BL-C Kit

WARNING: NOT FOR INTRATHECAL USE Inadvertent intrathecal administration may cause death, convulsions/seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema [see Contraindications ( 4 ) and Adverse Reactions ( 5.1 )] . WARNING: NOT FOR INTRATHECAL USE See full prescribing information for complete boxed warning Inadvertent intrathecal administration may cause death, convulsions/seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema. ( 4 , 5.1 )

WARNINGS Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension should not be administered intravenously. Serious Neurologic Adverse Reactions with Epidural Administration Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use. General Rare instances of anaphylactoid/anaphylactic reactions with a possibility of shock have occurred in patients receiving parenteral corticosteroid therapy (see ADVERSE REACTIONS ). Use caution in patients who have a history of allergic reaction to corticosteroids. In patients on corticosteroid therapy subjected to any unusual stress, hydrocortisone or cortisone is the drug of choice as a supplement during and after the event. Cardio-Renal Average and large doses of corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients. Endocrine Corticosteroids can produce reversible hypothalamic pituitary adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage. Infections General Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan, or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents. These infections may be mild to severe. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection. Fungal Infections Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control drug reactions. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS, Drug Interactions, Amphotericin B Injection and Potassium-Depleting Agents section). Special Pathogens Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis , and Toxoplasma . It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Corticosteroids should not be used in cerebral malaria. Tuberculosis The use of corticosteroids in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Vaccination Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines cannot be predicted. Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease. Viral Infections Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents should be considered. Neurologic Reports of severe medical events have been associated with the intrathecal route of administration (see ADVERSE REACTIONS, Gastrointestinal and Neurologic/Psychiatric sections ). Results from one multicenter, randomized, placebo-controlled study with methylprednisolone hemisuccinate, an intravenous corticosteroid, showed an increase in early mortality (at 2 weeks) and late mortality (at 6 months) in patients with cranial trauma who were determined not to have other clear indications for corticosteroid treatment. High doses of corticosteroids, including Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension, should not be used for the treatment of traumatic brain injury. Ophthalmic Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Consider referral to an ophthalmologist for patients who develop ocular symptoms or use corticosteroid-containing products for more than 6 weeks. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex.

WARNINGS LIDOCAINE HYDROCHLORIDE INJECTION FOR INFILTRATION AND NERVE BLOCK SHOULD BE EMPLOYED ONLY BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER ENSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT AND THE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (see also ADVERSE REACTIONS and PRECAUTIONS ). DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH. Methemoglobinemia Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue lidocaine hydrochloride and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2 nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement. To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided. Anaphylactic reactions may occur following administration of lidocaine hydrochloride (see ADVERSE REACTIONS ). In the case of severe reaction, discontinue the use of the drug.

