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Oxilan

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Oxilan

CLINICAL PHARMACOLOGY

General

Ioxilan (ioxilan (ioxilan) ) is a nonionic, water soluble, triiodinated x-ray contrast agent for intravascular injection. Intravascular injection of a radiopaque diagnostic agent opacifies those vessels in the path of flow of the contrast medium, permitting radiographic visualization of the internal structures of the human body until significant hemodilution occurs.

Pharmacokinetics

In healthy young (21-27 years) male (n = 4) and female volunteers (n = 4) who each received OXILAN® Injection, 72.8 g ioxilan (ioxilan (ioxilan) ) (35.0 g iodine), the drug showed biphasic and first order pharmacokinetics. Ioxilan (ioxilan (ioxilan) ) is distributed mainly in the blood as suggested by the apparent volume of distribution (central compartment), 7.2 ± 1.0 L in women and 10.0 ± 2.4 L in men (mean ± sd). The total clearance values were 95.4 ± 11.1 mLmin-1 and 101.0 ±14.7 mLmin-1 and the renal clearance values were 89.4 ± 13.3 mLmin-1 and 94.9 ±16.6 mLmin-1 for women and men, respectively. An initial fast distribution phase with a half-life of 13.1 ± 4.2 minutes (women) or 23.5 ± 15.3 minutes (men) was followed by an elimination phase with a half-life of 102.0 ± 16.9 minutes (women) and 137 ± 35.4 minutes (men). Binding of ioxilan (ioxilan (ioxilan) ) to plasma protein is negligible.

The average amount of ioxilan (ioxilan (ioxilan) ) excreted unchanged in urine at 24 hours represents 93.7% of the dose in young healthy subjects (21-27 years) after intravenous administration of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection. This finding suggests that, compared to the renal excretion, biliary and/or gastrointestinal excretion are not important for OXILAN® (ioxilan (ioxilan (ioxilan) ) ) .

The pharmacokinetics profile and total clearance of ioxilan (ioxilan (ioxilan) ) in patients with significantly impaired renal function have not been studied. In pooled data from 80 subjects with abnormal baseline BUNS or creatinines, who received either ioxilan (ioxilan (ioxilan) ) (n = 44) or iohexol (n = 36), there was a higher occurrence of post-procedure increased creatinine levels (p = 0.008); also, the systolic pressure was lower at 2-6 hours (p = 0.043). Dose adjustment in patients with renal failure and blood brain barrier interaction has not been studied. OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection binds negligibly to plasma or serum protein and can be dialyzed.

Metabolism

There is no evidence for metabolism of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection.

Pharmacodynamics

As with other iodinated contrast agents, following OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection, the degree of contrast enhancement is directly related to the iodine content in the administered dose; peak iodine plasma levels occur immediately following rapid intravenous injection. Iodine plasma levels fall rapidly within 5 to 10 minutes. This can be accounted for by the dilution in the vascular and extravascular fluid compartments.

Intravascular Contrast: Contrast enhancement appears to be greatest immediately after bolus injections (15 seconds to 120 seconds). Thus, greatest enhancement may be detected by a series of consecutive two-to-three second scans performed within 30 to 90 seconds after injection (i.e., dynamic computed tomographic imaging).

OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection may be visualized in the renal parenchyma within 30-60 seconds following rapid intravenous injection. Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1-3 minutes, with optimum contrast occurring within 5-15 minutes.

Contrast Enhanced Computerized Tomography (CECT): AS WITH OTHER IODINATED CONTRAST AGENTS, THE USE OF OXILAN® (ioxilan (ioxilan (ioxilan) ) ) INJECTION CONTRAST ENHANCEMENT MAY OBSCURE SOME LESIONS WHICH WERE SEEN ON PREVIOUSLY UNENHANCED CT SCANS.

In CECT some performance characteristics are different in the brain and body. In CECT of the body, iodinated contrast agents diffuse rapidly from the vascular into the extravascular space. Following the administration of iodinated contrast agents, the increase in tissue density to x-rays is related to blood flow, the concentration of the contrast agent, and the extraction of the contrast agent by various interstitial tissues. Contrast enhancement is thus due to any relative differences in extravascular diffusion between adjacent tissues.

In the normal brain with an intact blood-brain barrier, contrast is generally due to the presence of iodinated contrast agent within the intravascular space. The radiographic enhancement of vascular lesions, such as arteriovenous malformations and aneurysms, depends on the iodine content of the circulating blood pool.

In tissues with a break in the blood-brain barrier, contrast agent accumulates within interstitial brain tissue. The time to maximum contrast enhancement can vary from the time that peak blood iodine levels are reached to 1 hour after intravenous bolus administration. This delay suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing medium within the lesion and outside the blood pool. The mechanism by which this occurs is not clear.

