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Dosage Forms And Strengths

Single use vials containing 5 mL solution for intravenous injection (2 mCi/mL at calibration time).

%medicine_name% (iobenguane i 123 injection for intravenous use) is supplied in 10 mL glass vials containing a total volume of 5.0 mL of solution with a total radioactivity of 370 MBq (10 mCi) at calibration time. Each vial is enclosed in a lead container of appropriate thickness.

NDC 17156-235-01

Storage

Store %medicine_name% (iobenguane i 123 injection for intravenous use) at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F). This product does not contain a preservative. Store within the original lead container or equivalent radiation shielding.

In accordance with USP recommendations Iobenguane I 123 Injection preparations should not be used after the expiration date and time stated on the label.

Handling

This preparation is approved for use by persons licensed by the Illinois Emergency Management Agency pursuant to 32 Ill. Adm. Code Section 330.260(a) and 355.4010 or equivalent licenses of the Nuclear Regulatory Commission or an Agreement State.

Manufactured and Distributed by GE Healthcare, Medi-Physics, Inc., Arlington Heights, IL 60004 U.S.A.

%medicine_name% (iobenguane i 123 injection for intravenous use) is a radiopharmaceutical indicated for use in the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests.

Radiation Safety

%medicine_name% (iobenguane i 123 injection for intravenous use) emits radiation and must be handled with appropriate safety measures to minimize radiation exposure to clinical personnel and patients. Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides. %medicine_name% (iobenguane i 123 injection for intravenous use) dosing is based upon the radioactivity determined using a suitable calibration system immediately prior to administration.

To minimize radiation dose to the bladder, prior to and following %medicine_name% (iobenguane i 123 injection for intravenous use) administration, encourage hydration to permit frequent voiding. Encourage the patient to void frequently for the first 48 hours following %medicine_name% administration .

Thyroid Blockade

Before administration of %medicine_name% (iobenguane i 123 injection for intravenous use) , administer Potassium Iodide Oral Solution or Lugol's Solution (equivalent to 100 mg iodide for adults, body-weight adjusted for children) or potassium perchlorate (400 mg for adults, body-weight adjusted for children) to block uptake of iodine 123 by the patient's thyroid. Administer the blocking agent at least one hour before the dose of %medicine_name%.

Preparation and Administration

Inspect the %medicine_name% (iobenguane i 123 injection for intravenous use) vial for particulate matter and discoloration prior to administration. Use aseptic procedures and a radiation shielding syringe during administration. Administer the dose as an intravenous injection over 1 to 2 minutes. A subsequent injection of 0.9% sodium chloride may be used to ensure full delivery of the dose.

Recommended Dose for Adults

For adults ( ≥ 16 years of age), the recommended dose is 10 mCi (370 MBq) .

Recommended Dose for Pediatric Patients

For pediatric patients < 16 years of age weighing ≥ 70 kg, the recommended dose is 10 mCi (370 MBq).

For pediatric patients < 16 years of age weighing < 70 kg, the recommended dose should be calculated according to patient body weight as shown in Table 1. The benzyl alcohol in %medicine_name% (iobenguane i 123 injection for intravenous use) may cause serious adverse reactions in premature or low birth-weight infants.

Table 1: %medicine_name% (iobenguane i 123 injection for intravenous use) Dose Preparation for Pediatric Patients*

Radiation Dosimetry

The estimated absorbed radiation doses to adults and children from intravenous administration of %medicine_name% (iobenguane i 123 injection for intravenous use) are as shown in Table 2:

Table 2: Estimated Absorbed Radiation Dose from %medicine_name% (iobenguane i 123 injection for intravenous use)

The effective dose resulting from an administered activity amount of 10 mCi is 5.07 mSv in an adult.

Imaging Guidelines

Begin whole body planar scintigraphy imaging 24 ± 6 hours following administration of %medicine_name% (iobenguane i 123 injection for intravenous use). Single photon emission computed tomography (SPECT) may be performed following planar scintigraphy, as appropriate.

