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)]
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
| 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.
