1 INDICATIONS AND USAGE OMNIPAQUE is a radiographic contrast agent indicated for intrathecal, intra-arterial, intravenous, oral, rectal, intraarticular, and body cavity imaging procedures in adults and pediatric patients.

( 1 ) 1.1 Intrathecal Procedures ‡ OMNIPAQUE is indicated for: Myelography and computerized tomography (CT) myelography (lumbar, thoracic, cervical, total columnar) in adults and pediatric patients aged 2 weeks and older CT cisternography in adults and pediatric patients aged 2 weeks and older 1.2 Intra-arterial Procedures ‡ OMNIPAQUE is indicated for: Cardiac ventriculography in adults and pediatric patients Aortography including studies of aorta and its branches in adults and pediatric patients Selective coronary arteriography in adults Cerebral arteriography in adults Peripheral arteriography in adults Intra-arterial digital subtraction angiography (IA-DSA) of the head, neck, abdominal, renal, and peripheral vessels in adults Pulmonary angiography in pediatric patients 1.3 Intravenous Procedures ‡ OMNIPAQUE is indicated for: Excretory urography in adults and pediatric patients CT of the head and body in adults and pediatric patients Peripheral venography (phlebography) in adults Intravenous digital subtraction angiography (IV-DSA) of the head, neck, abdominal, renal, and peripheral vessels in adults 1.4 Oral or Rectal Procedures ‡ OMNIPAQUE is indicated for: Radiographic examination of the gastrointestinal (GI) tract by oral administration in adult patients and by oral or rectal administration in pediatric patients CT of the abdomen and pelvis by oral administration in adult and pediatric patients, in conjunction with intravenous administration of OMNIPAQUE 1.5 Intraarticular Procedures ‡ OMNIPAQUE is indicated for: Arthrography in adults 1.6 Body Cavity Procedures ‡ OMNIPAQUE is indicated for: Endoscopic retrograde pancreatography (ERP) and cholangiopancreatography (ERCP) in adults Herniography in adults Hysterosalpingography in adults Voiding cystourethrography (VCU) in pediatric patients ‡ Specific dosage forms, concentrations, and presentations of OMNIPAQUE are recommended for each type of imaging procedure [see Dosage and Administrations (2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9) and Warnings and Precautions (5.1 , 5.2) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risks Associated with Intrathecal Administration of OMNIPAQUE Injection 140 mg Iodine/mL and 350 mg Iodine/mL [see Warnings and Precautions (5.1) ] Risks Associated with Parenteral Administration of OMNIPAQUE Oral Solution [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Acute Kidney Injury [see Warnings and Precautions (5.4) ] Cardiovascular Adverse Reactions [see Warnings and Precautions (5.5) ] Thromboembolic Events [ see Warnings and Precautions (5.6) ] Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings and Precautions (5.9) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.12) ] Most common adverse reactions (incidence ≥ 1%) in adult patients Intrathecal: Headaches, pain including backache, neckache, stiffness and neuralgia, nausea, vomiting, dizziness Intra-arterial or intravenous: Pain, vision abnormalities (including blurred vision and photomas), headache, taste perversion, arrhythmias including premature ventricular contractions (PVCs) and premature atrial contractions (PACs), angina/chest pain, nausea Oral: Diarrhea, nausea, vomiting, abdominal pain, flatulence, headache Body Cavity: Pain, swelling, heat sensation ( 6.1 ) 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 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.

Intrathecal Administration Adults Adverse reactions (≥1%) in 1,531 adult patients following intrathecal administration of OMNIPAQUE in clinical trials are presented in Table 16.

Table 16.

Adverse Reactions (≥1%) in in Adult Patients Following Intrathecal Administration of OMNIPAQUE in Clinical Trials System Organ Class Adverse Reaction Incidence N=1,531 Nervous system disorders Headaches 18% Musculoskeletal and connective tissue disorders Pain including backache, neckache, stiffness, neuralgia 8% Gastrointestinal disorders Nausea 6% Vomiting 3% Nervous System disorders Dizziness 2% Other adverse reactions (<1%) were: Ear and labyrinth disorders : tinnitus, vertigo Eye disorders : photophobia General disorders and administration site conditions : sensation of heat Metabolism and nutrition disorders : loss of appetite Musculoskeletal and connective tissue disorders : feeling of heaviness Nervous system disorders : drowsiness, hypertonia, neuralgia, neurological changes, paresthesia, syncope Renal and urinary disorders : difficulty in micturition Skin and subcutaneous tissue disorders : sweating Vascular disorders : hypertension, hypotension Pediatric Patients The adverse reactions reported in pediatric patients following intrathecal administration of OMNIPAQUE were generally similar to those reported in adults.

