Iopamidol (DB08947): A Comprehensive Monograph on a Non-Ionic, Low-Osmolar Radiographic Contrast Agent

Executive Summary

Iopamidol is a second-generation, non-ionic, low-osmolar iodinated radiographic contrast agent, representing a significant advancement in safety and tolerability over the first-generation ionic contrast media. As a small molecule diagnostic agent, its fundamental mechanism of action is the physical attenuation of X-rays, a property conferred by the three iodine atoms covalently bound to its benzene ring core. This allows for enhanced visualization of vascular structures, organs, and other non-bony tissues during diagnostic imaging procedures.

Developed by Bracco and marketed primarily under the brand name ISOVUE, Iopamidol has a broad spectrum of U.S. Food and Drug Administration (FDA)-approved indications. It is a workhorse agent in modern radiology, utilized extensively for intra-arterial and intravenous procedures, including cerebral, peripheral, and coronary angiography, as well as contrast-enhanced computed tomography (CECT) of the head and body in both adult and pediatric populations. Specific formulations, designated ISOVUE-M, are approved for intrathecal use in neuroradiology.

The clinical pharmacology of Iopamidol is characterized by its biological inertness. Its pharmacokinetic profile is defined by an open two-compartment model with a plasma half-life of approximately two hours in patients with normal renal function. Following intravascular administration, it distributes rapidly throughout the extracellular fluid without significant protein binding or metabolism. Elimination is almost exclusively via renal excretion, with the drug being cleared from the body chemically unchanged.

This renal-dependent clearance pathway is central to Iopamidol's safety profile. The primary risks associated with its use are hypersensitivity reactions, which are typically pseudoallergic, and contrast-induced nephropathy (CIN), a form of acute kidney injury that is of particular concern in patients with pre-existing renal impairment, diabetes, and other risk factors. A critical drug interaction exists with metformin; the potential for Iopamidol to transiently impair renal function can lead to metformin accumulation and subsequent lactic acidosis, necessitating strict clinical management protocols. Despite these risks, Iopamidol's low osmolality compared to older agents results in a favorable tolerability profile. Its safe and effective use is contingent upon a robust clinical framework of patient screening, adequate hydration, and vigilant monitoring, solidifying its role as a versatile and foundational tool in diagnostic imaging.

Compound Identification and Physicochemical Properties

Introduction

Iopamidol is a small molecule pharmaceutical agent classified as a radiographic contrast medium.[1] Its utility in diagnostic imaging is derived from its chemical nature as an organoiodine compound, specifically a tri-iodinated derivative of a benzenedicarboxamide scaffold.[2] This structure is fundamental to its ability to opacify bodily structures during X-ray-based examinations.[4]

Chemical Nomenclature and Identifiers

To ensure unambiguous identification across scientific, clinical, and regulatory domains, Iopamidol is cataloged under a comprehensive set of names and identifiers.

• Generic Name: Iopamidol [1]
• IUPAC Name: 1-N,3-N-bis(1,3-dihydroxypropan-2-yl)-5-amino]-2,4,6-triiodobenzene-1,3-dicarboxamide [2]
• Systematic Names and Synonyms: A variety of synonyms and systematic names are used in literature and databases, including:
• (S)-N1,N3-Bis(1,3-dihydroxypropan-2-yl)-5-(2-hydroxypropanamido)-2,4,6-triiodoisophthalamide [7]
• N,N'-Bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-amino]-2,4,6-triiodo-1,3-benzenedicarboxamide [7]
• Iomapidol [8]
• Niopam [4]
• Solutrast [4]
• Key Database Identifiers:
• CAS Number: 60166-93-0 [2]
• DrugBank ID: DB08947 [2]
• PubChem CID: 65492 [6]
• UNII: JR13W81H44 [2]
• ATC Code: V08AB04 [1]
• ChEBI ID: CHEBI:31711 [2]

Chemical Structure and Molecular Data

The molecular composition and structure of Iopamidol are precisely defined.

• Molecular Formula: C17​H22​I3​N3​O8​ [2]
• Molecular Weight: The average molecular weight is approximately 777.09 g/mol. The monoisotopic mass is 776.8541 Da.[1]
• Structural Representations:
• SMILES: C[C@@H](C(=O)NC1=C(C(=C(C(=C1I)C(=O)NC(CO)CO)I)C(=O)NC(CO)CO)I)O [2]
• InChIKey: XQZXYNRDCRIARQ-LURJTMIESA-N [2]

Physical and Chemical Properties

Iopamidol exhibits physical and chemical properties that are essential for its formulation as an injectable diagnostic agent.

• Appearance: It is a white to almost white crystalline powder or solid.[3]
• Solubility: The molecule is designed for high water solubility, a critical attribute for its use in aqueous solutions for intravascular administration.[1]
• Computed Properties: Computational analysis indicates a highly hydrophilic nature, with an XLogP3 value of -2.4, a Hydrogen Bond Donor Count of 8, a Hydrogen Bond Acceptor Count of 8, and a Rotatable Bond Count of 10.[12] These features contribute to its excellent water solubility and rapid distribution in the body's aqueous compartments.

Commercial Formulations (ISOVUE): Physicochemical Characteristics

Iopamidol is commercially available as sterile, aqueous, nonpyrogenic solutions under the brand name ISOVUE.[13] These formulations are precisely buffered to a pH range of 6.5 to 7.5.[14] A key characteristic of all formulations is that they are hypertonic relative to human plasma (approx. 285 mOsm/kg water) and cerebrospinal fluid (approx. 301 mOsm/kg water).[14] The specific physicochemical properties vary by concentration, allowing for procedure-specific selection.

Table 1: Physicochemical Properties of Iopamidol Formulations (ISOVUE)

Formulation (Iopamidol Concentration)	Iodine Concentration (mgI/mL)	Osmolality @ 37°C (mOsm/kg water)	Viscosity @ 37°C (cP)	Viscosity @ 20°C (cP)	Specific Gravity @ 37°C
ISOVUE-200 (41%)	200	413	2.0	3.3	1.227
ISOVUE-250 (51%)	250	524	3.0	5.1	1.281
ISOVUE-300 (61%)	300	616	4.7	8.8	1.339
ISOVUE-370 (76%)	370	796	9.4	20.9	1.405
Data compiled from.14

The chemical structure of Iopamidol is a product of deliberate molecular engineering designed to optimize its function while enhancing its safety profile. The tri-iodinated benzene ring serves as the functional core, providing the necessary radiopacity for imaging. Attached to this core are highly hydrophilic side chains, including N-substituted carbamoyl groups and a (2S)-2-hydroxypropanamido group, which ensure the molecule's high water solubility.[2] The most critical design feature is the absence of a carboxylic acid group, which renders the molecule non-ionic in solution.[1]

This non-ionic nature represents a fundamental innovation over first-generation contrast media. Older agents, such as diatrizoate, are ionic salts. When dissolved, they dissociate into two particles in solution: a radiopaque anion and a non-radiopaque cation (e.g., sodium or meglumine).[17] This dissociation effectively doubles the number of osmotically active particles for each iodine-carrying molecule, resulting in solutions with extremely high osmolality, often five to eight times that of human plasma.[17] This hyperosmolality was a primary cause of adverse effects, including pain on injection, heat sensations, and significant hemodynamic disturbances.[20] In contrast, because Iopamidol does not ionize, it contributes only one particle to the solution's osmolality for each molecule. Consequently, for a given concentration of iodine, its osmolality is approximately half that of a corresponding ionic agent.[17] This direct link from its non-ionic molecular structure to its lower osmolality is the principal reason for its improved safety and patient tolerability, classifying it as a "low-osmolar" contrast medium.