Warnings: Section Text FOR EXTERNAL USE ONLY

Warnings For external use only Flammable - keep away from fire or flame Do not use with electrocautery procedures When using this product do not get into eyes apply over large areas of the body in case of deep or puncture wounds, animal bites or serious burns consult a doctor Stop use and ask a doctor if condition persists or gets worse or lasts for more than 72 hours do not use longer than 1 week unless directed by a doctor Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risks Associated with Inadvertent Intrathecal Administration [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Contrast-Induced Kidney Injury [see Warnings and Precautions (5.3) ] Cardiovascular Adverse Reactions [see Warnings and Precautions (5.4) ] Thromboembolic Events [see Warnings and Precautions (5.5) ] Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings and Precautions (5.8) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.11) ] Most common adverse reactions (incidence greater than 0.5%) in adult patients after iodixanol injection: Discomfort, warmth, pain; Cardiovascular: angina. Gastrointestinal: diarrhea, nausea, vomiting. Nervous System: agitation, anxiety, insomnia, nervousness, dizziness, headache, migraine, unusual skin sensations, sensory disturbance, fainting, sensation of spinning. Skin: itchy rash, severe itching, hives. Special Senses: Smell, taste, and vision alteration. ( 6.1 ) Pediatric patients experienced similar adverse reactions. ( 6.3 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Iodixanol is often associated with sensations of discomfort, warmth or pain. In a subgroup of 1,259 patients; 30% who received iodixanol or a comparator had application site discomfort, pain, warmth or cold. Iodixanol had a trend toward fewer patient reports of moderate or severe pain or warmth. Pain was reported in 2% of patients receiving iodixanol and 10% of patients receiving a comparator. Heat was reported in 29% of patients receiving iodixanol and 51% of patients receiving a comparator. Table 3 shows the incidence of events reported in blinded, controlled clinical studies of iodixanol in a total of 1,244 adult patients. Adverse events (AEs) are listed by body system and in decreasing order of occurrence greater than 0.5% of patients. One or more adverse events were reported in 20% of patients during the study period (24 to 72 hours). In a 757 patient subgroup, the number of women reporting adverse events was 83/299 (28%) and the number of men was 77/458 (16%). A total of 3% of women and 0.8% of men reported chest pain. TABLE 3 ADVERSE EVENTS REPORTED IN CONTROLLED CLINICAL TRIALS IN GREATER THAN 0.5% OF 1,244 ADULT PATIENTS RECEIVING IODIXANOL OR OTHER IODINATED CONTRAST AGENTS NUMBER OF PATIENTS EXPOSED Iodixanol N (%)= 1,244 Pooled Comparators N (%) = 861 Number of Patients with Any Adverse Event 248 (19.9) 194 (22.5) Body As a Whole Patients With Any Event 41 (3.3) 22 (2.6) Edema (any location) 7 (0.6) 0 (0) Cardiovascular Patients With Any Event 37 (3.0) 39 (4.5) Angina Pectoris/Chest Pain 28 (2.2) 22 (2.6) Gastrointestinal Patients With Any Event 51 (4.1) 46 (5.3) Diarrhea 7 (0.6) 6 (0.7) Nausea 35 (2.8) 32 (3.7) Vomiting 10 (0.8) 11 (1.3) Nervous System Patients With Any Event 101 (8.1) 60 (7.0) Agitation, Anxiety, Insomnia, Nervousness 10 (0.8) 0 (0) Dizziness 8 (0.7) 8 (0.9) Headache/Migraine 31 (2.5) 15 (1.7) Paresthesia 12 (1.0) 1 (0.1) Sensory Disturbance 10 (0.8) 9 (1.0) Syncope 8 (0.6) 1 (0.1) Vertigo 30 (2.4) 20 (2.3) Skin (not including application site) Patients With Any Event 42 (4.6) 18 (2.1) Nonurticarial Rash or Erythema 26 (2.1) 4 (0.5) Pruritus 20 (1.6) 3 (0.3) Urticaria 6 (0.5) 10 (1.2) Special Senses Patients With Any Event 57 (4.6) 38 (4.4) Parosmia 6 (0.5) 4 (0.5) Taste Perversion 43 (3.5) 32 (3.7) Scotoma 14 (1.1) 2 (0.2) The following selected adverse events were reported in ≤0.5% of the 1,244 patients. Body as a Whole—General Disorders: back pain, fatigue, malaise Cardiovascular Disorders: arrhythmias, cardiac failure, conduction abnormalities, hypotension, myocardial infarction Gastrointestinal System Disorders: dyspepsia Hypersensitivity Disorders: pharyngeal edema Nervous System: cerebral vascular disorder, convulsions, hypoesthesia, stupor, confusion Peripheral Vascular Disorders: flushing, peripheral ischemia Renal System Disorders: abnormal renal function, acute renal failure, hematuria Respiratory System Disorders: asthma, bronchitis, dyspnea, pulmonary edema, rhinitis Skin and Appendage Disorders: hematoma, increased sweating Special Senses, Other Disorders: tinnitus Vision Disorders: abnormal vision 6.2 Post-marketing Experience The following additional adverse reactions have been identified during post approval use of iodixanol. Because these 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 exposure. Cardiovascular Disorders: Cardiac arrest, palpitations, spasms of coronary arteries, hypertension, and flushing Endocrine Disorders: Hyperthyroidism, hypothyroidism Eye Disorders: Transient visual impairment including cortical blindness, diplopia, and blurred vision Gastrointestinal Disorders: Abdominal pain, pancreatitis, salivary gland enlargement General Disorders and Administration Site Conditions: Chills, pyrexia, pain and discomfort, administration site reactions including extravasation Immune System Disorders: Hypersensitivity reactions, anaphylactic shock including, life-threatening or fatal anaphylaxis Nervous System Disorders: Tremor (transient), coma, disturbance in consciousness, transient contrast-induced encephalopathy caused by extravasation of contrast media (including amnesia, hallucination, paralysis, paresis, transient speech disorder, aphasia, dysarthria) Psychiatric Disorders: Anxiety, agitation Respiratory, Thoracic, and Mediastinal Disorders: Cough, sneezing, throat irritation or tightness, laryngeal edema, pharyngeal edema, bronchospasm Skin and subcutaneous tissue disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticaria, and 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)] 6.3 Pediatric Adverse Reactions The overall character, quality, and severity of adverse reactions in pediatric patients is similar to that reported in adult patients from post marketing surveillance and other information. Additional safety data was obtained in studies of iodixanol in 459 pediatric patients. A total of 26 patients ranged in age from birth to <29 days, 148 ranged from 29 days to 2 years, 263 from 2 to <12 years, and 22 from 12 to 18 years. A total of 252 (55%) of the patients were male. The racial distribution was: Caucasian-81%, Black-14%, Oriental-2%, and other or unknown-4%. The proportion of patients undergoing an intra-arterial procedure by age was: 92 % (<29 days), 55% (29 days to 6 months), and 29 % (>6 months). In these studies, adverse events were numerically higher in pediatric patients less than one year of age compared to older pediatric patients. In pediatric patients who received intravenous injections of iodixanol for computerized tomography or excretory urography, a concentration of 270 mg Iodine/mL was used in 144 patients, and a concentration of 320 mg Iodine/mL in 154 patients. All patients received one intravenous injection of 1 mL/kg to 2 mL/kg. In pediatric patients who received intra-arterial and intracardiac studies, a concentration of 320 mg Iodine/mL was used in 161 patients. Twenty-two patients were <29 days of age; 78 were 29 days to 2 years of age; and 61 were over 2 years. Most of these pediatric patients received initial volumes of 1 mL/kg to 2 mL/kg and most patients received a maximum of 3 injections.

