Iodixanol

Iodixanol injection is indicated in for:

Injection: Non-ionic, isotonic, water-soluble, sterile, pyrogen-free, colorless to pale yellow solution in the following strengths:

• 270 mg of organically bound iodine per mL (550 mg Iodixanol per mL).
• 320 mg of organically bound iodine per mL (652 mg Iodixanol per mL).

Available in the following format: Single-dose polypropylene bottle.

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Risks Associated with Inadvertent Intrathecal Administration
  
  [see
  

  5.1 Risks Associated with Inadvertent Intrathecal Administration

  Iodixanol is for intravascular use only and is contraindicated for intrathecal use

  [see Contraindications (4)and Dosage and Administration (2.1)]

  . Inadvertent Intrathecal administration can cause death, convulsions/seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema.

  ]
  
• Hypersensitivity Reactions
  
  [see
  

  5.2 Hypersensitivity Reactions

  Iodixanol can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock. Most severe reactions develop shortly after the start of the injection (within 3 minutes), but reactions can occur up to hours later. There is an increased risk in patients with a history of a previous reaction to contrast agent, and known allergies (i.e., bronchial asthma, drug, or food allergies) or other hypersensitivities. Premedication with antihistamines or corticosteroids does not prevent serious life-threatening reactions, but may reduce both their incidence and severity.

  Obtain a history of allergy, hypersensitivity, or hypersensitivity reactions to iodinated contrast agents and always have emergency resuscitation equipment and trained personnel available prior to iodixanol administration. Monitor all patients for hypersensitivity reactions.

  ]
  
• Contrast-Induced Kidney Injury
  
  [see
  

  5.3 Contrast-Induced Acute Kidney Injury

  Acute kidney injury, including renal failure, may occur after iodixanol administration. Risk factors include: pre-existing renal impairment, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma/paraproteinaceous diseases, repetitive and/or large doses of an iodinated contrast agent.

  Use the lowest necessary dose of iodixanol in patients with renal impairment. Adequately hydrate patients prior to and following iodixanol administration. Do not use laxatives, diuretics, or preparatory dehydration prior to iodixanol administration.

  ]
  
• Cardiovascular Adverse Reactions
  
  [see
  

  5.4 Cardiovascular Adverse Reactions

  Life-threatening or fatal cardiovascular reactions including hypotension, shock, cardiac arrest have occurred with the use of iodixanol. Most deaths occur during injection or five to ten minutes later, with cardiovascular disease as the main aggravating factor. Cardiac decompensation, serious arrhythmias, and myocardial ischemia or infarction can occur during coronary arteriography and ventriculography.

  Based upon clinical literature reported deaths from the administration of iodinated contrast agents range from 6.6 per million (0.00066%) to 1 in 10,000 (0.01%). Use the lowest necessary dose of iodixanol in patients with congestive heart failure and always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions.

  ]
  
• Thromboembolic Events
  
  [see
  

  5.5 Thromboembolic Events

  Angiocardiography

  
  
  Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiocardiography procedures with both ionic and nonionic contrast media. During these procedures, increased thrombosis and activation of the complement system occurs. Risk factors for thromboembolic events include: length of procedure, catheter and syringe material, underlying disease state, and concomitant medications.

  To minimize thromboembolic events, use meticulous angiographic techniques, and minimize the length of the procedure. Avoid blood remaining in contact with syringes containing iodinated contrast agents, which increases the risk of clotting. Avoid angiocardiography in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

  ]
  
• Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age
  [see

  5.8 Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age

  Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media (ICM) in pediatric patients 0 to 3 years of age.

  Younger age, very low birth weight, prematurity, underlying medical conditions affecting thyroid function, admission to neonatal or pediatric intensive care units, and congenital cardiac conditions are associated with an increased risk of hypothyroidism after ICM exposure. Pediatric patients with congenital cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures.

  An underactive thyroid during early life may be harmful for cognitive and neurological development and may require thyroid hormone replacement therapy. After exposure to ICM, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates.

  ]
• Severe Cutaneous Adverse Reactions
  
  [see
  

  5.11 Severe Cutaneous Adverse Reactions

  Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agents; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering iodixanol to patients with a history of a severe cutaneous adverse reaction to iodixanol.

  ]
  

Intravascular injection of iodixanol opacifies vessels in the path of flow of the contrast agent, permitting visualization of internal structures.

In imaging of the body, iodinated contrast agents diffuse from the vascular into the extravascular space. In a normal brain with an intact blood-brain barrier, contrast does not diffuse into the extravascular space. In patients with a disrupted blood- brain barrier, contrast agent accumulates in the interstitial space in the region of disruption.