TECHNESCAN PYP

Drug Characteristics Technescan™ PYP™ (kit for the preparation of technetium Tc 99m pyrophosphate injection) is a radioactive diagnostic drug for intravenous use after radiolabeling with sodium pertechnetate Tc 99m injection or after reconstitution with 0.9% sodium chloride injection in conjunction with sodium pertechnetate Tc 99m injection. Each vial contains 11.9 mg sodium pyrophosphate, 3.2 mg (minimum) stannous chloride (SnCl 2 •2H 2 O), and 4.4 mg (maximum) total tin expressed as stannous chloride (SnCl 2 •2H 2 O). Prior to lyophilization, the pH is adjusted with hydrochloric acid. The pH of the reconstituted drug is between 4.5 and 7.5. No bacteriostatic preservative is present. The vial contains a sterile, non-pyrogenic, lyophilized powder packaged under nitrogen. The precise structures of the stannous-pyrophosphate and technetium Tc 99m pyrophosphate complexes are not known.

Technescan PYP, after radiolabeling with sodium pertechnetate Tc 99m, is indicated for: • Skeletal imaging to demonstrate areas of altered osteogenesis in adults • Cardiac imaging as an adjunct in the diagnosis of acute myocardial infarction in adults (See WARNINGS ) Technescan PYP, in conjunction with sodium pertechnetate Tc 99m injection for red blood cell (RBC) labeling, is indicated for gated cardiac blood pool imaging and for the detection of gastrointestinal bleeding sites in adults.