Furthermore, the availability of multiple concentrations, from ISOVUE-200 to ISOVUE-370, is a strategic element of its clinical utility. This range allows clinicians to tailor the contrast agent to the specific demands of the imaging procedure. For example, coronary multidetector computed tomography (MDCT) requires the rapid delivery of a concentrated bolus of contrast to adequately opacify small, rapidly moving coronary arteries. In this context, a high-iodine-concentration formulation like Iopamidol-370 provides superior vascular contrast and better depiction of anatomical detail.[23] Conversely, procedures like excretory urography may achieve excellent diagnostic quality with a lower iodine dose and osmotic load, making ISOVUE-250 or ISOVUE-300 a more appropriate choice.[24] Intrathecal applications have the most stringent requirements, necessitating the use of the lowest, near-isotonic concentrations (ISOVUE-M 200) to minimize the risk of neurotoxicity.[26] This range of formulations embodies a clinical risk-management philosophy, allowing practitioners to adhere to the principle of using the lowest necessary dose to achieve the diagnostic objective, thereby balancing imaging efficacy with patient safety.

Clinical Pharmacology

Mechanism of Action

The clinical utility of Iopamidol is based on its physical properties as a radiopaque diagnostic agent. Its mechanism of action is defined as X-Ray Contrast Activity.[2]

• Primary Mechanism: X-Ray Attenuation: The fundamental principle behind Iopamidol's function is the differential absorption of X-rays. The three organically bound iodine atoms within its molecular structure are highly effective at attenuating X-ray photons as they pass through the body.[3] This property allows tissues and structures that have been opacified with the agent to be clearly distinguished from surrounding soft tissues, which are largely transparent to X-rays.[11]
• Physics of Contrast: The high atomic number of iodine (Z=53) results in a significantly increased probability of photoelectric absorption, the primary interaction between diagnostic X-rays and matter. This effect is most pronounced when the energy of the incident X-ray beam is close to the K-shell binding energy (k-edge) of iodine, which is 33.2 keV, an energy level that falls within the typical spectrum used for diagnostic imaging.[11] When Iopamidol is injected into the bloodstream, it opacifies the vessels in its path, permitting radiographic visualization of the internal structures of the body until it is diluted and cleared.[15]
• Dose-Response Relationship: The degree of contrast enhancement, or radiographic opacity, is directly proportional to the concentration of iodine within the tissue or vessel being imaged.[3] This relationship explains the need for different concentrations of Iopamidol for various procedures; applications that require high levels of vascular opacification, such as coronary arteriography, benefit from higher iodine concentrations to achieve a sufficient contrast-to-noise ratio.[23]

Pharmacodynamics

Beyond its primary physical mechanism, Iopamidol has several pharmacodynamic properties that contribute to its clinical profile.

• Protein Binding: Iopamidol exhibits a very low tendency to bind to serum or plasma proteins.[15] This is a significant characteristic, as it ensures that the vast majority of the administered dose remains free in the circulation. Unbound drug is readily available to distribute into the extracellular fluid and is freely filtered by the renal glomeruli, facilitating its rapid elimination.
• Complement Activation: In studies of normal subjects, Iopamidol has shown no evidence of in vivo complement activation.[15] The activation of the complement system is a potential pathway for triggering anaphylactoid reactions, and the absence of this effect may contribute to the improved hypersensitivity profile of Iopamidol compared to older, high-osmolar agents.
• Hemodynamic Effects: As a low-osmolar contrast medium, Iopamidol induces less significant hemodynamic changes than high-osmolar ionic agents. For example, in comparative studies during coronary angiography, Iopamidol demonstrated significantly less effect on sinus node activity and atrioventricular nodal conduction than the ionic agent Diatrizoate.[31] This contributes to greater patient safety, particularly in cardiac procedures. Nonetheless, the administration of any hypertonic solution results in a transitory increase in the circulatory osmotic load. This can cause a transient shift of fluid into the intravascular space, which requires caution in patients with compromised cardiac function, such as those with congestive heart failure, who should be monitored for delayed hemodynamic disturbances.[21]

The ideal radiographic contrast agent should function as a biologically inert substance, passing through the body to provide diagnostic information without participating in significant metabolic or physiological interactions. Iopamidol largely fulfills this objective. Its primary function is based on a physical principle—X-ray attenuation—rather than a pharmacological one, such as receptor binding. Its minimal plasma protein binding ensures it does not linger in the bloodstream or interfere with the transport of other substances.[15] The complete absence of metabolism means that no active or potentially toxic metabolites are generated; the molecule that is injected is the same molecule that is excreted.[14] Furthermore, its minimal interaction with the complement system reduces the probability of initiating severe immune-like reactions.[15] This overall "inertness" is a central goal in the design of modern contrast media. The primary deviations from this ideal are the unavoidable physical effects related to its osmolality and viscosity, along with a low level of inherent chemotoxicity. These physical and chemical properties, rather than any specific pharmacological activity, are the main sources of potential adverse events, such as sensations of warmth, hemodynamic shifts, and, most importantly, contrast-induced nephropathy. Therefore, a thorough understanding of Iopamidol's safety profile requires an appreciation of the consequences of its physical presence in the body, not its pharmacological engagement.

Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)

Introduction

The pharmacokinetic profile of Iopamidol describes its movement into, through, and out of the body. As Iopamidol is administered directly into the vascular system (intravenously or intra-arterially), the absorption phase is circumvented, and bioavailability is considered to be 100%.[32] The analysis thus focuses on its distribution, metabolism, and excretion.

Distribution

• Compartment Model: Following intravenous administration, the pharmacokinetics of Iopamidol in subjects with normal renal function are well-described by an open two-compartment model with first-order elimination. This model comprises a rapid initial phase (alpha phase) representing the distribution of the drug from the central (vascular) compartment to the peripheral (extracellular fluid) compartment, followed by a slower elimination phase (beta phase).[14]
• Volume of Distribution: Upon injection, Iopamidol is immediately diluted in the circulating plasma and distributes rapidly from the vascular space into the extravascular, extracellular fluid. Calculations of its apparent volume of distribution at steady-state confirm this pattern, with no evidence of significant deposition or accumulation in tissues.[14] This uniform distribution throughout the extracellular fluid is the basis for its utility in CECT of the body, where contrast enhancement depends on the differential accumulation of the agent in the interstitial space of normal versus abnormal tissues.[14]
• Blood-Brain Barrier (BBB): Under normal physiological conditions, Iopamidol does not significantly cross the intact blood-brain barrier.[15] Consequently, in CECT of the head, the observed increase in X-ray absorption in normal brain tissue is due to the presence of the contrast agent within the blood pool. However, in pathological conditions where the BBB is disrupted, such as in malignant brain tumors or areas of active infection, Iopamidol can extravasate from the capillaries and accumulate within the interstitial tissue of the lesion. This creates a clear contrast between the enhancing lesion and the adjacent, non-enhancing normal brain tissue, which is a key principle of its diagnostic utility in neuroradiology.[14]

Metabolism

• Biotransformation: Iopamidol is not subject to metabolic alteration in the body. Studies have shown no significant metabolism, deiodination, or biotransformation following administration.[14] The compound is excreted from the body chemically unchanged, a hallmark of a well-designed, inert diagnostic agent.[28]

Excretion

• Primary Route: The primary and almost exclusive route of elimination for Iopamidol is renal excretion.[11] The drug is freely filtered by the glomeruli and is not significantly reabsorbed or secreted by the renal tubules.
• Elimination Half-Life: In individuals with normal renal function, the elimination serum or plasma half-life (t1/2​) is approximately two hours.[14] This half-life has been shown to be independent of the administered dose.
• Urinary Excretion Profile: The rate of urinary excretion is rapid. In subjects with normal renal function, approximately 35% to 40% of the injected dose is recovered in the urine within 60 minutes. This increases to 80% to 90% by 8 hours, with 90% or more of the total dose being excreted via the urine within a 72- to 96-hour period.[14]
• Fecal Excretion: The contribution of hepatobiliary or other non-renal pathways to elimination is negligible. In normal subjects, 1% or less of the administered dose is recovered in fecal specimens over 72 to 96 hours.[15]
• Impact of Renal Impairment: The reliance on renal clearance means that the pharmacokinetic profile of Iopamidol is significantly altered in patients with impaired renal function. In these individuals, the elimination half-life is prolonged, with the degree of prolongation being directly dependent on the severity of the renal impairment.[14] This extended exposure time is a critical factor that increases the risk of adverse events, particularly contrast-induced nephropathy.