A total of 152 pediatric patients were administered OMNIPAQUE 180 mg iodine/mL intrathecally by lumbar puncture for pediatric myelography in clinical trials.

Adverse reactions (≥1%) are presented in Table 17.

Table 17.

Adverse Reactions (≥1%) in Pediatric Patients Following Intrathecal Administration of OMNIPAQUE 180 mg iodine/mL by Lumbar Puncture for Myelography in Clinical Trials System Organ Class Adverse Reaction Incidence N=152 Nervous system disorders Headache 9% Gastrointestinal disorders Vomiting 6% Musculoskeletal and connective tissue disorders Backache 1.3% Other adverse reactions (<1%) were: Gastrointestinal disorders: stomachache General disorders and administration site conditions: fever Nervous system disorders : neurological changes Psychiatric disorders : visual hallucination Skin and subcutaneous tissue disorders : hives Intra-arterial or Intravenous Administration Adults Adverse reactions (≥1%) in 1,485 adult patients following intra-arterial or intravenous administration of OMNIPAQUE in clinical trials are presented in Table 18.

Table 18.

Adverse Reactions (≥1%) in Adult Patients Following Intra-arterial or Intravenous Administration of OMNIPAQUE in Clinical Trials System Organ Class Adverse Reaction Incidence (N=1,485) Cardiac disorders Arrhythmias including PVCs and PACs 2% Nervous system disorders Pain 3% Vision abnormalities including blurred vision and photomas 2% Taste perversion 1% Gastrointestinal disorders Nausea 2% Other adverse reactions (<1%) were: Cardiac disorders: hypotension, cardiac failure, asystole, bradycardia, tachycardia, vasovagal reaction Respiratory, thoracic and mediastinal disorders: dyspnea, rhinitis, coughing, laryngitis Gastrointestinal disorders : vomiting, diarrhea, dyspepsia, cramp, dry mouth General disorders and administration site conditions: fever, shivering Nervous system disorders: cerebral infarction, convulsion, hemiparesis, motor and speech dysfunction, nystagmus, paresthesia, somnolence, transient ischemic attack, vertigo including dizziness and lightheadedness Musculoskeletal and connective tissue disorders: still neck Skin and subcutaneous tissue disorders : urticaria, abscess, pruritus, purpura Psychiatric disorders : anxiety, syncope Pediatric Patients Adverse reactions reported in pediatric patients following intra-arterial or intravenous administration of OMNIPAQUE were generally similar in quality and frequency to those reported in adults.

A total of 391 pediatric patients in clinical trials were administered OMNIPAQUE 240 mg iodine/mL, 300 mg iodine/mL, or 350 mg iodine/mL by intra-arterial or intravenous injection for pediatric cardiac ventriculography, excretory urography, and CT head imaging.

Adverse reactions (≥1%) were vomiting (2%) and nausea (1%).

Other adverse reactions (<1%) were: Cardiac disorders: Ventricular tachycardia, 2:1 heart block, hypertension, anemia General disorders and administration site conditions: Pain, fever Nervous system disorders: Convulsion, taste abnormality Respiratory, thoracic and mediastinal disorders: Congestion, apnea Endocrine disorders: Hypoglycemia Skin and subcutaneous tissue disorders: Rash Oral or Rectal Administration for Examination of the Gastrointestinal Tract Adults A total of 54 adult patients were administered undiluted OMNIPAQUE 350 mg iodine/mL by oral route for radiographic examination of the gastrointestinal tract in clinical trials.

Adverse reactions (≥1%) are presented in Table 19.

Table 19.

Adverse Reactions (≥1%) in Adult Patients Following Oral Administration of Undiluted OMNIPAQUE 350 mg Iodine/mL in Clinical Trials System Organ Class Adverse Reaction Incidence N=54 Gastrointestinal disorders Diarrhea 42% Nausea 15% Vomiting 11% Abdominal Pain 7% Flatulence 2% Nervous system disorders Headache 2% Pediatrics Patients A total of 58 pediatric patients were administered OMNIPAQUE by oral or rectal administration in clinical trials.

Adverse reactions (≥1%) are presented in Table 20.

Table 20.

