DRAXIMAGE DTPA

1 INDICATIONS AND USAGE DRAXIMAGE ® DTPA, after radiolabeling with Technetium Tc 99m, is indicated for DRAXIMAGE ® DTPA is a kit for the preparation of Technetium Tc 99m pentetate injection. Technetium Tc 99m pentetate is a radioactive diagnostic agent indicated for: Brain imaging in adults ( 1.1 ). Renal visualization, assessment of renal perfusion, and estimation of glomerular filtration rate in adult and pediatric patients ( 1.2 ). Lung ventilation imaging and evaluation of pulmonary embolism when paired with perfusion imaging in adult and pediatric patients ( 1.3 ). 1.1 Brain Imaging Brain imaging in adults by intravenous administration. 1.2 Renal Scintigraphy Renal visualization, assessment of renal perfusion, and estimation of glomerular filtration rate in adult and pediatric patients by intravenous administration. 1.3 Lung Ventilation Imaging Lung ventilation imaging and evaluation of pulmonary embolism when paired with perfusion imaging in adult and pediatric patients when administered by nebulizer for inhalation.

2 DOSAGE AND ADMINISTRATION During preparation and handling, use water proof gloves and effective shielding, to minimize radiation exposure ( 2.1 , 5.3 ). See the Full Prescribing Information for detailed information regarding recommended Dosage and Image Acquisition Instructions ( 2.2 ) and Instructions for Drug Preparation ( 2.4 ). Do not administer more than one dose ( 2.2 ). 2.1 Radiation Safety – Drug Handling Tc 99m labeled DRAXIMAGE ® DTPA injection is a radioactive drug and should be handled with appropriate safety measures to minimize radiation exposure to the patient and healthcare worker. During preparation and handling, use water proof gloves and effective shielding, including syringe shields [see Warnings and Precautions ( 5.3 )] . 2.2 Recommended Dosage and Image Acquisition Instructions The recommended dose ranges for intravenous or inhalation administration of DRAXIMAGE® DTPA, after reconstitution, are presented in Table 1 through Table 3. Do not administer more than one dose. Table 1 Tc 99m Labeled DRAXIMAGE ® DTPA Injection – Intravenous Administration, Adults Indication Route of Administration Dose Image Acquisition Brain Imaging Intravenous Injection 370 MBq to 740 MBq (10 mCi to 20 mCi) Immediate dynamic imaging. Obtain at least one blood-pool image in same position as flow. Delayed images can be obtained 1 hour later. Renal Visualization and Perfusion Assessment Intravenous Injection 370 MBq to 740 MBq (10 mCi to 20 mCi) Immediate dynamic imaging. Static imaging 1 to 30 minutes after injection. Renal Visualization with Estimation of Glomerular Filtration Rate Intravenous Injection 111 MBq to 185 MBq (3 mCi to 5 mCi) Immediate dynamic imaging. Static imaging 1 to 30 minutes after injection. Estimation of Glomerular Filtration Rate (with no renal imaging) Intravenous Injection 7.4 MBq to 18.5 MBq (0.2 mCi to 0.5 mCi) Blood sampling only is performed. Table 2 Tc 99m Labeled DRAXIMAGE ® DTPA Injection – Intravenous Administration, Pediatric Patients Indication Route of Administration Dose Image Acquisition Renal Visualization and Perfusion Assessment Intravenous Injection 3.7 MBq/kg to 7.4 MBq/kg (0.1 mCi/kg to 0.2 mCi/kg) Minimum 37 MBq (1 mCi) Maximum 185 MBq (5 mCi) Immediate dynamic imaging. Static imaging 1 to 30 minutes after injection. Estimation of Glomerular Filtration Rate (with no renal imaging) Intravenous Injection 7.4 MBq to 18.5 MBq (0.2 mCi to 0.5 mCi) Blood sampling only is performed. Table 3 Tc 99m Labeled DRAXIMAGE ® DTPA – Aerosol Inhalation Administration * For lung imaging performed after perfusion imaging, target count rate should be approximately three times that of perfusion count rate. Indication Route of Administration Dose Image Acquisition Lung Ventilation Adults Aerosol Inhalation 925 MBq to 1850 MBq (25 mCi to 50 mCi) in the nebulizer to achieve a lung dose of approximately 18.5 MBq to 37 MBq (0.5 mCi to 1.0 mCi) For lung imaging performed prior to perfusion imaging, the target administered dose to the lungs is achieved after 3 to 5 minutes of inhalation or at an imaging count rate of 50,000 to 100,000 per minute * . Lung Ventilation Pediatric Patients Aerosol Inhalation 925 MBq (25 mCi) in the nebulizer to achieve a lung dose of approximately 18.5 MBq (0.5 mCi) For lung imaging performed prior to perfusion imaging, the target administered dose to the lungs is achieved at an imaging count rate of approximately 10,000 to 50,000 per minute * . 