The pharmacokinetic profile of Iopamidol is the cornerstone upon which its clinical risk profile is built. The fact that the drug is almost exclusively cleared by the kidneys without undergoing metabolism has profound implications. This renal-dependent pathway makes the kidneys the organ system exposed to the highest and most prolonged concentration of the drug. Any inherent nephrotoxic potential of the molecule is therefore maximally expressed in the renal tubules, which explains why CIN is the most significant organ-specific toxicity associated with Iopamidol. This risk is logically amplified in patients with pre-existing renal dysfunction, as their reduced clearance capacity prolongs the duration of this high-concentration exposure.

This same pharmacokinetic principle underpins the critical interaction with metformin. The risk of metformin-associated lactic acidosis is not a direct chemical interaction between the two drugs but rather a sequential pharmacokinetic event. If Iopamidol administration leads to a transient or sustained decrease in renal function (i.e., CIN), the clearance of metformin, which is also excreted by the kidneys, is consequently reduced. This can lead to the accumulation of metformin to toxic levels, increasing the risk of its most severe adverse effect, lactic acidosis.[1] The entire clinical protocol of withholding metformin before and after contrast administration is a safety measure designed specifically to prevent this predictable pharmacokinetic cascade. Thus, understanding that Iopamidol's ADME is effectively just "Distribution and renal Excretion" provides a unifying framework for its major clinical risks.

The kinetics of contrast enhancement observed during imaging procedures are also a direct reflection of Iopamidol's pharmacokinetic properties. Peak iodine concentration in the blood occurs immediately following a rapid intravenous injection, corresponding to the arterial phase of enhancement, which is ideal for angiographic studies.[14] Subsequently, these blood levels decline rapidly over the next five to ten minutes as the drug distributes from the vascular compartment into the much larger extracellular fluid compartment—the alpha phase of the two-compartment model.[14] This period corresponds to the portal venous or equilibrium phases in CT imaging. Interestingly, the maximum contrast enhancement within many pathological lesions, especially tumors with a compromised blood-brain barrier, is often delayed, occurring 5 to 40 minutes after injection, well after peak blood iodine levels have passed.[14] This lag demonstrates that tissue enhancement is not merely a reflection of the iodine content in the blood pool but is dependent on the slower process of drug accumulation within the interstitial space of the lesion. This kinetic behavior is the rationale behind dynamic CT scanning protocols, which involve a series of rapid scans performed 30 to 90 seconds post-injection to capture the period of greatest tissue enhancement.[14]

Approved Clinical Indications and Usage

Introduction

Iopamidol is a broadly applicable diagnostic imaging agent approved by the U.S. Food and Drug Administration (FDA) for a wide array of procedures. Its primary function is to provide contrast enhancement for X-ray-based imaging modalities, including conventional angiography, digital subtraction angiography (DSA), venography, and computed tomography (CT).[11] The selection of a specific Iopamidol formulation and concentration is tailored to the requirements of the particular diagnostic procedure.[39]

Intra-arterial Procedures (Adults)

Intra-arterial administration delivers a concentrated bolus of contrast medium directly to a target vascular territory, providing high-resolution images of the arterial system. Iopamidol is indicated for:

• Cerebral Arteriography: Visualization of the arterial circulation of the brain to diagnose conditions such as aneurysms, arteriovenous malformations (AVMs), and arterial stenosis.[14]
• Peripheral Arteriography: Imaging of the arteries in the upper and lower extremities to evaluate for peripheral artery disease.[14]
• Coronary Arteriography and Cardiac Ventriculography: A cornerstone application for the diagnosis and assessment of coronary artery disease, evaluation of cardiac chamber size, and assessment of ventricular function.[14]
• Selective Visceral Arteriography and Aortography: Imaging of the aorta and its major branches, such as the renal, celiac, and mesenteric arteries, to evaluate for aneurysms, dissections, and organ-specific vascular pathologies.[14]

Intravenous Procedures (Adults and Pediatrics)

Intravenous administration allows for systemic distribution of the contrast agent, enabling visualization of organs and vascular structures during the enhancement phase. Indications include:

• Contrast-Enhanced Computed Tomography (CECT) of the Head and Body: Iopamidol is widely used to enhance the diagnostic yield of CT scans. It helps in the detection and evaluation of lesions in the brain, liver, pancreas, kidneys, aorta, mediastinum, and retroperitoneal space.[14] CECT is valuable for investigating malignancies (e.g., gliomas, meningiomas, and metastatic disease), nonneoplastic conditions (e.g., recent-onset cerebral infarctions, abscesses), and vascular abnormalities.[14]
• Excretory Urography: This procedure utilizes the renal excretion of Iopamidol to visualize the anatomy and function of the urinary tract, including the renal parenchyma, calyces, pelves, ureters, and bladder.[26]
• Peripheral Venography (Phlebography) (Adults): Used for the visualization of the venous system of the extremities, primarily to diagnose deep vein thrombosis.[6]

Pediatric-Specific Indications

Iopamidol is approved for several key indications in the pediatric population:

• Angiocardiography: For the evaluation of congenital and acquired heart disease in pediatric patients.[14]
• CECT of the Head and Body: As in adults, it is used to enhance CT imaging.[39]
• Excretory Urography: For assessment of the pediatric urinary tract.[39]

Intrathecal Procedures (ISOVUE-M Formulations)

It is of critical importance to distinguish standard ISOVUE formulations from those specifically designed and approved for intrathecal administration, which are marketed under the brand name ISOVUE-M. Standard ISOVUE is strictly contraindicated for intrathecal use.

• Adult Neuroradiology: ISOVUE-M is indicated for myelography (lumbar, thoracic, cervical, and total columnar) to visualize the spinal cord and nerve roots. It is also used for contrast enhancement of computed tomographic (CECT) cisternography and ventriculography.[6]
• Pediatric Neuroradiology: The lower concentration formulation, ISOVUE-M 200 (41%), is indicated for thoraco-lumbar myelography in children over the age of two years.[6]

The regulatory and branding distinction between standard ISOVUE and the ISOVUE-M formulations represents a critical, built-in safety control. The central nervous system is exquisitely sensitive to chemical and osmotic changes. Historical experience has shown that the inadvertent intrathecal injection of standard, higher-concentration intravascular contrast media can lead to severe and often fatal neurotoxicity, including seizures, paralysis, and death.[21] This represents the single most catastrophic medication error associated with this class of drugs. To mitigate this risk, formulations intended for intrathecal use are specifically prepared at lower, near-isotonic concentrations (e.g., 200 mgI/mL) to be osmotically compatible with cerebrospinal fluid (CSF) and to reduce their neurotoxic potential.[26] The separate branding—with "-M" signifying its use in Myelography—coupled with the explicit and repeated warnings against the intrathecal use of standard ISOVUE, serves as a vital administrative safeguard to prevent such devastating errors.[35] This distinction is not a matter of marketing but a direct reflection of a harsh lesson in pharmacovigilance and a deliberate design feature to enhance patient safety.

Dosage and Administration Guidelines

General Principles of Administration

The safe and effective use of Iopamidol requires adherence to several key principles of administration that are designed to optimize diagnostic quality while minimizing patient risk.

• Dose Individualization: The lowest dose of Iopamidol necessary to achieve adequate diagnostic visualization should always be used.[26] The specific volume, concentration, and rate of injection must be individualized for each patient. Clinicians should consider a range of factors, including the patient's age, body weight, the size and flow rate of the vessel to be imaged, the anticipated pathology, the imaging equipment and technique employed, and any concomitant medical conditions.[39]
• Hydration: Adequate patient hydration is a critical safety measure. Preparatory dehydration is dangerous and is contraindicated, as it can contribute to acute renal failure. Patients should be well-hydrated both before and after the administration of Iopamidol to minimize the risk of contrast-induced nephropathy (CIN).[11]
• Preparation and Handling:
• Iopamidol solutions may be administered at either room temperature (20°C to 25°C) or warmed to body temperature (37°C). Warming the solution can reduce its viscosity, which may facilitate easier injection, particularly for higher-concentration formulations.[39]
• Strict aseptic technique must be used for all handling and administration procedures.[39]
• Before administration, the solution should be visually inspected for any particulate matter or discoloration. If either is observed, the solution must not be used.[39]
• Iopamidol should not be mixed with other drugs, nor should it be injected into intravenous lines containing other medications or total parenteral nutrition admixtures.[39]
• Single-dose containers are intended for one procedure only, and any unused portion must be discarded.[39]

Recommended Dosage and Administration Guidelines

The following table synthesizes the recommended dosages for Iopamidol (ISOVUE) across its major approved indications for adult and pediatric populations.