%medicine_name% (iobenguane i 123 injection for intravenous use) is contraindicated in patients with known hypersensitivity to iobenguane or iobenguane sulfate.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions have been reported following %medicine_name% (iobenguane i 123 injection for intravenous use) administration. Prior to administration, question the patient for a history of prior reactions to iodine, an iodine-containing contrast agent or other products containing iodine. If the patient is known or strongly suspected to have hypersensitivity to iodine, an iodine-containing contrast agent or other products containing iodine, the decision to administer %medicine_name% (iobenguane i 123 injection for intravenous use) should be based upon an assessment of the expected benefits compared to the potential hypersensitivity risks. Have anaphylactic and hypersensitivity treatment measures available prior to %medicine_name% administration.

Risks for Benzyl Alcohol Toxicity in Infants

%medicine_name% (iobenguane i 123 injection for intravenous use) contains benzyl alcohol at a concentration of 10.3 mg/mL. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants and infants of low birth weight. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol..

Observe infants for signs or symptoms of benzyl alcohol toxicity following %medicine_name% (iobenguane i 123 injection for intravenous use) administration. %medicine_name% (iobenguane i 123 injection for intravenous use) safety and effectiveness have not been established in neonates (pediatric patients below the age of 1 month).

Increased Radiation Exposure in Patients with Severe Renal Impairment

%medicine_name% (iobenguane i 123 injection for intravenous use) is cleared by glomerular filtration and is not dialyzable. The radiation dose to patients with severe renal impairment may be increased due to the delayed elimination of the drug. Delayed %medicine_name% (iobenguane i 123 injection for intravenous use) clearance may also reduce the target to background ratios and decrease the quality of scintigraphic images. These risks importantly may limit the role of %medicine_name% (iobenguane i 123 injection for intravenous use) in the diagnostic evaluation of patients with severe renal impairment. %medicine_name% (iobenguane i 123 injection for intravenous use) safety and efficacy have not been established in these patients.

Thyroid Accumulation

Failure to block thyroid uptake of iodine 123 may result in an increased long term risk for thyroid neoplasia. Administer thyroid blocking medications before %medicine_name% administration.

Risks with Concomitant Medication Withdrawal

Drugs which interfere with norepinephrine uptake or retention may decrease the uptake of %medicine_name% (iobenguane i 123 injection for intravenous use) in neuroendocrine tumors and lead to false negative imaging results. When medically feasible, stop these drugs before %medicine_name% (iobenguane i 123 injection for intravenous use) administration and monitor patients for the occurrence of clinically significant withdrawal symptoms, especially patients with elevated levels of circulating catecholamines and their metabolites.

Hypertension

Assess the patient's pulse and blood pressure before and intermittently for 30 minutes after %medicine_name% (iobenguane i 123 injection for intravenous use) administration. %medicine_name% (iobenguane i 123 injection for intravenous use) may increase release of norepinephrine from chromaffin granules and produce a transient episode of hypertension, although this was not observed in the clinical study. Prior to %medicine_name% (iobenguane i 123 injection for intravenous use) administration, ensure emergency cardiac and anti-hypertensive treatments are readily available.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Iobenguane sulfate was not mutagenic in vitro in the Ames bacterial mutation assay and in the in vitro mouse lymphoma test, and was negative in the in vivo micronucleus test in rats.

Long-term animal studies have not been conducted to evaluate %medicine_name% (iobenguane i 123 injection for intravenous use) 's carcinogenic potential or potential effects on fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C: Any radiopharmaceutical, including %medicine_name% (iobenguane i 123 injection for intravenous use) , has a potential to cause fetal harm. It is not known whether %medicine_name% (iobenguane i 123 injection for intravenous use) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with %medicine_name% (iobenguane i 123 injection for intravenous use). %medicine_name% (iobenguane i 123 injection for intravenous use) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether %medicine_name% (iobenguane i 123 injection for intravenous use) is excreted into human milk. However, iodine 123 is excreted into human milk. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to interrupt nursing after administration of %medicine_name% (iobenguane i 123 injection for intravenous use) or not to administer %medicine_name% (iobenguane i 123 injection for intravenous use) , taking into account the importance of the drug to the mother. Based on the physical half-life of iodine 123 (13.2 hours) nursing women may consider interrupting nursing for 6 days after %medicine_name% (iobenguane i 123 injection for intravenous use) administration in order to minimize risks to nursing infants.