2.3 Administration Instructions Use aseptic technique for all drug preparation and handling. Visually inspect the Tc 99m labeled DRAXIMAGE ® DTPA injection after reconstitution for particulate matter prior to administration. Do not use or administer if there is evidence of foreign matter or the solution is not clear. Measure the patient dose by a radioactivity calibration system immediately prior to administration. Intravenous Use Instruct the patient to increase fluid intake and to void frequently for the next 4 to 6 hours after Tc 99m labeled DRAXIMAGE ® DTPA administration by injection to minimize the radiation dose to the bladder. Inhalation Use Use the selected nebulizer in accordance with the manufacturer’s instructions. Instruct the patient to rinse their mouth and expectorate after Tc 99m labeled DRAXIMAGE ® DTPA administration by inhalation to minimize the radiation dose to the mouth and esophagus. 2.4 Instructions for Drug Preparation The prepared solution can either be administered via intravenous injection or aerosolized by nebulizer for inhalation use. Before reconstitution, inspect the integrity of the vial. Add 2 to 10 mL [maximum amount 18.5 gigabecquerels (500 mCi)] of sodium pertechnetate Tc 99m injection USP to the reaction vial. The volume of pertechnetate added should be balanced by the removal of the same volume of air. Cover the vial shield and invert to mix the contents. Assay the preparation in a calibrator, record the radio assay information on the label with radiation warning symbol, and affix it to the reaction vial. After reconstitution, store the solution at 25 °C (77 °F) in a lead shield and discard after 12 hours; excursions permitted between 15 °C and 30 °C (59 °F and 86°F). Allow the preparation to stand for 15 minutes before determining the radiochemical purity of Tc 99m labeled DRAXIMAGE ® DTPA injection. After reconstitution, do not vent the vial. 2.5 Determination of Radiochemical Purity Obtain the following: Two ITLC-SG (1 x 10 cm) 0.9% Sodium Chloride Injection USP (for determination of reduced hydrolyzed technetium) Acetone (for determination of free pertechnetate) Two glass test tubes (18 mm x 150 mm) with stoppers Step 1: System A : Add 1 mL of 0.9% Sodium Chloride Injection USP in an 18 mm x 150 mm test tube. Place the stopper and allow the atmosphere in the tube to equilibrate for 1 minute. System B : Repeat with Acetone in a separate test tube. Step 2: Mark each chromatographic strip with a pencil mark 1.5 cm (see Figure 1 and Figure 2 ) from one end of the strip (mark as origin). Place one drop (approximately 0.01 to 0.02 mL) of the Technetium Tc 99m pentetate injection at the origin. For System A (saline), do not allow the strip to dry. For System B (acetone), dry the strip using a gentle stream of nitrogen gas. Step 3: Place each strip with the origin end towards the bottom of the previously equilibrated test tube to develop (the origin must be above the surface of the solvent). Place stopper in the test tube and keep upright. Step 4: When the solvent front has reached the top of the strip, remove the strip with forceps and allow it to dry. Step 5: System A – Determination of reduced hydrolyzed technetium: In System A (saline), reduced hydrolyzed technetium ( 99m TcO 2 ) stays at the origin (R f 0 to 0.1), while the bound technetium and free pertechnetate ( 99m TcO 4 – ) migrates to the solvent front (R f 0.85 to 1.0). Cut the dried strip 3 cm from the origin. The short piece is marked as Part I and the long piece is marked as Part II . Count the pieces in a counter and determine the percentage of reduced hydrolyzed technetium according to the following formula: Figure 1 System A Diagram System B – Determination of free pertechnetate: In System B (acetone), the bound technetium ( 99m Tc) and reduced hydrolyzed technetium ( 99m TcO 2 ) stay at the origin (R f 0 to 0.1), while free pertechnetate ( 99m TcO 4 – ) migrates to the solvent front (R f 0.85 to 1.0). Cut the dried strip 2 cm