"The U.S. Food and Drug Administration today approved Zarxio (filgrastim-sndz), the first biosimilar product approved in the United States.
Biological products are generally derived from a living organism. They can come from many sources, in"...
Mechanism of Action
Iobenguane is similar in structure to the antihypertensive drug guanethedine and to the neurotransmitter norepinephrine (NE). Iobenguane is, therefore, largely subject to the same uptake and accumulation pathways as NE. Iobenguane is taken up by the NE transporter in adrenergic nerve terminals and stored in the presynaptic storage vesicles. Iobenguane accumulates in adrenergically innervated tissues such as the adrenal medulla, salivary glands, heart, liver, spleen and lungs as well as tumors derived from the neural crest. By labeling iobenguane with the isotope iodine 123, it is possible to obtain scintigraphic images of the organs and tissues in which the radiopharmaceutical accumulates.
AdreView (iobenguane i 123 injection for intravenous use) is a diagnostic radiopharmaceutical which contains a small quantity of iobenguane that is not expected to produce a pharmacodynamic effect [see DESCRIPTION]. To minimize radiation dose to the thyroid gland, this organ should be blocked before dosing [see DOSAGE AND ADMINISTRATION]. Since iobenguane is excreted mainly via the kidneys, patients with severe renal insufficiency may experience increased radiation exposure and impaired imaging results. Frequent voiding should be encouraged after administration to minimize the radiation dose to the bladder [see WARNINGS AND PRECAUTIONS]. The calculation of the estimated radiation dose is shown in Table 2 [see DOSAGE AND ADMINISTRATION].
Iobenguane is rapidly cleared from the blood and accumulates in adrenergically innervated tissues [see CLINICAL PHARMACOLOGY]. Retention is especially prolonged in highly adrenergically innervated tissues (e.g., the adrenal medulla, heart, and salivary glands).
The majority of the iobenguane dose is excreted unaltered by the kidneys via glomerular filtration. A rapid initial clearance of circulating iobenguane is observed, followed by a slow clearance as iobenguane is released from other compartments. In patients with normal renal function, 70 to 90% of the administered dose is recovered unaltered in urine within 4 days. Iobenguane is not cleared by dialysis [see WARNINGS AND PRECAUTIONS]. Most of the remaining radioactivity recovered in the urine is in the form of the radioiodinated metabolite m-iodohippuric acid (MIHA) (typically ≤ 10%) and free radioiodide (typically ≤ 6%). The enzymatic process responsible for metabolism has not been well characterized and the pharmacologic activity of these metabolites has not been studied. Only a small amount ( < 1%) of the injected dose is eliminated via the feces.
Animal Toxicology and/or Pharmacology
Iobenguane sulfate testing in dogs revealed electrocardiographic (ECG) changes after administration of 202 times the mg/m2 conversion of the maximum human dose for a 60 kg adult; the no observable effect level (NOEL) was not determined. When iobenguane was tested in a cell system stably expressing hERG-1 potassium channels, inhibition of potassium channels was not observed at an 80 µM iobenguane concentration and the IC50 was 487 µM.
Pheochromocytomas and Neuroblastomas
The safety and efficacy of AdreView (iobenguane i 123 injection for intravenous use) were assessed in an open-label, multicenter, multinational trial of 251 subjects with known or suspected neuroblastoma or pheochromocytoma. Diagnostic efficacy for the detection of metabolically active neuroblastoma or pheochromocytoma was determined by comparison of focal increased radionuclide uptake on planar scintigraphy at 24 ± 6 hours post-administration of AdreView (iobenguane i 123 injection for intravenous use) against the definitive diagnosis (standard of truth). Anterior and posterior planar whole-body images, or alternatively whole-body overlapping spot images, were acquired from the head to below the knees. Additional spot images were performed as deemed appropriate at the discretion of the clinical image reviewer. SPECT imaging of the thorax and abdomen was then obtained when possible.
Of the 251 subjects dosed with AdreView (iobenguane i 123 injection for intravenous use) , 100 had known or suspected neuroblastoma and 151 had known or suspected pheochromocytoma. The population included 154 adults and 97 pediatric patients; the majority of adults were female (59%), the majority of pediatric subjects were male (58%). The adult subjects had a mean age of 49 years (range 17 to 88 years). The pediatric patients (56 males and 41 females) consisted of 32 infants (1 month up to 2 years of age), 62 children (2 years up to 12 years) and three adolescents (12 years up to 16 years).
The definitive diagnosis (standard of truth) for the presence or absence of metabolically active pheochromocytoma or neuroblastoma was determined by histopathology or, when histopathology was unavailable, a composite of imaging (i.e., CT, MRI, [131I]-mIBG scintigraphy), plasma/urine catecholamine and/or catecholamine metabolite measurements, and clinical follow-up. A standard of truth was available for 211 subjects (127 with pheochromocytoma, 84 with neuroblastoma) and this group comprised the diagnostic efficacy population. For 93 of these subjects, the standard of truth was based solely upon histopathology. Of 211 subjects in the efficacy population, all had planar scintigraphy and 167 subjects had SPECT in addition to planar imaging. All images were assessed independently by three readers blinded to all clinical data. Table 5 summarizes the AdreView (iobenguane i 123 injection for intravenous use) performance characteristics, by reader.
Table 5. AdreView (iobenguane i 123 injection for intravenous use) Planar Imaging: Sensitivity and Specificity
|Outcome||Reader A||Reader B||Reader C|
|Sensitivity (n = 159)|
|95% confidence interval||0.73 - 0.86||0.70 - 0.84||0.71 – 0.85|
|Specificity (n = 52)|
|95% confidence interval||0.63 - 0.87||0.59 - 0.84||0.55 – 0.81|
Performance characteristics (sensitivity and specificity) of AdreView (iobenguane i 123 injection for intravenous use) planar imaging in patients with known or suspected neuroblastoma were similar to those in patients with known or suspected pheochromocytoma. Among the selected patients who also underwent SPECT imaging, similar performance characteristics of AdreView (iobenguane i 123 injection for intravenous use) scintigraphy were observed when SPECT plus planar imaging was compared to planar imaging alone.
Last reviewed on RxList: 10/2/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional AdreView Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.