Prescription Drug Information: Choletec

CHOLETEC- mebrofenin injection, powder, lyophilized, for solution
Bracco Diagnostics Inc

For Diagnostic Use

DESCRIPTION

Each reaction vial contains a nonradioactive, sterile, nonpyrogenic mixture of 45 mg mebrofenin, 0.54 mg (minimum) stannous fluoride dihydrate, SnF2 •2H2 O and 1.03 mg total tin, maximum (as stannous fluoride dihydrate, SnF2 •2H2 O), not more than 5.2 mg methylparaben, and 0.58 mg propylparaben. The pH is adjusted with sodium hydroxide or hydrochloric acid prior to lyophilization. The contents of the vial are lyophilized and sealed under nitrogen at the time of manufacture.

The pH of the reconstituted product is 4.2 to 5.7.

The structure of mebrofenin (2,2’-[[2-[(3-Bromo-2,4,6-trimethylphenyl)-amino]-2-oxoethyl]imino] bisacetic acid) is shown below:

Choletec-struct
(click image for full-size original)

When sterile, pyrogen-free sodium pertechnetate Tc 99m injection is added to the vial, the diagnostic agent Technetium Tc 99m Mebrofenin is formed for administration by intravenous injection.

PHYSICAL CHARACTERISTICS

Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours.1 The principal photon that is useful for detection and imaging studies is listed in Table 1.

TABLE 1
1 Kocher, David C., “Radioactive Decay Data Tables”, DOE/ TIC-11026, (1981) p.108.
Principal Radiation Emission Data
Radiation Mean % perDisintegration Mean Energy(keV)
Gamma-2 89.07 140.5

External Radiation

The specific gamma ray constant for Tc 99m is 0.78 R/hour-millicurie at 1 cm. The first half value layer is 0.017 cm of lead (Pb). A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 2. To facilitate control of the radiation exposure from millicurie amounts of this radionuclide, the use of a 0.25 cm thickness of Pb will attenuate the radiation emitted by a factor of about 1,000.

TABLE 2
Radiation Attenuation by Lead Shielding
Shield Thickness(Pb) cm Coefficientof Attenuation
0.017 0.5
0.08 10-1
0.16 10-2
0.25 10-3
0.33 10-4

To correct for physical decay of technetium Tc 99m, the fractions that remain at selected intervals after the time of calibration are shown in Table 3.

TABLE 3
*Calibration time
Physical Decay Chart: Tc 99m half-life 6.02 hours
Hours FractionRemaining Hours FractionRemaining
0* 1.000 7 0.447
1 0.891 8 0.398
2 0.794 9 0.355
3 0.708 10 0.316
4 0.631 11 0.282
5 0.562 12 0.251
6 0.501 18 0.126

CLINICAL PHARMACOLOGY

Mebrofenin is an iminodiacetic acid (HIDA) derivative with no known pharmacologic action at the recommended doses.

Following intravenous administration in normal subjects, Technetium Tc 99m Mebrofenin was rapidly cleared from the circulation. The mean percent injected dose remaining in the blood at 10 minutes was 17%. The injected activity was cleared through the hepatobiliary system with visualization of the liver by 5 minutes and maximum liver uptake occurring at 11 minutes post-injection. Hepatic duct and gallbladder visualization occurred by 10 to 15 minutes and intestinal activity was visualized by 30 to 60 minutes in subjects with normal hepatobiliary function. The mean percent injected dose excreted in the urine during the first 3 hours was 1% (0.4 to 2.0%).

Elevated serum bilirubin levels increase renal excretion of Tc 99m HIDA agents. In two studies in which Tc 99m Mebrofenin was administered to patients having mean elevated serum bilirubin levels of 9.8 mg/dL (1.7 to 46.3 mg/dL), the mean percent injected dose excreted in the urine during the first 3 hours was 3% (0.2 to 11.5%). The mean percent injected dose excreted in the urine during 3-24 hours was 14.9% (0.4 to 34.8%).

