FDA label 1c350dda-7fc4-18c2-e063-6394a90ad36a

WARNING: NOT FOR INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS (NSF) WARNING: NOT FOR INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS (NSF) See full prescribing information for complete boxed warning. NOT FOR INTRATHECAL USE: Inadvertent intrathecal use of OMNISCAN has caused convulsions, coma, sensory and motor neurologic deficits ( 5.1 ). NSF: Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. Do not administer OMNISCAN to patients with: chronic, severe kidney disease (GFR < 30 mL/min/1.73m 2 ), or acute kidney injury ( 4 ). Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing ( 5.2 ). NOT FOR INTRATHECAL USE: Inadvertent intrathecal use of OMNISCAN has caused convulsions, coma, sensory and motor neurologic deficits [ see Warnings and Precautions (5.1) ]. NSF: Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Do not administer OMNISCAN to patients with: chronic, severe kidney disease (GFR < 30 mL/min/1.73m 2 ), or acute kidney injury [ see Contraindications (4) ]. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. Do not exceed the recommended OMNISCAN dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration [ see Warnings and Precautions (5.2) ].

5 WARNINGS AND PRECAUTIONS Nephrogenic Systemic Fibrosis (NSF) has occurred in patients with impaired elimination of GBCAs. Higher than recommended dosing or repeat dosing appears to increase the risk ( 5.2 ). 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 is retained for months or years in brain, bone, and other organs. ( 5.4 ). 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 Not for Intrathecal Use Inadvertent intrathecal use of OMNISCAN has occurred and caused convulsions, coma, sensory and motor neurologic deficits. 5.2 Nephrogenic Systemic Fibrosis Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs 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 30-59 mL/min/1.73m 2 ) and little, if any, for patients with chronic, mild kidney disease (GFR 60-89 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 (6.3) ] . 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 12-24 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.

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Nephrogenic systemic fibrosis [see Warnings and Precautions (5.2) ] Hypersensitivity reactions [see Warnings and Precautions (5.3) ] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most frequent adverse reactions (≤ 3%) observed during OMNISCAN adult clinical studies were nausea, headache, and dizziness ( 6.1 ) Serious or life-threatening reactions include: cardiac failure, arrhythmia and myocardial infarction ( 6.1 , 6.3 ) To report SUSPECTED ADVERSE REACTIONS, contact GE Healthcare at 1-800-654-0118 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience (Adults) In clinical studies 1160 patients were exposed to OMNISCAN. The most frequent adverse reactions were nausea, headache, and dizziness that occurred in 3% or less of the patients. The majority of these reactions were of mild to moderate intensity. The following adverse reactions occurred in 1% or less of patients: Application Site Disorders: Injection site reaction. Autonomic Nervous System Disorders: Vasodilation. Body as a Whole-General Disorders: Anaphylactoid reactions (characterized by cardiovascular, respiratory, and cutaneous symptoms), fever, hot flushes, rigors, fatigue, malaise, pain, syncope. Cardiovascular Disorders: Cardiac failure, rare arrhythmia and myocardial infarction resulting in death in patients with ischemic heart disease, flushing, chest pain, deep thrombophlebitis. Central and Peripheral Nervous System Disorders: Convulsions including grand mal, ataxia, abnormal coordination, paresthesia, tremor, aggravated multiple sclerosis (characterized by sensory and motor disturbances), aggravated migraine. Gastrointestinal System Disorders: Abdominal pain, diarrhea, eructation, dry mouth/vomiting, melena. Hearing and Vestibular Disorders: Tinnitus. Liver and Biliary System Disorders: Abnormal hepatic function. Musculoskeletal System Disorders: Arthralgia, myalgia. Respiratory System Disorders: Rhinitis, dyspnea. Skin and Appendage Disorders: Pruritus, rash, erythematous rash, sweating increased, urticaria. Special Senses, Other Disorders: Taste loss, taste perversion. Urinary System Disorders: Acute reversible renal failure. Vision Disorders: Abnormal vision. 6.2 Clinical Studies Experience (Pediatrics) In the 97 pediatric patients in CNS studies with OMNISCAN [see Clinical Studies (14.1) ] and the 144 pediatric patients in published literature, the adverse reactions were similar to those reported in adults. 6.3 Postmarketing Experience Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during the postmarketing use of OMNISCAN: Nervous System Disorders: Inadvertent intrathecal use causes convulsions, coma, paresthesia, paresis. Convulsions have also been reported with intravenous use in patients with and without a history of convulsions or brain lesions. General Disorders : Nephrogenic Systemic Fibrosis (NSF) [see Warnings and Precautions (5.2) ]. Adverse events with variable onset and duration have been reported after GBCA administration [ see Warnings and Precautions (5.4) ] . These include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems . Renal and Urinary System Disorders: In patients with pre-existing renal insufficiency: acute renal failure, renal impairment, blood creatinine increased [see Warnings and Precautions (5.5) ]. Skin : Gadolinium associated plaques.