Feridex I.V. (ferumoxides injectable solution) is an intravenously injected colloidal superparamagnetic iron
oxide associated with dextran. It is a magnetic resonance imaging (MRI) contrast
agent and is taken up by cells of the reticuloendothelial system (RES).
Three healthy, adult male volunteers received a dose of
Feridex I.V. (ferumoxides injectable solution) 0.56 mg of Fe/kg (diluted in 100 mL of 5% dextrose and intravenously
infused over 30 minutes). In these subjects, the mean ± SD peak serum iron
concentration was 5.5 ± 0.6 μg/mL, elimination half-life was 2.4 ± 0.2
hours and total clearance 28.5 ± 1.6 mL/min. Feridex I.V. (ferumoxides injectable solution) was completely
cleared from the blood by 25 hours after administration. Less than 2% of the
drug was excreted in the urine, as expected for iron.
At 24 hours, serum iron increased and the percent saturation
of iron binding capacity decreased in a dose-dependent fashion. By 7 days,
serum iron returned to pre-administration levels, and serum ferritin increased.
These results are consistent with the iron in Feridex I.V. (ferumoxides injectable solution) entering the usual
iron metabolism cycle. Animal pharmacokinetics studies were consistent with these
results in humans.
Imaging studies in rats showed a large decrease in liver
signal intensity for the first 24 hours after dosing, followed by a gradual return
to normal over 7 days. Radiotracer studies in rats were consistent with the
iron in Feridex I.V. (ferumoxides injectable solution) becoming part of the body iron pool. Histological studies
in rats showed that the iron was in the RES and that it disappeared from the
RES over 7 to 14 days with all evidence of iron gone by 14–28 days.
In human clinical studies, there was no difference in loss
of signal intensity on images obtained between 0–3.5 hours after infusion. Loss
of signal intensity decreased at 1 and 2 days.
The iron in Feridex I.V. (ferumoxides injectable solution) enters the normal body iron
metabolism cycle as evidenced by transient increases in serum iron values one
day after administration and increase in serum ferritin values 7 days after
administration. The amount of iron contained in a single dose is 39 mg for a 70
kg individual. This is less than 1/5 the amount of iron contained in one unit of
Geriatric/Pediatric: Pharmacokinetics in these populations were
not studied. Patients enrolled in clinical trials were between 11 and 89 years
Gender: Women showed a higher pre-contrast signal intensity and
hence a larger decrease in liver signal intensity in images. This is consistent
with a lower baseline iron in women.
Race: Differences due to race were not noted.
Renal Insufficiency: Feridex I.V. (ferumoxides injectable solution) is not renally cleared; no
studies were performed in patients with renal insufficiency.
Hepatic Insufficiency: Patients with cirrhosis had less of a
decrease in liver signal intensity than other patients with known or suspected
liver lesions. Patients with cirrhosis also had a higher incidence of back pain.
(See ADVERSE REACTIONS section.)
Hemochromatosis: Individuals with iron overload were not studied.
Feridex I.V. (ferumoxides injectable solution) contains iron. Literature reports suggested that Feridex I.V. (ferumoxides injectable solution) will
not add information to their MRI evaluations, since iron overload causes loss
in liver signal intensity.
In rats, the simultaneous administration of heparin was found to prolong the
half-life of Feridex I.V. (ferumoxides injectable solution) in the blood. The effects of Feridex I.V. (ferumoxides injectable solution) administration
on heparin anticoagulation are not known.
Feridex I.V. (ferumoxides injectable solution) shortens the relaxation times for nearby hydrogen atoms and reduces
signal intensity in normal tissues. This results in signal loss (image darkening)
on mid T1/T2 or strongly T2-weighted images. Tissues with decreased RES function
(e.g., metastases, primary liver cancer, cysts and various benign tumors, adenomas,
and hyperplasia) retain their native signal intensity, so the contrast between
normal and abnormal tissue is increased.