ADVERSE REACTIONS (listed alphabetically, under each subsection) Allergic Reactions Anaphylactoid reaction, anaphylaxis, angioedema. Cardiovascular Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS ), pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis. Dermatologic Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria. Endocrine Decreased carbohydrate and glucose tolerance, development of cushingoid state, glucosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients. Fluid and Electrolyte Disturbances Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention. Gastrointestinal Abdominal distention, bowel/bladder dysfunction (after intrathecal administration), elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis. Metabolic Negative nitrogen balance due to protein catabolism. Musculoskeletal Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, postinjection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures. Neurologic/Psychiatric Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration (see WARNINGS, Neurologic section). Ophthalmic Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, rare instances of blindness associated with periocular injections, vision blurred. Other Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.

ADVERSE REACTIONS Systemic Adverse experiences following the administration of lidocaine hydrochloride are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption or inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported: Central Nervous System CNS manifestations are excitatory and/or depressant and may be characterized by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. Drowsiness following the administration of lidocaine hydrochloride is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption. Cardiovascular System Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest. Allergic Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Allergic reactions may occur as a result of sensitivity to local anesthetic agents. Allergic reactions, including anaphylactic reactions, may occur as a result of sensitivity to lidocaine, but are infrequent. If allergic reactions do occur, they should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value. There have been no reports of cross sensitivity between lidocaine hydrochloride and procainamide or between lidocaine hydrochloride and quinidine. Neurologic The incidences of adverse reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration and the physical status of the patient. In a prospective review of 10,440 patients who received lidocaine hydrochloride for spinal anesthesia, the incidences of adverse reactions were reported to be about 3 percent each for positional headaches, hypotension and backache; 2 percent for shivering; and less than 1 percent each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic. In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter may occur. Subsequent adverse effects may depend partially on the amount of drug administered subdurally. These may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances when caudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anesthetic procedures. There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration. Hematologic Methemoglobinemia.

