ISOVUE-M

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Life-threatening or fatal reactions can occur. Always have emergency resuscitation equipment and trained personnel available. ( 5.1 ) Acute Kidney Injury: Acute injury including renal failure can occur. Use the lowest dose and maintain adequate hydration to minimize risk. ( 5.2 ) Cardiovascular Adverse Reactions: Hemodynamic disturbances including shock and cardiac arrest may occur during or after ISOVUE-M administration. ( 5.4 ) Thyroid Dysfunction in Pediatric Patients 0 Years to 3 Years of Age: Individualize thyroid function monitoring based on risk factors such as prematurity. ( 5.6 ) 5.1 Hypersensitivity Reactions ISOVUE-M can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock [see Adverse Reactions ( 6.2 )] . Most severe reactions develop shortly after the start of injection (e.g., within 1 to 3 minutes), but delayed reactions can also occur. There is increased risk of hypersensitivity reactions in patients with a history of previous reactions to contrast agents, and known allergic disorders (i.e., bronchial asthma, allergic rhinitis, and food allergies) or other hypersensitivities. Premedication with antihistamines or corticosteroids does not prevent serious life-threatening reactions, but may reduce their incidence and severity. Obtain a history of allergy or hypersensitivity reactions to iodinated contrast agents and always have emergency resuscitation equipment and trained personnel available prior to ISOVUE-M administration. Monitor all patients for hypersensitivity reactions. 5.2 Acute Kidney Injury Acute kidney injury, including renal failure, may occur after administration of iodinated contrast agents. Risk factors include pre-existing renal insufficiency, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma or other paraproteinemias, and repetitive or large doses of iodinated contrast agents. Use the lowest dose of ISOVUE-M, especially in patients with risk factors for acute kidney injury. Adequately hydrate patients prior to and following ISOVUE-M administration . 5.3 Increased Risk of Seizures Focal and generalized motor seizures have been reported after intrathecal use of iodinated contrast agents including ISOVUE-M. In several of the cases, higher than recommended doses were administered. Use of medications that may lower the seizure threshold (phenothiazine derivatives, including those used for their antihistaminic properties; tricyclic antidepressants; MAO inhibitors; CNS stimulants; analeptics; antipsychotic agents) should be carefully evaluated. Consider discontinuing these agents at least 48 hours before and for at least 24 hours following intrathecal administration of ISOVUE-M. 5.4 Cardiovascular Adverse Reactions Iodinated contrast agents increase the circulatory osmotic load and may induce acute or delayed hemodynamic disturbances in patients with congestive heart failure, severely impaired renal function, combined renal and hepatic disease, and combined renal and cardiac disease, particularly when repetitive or large doses are administered. Fatal cardiovascular reactions have occurred mostly within 10 minutes of injection of iodinated contrast agent by an intravascular route; the main feature was cardiac arrest with cardiovascular disease as the main underlying factor. Hypotensive collapse and shock have occurred. The administration of iodinated contrast agent may cause pulmonary edema in patients with heart failure. Based upon published reports, deaths associated with the administration of iodinated contrast agents range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients (0.01 percent). Use the lowest necessary dose of ISOVUE-M in patients with congestive heart failure and always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions. 5.5 Thyroid Storm in Patients with Hyperthyroidism Thyroid storm has occurred after the use of iodinated contrast agents in patients with hyperthyroidism, or with an autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of ISOVUE-M. 5.6 Thyroid Dysfunction in Pediatric Patients 0 Years 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 agents in pediatric patients 0 years 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 iodinated contrast agent exposure. Pediatric patients with congenital cardiac conditions may be at 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 iodinated contrast agent, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates. ISOVUE-M is not indicated for use in pediatric patients younger than 2 years of age [see Use in Specific Populations ( 8.4 )] . 5.7 Hypertensive Crisis in Patients with Pheochromocytoma Hypertensive crisis in patients with pheochromocytoma has occurred with iodinated contrast agents. Closely monitor patients when administering ISOVUE-M if pheochromocytoma or catecholamine-secreting paragangliomas are suspected. Inject the minimum amount of ISOVUE-M necessary and have measures for treatment of hypertensive crisis readily available. 5.8 Sickle Cell Crisis in Patients with Sickle Cell Disease Iodinated contrast agents may promote sickling in individuals who are homozygous for sickle cell disease. Hydrate patients prior to and following ISOVUE-M administration and use only if the necessary imaging information cannot be obtained with alternative imaging modalities. 5.9 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after administration of iodinated contrast agent. 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 ISOVUE-M to patients with a history of a severe cutaneous adverse reaction to ISOVUE-M. 5.10 Interference with Laboratory Test ISOVUE-M can interfere with protein-bound iodine test [see Drug Interactions ( 7.2 )] .