Table 2: Recommended Dosage and Administration Guidelines for Iopamidol (ISOVUE)

Procedure Type	Specific Imaging Procedure	Patient Population	Recommended Concentration (mgI/mL)	Typical Volume/Dose	Maximum Cumulative Total Dose
Intra-arterial	Cerebral Arteriography	Adult	300	8-12 mL per injection	90 mL
	Peripheral Arteriography	Adult	300	5-40 mL (femoral/subclavian); 25-50 mL (aortic runoff)	250 mL
	Selective Visceral Arteriography & Aortography	Adult	370	Up to 10 mL (renal); Up to 50 mL (aorta/celiac)	225 mL
	Coronary Arteriography	Adult	370	2-10 mL per selective injection	200 mL
	Cardiac Ventriculography	Adult	370	25-50 mL per injection	200 mL
	Angiocardiography	Pediatric (<2 years)	370	10-15 mL per injection	40 mL
	Angiocardiography	Pediatric (2-9 years)	370	15-30 mL per injection	50 mL (2-4 yrs); 100 mL (5-9 yrs)
	Angiocardiography	Pediatric (10-18 years)	370	20-50 mL per injection	125 mL
Intravenous	Excretory Urography	Adult	250, 300, or 370	50-100 mL (250); 50 mL (300); 40 mL (370)	Not to exceed 100 mL
	Excretory Urography	Pediatric	250 or 300	1.2-3.6 mL/kg (250); 1.0-3.0 mL/kg (300)	Not to exceed 30 g of iodine
	CECT of the Head	Adult	250 or 300	130-240 mL (250); 100-200 mL (300)	240 mL (250); 200 mL (300)
	CECT of the Body	Adult	250, 300, or 370	130-240 mL (250); 100-200 mL (300); 80-160 mL (370)	240 mL (250); 200 mL (300); 160 mL (370)
	CECT of Head/Body	Pediatric	250 or 300	1.2-3.6 mL/kg (250); 1.0-3.0 mL/kg (300)	Not to exceed 30 g of iodine
	Peripheral Venography	Adult	200	25-150 mL per lower extremity	350 mL
Intrathecal	Myelography, Cisternography, Ventriculography	Adult	200 or 300	Total dose of 2000-3000 mg iodine	N/A
	Thoraco-lumbar Myelography	Pediatric (>2 years)	200	Total dose of 1400-2400 mg iodine	N/A
Data compiled from.26 Note: This table is a summary; prescribers must consult the full prescribing information for complete details.

The maximum cumulative doses outlined in the official prescribing information are not arbitrary figures but are critical safety thresholds established primarily to limit the total iodine load delivered to the kidneys. The risk of CIN is known to be dose-dependent, with larger volumes of contrast media being a key risk factor.[47] Therefore, the specified maximum doses, such as 90 mL for cerebral arteriography or 250 mL for peripheral arteriography, represent a clinically determined balance point.[39] They are designed to allow for sufficient diagnostic opacification while keeping the risk of inducing acute kidney injury within an acceptable range. This principle is even more pronounced in pediatric dosing, where strict limits based on age and body weight are enforced to protect the developing and more vulnerable renal systems of young patients.[35] The dosing guidelines are a direct implementation of a risk mitigation strategy, reflecting an empirically derived consensus on the trade-off between diagnostic efficacy and renal safety.

Comprehensive Safety Profile and Risk Management

Introduction

Iopamidol is generally well-tolerated, and its development as a non-ionic, low-osmolar agent marked a substantial improvement in safety compared to the first-generation high-osmolar ionic contrast media.[22] However, like all iodinated contrast agents, it is associated with a range of potential adverse reactions, from mild and transient to severe and life-threatening. Effective risk management requires a thorough understanding of this safety profile, careful patient screening, and preparedness for emergency situations.

Boxed Warning-Equivalent: Risks of Inadvertent Intrathecal Administration

While Iopamidol does not carry a formal black box warning from the FDA, the severity and catastrophic nature of medication errors involving its intrathecal use warrant equivalent clinical attention.

• The Warning: Standard ISOVUE formulations (ISOVUE-200, -250, -300, and -370) are for intra-arterial or intravenous administration ONLY. They are absolutely contraindicated for intrathecal administration.[35] Only specifically designated formulations (ISOVUE-M) are approved for this route.
• Consequences: The inadvertent intrathecal injection of a standard, hypertonic Iopamidol solution is a medical emergency with potentially fatal consequences. Reported outcomes include death, intractable convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, and severe brain edema.[21] This represents the most severe potential risk associated with the misuse of this drug class.

Hypersensitivity and Anaphylactoid Reactions

• Nature of Reactions: Iopamidol can cause life-threatening or fatal hypersensitivity reactions, including anaphylaxis and anaphylactic shock.[39] These reactions are generally considered pseudoallergic, resulting from the direct release of histamine and other mediators from mast cells and basophils, rather than a true immunoglobulin E (IgE)-mediated allergic response.[18]
• Manifestations: Clinical manifestations can range from mild to severe and include urticaria (hives), pruritus (itching), rash, angioedema, bronchospasm, laryngospasm, respiratory arrest, and cardiovascular collapse.[41]
• Timing: The majority of severe reactions occur immediately, typically within one to three minutes of injection. However, delayed hypersensitivity reactions can also manifest from one hour to several days after administration.[41]
• Risk Factors: The risk of a hypersensitivity reaction is significantly increased in patients with a history of a previous reaction to any contrast medium. Other major risk factors include a history of bronchial asthma, and known clinical hypersensitivities such as hay fever or food allergies.[21]
• Severe Cutaneous Adverse Reactions (SCARs): Although rare, Iopamidol administration can trigger severe, potentially fatal cutaneous reactions. These include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). These reactions may develop from one hour to several weeks after exposure.[21]

Contrast-Induced Nephropathy (CIN)

• Definition: CIN, also referred to as contrast-associated acute kidney injury (CA-AKI), is defined as an acute deterioration in renal function following the intravascular administration of iodinated contrast media, for which other causes have been excluded. It is typically identified by a rise in serum creatinine of ≥25% or ≥0.5 mg/dL (44 µmol/L) from baseline, occurring within 24 to 72 hours post-procedure.[54]
• Incidence and Risk Factors: The incidence of CIN is low (less than 5%) in the general population with normal renal function. However, the risk is substantially higher (15% to 50%) in patients with pre-existing risk factors.[47] The most significant risk factors are pre-existing chronic kidney disease (CKD), particularly an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m², and diabetes mellitus, especially in combination with renal impairment. Other risk factors include dehydration, congestive heart failure, advanced age, multiple myeloma, and the concomitant administration of other nephrotoxic drugs.[11]
• Clinical Comparison and Osmolality: The development of lower osmolality agents like Iopamidol was driven in part by efforts to reduce nephrotoxicity. Numerous studies have compared low-osmolar agents (like Iopamidol) to iso-osmolar agents (like Iodixanol). The PREDICT study, a randomized, double-blind trial in patients with both diabetes and moderate-to-severe CKD, found no statistically significant difference in the incidence of CIN between Iopamidol-370 (a low-osmolar agent) and Iodixanol-320 (an iso-osmolar agent).[55] This and other analyses suggest that while osmolality is a factor, the inherent chemotoxicity of the contrast molecule itself also plays a significant role, and that Iopamidol and Iodixanol have comparable renal safety profiles, positioning them as agents of choice in high-risk patients.[47]

Cardiovascular Adverse Reactions

• Serious, and in rare cases fatal, cardiovascular events have been reported during or shortly after Iopamidol administration. Fatal reactions have occurred mostly within 10 minutes of injection, with cardiac arrest being the main feature, often in patients with underlying cardiovascular disease.[41]
• Hemodynamic disturbances, hypotensive collapse, and shock can occur.[39]
• Serious thromboembolic events, including myocardial infarction and stroke, have been reported during angiographic procedures. These events are multifactorial, related to the procedure itself, catheter materials, and the patient's underlying condition, in addition to the contrast agent.[34]

