients

The dosage of undiluted OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL, is dependent on the nature of the examination and the size of the patient. Based on clinical experience, it is recommended that OMNIPAQUE 180 (available in single use vials), be used in pediatric patients less than 3 months of age. OMNIPAQUE 300 may be used in pediatric patients 3 months of age and older.

The following dosage guidelines are recommended:

Age	Volume of OMNIPAQUE
Less than 3 months	5 — 30 mL
Three months to 3 years	Up to 60 mL
Four years to 10 years	Up to 80 mL
Greater than 10 years	Up to 100 mL

When given rectally, larger volumes may be used.

The recommended oral dosage of OMNIPAQUE diluted to concentrations of 9 mg Iodine/mL to 21 mg Iodine/mL for contrast computed tomography of the abdomen in pediatric patients is 180 mL to 750 mL. Smaller administered volumes are needed as the concentration of the final solution is increased (see Table below). The total oral dose in grams of iodine should generally not exceed 5 g Iodine for pediatric patients under 3 years of age and 10 g Iodine for pediatric patients from 3 to 18 years of age. The oral dosage may be given all at once or over a period of 30 to 45 minutes if there is difficulty in consuming the required volume. In conjunction with dilute oral administration the recommended dosage of OMNIPAQUE 300 is 2mL/kg when administered intravenously with a range of 1 mL/kg to 2 mL/kg. Dosage pediatric patients should be administered in proportion to age and body weight. The total intravenously administered dose should not exceed 3 mL/kg. The oral dose is administered about 30 to 60 minutes prior to the intravenous dose and image acquisition.

OMNIPAQUE may be diluted with water or beverage as follows:

To Achieve	Add		To
One Liter of Contrast Medium at A Final Concentration(mg Iodine/mL) of	Stock Concentration of OMNIPAQUE(mg Iodine/mL)	Volume(mL)	Water, Carbonated Beverage, Milk, or Juice(mL)
6	300	20	980
	350	17	983
9	300	30	970
	350	26	974
12	300	40	960
	350	35	965
15	300	50	950
	350	43	957
18	300	60	940
	350	52	948
21	300	70	930
	350	60	940

Dilutions of OMNIPAQUE should be prepared just prior to use and any unused portion discarded after the procedure.

VOIDING CYSTOURETHROGRAPHY (VCU)

OMNIPAQUE diluted to concentrations from 50 mg Iodine/mL to 100 mg Iodine/mL is indicated in pediatric patients for voiding cystourethrography. VCUs are often performed in conjunction with excretory urography.

Precautions

See PRECAUTIONS—General.

Since the VCU procedure requires instrumentation, special precautions should be observed in those patients known to have an acute urinary tract infection. Filling of the bladder should be done at a steady rate, exercising caution to avoid excessive pressure. Sterile procedures are essential.

Adverse Reactions

See ADVERSE REACTIONS—General.

Dosage and Administration

OMNIPAQUE may be diluted, utilizing aseptic technique, with Sterile Water for Injection to a concentration of 50 mg Iodine/mL to 100 mg Iodine/mL for voiding cystourethrography. The concentration may vary depending upon the patient's size and age and also with the technique and equipment used. Sufficient volume of contrast medium should be administered to adequately fill the bladder. The usual volume ranges from 50 mL to 300 mL of OMNIPAQUE at a concentration of 100 mg Iodine/mL and 50 mL to 600 mL of OMNIPAQUE at a concentration of 50 mg Iodine/mL.

OMNIPAQUE may be diluted with Sterile Water for Injection as indicated in the table below:

To Achieve	Add To
A Final Concentration	Each 100 mL of OMNIPAQUE Sterile Water for Injection, USP (mL)
(mg Iodine/mL)	OMNIPAQUE 300	OMNIPAQUE 350
100	200	250
90	233	289
80	275	338
70	330	400
60	400	483
50	500	600

Dilutions of OMNIPAQUE should be prepared just prior to use and any unused portion discarded after the procedure.

ARTHROGRAPHY

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL or OMNIPAQUE 350 at a concentration of 350 mg Iodine/mL is indicated in radiography of the knee joint in adults, and OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in radiography of the shoulder joint in adults, and OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in radiography of the temporomandibular joint in adults. Arthrography may be helpful in the diagnosis of posttraumatic or degenerative joint diseases, synovial rupture, the visualization of communicating bursae or cysts, and in meniscography.

Precautions

See PRECAUTIONS—General.

Strict aseptic technique is required to prevent infection. Fluoroscopic control should be used to ensure proper needle placement, prevent extracapsular injection, and prevent dilution of contrast medium. Undue pressure should not be exerted during injection.

Adverse Reactions

Injection of OMNIPAQUE into the joint is associated with transient discomfort, ie, pain, swelling. However, delayed, severe or persistent discomfort may occur occasionally. Severe pain may often result from undue use of pressure or the injection of large volumes. Joint swelling after injection is less with OMNIPAQUE than with high osmolar ionic contrast medium. These types of reactions are generally procedurally dependent and of greater frequency when double-contrast technique is employed.

