iodixanol (Rx)

>10%

Discomfort at injection site (<30%)

1-10%

Angina pectorin (<2%)

Chest pain (<2%)

Headache (<3%)

Migraine (<3%)

Vertigo (<2%)

Parethesia (1%)

Pruritus (2%)

Skin rash (<2%)

Erythema (<2%)

Dysguesia (4%)

Postmarketing Reports

Cardiovascular Disorders: Cardiac arrest, palpitations, spasms of coronary arteries, hypertension, and flushing

Endocrine Disorders: Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to adult and pediatric patients, including infants; some patients were treated for hypothyroidism; hypoglycemia, hyperthyroidism

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)]

Contraindications

Hypersensitivity to product or components

Intrathecal use

In children, prolonged fasting and use of laxative before administration is contraindicated

Product label has additional procedure-specific contraindications

Cautions

Maintain adequate hydration

Use caution in renal/hepatic impairment, cardiovascular disease, multiple myeloma, pheochromocytoma, sickle cell disease, elderly patients, and thyroid dysfunction

Increased risk of adverse effects including heart disease, asthma patients, and sensitivity to allergens or medications

Renal failure may occur in patients with diabetes during preparatory dehydration; maintain normal hydration in these patients

Patients with homocystinuria may be at risk for thrombosis and embolism; avoid angiography in these patients

Avoid extravasation, especially in patients with severe arterial or venous disease

Thromboembolic events causing myocaridal infarction and stroke reported; use meticulous intravascular administration techniques, especially during angiographic procedures

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

Thyroid dysfunction in pediatric patients

• Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression reported after both single exposure and multiple exposures to iodinated contrast media; among patients 0- 3 years of age exposed to iodinated contrast media, thyroid dysfunction reported depending on age of patient and dose of the iodinated contrast agent
• Younger age, very low birth weight, prematurity, and presence of other conditions, such as, admission to neonatal or pediatric intensive care units, and cardiac conditions are associated with an increased risk; pediatric patients with cardiac conditions may be at greatest risk given that they often require high doses of contrast during invasive cardiac procedures, such as catheterization and computed tomography (CT)
• Pediatric patients 0-3 years of age warrant closer monitoring because an underactive thyroid during early life may be harmful for motor, hearing, and cognitive development and may require transient T4 replacement therapy; evaluate thyroid function in all pediatric patients 0-3 years of age within 3 weeks following exposure to iodinated contrast media, especially in term and preterm neonates; if thyroid dysfunction detected, treat and monitor thyroid function as clinically needed
• The safety and effectiveness of this drug in pediatric patients < 2 years of age have not been established, and the drug is not approved for use in pediatric patients < 2 years of age

FDA MedWatch

• March 30, 2022: FDA recommended newborns and children aged ≤3 years have follow-up thyroid monitoring within 3 weeks after receiving iodinated contrast media (ICM) for X-rays and other medical imaging procedures
• Published studies found underactive thyroid and temporary decreases in thyroid hormone levels were uncommon; however, if identified and treated early, future complications may be prevented
• Appropriately monitor for signs and symptoms of hypothyroidism and decreased thyroid hormone levels following ICM exposure; consider evaluating thyroid function within 3 weeks, especially in term and preterm neonates and children with some underlying conditions
• If thyroid dysfunction detected, treat and monitor thyroid function as needed to avoid future complications
• Certain pediatric patients are at increased risk, including newborns or have very low birth weight, prematurity, or presence of cardiac or other conditions (eg, requiring care in neonatal or pediatric ICUs)
• Patients with cardiac conditions may be at greatest risk since they often require high doses of contrast during invasive cardiac procedures

Pregnancy

There are no data with iodixanol use in pregnant women to inform any drug-associated risks; in animal reproduction studies, no developmental toxicity occurred with intravenous iodixanol administration to rats and rabbits at doses up to 0.24 (rat) or 0.48 (rabbit) times the maximum recommended human intravenous dose

Lactation

There are no data on presence of iodixanol in human milk, the effects on breastfed infant or effects on milk production. Iodinated contrast agents are poorly excreted into human milk and are poorly absorbed by gastrointestinal tract of a breastfed infant; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for iodixanol and any potential adverse effects on breastfed infant from iodixanol or from underlying maternal condition

Interruption of breastfeeding after exposure to iodinated contrast agents is not necessary because the potential exposure of breastfed infant to iodine is small; however, a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hr (approximately 5 elimination half-lives) after iodixanol administration in order to minimize drug exposure to a breast fed infant

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Dimeric, isosmolar, nonionic, water-soluble, iodinated x-ray contrast agent for intravascular administration; opacifies vessels within path of flow, thereby permitting radiographic visualization of internal structures until significant dilution and elimination occurs

Pharmacokinetics

Vd: 0.26 L/kg

Excretion: 97% excreted unchanged in urine within 24 hr

Half-life: 2-4 hr (children); 2 hr (adults)

Peak plasma time: Immediate; 15-120 sec (peak enhancement); 5-15 min (optimum renal contrast); up to 1 hr (brain contrast)