Other Warnings and Precautions

• Thyroid Dysfunction: The iodine load from Iopamidol can precipitate a thyroid storm in patients with pre-existing hyperthyroidism or an autonomously functioning thyroid nodule.[43] Transient hypothyroidism has been reported in pediatric patients under 3 years of age following exposure, particularly in neonates, premature infants, and those with congenital cardiac conditions. Thyroid function monitoring is recommended in this vulnerable population.[43]
• High-Risk Populations: Special caution is required in certain patient populations:
• Pheochromocytoma: Administration can trigger a severe hypertensive crisis.[13]
• Sickle Cell Disease: Contrast agents may promote sickling in individuals homozygous for the disease.[13]
• Multiple Myeloma: These patients are at a particularly high risk of developing renal failure after contrast administration.[13]
• Extravasation: If the contrast agent leaks from the vein into the surrounding soft tissues during injection, it can cause local pain, swelling, and inflammation. While most cases are mild, severe reactions including blistering, skin necrosis, and compartment syndrome have been reported, particularly in patients with compromised peripheral circulation.[48]

Common Adverse Reactions

The most frequently reported adverse reactions to Iopamidol are typically mild, transient, and self-limiting. These include a sensation of warmth or hot flashes, flushing, nausea, vomiting, a metallic taste, headache, dizziness, and mild urticaria or rash.[11]

The safety profile of Iopamidol is not a single, monolithic entity but rather a spectrum of risks that must be assessed in the context of the individual patient and the specific clinical scenario. For the majority of patients with no significant comorbidities, the profile is excellent, characterized by minor and transient side effects.[42] However, for patients with specific underlying conditions, the risk-benefit calculation shifts dramatically. In a patient with a history of severe allergy or asthma, the primary concern becomes the potential for a hypersensitivity reaction, often necessitating premedication and heightened vigilance.[15] For a patient with diabetic nephropathy, the focus shifts entirely to the prevention of CIN through meticulous hydration and dose limitation.[47] For a neonate undergoing a cardiac procedure, the potential for transient hypothyroidism becomes a key consideration.[43] The most severe risk, profound neurotoxicity, is not an inherent property of the drug's pharmacology but a direct consequence of a specific and preventable medication error—the intrathecal administration of the wrong formulation.[39] Therefore, an expert understanding of Iopamidol's safety profile involves moving beyond a simple list of side effects to a stratified, context-dependent risk assessment. The safe clinical use of the drug is entirely contingent on this nuanced approach.

Drug and Laboratory Test Interactions

Clinically Significant Drug Interactions

Iopamidol can interact with several other medications. These interactions can alter the safety profile of Iopamidol or the concomitant drug. The most significant interactions are summarized below.

Table 3: Clinically Significant Drug Interactions with Iopamidol

Interacting Drug/Class	Nature of the Interaction	Recommended Clinical Management
Metformin	Iopamidol can cause transient renal impairment (CIN), which decreases the renal clearance of metformin. This can lead to metformin accumulation and an increased risk of metformin-associated lactic acidosis, a rare but potentially fatal adverse effect.	Temporarily discontinue metformin at the time of or prior to the procedure in patients with risk factors (e.g., eGFR 30-60 mL/min/1.73 m², hepatic impairment, alcoholism, heart failure). Do not resume metformin for at least 48 hours post-procedure and only after renal function has been re-evaluated and found to be stable.
Aldesleukin (Interleukin-2)	Patients who have been treated with aldesleukin may be at an increased risk of developing hypersensitivity reactions to iodinated contrast media. Reactions can be delayed and may include fever, chills, nausea, vomiting, and rash.	The risk of a hypersensitivity reaction is increased. Monitor patients closely.
Nephrotoxic Agents (e.g., aminoglycosides, cisplatin, NSAIDs, voclosporin)	Concomitant use of other nephrotoxic drugs may potentiate the risk of contrast-induced nephropathy (CIN).	Use with caution. Ensure adequate patient hydration. Consider alternative agents if possible. Monitor renal function closely post-procedure.
Agents that Lower Seizure Threshold (e.g., phenothiazines, MAO inhibitors, tricyclic antidepressants, CNS stimulants)	For intrathecal administration of Iopamidol (ISOVUE-M), concomitant use of drugs that lower the seizure threshold may increase the risk of seizures.	These medications should be discontinued at least 48 hours before myelography and not resumed for at least 24 hours post-procedure.
Radioactive Iodine (I-123, I-131)	The stable iodine in Iopamidol competes for uptake by the thyroid gland, which can interfere with thyroid function tests and reduce the efficacy of diagnostic thyroid scans or therapeutic radioactive iodine treatment.	Thyroid uptake studies and radioactive iodine therapy should be performed prior to Iopamidol administration. This interference can last for several weeks.
Data compiled from.1

• Detailed Analysis of the Metformin Interaction: The interaction between iodinated contrast media and metformin is of paramount clinical importance due to the severity of potential outcomes. It is not a direct drug-drug interaction but a sequential pharmacokinetic event. The administration of Iopamidol carries a risk of inducing CIN, even if transient.[54] Since metformin is primarily eliminated by the kidneys, any reduction in renal function can lead to its accumulation in the blood. High concentrations of metformin inhibit hepatic gluconeogenesis and increase lactate production, which can precipitate metformin-associated lactic acidosis, a metabolic emergency with a high mortality rate.[38] The clinical management guidelines from bodies like the American College of Radiology are designed to interrupt this potential cascade by temporarily withholding metformin in at-risk patients until it is certain that their renal function has not been compromised by the contrast agent.[35]

Interference with Laboratory Tests

In addition to direct drug interactions, Iopamidol can interfere with the results of certain laboratory tests through various mechanisms.

• Thyroid Function Tests: As noted in the table, the large iodine load from an Iopamidol dose can saturate the thyroid gland's iodine uptake mechanism. This significantly interferes with diagnostic tests that rely on the uptake of radioactive iodine (I-123 or I-131), such as a thyroid scan or uptake measurement. This interference can render these tests unreliable for a period ranging from two to as long as sixteen days, or even 6-8 weeks, following contrast administration.[35]
• Coagulation Tests: In vitro studies have demonstrated that many radiopaque contrast agents, including non-ionic ones like Iopamidol, can have a mild anticoagulant effect, producing a slight depression of plasma coagulation factors.[62] Furthermore, clotting has been reported when blood is allowed to remain in contact with plastic syringes containing non-ionic contrast media, emphasizing the need for meticulous angiographic technique, including frequent flushing of catheters.[45]
• Physical and Analytical Interference:
• Sample Separation: Following administration, the high concentration of Iopamidol in a patient's blood can increase the specific gravity of the serum or plasma. This increased density can exceed that of the thixotropic gel in serum separator tubes (SSTs), causing the gel barrier to fail to form correctly or to float, resulting in incomplete separation of serum/plasma from blood cells. This can lead to erroneous results for any analyte affected by contact with cellular components.[63]
• Specific Assays: Interference has been reported for specific laboratory assays. For example, a positive bias in the measurement of cardiac troponin I was observed with one specific immunoassay system in the presence of iodinated contrast media.[63]
• Management of Laboratory Interference: To avoid spurious results, it is recommended that any laboratory tests that might be affected by contrast media should be performed prior to the administration of Iopamidol.[62] If post-procedure testing is necessary, waiting at least 4 hours, or approximately two elimination half-lives, may allow for sufficient clearance of the agent to minimize interference, though some effects (like on thyroid tests) persist much longer.[63]

The interactions associated with Iopamidol are not uniform in their mechanism, and understanding these differences is key to appropriate clinical management. The interaction with metformin is a classic example of a sequential pharmacokinetic event, where one drug (Iopamidol) alters the excretion of another (metformin), leading to toxicity. In contrast, the interference with radioactive iodine is a competitive pharmacodynamic interaction at the site of uptake in the thyroid gland. The issues with laboratory tests, such as the failure of gel separator tubes, are often purely physical phenomena, driven by the high density of the contrast-laden serum. Finally, the effects on coagulation are a direct chemical interaction in an in vitro setting. Recognizing these distinct mechanisms explains the different management strategies: metformin is withheld to prevent a systemic physiological risk; a thyroid scan is delayed due to target competition; and a blood sample may need to be redrawn to avoid a physical artifact in the collection tube. This mechanistic understanding allows for more precise and intelligent problem-solving in clinical practice.

