iopromide (Rx)

1-10%

Headache (6%)

Nausea (4%)

Injection Site Reactions (3%)

Vasodilatation (4%)

Vomiting (2%)

Back pain (3%)

Urinary urgency (3%)

Chest pain (3%)

Pain (2%)

Dysgeusia (1%)

Abnormal vision (2%)

<1%

Cardiac disorders: atrioventricular block (complete), bradycardia, ventricular extrasystole

Gastrointestinal disorders: abdominal discomfort, abdominal pain, , constipation, diarrhea, dry mouth, dyspepsia, salivation increased, rectal tenesmus

General disorders and administration site conditions: asthenia, chest discomfort, chills, excessive thirst, extravasation, hyperhidrosis, malaise, edema peripheral, pyrexia

Immune system disorders: asthma, face edema

Investigations: increased blood lactate dehydrogenase, blood urea increased, increased hemoglobin, increased white blood cell count

Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal pain, myasthenia, neck pain

Nervous system disorders: agitation, confusion, convulsion, dizziness, hypertonia, hypesthesia, incoordination, neuropathy, somnolence, speech disorder, tremor, paresthesia, visual field defect

Psychiatric disorders: anxiety

Renal and urinary disorders: dysuria, urinary retention

Respiratory, thoracic and mediastinal disorders: apnea, dyspnea, hypoxia, pharyngeal edema, pharyngitis, pleural effusion, pulmonary hypertension, respiratory disorder, sore throat

Skin and subcutaneous tissue disorders: erythema, pruritus, rash, urticaria

Vascular disorders: coronary artery thrombosis, flushing, hypertension, hypotension, peripheral vascular disorder, syncope

Frequency Not Defined

Additional adverse effects observed in children include

• Epistaxis
• Angioedema
• Migraine
• Joint disorder (effusion)
• Muscle cramps
• Mucous membrane disorder (mucosal swelling)
• Conjunctivitis
• Hypoxia
• Fixed eruptions
• Vertigo
• Diabetes insipidus
• Cerebral edema

Postmarketing Reports

Cardiac disorders: cardiac arrest, ventricular fibrillation, atrial fibrillation, tachycardia, palpitations, congestive heart failure, myocardial infarction, angina pectoris Ear and labyrinth disorders: vertigo, tinnitus Endocrine disorders: hyperthyroidism, thyrotoxic crisis, hypothyroidism

Eye disorders: mydriasis, lacrimation disorder

Gastrointestinal disorders: dysphagia, swelling of salivary glands Immune system disorders: anaphylactoid reaction (including fatal cases), respiratory arrest, anaphylactoid shock, angioedema, laryngeal edema, laryngospasm, bronchospasm, hypersensitivity

Musculoskeletal and connective tissue disorders: compartment syndrome in case of extravasation

Nervous system disorders: cerebral ischemia/infarction, paralysis, paresis, transient cortical blindness, aphasia, coma, unconsciousness, amnesia, hypotonia, aggravation of myasthenia gravis symptoms

Renal and urinary disorders: renal failure, hematuria

Respiratory, thoracic and mediastinal disorders: pulmonary edema, acute respiratory distress syndrome, asthma

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)]

Vascular disorders: vasospasm

Contraindications

Intrathecal administration

Preparatory dehydration (prolonged fasting, bowel prep) before injection in pediatric patients is contraindicated due to risk of acute renal failure

Cautions

Intrathecal administration, even if inadvertent, can cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema; use for intra-arterial or intravenous administration only; not approved for intrathecal use

Severe cutaneous adverse reactions (SCAR) may develop from 1 hr to several weeks after intravascular contrast agent administration; 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 agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions; avoid administering therapy to patients with history of a severe cutaneous adverse reaction to therapy

Delayed adverse reactions may occur; monitor patient for 30-60 min after injection

Consider monitoring for thyroid storm in patients with hyperthyroidism,

Caution in patients with seizures, thromboembolic diseases including IM and stroke, chronic alcoholism, heart failure, diabetes mellitus, hepatorenal insufficiency, multiple myeloma, pheochromocytoma, renal disease, sickle cell disease

Hypertensive crisis in patients with pheochromocytoma reported with iodinated contrast agents; closely monitor patients when administering if pheochromocytoma or catecholamine-secreting paragangliomas are suspected; inject minimum amount necessary and have measures for treatment of a hypertensive crisis readily available

Iodinated contrast agents may promote sickling in individuals who are homozygous for sickle cell disease; hydrate patients prior to and following administration and use only if necessary imaging information cannot be obtained with alternative imaging modalities

Thromboembolic events

• Serious, in some cases fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiography procedures; during these procedures, increased thrombosis and activation of complement system can occur; risk of thromboembolic events can be influenced by length of procedure, catheter and syringe material, underlying disease state, and concomitant medications
• To decrease thromboembolic events, use meticulous angiographic techniques and minimize length of the procedure; avoid blood remaining in contact with syringes containing iodinated contrast agents, which increases risk of clotting; avoid angiography in patients with homocystinuria because of risk of inducing thrombosis and embolism