<table width="75%"><caption>ADVERSE EVENTS REPORTED IN CONTROLLED CLINICAL TRIALS IN GREATER THAN 0.5% OF 1,244 ADULT PATIENTS RECEIVING IODIXANOL OR OTHER IODINATED CONTRAST AGENTS</caption><col width="25%" align="left" valign="top"/><col width="25%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr styleCode="First Last"><th colspan="2" align="left" styleCode="Lrule">NUMBER OF PATIENTS EXPOSED</th><th align="center" styleCode="Lrule" valign="bottom">Iodixanol N (%)= 1,244 </th><th align="center" styleCode="Lrule Rrule" valign="bottom">Pooled Comparators N (%) = 861 </th></tr></thead><tbody><tr styleCode="Botrule First"><td colspan="2" align="left" styleCode="Lrule">Number of Patients with Any Adverse Event</td><td align="center" styleCode="Lrule">248 (19.9)</td><td align="center" styleCode="Lrule Rrule">194 (22.5)</td></tr><tr styleCode="Botrule"><td rowspan="2" align="left" styleCode="Lrule">Body As a Whole</td><td align="left" styleCode="Lrule">Patients With Any Event</td><td align="center" styleCode="Lrule">41 (3.3)</td><td align="center" styleCode="Lrule Rrule">22 (2.6)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Edema (any location)</td><td align="center" styleCode="Lrule">7 (0.6)</td><td align="center" styleCode="Lrule Rrule">0 (0)</td></tr><tr styleCode="Botrule"><td rowspan="2" align="left" styleCode="Lrule">Cardiovascular</td><td align="left" styleCode="Lrule">Patients With Any Event</td><td align="center" styleCode="Lrule">37 (3.0)</td><td align="center" styleCode="Lrule Rrule">39 (4.5)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Angina Pectoris/Chest Pain</td><td align="center" styleCode="Lrule">28 (2.2)</td><td align="center" styleCode="Lrule Rrule">22 (2.6)</td></tr><tr styleCode="Botrule"><td rowspan="4" align="left" styleCode="Lrule">Gastrointestinal</td><td align="left" styleCode="Lrule">Patients With Any Event</td><td align="center" styleCode="Lrule">51 (4.1)</td><td align="center" styleCode="Lrule Rrule">46 (5.3)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Diarrhea</td><td align="center" styleCode="Lrule">7 (0.6)</td><td align="center" styleCode="Lrule Rrule">6 (0.7)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Nausea</td><td align="center" styleCode="Lrule">35 (2.8)</td><td align="center" styleCode="Lrule Rrule">32 (3.7)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Vomiting</td><td align="center" styleCode="Lrule">10 (0.8)</td><td align="center" styleCode="Lrule Rrule">11 (1.3)</td></tr><tr styleCode="Botrule"><td rowspan="8" align="left" styleCode="Lrule">Nervous System</td><td align="left" styleCode="Lrule">Patients With Any Event</td><td align="center" styleCode="Lrule">101 (8.1)</td><td align="center" styleCode="Lrule Rrule">60 (7.0)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Agitation, Anxiety, Insomnia, Nervousness</td><td align="center" styleCode="Lrule">10 (0.8)</td><td align="center" styleCode="Lrule Rrule">0 (0)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Dizziness</td><td align="center" styleCode="Lrule">8 (0.7)</td><td align="center" styleCode="Lrule Rrule">8 (0.9)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Headache/Migraine</td><td align="center" styleCode="Lrule">31 (2.5)</td><td align="center" styleCode="Lrule Rrule">15 (1.7)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Paresthesia</td><td align="center" styleCode="Lrule">12 (1.0)</td><td align="center" styleCode="Lrule Rrule">1 (0.1)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Sensory Disturbance</td><td align="center" styleCode="Lrule">10 (0.8)</td><td align="center" styleCode="Lrule Rrule">9 (1.0)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Syncope</td><td align="center" styleCode="Lrule">8 (0.6)</td><td align="center" styleCode="Lrule Rrule">1 (0.1)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Vertigo</td><td align="center" styleCode="Lrule">30 (2.4)</td><td align="center" styleCode="Lrule Rrule">20 (2.3)</td></tr><tr styleCode="Botrule"><td rowspan="4" align="left" styleCode="Lrule">Skin (not including application site)</td><td align="left" styleCode="Lrule">Patients With Any Event</td><td align="center" styleCode="Lrule">42 (4.6)</td><td align="center" styleCode="Lrule Rrule">18 (2.1)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Nonurticarial Rash or Erythema</td><td align="center" styleCode="Lrule">26 (2.1)</td><td align="center" styleCode="Lrule Rrule">4 (0.5)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Pruritus</td><td align="center" styleCode="Lrule">20 (1.6)</td><td align="center" styleCode="Lrule Rrule">3 (0.3)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Urticaria</td><td align="center" styleCode="Lrule">6 (0.5)</td><td align="center" styleCode="Lrule Rrule">10 (1.2)</td></tr><tr styleCode="Botrule"><td rowspan="4" align="left" styleCode="Lrule">Special Senses</td><td align="left" styleCode="Lrule">Patients With Any Event</td><td align="center" styleCode="Lrule">57 (4.6)</td><td align="center" styleCode="Lrule Rrule">38 (4.4)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Parosmia</td><td align="center" styleCode="Lrule">6 (0.5)</td><td align="center" styleCode="Lrule Rrule">4 (0.5)</td></tr><tr styleCode="Botrule"><td align="left" styleCode="Lrule">Taste Perversion</td><td align="center" styleCode="Lrule">43 (3.5)</td><td align="center" styleCode="Lrule Rrule">32 (3.7)</td></tr><tr><td align="left" styleCode="Lrule">Scotoma</td><td align="center" styleCode="Lrule">14 (1.1)</td><td align="center" styleCode="Lrule Rrule">2 (0.2)</td></tr></tbody></table>