Patient Management Protocols

Pre-Procedure Patient Care

A systematic approach to patient preparation is essential to ensure safety and minimize the risk of adverse events associated with Iopamidol administration.

• Patient Screening and History: A thorough medical history is the cornerstone of pre-procedure risk assessment. Clinicians must specifically inquire about:
• Allergies and Hypersensitivities: A history of a previous reaction to any iodinated contrast medium is the single greatest predictor of a future reaction. A general history of allergies, particularly bronchial asthma, hay fever, or food allergies, also confers an increased risk.[37]
• Renal Function: The presence of chronic kidney disease, diabetes mellitus, or diabetic nephropathy must be identified, as these are major risk factors for CIN.[13] Serum creatinine and calculation of eGFR are often performed.
• Comorbid Conditions: The presence of severe cardiovascular disease (especially congestive heart failure), multiple myeloma, pheochromocytoma, hyperthyroidism, and homozygous sickle cell disease must be ascertained, as these conditions increase the risk of specific adverse events.[13]
• Medication Review: A comprehensive review of the patient's current medications is mandatory.
• Metformin: Identify all patients taking metformin to ensure adherence to withholding protocols.[53]
• Nephrotoxic Drugs: Note the use of other potentially nephrotoxic agents (e.g., NSAIDs, aminoglycosides) as their concurrent use may increase the risk of CIN.[66]
• Seizure Threshold: For patients scheduled for an intrathecal procedure with ISOVUE-M, identify any medications that may lower the seizure threshold (e.g., certain antidepressants, antipsychotics) so they can be temporarily discontinued.[45]
• Hydration: Ensuring adequate hydration is a key preventative measure against CIN. Preparatory dehydration is dangerous and strictly contraindicated. Unless medically restricted, patients should be encouraged to be well-hydrated with oral or intravenous fluids before and after the procedure.[11]
• Premedication: For patients identified as being at high risk for a hypersensitivity reaction (e.g., those with a prior reaction or significant allergic history), a premedication regimen with antihistamines and/or corticosteroids may be considered. While such regimens do not prevent all serious, life-threatening reactions, they may reduce both their incidence and severity.[15]
• Patient Counseling: Patients should be informed about the nature of the procedure, the reason for the contrast injection, and common, expected sensations such as a feeling of warmth or a metallic taste. They should also be instructed to immediately report any unusual symptoms, such as difficulty breathing, itching, or feeling faint, to the medical staff.[53]

Post-Procedure Patient Care

Vigilant monitoring and appropriate aftercare are crucial for detecting and managing any delayed adverse reactions.

• Monitoring: Following the procedure, patients should be observed by competent personnel in a setting equipped for emergency treatment for at least 30 to 60 minutes. This is because severe, delayed hypersensitivity reactions can occur.[50] Patients with conditions like congestive heart failure may require longer observation for delayed hemodynamic changes.[21]
• Hydration: Post-procedure hydration is as important as pre-procedure hydration. Patients should be encouraged to drink plenty of non-caffeinated fluids for several hours after the procedure to promote the renal clearance of the contrast agent, unless there is a medical reason to restrict fluids.[50]
• Renal Function Monitoring: For patients with pre-existing renal impairment or other risk factors for CIN, post-procedure monitoring of renal function (e.g., checking serum creatinine at 48-72 hours) may be warranted to detect any acute kidney injury.[50]
• Patient Discharge Instructions: Upon discharge, patients should be clearly instructed on the signs and symptoms of potential delayed reactions and when to seek medical attention. This includes instructions to report any new skin rashes, swelling, difficulty breathing, or signs of kidney problems such as decreased urination or swelling in the legs.[13] They should also be reminded to inform any other healthcare providers they see in the following weeks that they have recently received an iodinated contrast agent, as it can interfere with certain lab tests.[37]

The comprehensive patient management protocols surrounding the use of Iopamidol function as a proactive, multi-layered safety system. This system is meticulously designed to anticipate and mitigate each of the drug's known risks. The risk of hypersensitivity is addressed through pre-procedure screening for allergy history, consideration of premedication, and post-procedure monitoring. The risk of CIN is managed by screening for renal disease and diabetes, ensuring robust hydration before and after the procedure, and adhering to the principle of using the lowest effective dose. The specific risk of metformin-associated lactic acidosis is prevented by screening for metformin use and strictly following the protocol for withholding the drug. The potential for a severe acute event like anaphylaxis is prepared for by ensuring that emergency resuscitation equipment and trained personnel are immediately available. This demonstrates that the safe application of Iopamidol is not an inherent property of the molecule alone but is achieved through the implementation of a robust clinical framework. The drug and the protocol are, in effect, inseparable components of a single diagnostic system.

Regulatory and Commercial Landscape

Brand Names and Formulations

• Primary Brand Name: Iopamidol was originally developed and is primarily marketed by Bracco Diagnostics under the brand name ISOVUE.[3]
• Other Brand Names: Internationally and from various manufacturers, Iopamidol is also known by other trade names, including Iopamiro, Gastromiro, Scanlux, Niopam, and Solutrast.[6]
• Formulations: ISOVUE is available in a range of concentrations to suit different clinical applications, typically containing 200, 250, 300, or 370 mg of organically bound iodine per mL (mgI/mL). These correspond to Iopamidol concentrations of 41%, 51%, 61%, and 76%, respectively.[13] A distinct line of formulations, ISOVUE-M, is specifically designated for intrathecal administration in neuroradiology.[13]

Manufacturers and Suppliers

• Originator: Bracco Diagnostics is the originator and a leading global manufacturer of Iopamidol.[3] Bracco maintains manufacturing facilities in Germany and Italy that supply the global market.[69]
• Generic Manufacturers: Following patent expiry, the market has seen the entry of several generic manufacturers. Companies that market or have marketed generic iopamidol injection in the U.S. and other regions include Hainan Poly, Hospira (a Pfizer company), Fresenius Kabi, and Slate Run Pharmaceuticals.[1]
• Active Pharmaceutical Ingredient (API) Suppliers: The market for the Iopamidol API is global, with numerous suppliers providing the raw drug substance to formulation manufacturers. These suppliers are located in countries including China (e.g., Zhejiang Starry, Zhejiang Wild Wind), India (e.g., Divis Labs), South Korea (e.g., Dong Wha Pharm, Dongkook Pharma), and Portugal (e.g., Hovione Farmaciencia).[72]

FDA Approval History

• Initial Approval: Iopamidol was first approved by the U.S. FDA on December 31, 1985. The initial New Drug Application (NDA 018735), held by Bracco Diagnostics, covered multiple formulations, including ISOVUE-300, ISOVUE-370, and the intrathecal versions ISOVUE-M 200 and ISOVUE-M 300.[71]
• Subsequent Approvals: Additional formulations and packaging configurations received approval in the subsequent years. For instance, the ISOVUE-250 formulation was approved under the same NDA in 1992. A separate NDA (020327) was approved on October 12, 1994, for additional presentations of ISOVUE-250, -300, and -370.[75]
• Generic Entry: The pathway for generic competition opened following the expiry of key patents. The first Abbreviated New Drug Application (ANDA) for a generic Iopamidol injection was approved by the FDA in August 1996. The agency determined the generic product to be bioequivalent to the Reference Listed Drug (RLD), ISOVUE.[76] The availability of generic versions has continued to expand, with new approvals as recently as 2024, indicating a mature and competitive market.[70]

The regulatory and commercial history of Iopamidol charts the classic lifecycle of a successful pharmaceutical product. Its initial approval in 1985 positioned it as a key agent in the second generation of contrast media, heralding the pivotal clinical shift away from the more toxic high-osmolar ionic agents toward the safer non-ionic class. Its sustained presence on the market for nearly four decades, marked by over 400 million doses administered worldwide, is a testament to its enduring clinical utility, efficacy, and accepted safety profile.[68] The approval of the first generic version in 1996 and the continued entry of new generic manufacturers into the 2020s signify its transition from a novel, innovative branded product to a mature, foundational drug. This evolution has significant implications for the healthcare market, fostering competition that generally leads to reduced costs and increased accessibility. Today, Iopamidol is no longer considered a novel agent but a well-understood standard of care in diagnostic radiology.

