Gadodiamide

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Anaphylactoid and other serious hypersensitivity reactions including fatal reactions have occurred particularly in patients with history of allergy or drug reactions. Monitor patients closely for need of emergency cardiorespiratory support ( 5.3 ). Gadolinium Retention: Gadolinium is retained for months or years in brain, bone, and other organs ( 5.4 ). Acute Renal Failure: Acute renal failure has occurred in patients with preexisting renal insufficiency. Use the lowest necessary dose of OMNISCAN and evaluate renal function in these patients ( 5.5 ). 5.1 Risk Associated with Intrathecal Use Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of OMNISCAN have not been established with intrathecal use. OMNISCAN is not approved for intrathecal use [see Dosage and Administration (2.1 , 2.2) ]. 5.2 Nephrogenic Systemic Fibrosis GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of OMNISCAN among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m 2 ) as well as patients with acute kidney injury. Do not administer OMNISCAN to these patients. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30 to 59 mL/min/1.73m 2 ) and little, if any, for patients with chronic, mild kidney disease (GFR 60 to 89 mL/min/1.73m 2 ). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following OMNISCAN administration to GE HealthCare (1-800-654-0118) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch). Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronically reduced renal function (e.g., age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing. Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and the degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. When administering a GBCA, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent prior to any readministration [see Boxed Warning , Contraindications (4) , Clinical Pharmacology (12.2) and Dosage and Administration (2) ]. 5.3 Hypersensitivity Reactions Anaphylactoid and anaphylactic reactions, with cardiovascular, respiratory and/or cutaneous manifestations, resulting in death have occurred. Personnel trained in resuscitation techniques and resuscitation equipment should be present prior to OMNISCAN administration. If a hypersensitivity reaction occurs, stop OMNISCAN Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after OMNISCAN Injection. 5.4 Gadolinium Retention Gadolinium is retained for months or years in several organs. The highest concentrations (nanomoles per gram of tissue) have been identified in the bone, followed by other organs (e.g., brain, skin, kidney, liver, and spleen). The duration of retention also varies by tissue and is longest in bone. Linear GBCAs cause more retention than macrocyclic GBCAs. At equivalent doses, gadolinium retention varies among the linear agents with Omniscan (gadodiamide) and Optimark (gadoversetamide) causing greater retention than other linear agents [Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), MultiHance (gadobenate dimeglumine)]. Retention is lowest and similar among the macrocyclic GBCAs [Dotarem (gadoterate meglumine), Gadavist (gadobutrol), ProHance (gadoteridol)]. Consequences of gadolinium retention in the brain have not been established. Pathologic and clinical consequences of GBCA administration and retention in skin and other organs have been established in patients with impaired renal function [see Warnings and Precautions (5.2) ]. There are rare reports of pathologic skin changes in patients with normal renal function. Adverse events involving multiple organ systems have been reported in patients with normal renal function without an established causal link to gadolinium retention [see Adverse Reactions (6.2) ]. While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients [see Use in Specific Populations (8.1 , 8.4) ], and patients with inflammatory conditions. Consider the retention characteristics of the agent when choosing a GBCA for these patients. Minimize repetitive GBCA imaging studies, particularly closely spaced studies, when possible. 5.5 Acute Renal Failure In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred, mostly within 48 hours of OMNISCAN Injection. The risk of renal failure may increase with increasing dose of gadolinium contrast. Use the lowest necessary dose of contrast and evaluate renal function in patients with renal insufficiency. Acute renal failure was observed in < 1% of patients in OMNISCAN clinical studies [see Adverse Reactions (6) ]. OMNISCAN is cleared by glomerular filtration. Hemodialysis also enhances OMNISCAN clearance [see Use in Specific Populations (8.5 , 8.6) ]. 5.6 Impaired Visualization of Lesions Detectable with Non-contrast MRI Paramagnetic contrast agents such as OMNISCAN might impair the visualization of lesions which are seen on the non-contrast MRI. This may be due to effects of the paramagnetic contrast agent, or imaging parameters. Exercise caution when OMNISCAN MRI scans are interpreted in the absence of a companion non-contrast MRI. 5.7 Laboratory Test Findings Asymptomatic, transitory changes in serum iron have been observed. The clinical significance is unknown. OMNISCAN interferes with serum calcium measurements with some colorimetric (complexometric) methods commonly used in hospitals, resulting in serum calcium concentrations lower than the true values. In patients with normal renal function, this effect lasts for 12 to 24 hours. In patients with decreased renal function, the interference with calcium measurements is expected to last during the prolonged elimination of OMNISCAN. After patients receive OMNISCAN, careful attention should be used in selecting the type of method used to measure calcium.