Radiation Safety – Drug Handling After radiolabeling of Technescan PYP, the reaction vial contains Technetium Tc 99m Pyrophosphate Injection. Handle Technetium Tc 99m Pyrophosphate Injection with appropriate safety measures to minimize radiation exposure. (See PRECAUTIONS, General .) Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Technetium Tc 99m Pyrophosphate Injection. Radiopharmaceuticals should be used by or under the control of healthcare providers 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 governmental agency authorized to license the use of radionuclides. Recommended Dosage, Administration, and Imaging Instructions for Skeletal and Cardiac Imaging Dosing and Administration Instructions The recommended activity of Technetium Tc 99m Pyrophosphate Injection for each type of imaging is presented in Table 4. Administer Technetium Tc 99m Pyrophosphate Injection intravenously over 10 seconds to 20 seconds. Measure the patient dose with a dose calibrator immediately before administration. If not contraindicated by patient’s condition, encourage patients to drink fluids before and after administration and void as often as possible to reduce unnecessary radiation exposure. For radiolabeling instructions, see Directions for Drug Preparation , Procedure for the Preparation of Technetium Tc 99m Pyrophosphate Injection. Table 4. Recommended Administered Activity of Technetium Tc 99m Pyrophosphate Injection for Skeletal and Cardiac Imaging in Adults Indication Activity of Technetium Tc 99m Pyrophosphate Fraction of Vial Contents Required for Pyrophosphate Skeletal Imaging 185 MBq to 555 MBq (5 mCi to 15 mCi) 0.07 to 0.91 Cardiac Imaging 370 MBq to 555 MBq (10 mCi to 15 mCi) 0.26 to 0.45 Skeletal Imaging Begin imaging 1 hour to 6 hours following administration. Cardiac Imaging The patient's cardiac condition should be stable before beginning the cardiac imaging procedure. Begin imaging 60 minutes to 90 minutes following administration. The acute myocardial infarct can be visualized from 24 hours to 9 days following onset of symptoms, with maximum localization at 48 to 72 hours. Cardiac imaging should be done with a gamma scintillation camera. It is recommended that images include anterior, left anterior oblique, and left lateral projections. Interference from chest wall lesions such as breast tumors and healing rib fractures can be minimized by employing the three recommended projections. Recommended Dosage, Administration, and Imaging Instructions for Gated Cardiac Blood Pool and Gastrointestinal Bleed Imaging Dose The recommended dose of Technescan PYP reconstituted in 0.9% sodium chloride injection for gated cardiac blood pool and gastrointestinal bleed imaging in adults is 1 mL, followed by 555 MBq to 740 MBq (15 mCi to 20 mCi) of sodium pertechnetate Tc 99m injection. Administration Instructions for In Vivo RBC Labeling Method a. Reconstitute Technescan PYP with 0.9% sodium chloride injection. (See Directions for Drug Preparation , Procedure for the Reconstitution of Technescan PYP.) b. Administer the patient dose of reconstituted Technescan PYP intravenously by direct venipuncture. Do not use heparinized catheters. (See WARNINGS .) c. Wait 15 minutes to 30 minutes. d. Administer sodium pertechnetate Tc 99m injection intravenously. Administration Instructions for Modified In Vivo/In Vitro RBC Labeling Method Using ACD a. Reconstitute Technescan PYP with 0.9% sodium chloride injection. (See Directions for Drug Preparation , Procedure for the Reconstitution of Technescan PYP.) b. Administer the patient dose of reconstituted Technescan PYP intravenously by direct venipuncture. Do not use heparinized catheters. (See WARNINGS .) c. Insert an intravenous line with a 3-way stopcock in a large peripheral vein and maintain the line with a continuous drip of 0.9% sodium chloride injection. d. 30 minutes post-injection: Clear the line by withdrawing and discarding approximately 5 mL of blood. Then draw approximately 5 mL of blood into a syringe containing 1 mL preservative-free acid-citrate-dextrose (ACD) and 555 MBq to 740 MBq (15 mCi to 20 mCi) of sodium pertechnetate Tc 99m injection. Turn the stopcock, flush the line, and adjust the flow of 0.9% sodium chloride injection. e. Gently rotate syringe to mix and incubate at room temperature for 10 minutes. f. Inject the mixture via the 3-way stopcock. Administration Instructions for Modified In Vivo/In Vitro RBC Labeling Method Using Heparin a. Reconstitute Technescan PYP with 0.9% sodium chloride injection. (See Directions for Drug Preparation , Procedure for the Reconstitution of Technescan PYP.) b. Administer the patient dose of reconstituted Technescan PYP intravenously by direct venipuncture. Do not use heparinized catheters. (See WARNINGS .) c. Insert an infusion set fitted with a 3-way stopcock in a large peripheral vein, and heparinize the intravenous line with 0.9% sodium chloride injection containing 5 units/mL to 10 units/mL of preservative-free heparin. d. Thirty minutes after Technescan PYP injection, draw 3 mL of blood into a syringe containing 555 MBq to 740 MBq (15 mCi to 20 mCi) of sodium pertechnetate Tc 99m injection. Anticoagulation of the blood is provided by residual heparin in the intravenous line. e. Gently rotate the syringe to mix and incubate at room temperature for 10 minutes. f. Inject the mixture via the 3-way stopcock. Gated Cardiac Blood Pool Imaging Begin cardiac imaging 10 minutes following the administration of sodium pertechnetate Tc 99m injection (in vivo method) or Tc 99m labeled red blood cells (modified in vivo/in vitro method) utilizing a scintillation camera interfaced to an electrocardiographic gating device. Gastrointestinal Bleed Imaging The imaging of gastrointestinal bleeding is dependent on factors such as the region of imaging, rate and volume of the bleed, efficacy of labeling of the red blood cells, and timeliness of imaging. Acquire sequential images over a period of time until a positive image is obtained or clinical conditions warrant the discontinuance of the procedure. The period of time for collecting the images may range up to 36 hours. Directions for Drug Preparation Procedural Precautions • The contents of the Technescan PYP reaction vial may be used for the preparation of Technetium Tc 99m Pyrophosphate Injection. Technescan PYP may also be reconstituted with preservative-free 0.9% sodium chloride injection and injected intravenously prior to labeling of red blood cells with sodium pertechnetate Tc 99m injection using either the in vivo or modified in vivo/in vitro method. • The components of the kit are sterile and non-pyrogenic. It is essential that the user follow the directions carefully and adhere to strict aseptic procedures during preparation. • Wear waterproof gloves during the entire preparation procedure and during subsequent patient dose withdrawals from the reaction vial. • Make all withdrawals and administration of sodium pertechnetate Tc 99m injection with an adequately shielded syringe. • Keep the prepared Technetium Tc 99m Pyrophosphate Injection in the lead shield described below (with cap in place) during the useful life of the radioactive preparation. Make all withdrawals and administration of the Technetium Tc 99m Pyrophosphate Injection with an adequately shielded syringe. • Any sodium pertechnetate Tc 99m injection that contains an oxidizing agent is not suitable for use in the preparation of Technetium Tc 99m Pyrophosphate Injection. Procedure for the Preparation of Technetium Tc 99m Pyrophosphate Injection 1. Remove a Technescan PYP reaction vial from the refrigerator and allow the vial contents to come to room temperature, 20°C to 25°C (68°F to 77°F), for approximately 5 minutes. 2. Attach the radioassay information label with radiation warning symbol to the reaction vial and place the vial in a lead Dispensing Shield fitted with a lead cap and having a minimum wall thickness of 1/8 inch. Do not remove the reaction vial from the Dispensing Shield, except temporarily, for Step 5 below. 3. Add 1 mL to 10 mL of sodium pertechnetate Tc 99m injection to the reaction vial. In choosing the amount of the sodium pertechnetate Tc 99m injection radioactivity to be used in the preparation of the Technetium Tc 99m Pyrophosphate Injection, the labeling efficiency, number of patients, administered radioactive dose, and radioactive decay must be taken into account. The recommended maximum activity of sodium pertechnetate Tc 99m injection to be added to the reaction vial is 3,700 MBq (100 mCi). 4. With the reaction vial in the Dispensing Shield (with cap in place), shake sufficiently to bring the lyophilized material into solution. Allow to stand for 5 minutes at room temperature. 5. Using proper shielding, visually inspect the reaction vial. The resulting solution should be clear and free of particulate matter. If not, do not use the product. 6. Assay the product in a suitable calibrator and record the time, date of preparation, and the activity of the Technetium Tc 99m Pyrophosphate Injection onto the radioassay information label. 7. Check the radiochemical purity prior to administration. 8. Store the reaction vial in the Dispensing Shield at 20°C to 25°C (68° to 77°F). Use within 6 hours of radiolabeling. 9. Dispose of unused drug in a safe manner in accordance with applicable regulations. Procedure for the Reconstitution of Technescan PYP a. Remove a Technescan PYP reaction vial from the refrigerator and allow the vial contents to come to room temperature, 20°C to 25°C (68°F to 77°F), for approximately 5 minutes. b. Add 3 mL of preservative-free 0.9% sodium chloride injection to the reaction vial. c. Shake the reaction vial sufficiently to bring the lyophilized material into solution. Allow to stand for 5 minutes at room temperature. d. Visually inspect the reaction vial. The resulting solution should be clear and free of particulate matter. If not, do not use the product. e. Store the reconstituted reaction vial upright at 20°C to 25°C (68°F to 77°F). Use within 6 hours of reconstitution. Radiation Dosimetry Skeletal and Cardiac Imaging Estimated absorbed radiation doses from an intravenous injection of Technetium Tc 99m Pyrophosphate Injection in adults are shown in Table 5. Table 5. Estimated Absorbed Radiation Doses in Organs and Tissues in Adults Who Received Technetium Tc 99m Pyrophosphate Injection Organ/Tissue Absorbed Dose per Unit Activity Administered (mGy/MBq) Skeleton* 0.010 Bone Marrow 0.008 Kidneys 0.038 Total Body 0.002 Bladder 2-hr. void 0.026 4.8-hr. void 0.062 Testes 2-hr. void 0.003 4.8-hr. void 0.004 Ovaries 2-hr. void 0.003 4.8-hr. void 0.004 Heart Normal 0.002 Impaired 0.004 *Dose at point of highest uptake may be a factor of 10 higher. Gated Cardiac Blood Pool and Gastrointestinal Bleed Imaging Estimated absorbed radiation doses from an intravenous administration of sodium pertechnetate Tc 99m injection, 30 minutes after the intravenous administration of Technescan PYP are shown in Table 6. Table 6. Estimated Absorbed Radiation Doses in Adults Who Received Sodium Pertechnetate Tc 99m Injection 30 minutes after Technescan PYP Administration* Organ/Tissue Absorbed Dose per Unit Activity Administered (mGy/MBq) Bladder Wall 0.009 Ovaries 0.006 Testes 0.004 Red Marrow 0.005 Spleen** 0.004 Blood 0.014 Total Body 0.004 *Assumes non-resting state, with 75% of the sodium pertechnetate Tc 99m labeling red blood cells and the other 25% remaining as pertechnetate. **Assumes no initial uptake in spleen.

None known.

The following adverse reactions associated with the use of Technescan PYP have been reported: flushing, hypotension, fever, chills, nausea, vomiting, and dizziness, as well as hypersensitivity reactions such as itching and various skin rashes.

The biodistribution of technetium Tc 99m pyrophosphate may be altered in the presence of high levels of certain cations (iron, calcium, and aluminum). This may result in reduced uptake of radionuclide in the skeleton and increased extraosseal uptake, which may potentially degrade imaging quality. In patients with high levels of these cations caused by concomitant medications, particularly patients receiving iron infusions, consider performing an imaging study with technetium Tc 99m pyrophosphate injection once the cation levels have normalized (e.g., after 3 to 5 half-lives of the cation). (See WARNINGS .)