Cardiovascular adverse reactions

• Therapy increases circulatory osmotic load and may induce acute or delayed hemodynamic disturbances in patients with congestive heart failure, severely impaired renal function, combined renal and hepatic disease, or combined renal and cardiac disease, particularly when repetitive and/or large doses are administered
• Fatal cardiovascular reactions have occurred mostly within 10 minutes of administration; the main feature was cardiac arrest with cardiovascular disease as the main underlying factor; hypotensive collapse and shock have occurred; cardiac decompensation, serious arrhythmias, and myocardial ischemia or infarction can occur during coronary arteriography and ventriculography
• Administration may cause pulmonary edema in patients with heart failure; based upon published reports, deaths from administration of iodinated contrast agents range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients (0.01 percent)
• Use lowest necessary dose in patients with congestive heart failure and always have emergency resuscitation equipment and trained personnel available; monitor all patients for severe cardiovascular reactions

Acute kidney injury

• Acute kidney injury, including renal failure, may occur after administration; risk factors include pre-existing renal insufficiency, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma or other paraproteinemia, and repetitive and/or large doses of the drug
• Use lowest necessary dose of in patients with renal impairment; hydrate patients prior to and following administration; do not use laxatives, diuretics, or preparatory dehydration prior to administration

Hypersensitivity reactions

• 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 start of injection (eg, within 1 to 3 minutes), but delayed reactions can also occur
• There is increased risk of hypersensitivity reactions in patients with history of previous reaction to contrast agent and known allergic disorders (that is, bronchial asthma, allergic rhinitis, and 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 history of allergy, hypersensitivity, or hypersensitivity reactions to iodinated contrast agents and have emergency resuscitation equipment and trained personnel available prior to administration; monitor all patients for hypersensitivity reactions

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 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 increased risk of hypothyroidism after ICM exposure
• Pediatric patients with congenital cardiac conditions may be at 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 iodinated contrast media, individualize thyroid function monitoring in pediatric patients 0-3 years of age based on underlying risk factors, especially in term and preterm neonates
• Pediatric patients 0-3 years of age warrant closer monitoring because an underactive thyroid during early life may be harmful to motor, hearing, and cognitive development and may require transient T4 replacement therapy

Extravasation and injection site reactions

• Extravasation can occur, particularly in patients with severe arterial or venous disease; inflammation, blistering, skin necrosis, and compartment syndrome reported following extravasation
• In addition, injection site reactions such as pain and swelling at injection site can also occur; ensure intravascular placement of catheters prior to injection
• Monitor patients for extravasation and advise patients to seek medical care for progression of sym

Drug interaction overview

• Iodinated contrast agents appear to increase risk of metformin-induced lactic acidosis, possibly as a result of worsening renal function; stop metformin at time of or prior to, administration in patients with an eGFR between 30 and 60 mL/min/1.73 m2
• In patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast agents; re-evaluate eGFR 48 hours after imaging procedure and reinstitute only after renal function is stable
• Therapy may interfere with thyroid uptake of radioactive iodine (I-131 and I-123) and decrease therapeutic and diagnostic efficacy; avoid thyroid therapy or testing for up to 6 weeks post-administration

Drug-laboratory Test Interactions

• Thyroid Function Tests: Protein-bound iodine and radioactive iodine uptake studies, may not accurately reflect thyroid function for at least 16 days following administration
• Laboratory Assay of Coagulation Parameters, Fibrinolysis and Complement System: The effect of iopromide on coagulation factors in in-vitro assays increased with the administered dose.

Pregnancy

There are no data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Drug crosses placenta and reaches fetal tissues in small amounts

Animal data

• In animal reproduction studies, intravenous administration of iopromide to pregnant rats and rabbits during organogenesis at doses up to 0.35 and 0.7 times, respectively, maximum recommended human dose based on body surface area resulted in no relevant adverse developmental effects

Lactation

There are no data on the presence of drug in human milk, effects on the breastfed infant, or the effects on milk production. Iodinated contrast agents are poorly excreted into human milk and are poorly absorbed by the gastrointestinal tract of a breastfed infant

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal condition

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

Nonionic, water soluble, tri-iodinated x-ray contrast agent for intravascular administration; opacifies vessels, permitting radiographic visualization of the internal structures until significant hemodilution occurs

Absorption

• Bioavailability Onset 15-120 seconds post bolus injection

Distribution

• Protein Bound: 1%
• Vd: 16 L suggesting distribution into extracellular space

Elimination

• Half-life: 0.24 hr (initial distribution); 2.4 hr (main elimination); 6.2 hr (terminal elimination)
• Dialyzable
• Renal clearance: 104 mL/min
• Total body clearance: 107 mL/min
• Excretion: Feces 2%, urine 97%

IV Incompatibilities

Due to potential for chemical incompatibility, do not mix or inject in intravenous administration lines containing other drugs, solutions, or total nutritional admixtures

IV Preparation

Withdraw from container under strict aseptic conditions using only sterile syringes and transfer devices. Use immediately contrast agents which have been transferred into other delivery systems

Hydrate patient adequately before and following administration

Warm contrast solution to body temperature shortly before administration to improve tolerability

Do not exceed cumulative iodine dose of 86 grams

Carefully individualize volume and concentration

Dosage volume and administration rate vary depending on injection site; see prescribing information for specific details

IV or Intra-arterial Administration

Administer at or close to body temperature

Storage

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) and protected from light