from the solvent front end. The short piece is marked Part III and the long piece is marked Part IV . Count the pieces in a counter and determine the percentage of free pertechnetate according to the following formula: Figure 2 System B Diagram Step 6: Determine the radiochemical purity according to the following formula: Use Technetium Tc 99m pentetate injection only if the radiochemical purity is 90% or greater. eq1 Figure_1 eq2 figure2 step-6-formula 2.6 Radiation Dosimetry The estimated radiation absorbed dose to various organs from an intravenous injection of Tc 99m pentetate in patients with normal and abnormal renal function is shown respectively in Table 4 and Table 5 . Table 4 Estimated Radiation Absorbed Dose for Technetium Tc 99m Pentetate Injection in Patients With Normal Renal Function Following Intravenous Injection Absorbed Dose Per Unit Activity Administered (microGy/MBq) Organ Adult 15 Years 10 Years 5 Years 1 Year Adrenals 1.4 1.8 2.7 4.0 7.2 Bone surfaces 2.4 2.9 4.3 6.1 10 Brain 0.86 1.1 1.7 2.8 4.9 Breast 0.72 0.92 1.3 2.2 4.1 Gallbladder wall 1.5 2.1 3.8 5.0 6.1 Gastrointestinal tract Esophagus 1.0 1.3 1.9 3.0 5.4 Stomach wall 1.3 1.7 2.8 4.0 6.8 Small intestine wall 2.5 3.1 4.9 7.0 10 Colon wall 3.1 3.9 6.0 8.1 11 Upper large intestine wall 2.1 2.8 4.3 6.5 9.2 Lower large intestine wall 4.3 5.4 8.2 10 13 Heart wall 1.2 1.5 2.2 3.3 5.9 Kidneys 4.4 5.3 7.5 11 18 Liver 1.2 1.6 2.5 3.8 6.4 Lungs 1.0 1.3 2.0 3.0 5.5 Muscles 1.6 2.0 3.0 4.3 6.8 Ovaries 4.2 5.3 7.7 10 13 Pancreas 1.4 1.8 2.8 4.3 7.4 Red marrow 1.5 1.8 2.7 3.7 5.7 Skin 0.87 1.0 1.7 2.6 4.4 Spleen 1.3 1.6 2.6 3.9 6.8 Testes 2.9 4.0 6.8 9.4 13 Thymus 1.0 1.3 1.9 3.0 5.4 Thyroid 1.0 1.3 2.1 3.3 6.0 Urinary bladder wall 62 78 110 150 170 Uterus 7.9 9.6 15 18 22 Remaining organs 1.7 2.1 3.0 4.2 6.6 Effective dose per unit activity (microSv/MBq) 4.9 6.3 9.4 12 16 Table 5 Estimated Radiation Absorbed Dose for Technetium Tc 99m Pentetate Injection in Patients With Abnormal Renal Function Following Intravenous Injection Absorbed Dose Per Unit Activity Administered (microGy/MBq) Organ Adult 15 Years 10 Years 5 Years 1 Year Adrenals 4.1 5.1 7.6 11 21 Bone surfaces 6.0 7.1 11 15 28 Brain 2.8 3.5 5.7 9.1 16 Breast 2.3 3.0 4.2 6.8 13 Gallbladder wall 4.2 5.7 9.2 13 16 Gastrointestinal tract Esophagus 3.3 4.2 6.2 9.6 17 Stomach wall 3.8 5.0 7.9 11 19 Small intestine wall 4.5 5.6 8.5 13 22 Colon wall 4.5 5.8 8.7 13 22 Upper large intestine wall 4.3 5.6 8.1 13 21 Lower large intestine wall 4.9 6.1 9.5 13 23 Heart wall 3.7 4.7 7.0 10 18 Kidneys 7.7 9.2 13 19 32 Liver 3.7 4.6 7.1 11 19 Lungs 3.3 4.2 6.2 9.5 17 Muscles 3.2 4.0 6.1 9.1 17 Ovaries 5.0 6.2 9.2 14 23 Pancreas 4.3 5.3 8.0 12 21 Red marrow 3.4 4.2 6.4 9.3 16 Skin 2.2 2.6 4.2 6.7 12 Spleen 3.8 4.7 7.3 11 19 Testes 3.5 4.5 6.9 10 18 Thymus 3.3 4.2 6.2 9.6 17 Thyroid 3.4 4.2 6.7 11 19 Urinary bladder wall 21 27 39 50 66 Uterus 6.1 7.4 11 16 25 Remaining organs 3.3 4.1 6.3 9.7 17 Effective dose per unit activity (microSv/MBq) 4.6 5.8 8.7 13 21 The estimated radiation absorbed dose to various organs from the inhalation of Tc 99m Pentetate Injection is shown in Table 6 . Table 6 Estimated Radiation Absorbed Dose for Technetium Tc 99m Pentetate Injection Administered by Inhalation Absorbed Dose Per Unit Activity Administered (microGy/MBq) Organ Adult 15 Years 10 Years 5 Years 1 Year Adrenals 2.1 2.9 4.4 6.7 12 Bone surfaces 1.9 2.4 3.5 5.3 9.8 Breast 1.9 1.9 3.3 4.8 7.8 Gastrointestinal tract Stomach wall 1.7 2.2 3.5 5.1 8.9 Small intestine wall 2.1 2.6 4.1 6.3 11 Upper large intestine wall 1.9 2.4 3.8 6.1 10 Lower large intestine wall 3.2 4.2 6.3 8.8 15 Kidneys 4.1 5.1 7.2 11 19 Liver 1.9 2.5 3.7 5.5 9.7 Lungs 17 26 36 54 100 Ovaries 3.3 4.1 6.1 8.9 15 Pancreas 2.1 2.6 4.0 6.1 11 Red marrow 2.7 3.4 4.7 6.2 9.6 Spleen 1.9 2.4 3.6 5.6 9.9 Testes 2.1 3.1 5.2 7.9 15 Thyroid 0.99 1.7 2.7 4.4 7.8 Urinary bladder wall 47 58 84 120 230 Uterus 5.9 7.2 11 16 27 Other tissue 1.8 2.2 3.2 4.9 8.6 Effective dose per unit activity (microSv/MBq) 5.9 8.0 11 17 31

4 CONTRAINDICATIONS Hypersensitivity to the active ingredient or to any component of the product [see Warnings and Precautions ( 5.1 )]. Hypersensitivity to the active ingredient or any component of this product ( 4 ).