Adverse Reactions (≥1%) in Pediatric Patients Following Oral or Rectal Administration of OMNIPAQUE in Clinical Trials System Organ Class Adverse Reaction Incidence N=58 Gastrointestinal disorders Diarrhea 36% Vomiting 9% Nausea 5% Abdominal pain 2% General disorders and administration site conditions Fever 5% Skin and subcutaneous tissue disorders Urticaria 2% Vascular disorders Hypotension 2% Oral Administration for CT of the Abdomen in Conjunction with Intravenous Administration Adults A total of 44 adult patients received diluted OMNIPAQUE (4-9 mg iodine/mL) by oral route in conjunction with intravenously injected OMNIPAQUE 300 mg iodine/mL for CT examination of the abdomen in clinical trials.

Adverse reactions (≥1%) were limited to a single report of vomiting (2.3%).

Pediatric Patients A total of 69 pediatric patients received diluted OMNIPAQUE (9-29 mg iodine/mL) by oral route in conjunction with intravenously administered OMNIPAQUE 240 mg iodine/mL or OMNIPAQUE 300 mg iodine/mL for CT examination of the abdomen in clinical trials.

Adverse reactions (≥1%) were limited to a single report of vomiting (1.4%).

Intraarticular Administration Arthrography in Adults A total of 285 adult patients received OMNIPAQUE 240 mg iodine/mL, 300 mg iodine/mL, or 350 mg iodine/mL for various body cavity examinations in clinical trials.

The most frequent adverse reactions (≥1%) were administration site pain (26%) and swelling (22%) in arthrography.

Patients also experienced heat (7%).

Body Cavity Use VCU in Pediatric Patients No new adverse reactions associated with the use of OMNIPAQUE for VCU procedures were reported in 51 pediatric patients studied.

6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of OMNIPAQUE.

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 drug exposure.

General Immune system disorders: Hypersensitivity reactions, anaphylactic or anaphylactoid reactions, anaphylactic or anaphylactoid shock including life-threatening or fatal anaphylaxis General disorders and administration site conditions: Pyrexia, chills, pain and discomfort, asthenia, administration site conditions including extravasation Intrathecal Administration Nervous system disorders: Meningism, aseptic meningitis, seizures or status epilepticus, disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia Musculoskeletal and connective tissue disorders : Pain, muscle spasms or spasticity Psychiatric disorders: Confusional state, agitation, anxiety Eye disorders: Transient visual impairment including cortical blindness Renal and urinary disorders: Acute kidney injury Intra-arterial or Intravenous Administration Cardiac disorders: Severe cardiac complications (including cardiac arrest, cardiopulmonary arrest), shock, peripheral vasodilatation, palpitations, vasospasm including spasm of coronary arteries, myocardial infarction, syncope, cyanosis, pallor, flushing, chest pain Vascular disorders: Vasospasm and thrombophlebitis following intravenous injection Blood and lymphatic system disorders: Neutropenia Nervous system disorders: Disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia Psychiatric disorders: Confusional state, agitation Eye disorders: Eye irritation or itchiness, periorbital edema, ocular or conjunctival hyperemia, lacrimation Renal and urinary disorders: Acute kidney injury, toxic nephropathy (CIN), transient proteinuria, oliguria or anuria, increased serum creatinine Gastrointestinal disorders: Abdominal pain, pancreatitis aggravated, salivary gland enlargement Endocrine disorders: Hyperthyroidism, hypothyroidism Respiratory, thoracic and mediastinal disorders: Respiratory distress, respiratory failure, pulmonary edema, bronchospasm, laryngospasm, throat irritation, throat tightness, laryngeal edema, wheezing, chest discomfort, asthmatic attack Skin and subcutaneous tissue disorders: Contrast media reactions range from mild (e.g., pleomorphic rashes, drug eruption, erythema and skin discoloration, blisters, hyperhidrosis, angioedema, localized areas of edema) to severe (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis [SJS/TEN], bullous or exfoliative dermatitis, acute generalized exanthematous pustulosis [AGEP] and drug reaction with eosinophilia and systemic symptoms [DRESS]) Oral Administration Gastrointestinal disorders: Dysphagia, abdominal pain Body Cavity Administration Gastrointestinal disorders: Pancreatitis Musculoskeletal and connective tissue disorders: Arthritis (arthrography) Hysterosalpingography : Injection of OMNIPAQUE for hysterosalpingography is associated with immediate, transient pain.

Monitor injection pressure and volume instilled to minimize pain and to avoid disruptive distention of the uterus and fallopian tubes.

Fluoroscopic monitoring is recommended.

Nervous system disorders : Pain (49%), somnolence and fever each with an individual incidence of 3% Gastrointestinal disorders : Nausea (3%)