Conclusion and Expert Insights

Iopamidol's introduction in 1985 represented a significant milestone in the evolution of radiographic contrast media. Its development was a direct response to the clinical need for agents with improved safety and patient tolerability compared to the first-generation high-osmolar ionic compounds. This objective was successfully achieved through rational drug design; its non-ionic chemical structure is the key innovation that directly results in a lower osmolality in solution, thereby mitigating many of the adverse effects, such as pain and hemodynamic instability, that were common with older agents.

Decades of widespread clinical use have solidified Iopamidol's position as a versatile, effective, and reliable diagnostic tool. Its broad range of FDA-approved indications—spanning angiography, venography, and computed tomography across both adult and pediatric populations—underscores its utility as a workhorse agent in modern radiology. The pharmacokinetic profile of Iopamidol is a model of simplicity and predictability: rapid distribution throughout the extracellular fluid followed by swift and complete renal excretion in an unchanged form. This profile is simultaneously the drug's greatest strength and its primary liability. Its predictability and lack of metabolism make it a clean agent to use, but its near-total reliance on renal clearance concentrates any potential toxicity directly on the kidneys, making contrast-induced nephropathy the most significant organ-specific risk.

Ultimately, the enduring success and safe application of Iopamidol serve as a prime example of a systems-based approach to clinical pharmacology. The molecule itself possesses inherent risks, including the potential for nephrotoxicity and hypersensitivity reactions. However, these risks have been thoroughly characterized over decades of study and are now effectively managed not by altering the drug itself, but by implementing a robust and evidence-based clinical framework around its use. This framework encompasses meticulous patient screening for risk factors, proactive hydration protocols, vigilant management of drug interactions like that with metformin, and established post-procedure monitoring. The safe use of Iopamidol is therefore a testament not only to its advanced molecular design but also to the clinical wisdom and safety protocols that have been co-developed alongside it. Its legacy is that of a well-understood tool whose known risks are rendered acceptable and manageable through disciplined clinical practice.