Two clinical studies evaluated a total of 211 patients, (107
men and 104 women, 22–83 years of age) with a variety of known or suspected
liver lesions. Of these patients, efficacy evaluations were completed on 96
patients in Study A, and 112 patients in Study B. At baseline, patients had a
CECT (contrast enhanced computerized tomography) scan with any iodinated
contrast agent and a noncontrast MRI (magnetic resonance imaging) within 24
hours before Feridex I.V. (ferumoxides injectable solution) administration. Feridex I.V. (ferumoxides injectable solution) (0.56 mg/kg) was
administered intravenously over 30 minutes. Images were acquired up to 3.5
hours after the end of the infusion. The CECT, unenhanced MRI, and Feridex I.V. (ferumoxides injectable solution)
enhanced MRI images were read blindly (i.e., by radiologists who were not told
of the patient's medical history or the presence of image contrast enhancing
drugs). Results from blindly read images were compared to the final clinical
diagnosis. The final clinical diagnoses were confirmed with histopathologic,
surgical, or biopsy findings in 86 (41%) of patients. MRI scans were evaluated
for the quantitative analysis of signal intensity in liver lesion(s), and by blinded
evaluations of the resulting images for changes in number and location of
lesions, delineation of lesion margins, presence or absence of lesions, and
characterization of lesions.
Based upon these two studies, Feridex I.V. (ferumoxides injectable solution) reduced the
signal intensity of normal liver on T2 weighted pulse sequences to improve MRI
contrast. Contrast to noise ratios were increased on T2 images and decreased on
T1 images. Image interpretations for contrast enhancement, the number of
lesions identified, and the sensitivity and specificity of the determination of
whether an abnormal lesion was present are shown in the following table. The
mean number of lesions seen before and after Feridex I.V. (ferumoxides injectable solution) were comparable. The
majority of new lesions (86%) were 0.5 cm–1.0 cm in size, but other lesions
were seen that were < 0.5 cm or > 1.0 cm.
IMAGE INTERPRETATION RESULTS AFTER UNENHANCED MRI, CECT**
AND FERIDEX I.V. (ferumoxides injectable solution) ENHANCED MRI IN TWO CLINICAL STUDIES OF PATIENTS WITH KNOWN
OR SUSPECTED LIVER LESIONS
(N = 96)
|Contrast between normal and abnormal liver
tissue seen on MRI
||MRI Contrast Better with Feridex I.V.
|MRI Contrast Same with Feridex I.V.
|MRI Contrast Worse with Feridex I.V.
|(p < 0.01)
||(p < 0.01)
|Number of Patients with Lesions Seen on MRI
| More before Feridex I.V.
| Same before and after Feridex I.V.
| More After Feridex I.V
|Number of liver lesions seen on MRI(Mean ±
||MRI before Feridex I.V. after Feridex I.V.
||7.3 ± 15.9
||6.7 ± 14.8
|6.7 ± 10.4
||7.3 ± 15.5
|Sensitivity/specificity for the detection of
abnormal liver lesions
||MRI before Feridex I.V. vs. Final diagnosis:* Sensitivity
|MRI after Feridex I.V. vs. Final diagnosis:*
|CECT vs. Final diagnosis:*
|* Final diagnosis: e.g., by biopsy, surgical
resection, autopsy, MRI procedures other than with Feridex I.V. (ferumoxides injectable solution) , CECT,
ultrasound, or other clinical information.
** MRI (magnetic resonance image), CECT (contrast enhanced computerized
In various types of liver lesions, Feridex I.V. (ferumoxides injectable solution) caused a smaller decrease in
the signal intensity (59%–105% of the unenhanced) than in the surrounding liver
(28%–41% of the unenhanced). The signal intensity changes are not characterized
sufficiently to support distinguishing between types of lesions or diseases.
Whether patients with cirrhosis have similar changes in signal intensity is
PERCENT DECREASE IN MRI SIGNAL INTENSITY (SI) ON T2 IMAGES
AFTER FERIDEX I.V. (ferumoxides injectable solution)
||Lesions in Question
||% decrease in SI after Feridex I.V.
||% decrease in SI after Feridex I.V.
|Patients with benign, malignant, hepatocellular and non-hepatocellular
lesions (excluding cirrhosis)
Imaging of the spleen by Feridex I.V. (ferumoxides injectable solution) has not been adequately studied.