The following adverse reactions are described in greater detail in elsewhere in the labeling: Risks Associated with Intrathecal Administration [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Acute 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 )] Extravasation and Injection Site Reactions [see Warnings and Precautions ( 5.6 )] 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 >1%) from intra-arterial or intravenous use are pain, hot flashes, burning sensation, nausea, and warmth.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bracco Diagnostics Inc. at 1-800-257-5181 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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. Adverse Reactions from Intra-arterial or Intravenous Use in Adults The safety of ISOVUE was evaluated in 2,246 adult patients receiving ISOVUE by intra-arterial or intravenous route in clinical studies.
Table 4 shows the common adverse reactions (>1%). Table 4: Adverse Reactions Reported in >1% of Patients Receiving Intra-arterial or Intravenous Injection of ISOVUE in Clinical Studies Adverse Reaction ISOVUE (N=2,246) % Pain
1.1 The following adverse reactions occurred in ≤ 1% of patients receiving intra-arterial or intravenous injection of ISOVUE: Cardiovascular disorders: tachycardia, hypotension, hypertension, myocardial ischemia, circulatory collapse, S-T segment depression, bigeminy, extrasystoles, ventricular fibrillation, angina pectoris, bradycardia, transient ischemic attack, thrombophlebitis Gastrointestinal disorders: vomiting, anorexia General disorders: headache, fever, chills, excessive sweating, back spasm Nervous system disorders: vasovagal reaction, tingling in arms, grimace, faintness Renal and urinary disorders: urinary retention Respiratory: throat constriction, dyspnea, pulmonary edema Skin and subcutaneous tissues: rash, urticaria, pruritus, flushing Special senses: taste alterations, nasal congestion, visual disturbances Adverse Reactions from Intra-arterial Use in Pediatric Patients In a clinical trial with 76 pediatric patients undergoing angiocardiography, two adverse reactions (2.6%) were reported: worsening cyanosis and worsening peripheral perfusion.
6.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of ISOVUE by intra-arterial or intravenous administration. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Blood and lymphatic system disorders: thrombocytopenia Cardiovascular disorders: cardiopulmonary arrest, cardiac decompensation, arrhythmias, myocardial infarction, shock, electrocardiographic changes (e.g., increased QTc, increased R-R, increased T-wave amplitude), decreased systolic pressure, deep vein thrombosis, arterial spasms, vasodilation, chest pain, pallor Endocrine disorders: hyperthyroidism, hypothyroidism Eye disorders: lacrimation increased, conjunctivitis, eye pruritus, transient blindness, visual disturbance, photophobia Gastrointestinal disorders: retching, abdominal pain, salivary hypersecretion, salivary gland enlargement General disorders and administration site conditions: injection site pain, malaise Immune system disorders: anaphylaxis characterized by cardiovascular, respiratory, and cutaneous manifestations (e.g., chest tightness, laryngeal edema, periorbital edema, facial edema); delayed hypersensitivity reactions including generalized maculopapular rash, erythema, pruritus, localized blistering, skin peeling Musculoskeletal disorders: compartment syndrome following extravasation, muscle spasm, musculoskeletal pain, muscular weakness Nervous system disorders: coma, seizure, tremors, syncope, depressed level of consciousness or loss of consciousness, encephalopathy Psychiatric disorders: confusional state Respiratory system disorders: respiratory arrest, respiratory failure, acute respiratory distress syndrome, respiratory distress, apnea, asthma, sneezing, choking, laryngeal edema, bronchospasm, rhinitis Skin and subcutaneous tissue disorders : Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), erythema multiforme and drug reaction with eosinophilia and systemic symptoms (DRESS), skin necrosis, face edema
