FDA label 1fc06256-bb10-3c8d-e063-6394a90ae8b7

WARNINGS—General SEVERE ADVERSE EVENTS - INADVERTENT INTRATHECAL ADMINISTRATION Serious 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 ensure that OMNIPAQUE 350 is not administered intrathecally. (OMNIPAQUE 300 is 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. Drugs which lower the seizure thresh old, 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: Deviations from recommended procedure or in myelographic management. Use in patients with a history of epilepsy. Overdosage. Intracranial entry of a bolus or premature diffusion of a high concentration of the medium. Medication with neuroleptic drugs or phenothiazine antinauseants. Failure to maintain elevation of the head during the procedure, on the stretcher, or in bed. Excessive and particularly active patient movement or straining.

WARNINGS—General Nonionic 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, 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 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. Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media (ICM) in pediatric patients 0 to 3 years of age. Younger age, very low birth weight, prematurity, underlying medical conditions affecting thyroid function, admission to neonatal or pediatric intensive care units, and congenital cardiac conditions are associated with an increased risk of hypothyroidism after ICM exposure. Pediatric patients with congenital cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures. An underactive thyroid during early life may be harmful for cognitive and neurological development and may require thyroid hormone replacement therapy. After exposure to ICM, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates. Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular OMNIPAQUE administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering OMNIPAQUE to patients with a history of a severe cutaneous adverse reaction to OMNIPAQUE. Urography should be performed with caution in patients with severely impaired renal function and patients with combined renal and hepatic disease.

WARNINGS—General See SECTION II, WARNINGS—General .

ADVERSE REACTIONS—Intrathecal The most frequently reported adverse reactions with OMNIPAQUE are headache, 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 usually last for a few hours, and usually disappear within 24 hours. Severe headaches persisting for days have been reported. 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: 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. General Adverse Reactions to Contrast Media Physicians 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 nonionic, water-soluble myelographic media including 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 (in 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, anaphylactic reactions, anaphylactic shock, and a case of Guillain-Barré syndrome. CNS Irritation: Transient 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, meningism, 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 been reported. They 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. Apprehension, agitation, or progressive withdrawal in several instances to the point of somnolence, stupor, and coma have been reported, as well as transitory hearing loss or other auditory symptoms and visual disturbances, 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. Persistent though transitory weakness in the leg or ocular muscles has been reported. Peripheral neuropathies have been reported. 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 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. Severe, life-threatening, fatal anaphylactic shock has been reported. 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.

ADVERSE REACTIONS: Intravascular—General 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 listed 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. S igns 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 )

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

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