Pediatric Use

The safety and effectiveness of %medicine_name% (iobenguane i 123 injection for intravenous use) have been established in the age groups 1 month to 16 years. Safety and effectiveness in pediatric patients below the age of 1 month have not been established.

Geriatric Use

The %medicine_name% (iobenguane i 123 injection for intravenous use) clinical study did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly population should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

%medicine_name% (iobenguane i 123 injection for intravenous use) is excreted by the kidneys, and the risks of adverse reactions, increased radiation dose, and occurrence of falsely negative imaging results, may be greater in patients with severely impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and image interpretation. Consider assessment of renal function in elderly patients prior to %medicine_name% (iobenguane i 123 injection for intravenous use) administration..

SIDE EFFECTS

Clinical Study Experience

Serious adverse reactions were not observed in the %medicine_name% (iobenguane i 123 injection for intravenous use) clinical study. The data described below reflect %medicine_name% (iobenguane i 123 injection for intravenous use) exposure to 251 patients with known or suspected pheochromocytoma or neuroblastoma. The average ages were 49 years (range 17 – 88 years) for adults and, for pediatric patients, 4 years (range 1 month - 16 years). Slightly less than half the patients were male. All patients were monitored for adverse reactions over a 24 hour period following %medicine_name% (iobenguane i 123 injection for intravenous use) administration.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions were all mild to moderate in severity and were predominantly isolated occurrences ( ≤ 2 patients) of one of the following reactions: dizziness, rash, pruritus, flushing or injection site hemorrhage.

Postmarketing Experience

Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions have uncommonly been reported during the postmarketing use of %medicine_name%.

DRUG INTERACTIONS

The following drugs have the potential to decrease the uptake of norepinephrine and cause false negative imaging results: antihypertensives that deplete norepinephrine stores or inhibit reuptake (e.g., reserpine, labetalol), antidepressants that inhibit norepinephrine transporter function (e.g., amitriptyline and derivatives, imipramine and derivatives, selective serotonin reuptake inhibitors), sympathomimetic amines (e.g., phenylephrine, phenylpropanolamine, pseudoephedrine and ephedrine), and cocaine. Clinical studies have not determined which specific drugs may cause false negative imaging results nor whether all drugs in any specific pharmacologic class have the same potential to produce the negative imaging results. Increasing the dose of %medicine_name% (iobenguane i 123 injection for intravenous use) will not overcome any potential uptake limiting effect of these drugs. Before %medicine_name% (iobenguane i 123 injection for intravenous use) administration, discontinue (for at least 5 biological half-lives) drugs known or expected to reduce norepinephrine uptake, as clinically tolerated.

Pregnancy Category C: Any radiopharmaceutical, including %medicine_name% (iobenguane i 123 injection for intravenous use) , has a potential to cause fetal harm. It is not known whether %medicine_name% (iobenguane i 123 injection for intravenous use) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with %medicine_name% (iobenguane i 123 injection for intravenous use). %medicine_name% (iobenguane i 123 injection for intravenous use) should be given to a pregnant woman only if clearly needed.

Clinical Study Experience

Serious adverse reactions were not observed in the %medicine_name% (iobenguane i 123 injection for intravenous use) clinical study. The data described below reflect %medicine_name% (iobenguane i 123 injection for intravenous use) exposure to 251 patients with known or suspected pheochromocytoma or neuroblastoma. The average ages were 49 years (range 17 – 88 years) for adults and, for pediatric patients, 4 years (range 1 month - 16 years). Slightly less than half the patients were male. All patients were monitored for adverse reactions over a 24 hour period following %medicine_name% (iobenguane i 123 injection for intravenous use) administration.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions were all mild to moderate in severity and were predominantly isolated occurrences ( ≤ 2 patients) of one of the following reactions: dizziness, rash, pruritus, flushing or injection site hemorrhage.

Postmarketing Experience

Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions have uncommonly been reported during the postmarketing use of %medicine_name%.

The major manifestations of overdose relate predominantly to increased radiation exposure, with the long term risks for neoplasia.

%medicine_name% (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. To minimize radiation dose to the thyroid gland, this organ should be blocked before dosing. 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. The calculation of the estimated radiation dose is shown in Table 2.

Iobenguane is rapidly cleared from the blood and accumulates in adrenergically innervated tissues. 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. 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.