IN PATIENTS WITH NORMAL BLOOD BRAIN BARRIERS and RENAL FAILURE, iodinated contrast agents have been associated with blood brain barrier DISRUPTION and ACCUMULATION OF CONTRAST IN THE BRAIN. (See PRECAUTIONS.)

The usefulness of contrast enhancement for the investigation of the retrobulbar space and of low grade or infiltrative glioma has not been demonstrated. Calcified lesions are less likely to enhance. The enhancement of tumors after therapy may decrease. The opacification of the inferior vermis following contrast agent administration has resulted in false-positive diagnosis. Cerebral infarctions of recent onset may be better visualized with contrast enhancement. Older infarctions are obscured by the contrast agent.

For information on coagulation parameters, fibrinolysis and complement system, please refer to the Laboratory Test Findings section.

Clinical Trials

OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection was administered to 834 patients in controlled and uncontrolled studies. Of these 679 patients were between 18 and 69 years of age, and 155 patients were 70 years of age or older; the mean age was 56.4 years (range 18-88). Of the 834 patients, 579 (69%) were male and 255 (31%) were female. The racial distribution was: Caucasian 668 (80%), Black 84 (10%), Hispanic 58 (7%), Asian 14 (2%), and other or unknown 10 (1%). The demographic information for patients who received the comparator (iohexol) was similar.

In the controlled studies, 530 patients given OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection and 540 patients given the comparator (iohexol) were evaluated for efficacy. Efficacy assessment was based on the global evaluation of the quality of the radiographs by rating visualization as either excellent, good, poor, or no image, and on the ability to make a diagnosis. Results were compared to those with the active control (iohexol injection) at concentrations which were identical to those of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection.

Four (4) intraarterial and three (3) intravenous procedures were studied with 1 of 2 concentrations (350 mgI/mL and 300 mgI/mL). These procedures were: aortography/visceral angiography, coronary arteriography and left ventriculography, cerebral arteriography, peripheral arteriography, contrast- enhanced computed tomography (CECT) of head and body, and excretory urography.

Cerebral arteriography was evaluated in 3 randomized, double-blind clinical trials of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 300 mgI/mL in patients with conditions such as altered cerebrovascular perfusion and/or permeability occurring in central nervous system diseases due to various CNS disorders. Results were assessed in 78 patients with OXILAN®(Ioxilan (ioxilan (ioxilan) ) Injection) and 83 with iohexol injection 300 mgI/mL. Visualization ratings were good or excellent in 95% of the patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection; a radiologic diagnosis was made in the majority of the patients. The results were similar to those with iohexol injection. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Coronary arteriography/left ventriculography was evaluated in 4 randomized, double-blind clinical trials of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 350 mgI/mL in patients with conditions such as altered coronary artery perfusion due to metabolic causes and in patients with conditions such as altered ventricular function. Results were assessed in 139 patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection and 142 with iohexol injection 350 mgI/mL. Visualization ratings were good or excellent in 99% or more of the patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection; a radiologic diagnosis was made in the majority of the patients. The results were similar to those with iohexol injection. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Aortography/visceral angiography was evaluated in 3 randomized, double-blind clinical trials of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 350 mgI/mL in patients with conditions such as altered aortic blood flow and/or visceral vascular disorders. The results were assessed in 51 patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 350 mgI/mL and 47 with iohexol injection 350 mgI/mL. Visualization ratings were good or excellent in the majority of the patients; a radiologic diagnosis was made in 90% of the patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection. The results were similar to those with iohexol injection. Confirmation of radiologic findings by other diagnostic methods was not obtained.

Intravenous excretory urography was evaluated in 2 randomized, double-blind clinical trials of OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 350 mgI/mL. The results were assessed in 61 patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 350 mgI/mL and 62 with iohexol injection 350 mgI/mL. Visualization ratings were good or excellent in all of the patients; a radiologic diagnosis was made in 100% of the patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection. The results were similar to those with iohexol injection. Confirmation of radiologic findings by other diagnostic methods was not obtained.

CECT of head and body was evaluated in 5 randomized, double-blind clinical trials in patients with vascular disorders. A total of 146 patients received OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection 300 mgI/mL and 149 received iohexol injection 300 mgI/mL. Visualization ratings were good or excellent in 98% of the patients with OXILAN® (ioxilan (ioxilan (ioxilan) ) ) Injection; a radiologic diagnosis was made in the majority of the patients. The results were similar to those with iohexol injection.

Last reviewed on RxList: 2/26/2009
This monograph has been modified to include the generic and brand name in many instances.

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