CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Following intravenous injection of technetium Tc 99m mertiatide, the appearance, concentration, and excretion of the tracer in the kidney can be monitored to assess renal function. Although technetium Tc 99m mertiatide is highly plasma protein bound following intravenous injection, the protein binding is reversible and the tracer is rapidly excreted by the kidneys via active tubular secretion and glomerular filtration. Following intravenous injection of technetium Tc 99m mertiatide in normal volunteers, 89% of the tracer was plasma protein bound. In healthy subjects with normal renal function (mean serum creatinine 1.2 mg/dL) technetium Tc 99m mertiatide was rapidly cleared from the blood. The plasma clearance was approximately 0.3 liters/minute and the amount of technetium Tc 99m mertiatide excreted in the urine in three hours was nearly 90% of the dose. In study performed in three patients with renal impairment (serum creatinine greater than 6.3 mg/dL), there was decreased blood clearance and decrease in the amount excreted in the urine over three hours. In these patients, 78% of the tracer was plasma protein bound after intravenous injection. The mean plasma clearance of technetium Tc 99m mertiatide was 0.03 liters/minute and 21.3% was excreted in three hours on average. In both healthy subjects and patients with renal impairment, the plasma concentration-time profile showed biexponential decline.

DESCRIPTION SECTION.

DESCRIPTION. Kit for the Preparation of Technetium Tc99m Mertiatide is used for the preparation of technetium Tc 99m mertiatide, diagnostic radiopharmaceutical. It is supplied as sterile, nonpyrogenic, lyophilized powder. Each vial contains betiatide (N-[N-[N-[(benzoylthio) acetyl]glycyl]glycyl]-glycine). After reconstitution with sterile sodium pertechnetate Tc 99m injection, the technetium Tc 99m mertiatide (disodium[N-[N-[N-(mercaptoacetyl) glycyl]glycyl] glycinato (2-) N,N,N,S]oxotechnetate (2-)) which is formed is suitable for intravenous administration.Each 10 milliliter vial contains milligram betiatide, 0.05 milligram (minimum) stannous chloride dihydrate (SnCl22H2O) and 0.2 milligram (maximum) total tin expressed as stannous chloride dihydrate (SnCl22H2O), 40 milligrams sodium tartrate dihydrate (Na2C4H2O62H2O), and 20 milligrams lactose monohydrate. Prior to lyophilization, sodium hydroxide or hydrochloric acid may be added for pH adjustment. The pH of the reconstituted drug is between 5.0 and 6.0. No bacteriostatic preservative is present. The contents are sealed under argon. Betiatide is light sensitive and must be protected from light. Betiatide and technetium Tc 99m mertiatide have the following structural formulas:. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. The suggested dose range employed in the average adult patient (70kg) for renal function and imaging studies is 185 MBq (5 mCi) to 370 MBq (10 mCi). In pediatric patients the recommended dose range is 2.6 MBq/kg (70 uCi/kg) to 5.2 MBq/kg (140 uCi/kg) with minimum dose of 37 MBq (1 mCi).The patient dose should be measured by suitable radioactivity calibration system immediately prior to administration.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.Aseptic procedures and shielded syringe should be employed in withdrawing doses for administration to patients. The user should wear waterproof gloves during the administration procedure.

GENERAL PRECAUTIONS SECTION.

General. 1. The contents of this kit are not radioactive. However, after sodium pertechnetate Tc 99m is added, adequate shielding of the final preparation must be maintained.2. Contents of the reaction vial are intended only for use in the preparation of technetium Tc 99m mertiatide and are NOT to be administered directly to the patient.3. To help reduce the radiation dose to the bladder, as well as other target organs, the patient should increase his or her fluid intake (unless medically contraindicated) and void as often as possible after the injection of technetium Tc 99m mertiatide for six hours after the imaging procedure.4. Technetium Tc 99m mertiatide should not be used more than six hours after preparation.5. The components of the kit are sterile and nonpyrogenic. It is essential that the user follow the directions carefully and use aseptic procedures normally employed in making additions and withdrawals from sterile, nonpyrogenic containers during the addition of pertechnetate solution and the withdrawal of doses for patient administration.6. The technetium Tc 99m labeling reactions involved in preparing technetium Tc 99m mertiatide depend on maintaining the stannous ion in the reduced state. Any oxidant present in the sodium pertechnetate Tc 99m may adversely affect the quality of the radiopharmaceutical. Therefore, sodium pertechnetate Tc 99m containing oxidants should not be employed.7. As in the use of any other radioactive material, care should be taken to insure minimum radiation exposure to the patient and to occupational workers.8. Radiopharmaceuticals should be used only by physicians who are qualified by specific training in the safe use and handling of radionuclides.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Kit for the Preparation of Technetium Tc 99m Mertiatide is supplied as lyophilized powder packaged in vials. Each reaction vial contains mg betiatide, 0.05 mg (minimum) stannous chloride dihydrate (SnCl22H2O), 0.2 mg (maximum) total tin expressed as stannous chloride dihydrate (SnCl22H2O), 40 mg sodium tartrate dihydrate (Na2C4H2O62H2O), and 20 mg lactose monohydrate.The pH of the reconstituted drug is between 5.0 and 6.0. No bacteriostatic preservative is present.Packages containing reaction vials (NDC 45567-0655-1) are available.. STORAGE. Kit for the Preparation of Technetium Tc 99m Mertiatide should be stored at controlled room temperature 20C to 25C (68-77F) and protected from light until use. The reconstituted vial should be stored at room temperature (15C to 30C) and must be used within six hours of preparation.

PRECAUTIONS SECTION.

PRECAUTIONS. General. 1. The contents of this kit are not radioactive. However, after sodium pertechnetate Tc 99m is added, adequate shielding of the final preparation must be maintained.2. Contents of the reaction vial are intended only for use in the preparation of technetium Tc 99m mertiatide and are NOT to be administered directly to the patient.3. To help reduce the radiation dose to the bladder, as well as other target organs, the patient should increase his or her fluid intake (unless medically contraindicated) and void as often as possible after the injection of technetium Tc 99m mertiatide for six hours after the imaging procedure.4. Technetium Tc 99m mertiatide should not be used more than six hours after preparation.5. The components of the kit are sterile and nonpyrogenic. It is essential that the user follow the directions carefully and use aseptic procedures normally employed in making additions and withdrawals from sterile, nonpyrogenic containers during the addition of pertechnetate solution and the withdrawal of doses for patient administration.6. The technetium Tc 99m labeling reactions involved in preparing technetium Tc 99m mertiatide depend on maintaining the stannous ion in the reduced state. Any oxidant present in the sodium pertechnetate Tc 99m may adversely affect the quality of the radiopharmaceutical. Therefore, sodium pertechnetate Tc 99m containing oxidants should not be employed.7. As in the use of any other radioactive material, care should be taken to insure minimum radiation exposure to the patient and to occupational workers.8. Radiopharmaceuticals should be used only by physicians who are qualified by specific training in the safe use and handling of radionuclides.. Carcinogenesis, Mutagenesis, Impairment of Fertility. No long term animal studies have been performed to evaluate carcinogenic or mutagenic potential, or whether this drug affects fertility in males or females.. Pregnancy. Pregnancy Category C. Animal reproduction studies have not been conducted with technetium Tc 99m mertiatide. It is also not known whether this drug can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. Technetium Tc 99m mertiatide should be given to pregnant woman only if clearly needed.. Nursing Mothers. Technetium Tc 99m is excreted in human milk during lactation, therefore, formula feedings should be substituted for breast feeding.. Pediatric Use. Safety and effectiveness in pediatric patients under the age of 30 days have not been established.