5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported during post-approval diagnostic use of Technetium Tc 99m pentetate injection. Monitor all patients for hypersensitivity reactions ( 5.1 ). Image interpretation risks in lung ventilation studies: If proximal airway deposition is observed, consider additional diagnostic options ( 5.2 ). Radiation exposure risk: Technetium Tc 99m pentetate contributes to a patient’s overall long-term radiation exposure ( 2.1 , 2.3 , 5.3 ). Bronchospasm in lung ventilation studies: Inhalation of Technetium Tc 99m pentetate solution may result in acute bronchoconstriction, especially in patients with heightened bronchoreactivity ( 5.4 ). 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported during post-approval diagnostic use of Technetium Tc 99m pentetate injection. Monitor all patients for hypersensitivity reactions and have access to cardiopulmonary resuscitation equipment and personnel. 5.2 Image Interpretation Risks in Lung Ventilation Studies In patients with obstructive pulmonary disease there may be deposition of particles in the proximal airways influencing image quality and interfering with diagnostic interpretation, therefore to ensure diagnostic quality, careful use of the nebulizer to assure optimal particle delivery is essential. If interfering particle deposition occurs, consider additional diagnostic options. 5.3 Radiation Exposure Risk Technetium Tc 99m contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Use the lowest dose of Technetium Tc 99m pentetate necessary for imaging. Encourage patients to drink fluids and void as frequently as possible after intravenous administration [see Dosage and Administration ( 2.1 , 2.3 )] . Radiation risks associated with the use of Technetium Tc 99m pentetate are greater in pediatric patients than in adults due to greater radiosensitivity and longer life expectancy. 5.4 Bronchospasm in Lung Ventilation Studies As with other inhaled medications, inhalation of Technetium Tc 99m pentetate solution may result in acute bronchoconstriction, especially in patients with heightened bronchoreactivity, such as patients with asthma or other lung or allergic disorders. Monitor all patients for bronchoconstriction.

6 ADVERSE REACTIONS The following adverse reactions have been identified post-approval. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their exact frequency or establish a causal relationship to Technetium Tc 99m pentetate exposure. Adverse reactions are presented in decreasing order of reported frequency: Immune system disorders: allergic reaction, anaphylactic reaction, angioedema. Skin and subcutaneous tissue disorders: rash, itching, hives, erythema. Respiratory, thoracic and mediastinal disorders: throat irritation, wheezing. Vascular disorders: hypotension, hypertension. Nervous system disorders: headache, fainting, dizziness. General disorders and administration site conditions: chills. Gastrointestinal disorders: nausea, vomiting. Cardiac disorders: cyanosis, tachycardia. Most common adverse reactions reported with Technetium Tc 99m pentetate injection include allergic reactions, rash, itching ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Jubilant DraxImage Inc. at 1-888-633-5343 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8.1 Pregnancy Risk Summary Limited available data with Technetium Tc 99m pentetate use in pregnant women are insufficient to inform a drug associated risk for major birth defects and miscarriage. Technetium Tc 99m pentetate is transferred across the placenta (see Data ) . No animal reproductive studies have been conducted with Technetium Tc 99m pentetate. All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering Technetium Tc 99m pentetate administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from Technetium Tc 99m pentetate and the gestational timing of exposure. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S., general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Human Data Limited published literature describes Technetium Tc 99m pentetate crossing the placental barrier. No adverse fetal effects or radiation-related risks have been identified for diagnostic procedures involving less than 50 mGy, which represents less than 10 mGy fetal doses.