In jaundiced patients, the percent injected dose remaining in the blood at 10 minutes may be twice as high or more than the level in normals. Hepatobiliary transit may be delayed and visualization times increased. As a consequence, the quality of the images obtained frequently diminishes.

INDICATIONS AND USAGE

Technetium Tc 99m Mebrofenin is indicated as a hepatobiliary imaging agent.

CONTRAINDICATIONS

Hypersensitivity to this compound.

WARNINGS

The theoretical possibility of allergic reactions should be considered in patients who receive multiple doses.

PRECAUTIONS

General

Contents of the reaction vial are intended only for use in the preparation of Technetium Tc 99m Mebrofenin and are not to be administered directly to the patient.

Delayed or non-visualization of the gallbladder may occur in the immediate post-prandial period or after prolonged fasting or parenteral feeding. Functional biliary obstruction may accompany chronic cholecystitis or pancreatitis. In addition, patients with hepatocellular disease may show non-visualization or delayed visualization of the gallbladder. Delayed intestinal transit may also be noted in such patients. Juvenile hepatitis may be associated with gallbladder non-visualization and the failure to visualize activity in the intestine. Administration of meperidine or morphine may delay intestinal transit of the imaging agent and may result in nonvisualization. Septic patients may show absent or delayed hepatobiliary clearance. Thus, a positive finding does not of itself permit a differential diagnosis of any of the above conditions and should be evaluated in the light of the total clinical picture and results of other diagnostic modalities.

The components of the kit are supplied sterile and nonpyrogenic. Aseptic procedures normally employed in making additions and withdrawals from sterile, nonpyrogenic containers should be used during the addition of the pertechnetate solution and the withdrawal of doses for patient administration.

The Technetium Tc 99m labeling reactions involved in preparing the agent depend on maintaining the stannous ion in the reduced state. Any oxidant present in the sodium pertechnetate Tc 99m supply may, thus, adversely affect the quality of the radiopharmaceutical. Hence, sodium pertechnetate Tc 99m containing oxidants should not be employed.

Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides.

As in the use of any radioactive material, care should be taken to minimize radiation exposure to the patient consistent with proper patient management and to ensure minimum radiation exposure to occupational workers.

Tc 99m Mebrofenin should be formulated no more than 18 hours prior to clinical use.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long term animal studies have been performed to evaluate carcinogenic potential or whether Technetium Tc 99m Mebrofenin may affect fertility in males or females.

Pregnancy

Animal reproduction studies have not been conducted with Technetium Tc 99m Mebrofenin. It is also not known whether Technetium Tc 99m Mebrofenin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Technetium Tc 99m Mebrofenin should be given to a pregnant woman only if the expected benefits to be gained clearly outweigh the potential hazards.

Nursing Mothers

Technetium Tc 99m is excreted in human milk during lactation. Therefore, formula feedings should be substituted for breast feedings.

Pediatric Use

Safety and effectiveness in children below the age of 18 have not be established.

ADVERSE REACTIONS

Urticaria and rash have been rarely reported with the use of Technetium Tc 99m Mebrofenin since market introduction. Rare cases of chills and nausea have been reported with related compounds. Infrequently, death has been reported in association with the use of this class of agents.

DOSAGE AND ADMINISTRATION

The suggested intravenous dose range of Technetium Tc 99m Mebrofenin in the average patient (70 kg) is:

Nonjaundiced patient: 74-185 MBq (2-5 mCi)
Patient with serum bilirubin level greater than 1.5 mg/dL: 111-370 MBq (3-10 mCi)

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration.

The patient should be in a fasting state, 4 hours is preferable. False positives (non-visualization) may result if the gallbladder has been emptied by ingestion of food.

An interval of at least 24 hours should be allowed before repeat examination.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Page 1 of 2 1 2

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2024. All Rights Reserved.