Works cited

1. Iopamidol: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed August 27, 2025, https://go.drugbank.com/drugs/DB08947
2. Iopamidol | C17H22I3N3O8 | CID 65492 - PubChem, accessed August 27, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Iopamidol
3. Iopamidol | 60166-93-0 - ChemicalBook, accessed August 27, 2025, https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5384796.htm
4. Definition of iopamidol - NCI Drug Dictionary, accessed August 27, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/iopamidol
5. Iopamidol - brand name list from Drugs.com, accessed August 27, 2025, https://www.drugs.com/ingredient/iopamidol.html
6. Iopamidol - Wikipedia, accessed August 27, 2025, https://en.wikipedia.org/wiki/Iopamidol
7. Iopamidol 60166-93-0 | Tokyo Chemical Industry Co., Ltd.(APAC), accessed August 27, 2025, https://www.tcichemicals.com/OP/en/p/I1011
8. Iopamidol | CAS 60166-93-0 | SCBT - Santa Cruz Biotechnology, accessed August 27, 2025, https://www.scbt.com/p/iopamidol-60166-93-0
9. Iopamidol | C17H22I3N3O8 - ChemSpider, accessed August 27, 2025, https://www.chemspider.com/Chemical-Structure.58940.html
10. CAS 60166-93-0 Iopamidol - Alfa Chemistry, accessed August 27, 2025, https://www.alfa-chemistry.com/product/iopamidol-cas-60166-93-0-1448.html
11. What is Iopamidol used for? - Patsnap Synapse, accessed August 27, 2025, https://synapse.patsnap.com/article/what-is-iopamidol-used-for
12. Iopamidol-d8 | C17H22I3N3O8 | CID 71749521 - PubChem, accessed August 27, 2025, https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=71749521
13. Iopamidol (injection route) - Side effects & uses - Mayo Clinic, accessed August 27, 2025, https://www.mayoclinic.org/drugs-supplements/iopamidol-injection-route/description/drg-20150965
14. ISOVUE® (Iopamidol Injection) - accessdata.fda.gov, accessed August 27, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018735s070lbl.pdf
15. ISOVUE® (Iopamidol Injection) - accessdata.fda.gov, accessed August 27, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018735s054lbl.pdf
16. 300 ISOVUE®-370 - accessdata.fda.gov, accessed August 27, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020327s023lbl.pdf
17. Iodinated contrast media | Radiology Reference Article | Radiopaedia.org, accessed August 27, 2025, https://radiopaedia.org/articles/iodinated-contrast-media-1
18. Intravenous Radiocontrast Media: A Review of Allergic Reactions - U.S. Pharmacist, accessed August 27, 2025, https://www.uspharmacist.com/article/intravenous-radiocontrast-media-a-review-of-allergic-reactions
19. Best Practices in the Use of Iodinated Contrast Media in the Clinical Setting: What the Pharmacist Needs to Know - ASHP Advantage®, accessed August 27, 2025, https://ashpadvantagemedia.com/contrastmedia/files/handout-contrastmedia.pdf
20. [Iopamidol, a new non-ionic roentgen contrast medium. Results of angiographic studies in more than 300 patients, with special reference to pain reactions] - PubMed, accessed August 27, 2025, https://pubmed.ncbi.nlm.nih.gov/7156393/
21. ISOVUE - ISOVUE, accessed August 27, 2025, https://isovue.com/
22. Iopamidol: new, nonionic contrast agent for excretory urography, accessed August 27, 2025, https://ajronline.org/doi/pdf/10.2214/ajr.142.2.329
23. Effects of Iopamidol-370 Versus Iodixanol-320 on Coronary Contrast, Branch Depiction, and Heart Rate Variability in Dual-Source Coronary MDCT Angiography | AJR - American Journal of Roentgenology, accessed August 27, 2025, https://ajronline.org/doi/10.2214/AJR.10.6154
24. Iopamidol: new, nonionic contrast agent for excretory urography | AJR, accessed August 27, 2025, https://ajronline.org/doi/abs/10.2214/ajr.142.2.329
25. Iopamidol: new, nonionic contrast agent for excretory urography | AJR, accessed August 27, 2025, https://ajronline.org/doi/10.2214/ajr.142.2.329
26. What are the guidelines for using iopamidol (contrast agent) in diagnostic imaging procedures? - Dr.Oracle AI, accessed August 27, 2025, https://www.droracle.ai/articles/161400/iopamidol
27. ISOVUE-M® 200 Iopamidol Injection 41% ISOVUE-M® 300 Iopamidol Injection 61% - DailyMed, accessed August 27, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=11e893d2-0183-4581-b908-c8b7302c7edb
28. What is the mechanism of Iopamidol? - Patsnap Synapse, accessed August 27, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-iopamidol
29. www.mims.com, accessed August 27, 2025, https://www.mims.com/philippines/drug/info/iopamidol?mtype=generic#:~:text=Mechanism%20of%20Action%3A%20Iopamidol%20is,from%20CSF%20after%20intravascular%20administration.
30. iopamidol injection, solution ISOVUE 370 - DailyMed, accessed August 27, 2025, https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=797a11d7-dcd4-43ff-311b-3b48a10da2f2
31. Iopamidol: a new contrast medium in coronary angiography. Comparison, on electrophysiological changes in man, with a commonly used contrast medium - PubMed, accessed August 27, 2025, https://pubmed.ncbi.nlm.nih.gov/6884375/
32. Pharmacokinetics: Definition & Use in Drug Development - Allucent, accessed August 27, 2025, https://www.allucent.com/resources/blog/what-pharmacokinetics-and-adme
33. What are the main ADME processes in pharmacokinetics? - Patsnap Synapse, accessed August 27, 2025, https://synapse.patsnap.com/article/what-are-the-main-adme-processes-in-pharmacokinetics
34. 300 ISOVUE -370 - accessdata.fda.gov, accessed August 27, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020327s012lbl.pdf
35. Isovue, Scanlux (iopamidol) dosing, indications, interactions, adverse effects, and more, accessed August 27, 2025, https://reference.medscape.com/drug/isovue-scanlux-iopamidol-343763
36. Isovue IBP_PI_CL72D07) redline_RevOct2019 - Bracco, accessed August 27, 2025, https://www.bracco.com/sites/default/files/2022-11/us-en-2022-04-27-spc-isovue-imaging-bulk-package.pdf
37. Iopamidol Advanced Patient Information - Drugs.com, accessed August 27, 2025, https://www.drugs.com/cons/iopamidol.html
38. Drug Interaction Report: iopamidol, metformin - Drugs.com, accessed August 27, 2025, https://www.drugs.com/interactions-check.php?drug_list=1373-0,1573-0&professional=1
39. ISOVUE® (iopamidol) injection, for intra-arterial or intravenous use - accessdata.fda.gov, accessed August 27, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/018735s073lbl.pdf
40. Iopamidol Injection: Package Insert / Prescribing Info - Drugs.com, accessed August 27, 2025, https://www.drugs.com/pro/iopamidol-injection.html
41. ISOVUE® (iopamidol) injection, for intra-arterial or intravenous use - Bracco, accessed August 27, 2025, https://www.bracco.com/us-en-2022-04-27-spc-isovue
42. Iopamidol-370 Solution for Injection: Clinical Profile - GlobalRx, accessed August 27, 2025, https://www.globalrx.com/articles?article=iopamidol-370-injection-profile&product_id=32071
43. Iopamidol: Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed August 27, 2025, https://www.rxlist.com/iopamidol/generic-drug.htm
44. ISOVUE-M® 200 (Iopamidol Injection 41%) - Bracco, accessed August 27, 2025, https://www.bracco.com/sites/default/files/2022-11/isovue-m-facs-template-24-july-2020-rd3.pdf
45. Iopamidol: Drug information - sniv3r2.github.io, accessed August 27, 2025, https://sniv3r2.github.io/d/topic.htm?path=iopamidol-drug-information
46. Iopamidol Injection, USP, 41% and Iopamidol Injection, USP, 61% - DailyMed, accessed August 27, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0b9e0d24-c6ca-4e22-9422-936e9d475eaa&type=display
47. Contrast-induced Nephropathy—Choice of Contrast Agents to Reduce Renal Risk - Radcliffe Cardiology, accessed August 27, 2025, https://assets.radcliffecardiology.com/s3fs-public/article-pdf/2020-12/katholi_0.pdf
48. ISOVUE®-200, -250, -300, -370 (Iopamidol Injection) - Bracco, accessed August 27, 2025, https://www.bracco.com/isovue-facs-template-10-nov-2021-rd3
49. Clinical Profile of Iopamidol 61% Solution for Injection - GlobalRx, accessed August 27, 2025, https://www.globalrx.com/articles?article=iopamidol-61-solution-clinical-profile&product_id=121190
50. Iopamidol Uses, Side Effects & Warnings - Drugs.com, accessed August 27, 2025, https://www.drugs.com/mtm/iopamidol.html
51. [Late reactions to a radiologic contrast media (Iopamidol-Bracco). Prospective study], accessed August 27, 2025, https://pubmed.ncbi.nlm.nih.gov/11155455/
52. Hypersensitivity reactions to iodinated contrast media: potential mechanisms and clinical management - PMC, accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12092453/
53. Iopamidol - Memorial Sloan Kettering Cancer Center, accessed August 27, 2025, https://www.mskcc.org/cancer-care/patient-education/medications/adult/iopamidol
54. Contrast-induced Nephropathy - Update and Practical Clinical Applications | USC Journal, accessed August 27, 2025, https://www.uscjournal.com/articles/contrast-induced-nephropathy-update-and-practical-clinical-applications?language_content_entity=en
55. The PREDICT Study: A Randomized Double-Blind Comparison of Contrast-Induced Nephropathy After Low- or Isoosmolar Contrast Agent Exposure | AJR - American Journal of Roentgenology, accessed August 27, 2025, https://ajronline.org/doi/10.2214/AJR.07.3370
56. Nephrotoxicity of iodixanol versus iopamidol in patients with acute coronary syndrome, accessed August 27, 2025, https://archivestsc.com/jvi.aspx?un=TKDA-81504
57. Isovue-300 Disease Interactions - Drugs.com, accessed August 27, 2025, https://www.drugs.com/disease-interactions/iopamidol,isovue-300.html
58. Iopamidol: Pediatric Medication | Memorial Sloan Kettering Cancer Center, accessed August 27, 2025, https://www.mskcc.org/cancer-care/patient-education/medications/pediatric/iopamidol?msk_tools_print=pdf
59. Iopamidol Disease Interactions - Drugs.com, accessed August 27, 2025, https://www.drugs.com/disease-interactions/iopamidol.html
60. What are the side effects of Iopamidol? - Patsnap Synapse, accessed August 27, 2025, https://synapse.patsnap.com/article/what-are-the-side-effects-of-iopamidol
61. reference.medscape.com, accessed August 27, 2025, https://reference.medscape.com/drug/isovue-scanlux-iopamidol-343763#:~:text=iopamidol%20increases%20levels%20of%20metformin,result%20of%20worsening%20renal%20function.
62. Isovue-M (Iopamidol Injection): Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed August 27, 2025, https://www.rxlist.com/isovue-drug.htm
63. Interference of medical contrast media on laboratory testing - PMC, accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC3936969/
64. Interference of medical contrast media on laboratory testing - ResearchGate, accessed August 27, 2025, https://www.researchgate.net/publication/260810489_Interference_of_medical_contrast_media_on_laboratory_testing
65. Drug-related Laboratory Test Interference - ASCLS, accessed August 27, 2025, https://ascls.org/wp-content/uploads/2012/11/Brochure_Interference_Providers_2020.pdf
66. iopamidol injection, solution - FFF Enterprises, accessed August 27, 2025, https://www.fffenterprises.com/assets/downloads/product-information/slate-run-pharmaceuticals/pi-IOPAMIDOL.pdf
67. Iopamidol | Memorial Sloan Kettering Cancer Center, accessed August 27, 2025, https://www.mskcc.org/cancer-care/patient-education/medications/adult/iopamidol?msk_tools_print=pdf
68. ISOVUE - Bracco, accessed August 27, 2025, https://www.bracco.com/en-ca/product/isovue
69. 1 Bracco Diagnostics Inc. May 6, 2022 Dear Valued Customer, As you may know, one of the major US suppliers of iodinated contrast - Strategic Health Care, accessed August 27, 2025, https://strategichealthcare.net/wp-content/uploads/2022/05/bracco-contrast-media-update-may-6.pdf
70. Generic IOPAMIDOL INN entry, pharmaceutical patent expiry and freedom to operate - DrugPatentWatch, accessed August 27, 2025, https://www.drugpatentwatch.com/p/generic-api/IOPAMIDOL
71. Generic Isovue-370 Availability - Drugs.com, accessed August 27, 2025, https://www.drugs.com/availability/generic-isovue-370.html
72. Iopamidol - Midas Pharma, accessed August 27, 2025, https://www.midas-pharma.com/en/products/drug-substances/iopamidol/
73. Iopamidol - Beijing Beilu Pharmaceutical Co., Ltd., accessed August 27, 2025, https://www.beilupharma.com/products/iopamidol.html
74. Iopamidol API Suppliers - Find All GMP Manufacturers - Pharmaoffer.com, accessed August 27, 2025, https://pharmaoffer.com/api-excipient-supplier/diagnostic-agents/iopamidol
75. Iopamidol - PharmaKB, accessed August 27, 2025, https://www.pharmakb.com/drug-report/iopamidol
76. center for drug evaluation and research - accessdata.fda.gov, accessed August 27, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/074629a.pdf
77. Bracco Puts on View Contrast Media Isovue | Imaging Technology News, accessed August 27, 2025, https://www.itnonline.com/content/bracco-puts-view-contrast-media-isovue