Kit for the Preparation of Technetium Tc 99m Mebrofenin

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

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. RADIATION DOSIMETRY The estimated absorbed radiation doses 1,2 to organs and tissues of an average subject (70 kg) from an intravenous injection of 370 MBq (10 millicuries) of Technetium Tc 99m Mebrofenin are shown in Table 4. TABLE 4 Estimated Absorbed Radiation Doses† Normal Subjects* Severely Jaundiced Patients** Tissue mGy/ 370 MBq rads/ 10 mCi mGy/ 370 MBq rads/ 10 mCi Total Body 2.0 0.2 1.7 0.17 Liver 4.7 0.47 8.1 0.81 Gallbladder Wall 13.7 1.37 12.5 1.25 Small Intestine 29.9 2.99 16.0 1.60 Upper Large Intestine Wall 47.4 4.74 24.8 2.48 Lower Large Intestine Wall 36.4 3.64 19.7 1.97 Kidney 2.2 0.22 1.9 0.19 Urinary Bladder Wall 2.9 0.29 24.2 2.42 Ovaries 10.1 1.01 6.4 0.64 Testes 0.5 0.05 1.1 0.11 Red Marrow 3.4 0.34 2.5 0.25 †Method of Calculation: (1) Loberg, M.D., Buddemeyer, E.V.: Application of pharmacokinetic modeling to the radiation dosimetry of hepatobiliary agents. In Third International Radiopharmaceutical Dosimetry Symposium, FDA No. 81-8166, U.S. Department of Health and Human Services, Public Health Service, FDA, Bureau of Radiological Health, Rockville, MD, (1981) pp. 318-332. (2) Values for S: "S", Absorbed Dose per Unit Cumulated Activity for Selected Radionuclides and Organs, MIRD Pamphlet No. 11 (1975). * Bilirubin <1.5 mg/dL Calculations assume that 98% of the injected activity is taken up by the liver; activity not removed in the urine in 24 hours is excreted in the intestines and no enterohepatic circulation of activity. ** Bilirubin >10 mg/dL (mean 21.8 mg/dL) Calculations assume that 66% of the injected activity is taken up by the liver; activity not removed in the urine in 24 hours is excreted in the intestines and no enterohepatic circulation of activity.

CONTRAINDICATIONS Hypersensitivity to this compound.

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

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.

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.