Ioxaglic Acid

Uses

Ioxaglic Acid is a tri-iodinated benzoate contrast agent used in various radiological procedures including angiography, phlebography, urography, computed tomography (CT), and hysterosalpingography.

This medicinal product is for diagnostic use only in adults and children as a low-osmolality medium , .

How Ioxaglic Acid works

Ioxaglic Acid is an iodine-containing, low osmolality contrast agent . Ioxaglate is a molecule that consists of six iodine atoms and achieves water solubility by ionization; thus, it is a 3.0 ratio ionic agent .

By far the most successful and widely used contrast agents in use today are the iodinated contrast media, which were introduced into clinical practice in the 1950s. Approximately 75 million doses of iodinated contrast agents are administered worldwide each year. The iodinated contrast agents fall into 4 groups. Each group has unique chemical, physical, and biologic properties. These various contrast agents are required to meet the demands of a broad variety of imaging modalities .

All agents share a similar function group—a tri-iodinated benzene ring. Iodine plays an imperative role in the attenuation of x-ray signal. The atomic radius of a covalently bonded iodine atom is about 133 picometers, falling within the same range of the wavelengths of x-rays: 10 to 10,000 picometers. Therefore, x-rays are easily attenuated by the iodine atoms. In addition, iodine atoms covalently bonded to a benzene ring have 2 main advantages: (1) 3 large atoms located in such close proximity increase the effective molecular size, attenuating longer-wavelength x-rays, and (2) covalent bonding to a stable organic functional group (for example, benzene) decrease the risk of toxic adverse effects from free iodide molecules .

Ionization is an important characteristic to note in contrast media preparations . Compounds are classified as either ionic or nonionic. The ionic compounds dissociate in aqueous solution and therefore have a higher osmolality. The anion is the radiopaque portion of the molecule, however, both the anion and cation are osmotically active . Compared with nonionic media such as ioxaglic acid, ionic contrast media have more adverse hemodynamic effects, especially in patients with heart disease. The nonionic media are water soluble but do not dissociate in solution. Nonionic agents possess lower osmolality because there are fewer particles in solution. The nonionic contrast agents are more hydrophilic than ionic agents, resulting in lower osmolality, reduced binding to plasma proteins, decreased tissue binding, and a decreased tendency to cross cell membranes .

The low-osmolality of ioxaglic acid reduces the risk of adverse events. The occurrence of adverse reactions is more common after the use of high-osmolarity agents: about 15% with a high-osmolarity agent versus 3% with a low-osmolarity agent .

The use of high-osmolarity agents has decreased significantly in recent years. Most adverse effects and adverse reactions to this group of drugs are multifactorial and are likely due to a combination of direct cellular toxicity, the ionic state (for example, ionic vs nonionic), or the osmolarity of the injected contrast drug .

Toxicity

Adverse reactions after administration of iodinated contrast agents may be worsened in patients displaying agitation, anxiety, and pain. Appropriate management, such as sedation, may be required before the procedure . Adequate hydration and normal electrolyte balance must be ensured, especially in elderly patients, infants, small children, patients with renal damage (oliguria, polyuria) or hyperuricemia, multiple myeloma, patients diagnosed with plasmacytoma or diabetes mellitus, particularly if it is longstanding .

As this drug is a contrast agent, it may cause minor or major reactions that may be serious or lethal . They may be rapid (within 60 minutes) or delayed (up to 1 week) .

Emergency measures must be immediately available in high risk individuals, especially in patients taking B-blockers in whom adrenaline and vascular perfusion would not be effective .

There are several conditions in which caution must be observed while administering this contrast drug :

Renal Disease/Hepatic Disease

Particular attention is required if the patient has both hepatic and renal failure, which increases the risk of contrast agent retention .

Cardiovascular Disease In patients with manifest or incipient heart failure, coronary disease, pulmonary hypertension, or valvular heart disease, the risks of pulmonary edema, myocardial ischemia and arrhythmia and severe hemodynamic disturbances is heightened after the administration of an iodinated contrast agent.

Cases of Torsade de Pointes have been identified in patients using sodium and meglumine ioxaglate, therefore loxaglic acid should be administered very carefully to patients who have/may develop prolongation of QTc, including patients taking other medicines that contribute to cardiovascular QT prolongation .

Pheochromocytoma Patients

Patients with phaeochromocytoma may suddenly develop hypertension after intravascular administration of a contrast agent, which may require appropriate management before the examination

Thyroid Disease

Following injection of iodinated contrast agent, specifically in patients with goiter or a history of hypothyroidism, there is a risk of either an episode of hyperthyroidism or induction of a new episode of hypothyroidism.

There is also a risk of hypothyroidism in newborns who have received, or whose mother has received, an iodinated contrast agent.

Screening for hypothyroidism should be performed routinely after administration of the product to newborns and judiciously to premature babies by assaying TSH and possibly free T4, 7-10 days and 1 month after iodine overload .

Asthma

Asthma should be controlled before injecting the iodinated contrast agent .

Particular attention is required if the asthmatic attack has occurred within eight days prior to administration of loxagic acid, because of the increased risk for bronchospasm.

Myasthenia gravis

Administration of a contrast agent may exacerbate the symptoms of myasthenia gravis .

Use in pregnancy

In the patient screening and with appropriate tests, it is advisable to identify possible pregnancy in women of childbearing age. Exposure of the female genital tract to x-rays warrants careful evaluation of the benefit-to-risk ratio .

Food Interaction

• Take separate from meals. Individuals may need to avoid eating before some procedures where ioxaglic acid is used.

Volume of Distribution

Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk .

Elimination Route

Following the intravascular route of injection, Ioxaglic Acid is rapidly transported through the circulatory system to the kidneys.

The pharmacokinetics of radiopaque contrast media given by the IV route are described by a two-compartment model with a rapid alpha phase for drug distribution and a slow beta phase for the elimination of the drug. Following the intravenous administration of 50 mL of ioxaglic acid in 10 healthy volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL.

Approximately 50 percent of the intravenously administered dose was recovered in the urine at two hours, and 90% percent was recovered at the 24 hour time point .

Half Life

Hexabrix 320 is rapidly eliminated by the kidneys with a half-life of about 90 minutes

Clearance

245 ml/kg

Elimination Route

Excreted unchanged in the urine The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases .

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