Nervous system: Swelling sensation (42%), pain (29%), heat sensation (13%), and muscle weakness (0.7%).

Skin and appendages: Hematoma at injection site (0.7%).

Dosage and Administration

Arthrography is usually performed under local anesthesia. The amount of OMNIPAQUE injected is dependent on the size of the joint to be examined and the technique employed. Lower volumes of contrast medium are usually injected for knee and shoulder arthrography when double-contrast examinations using 15 mL to 100 mL of air are performed.

The following concentrations and volumes are recommended for normal adult knee, shoulder, and temporomandibular joints but should serve as guidelines since joints may require more or less contrast medium for optimal visualization.

KNEE OMNIPAQUE 300   5 mL to 15 mLOMNIPAQUE 350   5 mL to 10 mL		Lower volumes recommended for double-contrast examinations; higher volumes recommended for single-contrast examinations.
SHOULDER OMNIPAQUE 300   10 mL
TEMPOROMANDIBULAR OMNIPAQUE 300   0.5 mL to 1 mL

Passive or active manipulation is used to disperse the medium throughout the joint space.

HYSTEROSALPINGOGRAPHY

OMNIPAQUE 300 at a concentration of 300 mg Iodine/mL is indicated in radiography of the internal group of adult female reproductive organs; ovaries, fallopian tubes, uterus, and vagina. Hysterosalpingography is utilized as a diagnostic and therapeutic modality in the treatment of infertility and other abnormal gynecological conditions.

Contraindications

OMNIPAQUE 300 for hysterosalpingography is contraindicated during pregnancy or suspected pregnancy, menstruation or when menstruation is imminent , within 6 months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract including the external genitalia, and when reproductive tract neoplasia is known or suspected because of the risk of peritoneal spread of neoplasm.

Adverse Reactions

Injection of OMNIPAQUE for hysterosalpingography is associated with immediate, transient pain. Monitor injection pressure and volume instilled to minimize pain and to avoid disruptive distention of the uterus and fallopian tubes. Fluoroscopic monitoring is recommended. Nervous system: Pain (49%), somnolence and fever each with an individual incidence of 3%. Gastrointestinal system: Nausea (3%).

Dosage and Administration

The recommended dosage of OMNIPAQUE 300 is 15 mL to 20 mL but will vary depending on individual anatomy and/or disease state.

Directions For Use

• The transfer of OMNIPAQUE (Iohexol Injection) from the Pharmacy Bulk Package is restricted to a suitable work area, such as a laminar flow hood.
• The container closure may be penetrated only one time, utilizing a suitable transfer device and aseptic technique.
• The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 8 hours from initial closure entry is permitted to complete fluid transfer operations. The container should not be removed from the aseptic area during the entire 8 hour period.
• The temperature of the container should not exceed 37°C, after the closure has been entered.

How Supplied

OMNIPAQUE 300500 mL in +PLUSPAKâ„¢ (polymer bottle), boxes of 10 Pharmacy Bulk Packages(NDC 0407-1413-68)

OMNIPAQUE 350500 mL in +PLUSPAKâ„¢ (polymer bottle), boxes of 10 Pharmacy Bulk Packages(NDC 0407-1414-98)

STORAGE AND HANDLING SECTION

Protect polymer bottles 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].

OMNIPAQUE Injection in all presentations may be stored in a contrast media warmer for up to one month at 37°C (98.6°F).

SPECIAL HANDLING AND STORAGE FOR POLYMER BOTTLES ONLY: DO NOT USE IF TAMPER-EVIDENT RING IS BROKEN OR MISSING.

Distributed by GE Healthcare Inc.,

Marlborough, MA 01752 U.S.A. Product of Norwegian Origin.

Omnipaque is a trademark of GE HealthCare or one of its subsidiaries. GE is a trademark of General Electric Company used under trademark license.

© 2023 GE HealthCare Revised 4/2023

Principal Display Panel - 300 Mg Bottle Box Label

NDC 0407-1413-68

GE Healthcare

Y-538B

Contains10 x 500 mL Bottles

OMNIPAQUEâ„¢ (iohexol) Injection

300 mg Iodine/mL

PHARMACY BULK PACKAGE Not for Direct Infusion

For Injection or Oral Use

Sterile Aqueous Solution

Principal Display Panel - 350 Mg Bottle Box Label

NDC 0407-1414-98

GE Healthcare

Y-548B

Contains10 x 500 mL Bottles

OMNIPAQUEâ„¢ (iohexol) Injection

350 mg Iodine/mL

PHARMACY BULK PACKAGE Not for Direct Infusion

For Injection or Oral Use

Sterile Aqueous Solution Not for Intrathecal Use