DRAXIMAGE MAA

11.1 Product Characteristics DRAXIMAGE MAA contains albumin aggregated obtained by fractionating material (source blood, plasma, serum, or placentas) from healthy human donors. The macroaggregated albumin (MAA) particles are formed by denaturation of albumin human in a heating and aggregation process. Each vial contains 3,000,000 to 8,000,000 particles. By light microscopy, more than 90% of the particles are between 10 and 70 micrometers, while the typical average size is 20 to 40 micrometers; none is greater than 150 micrometers. DRAXIMAGE MAA (kit for the preparation of technetium Tc 99m albumin aggregated) injection provides a sterile, non-pyrogenic, non-radioactive, white lyophilized powder supplied in a multiple-dose reaction vial, sealed under an atmosphere of nitrogen, for radiolabeling with Sodium Pertechnetate Tc 99m Injection to prepare Technetium Tc 99m Albumin Aggregated Injection, a radioactive diagnostic agent, for intravenous or intraperitoneal use. Each reaction vial contains 2.5 mg of albumin aggregated, albumin human (5 mg), stannous chloride (0.06 mg minimum; 0.11 mg maximum stannous and stannic chloride) and sodium chloride (1.2 mg). Sodium hydroxide or hydrochloric acid has been added for pH adjustment. The pH is 5.2 to 6. It contains no preservative. 11.2 Physical Characteristics Technetium-99m decays by isomeric transition with a physical half-life of 6.02 hours. The principal photon that is useful for detection and imaging studies is listed in Table 5. Table 5. Principal Radiation Emission Data for Technetium-99m Radiation Mean % per Disintegration Mean Energy (keV) Gamma 89.07 140.5 11.3 External Radiation The specific gamma ray constant for technetium-99m is 0.78 R/mCi-hr 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 resulting from the interposition of various thicknesses of lead is shown in Table 6. For example, the use of 0.25 cm thickness of lead will attenuate the radiation emitted by a factor of about 1,000. Table 6. Radiation Attenuation by Lead Shielding Shield Thickness (Pb) cm Coefficient of 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 this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 7. Table 7. Physical Decay Chart for Technetium-99m, half-life 6.02 hours Hours Fraction Remaining Hours Fraction Remaining 0* 1.000 5 0.562 1 0.891 6 0.501 2 0.794 8 0.398 3 0.708 10 0.316 4 0.631 12 0.251 *Calibration time

DRAXIMAGE MAA, after radiolabeling with sodium pertechnetate Tc 99m, is indicated for: Lung scintigraphy as an adjunct in the evaluation of pulmonary perfusion in adults and pediatric patients. Peritoneovenous shunt scintigraphy as an aid in the evaluation of its patency in adult patients. DRAXIMAGE MAA, after radiolabeling with sodium pertechnetate Tc 99m, is a radioactive diagnostic agent indicated for: Lung scintigraphy as an adjunct in the evaluation of pulmonary perfusion in adults and pediatric patients. (1) Peritoneovenous shunt scintigraphy as an aid in the evaluation of its patency in adults. (1)

For lung scintigraphy, the following recommended activity is administered by intravenous injection: Adults: 37 MBq to 148 MBq (1 mCi to 4 mCi); 200,000 particles to 700,000 particles. (2.3) Pediatric patients aged 4 weeks and older : 0.925 MBq/kg to 1.85 MBq/kg of body weight (0.025 mCi/kg to 0.05 mCi/kg); The minimum activity is 7.4 MBq (0.2 mCi). The number of particles will vary with age and body weight of the pediatric patient. (2.3) Pediatric patients aged less than 4 weeks : 7.4 MBq to 18.5 MBq (0.2 mCi to 0.5 mCi); 10,000 particles to 50,000 particles. (2.3) For scintigraphy of peritoneovenous shunts in adults: 37 MBq to 111 MBq (1 mCi to 3 mCi); 200,000 particles to 700,000 particles by intraperitoneal injection. (2.4) See Full Prescribing Information for radiation safety, patient preparation, drug preparation, administration, imaging, and radiation dosimetry information. (2.1 , 2.2 , 2.5 , 2.6 , 2.7) 2.1 Radiation Safety – Drug Handling After radiolabeling of DRAXIMAGE MAA, the vial contains Technetium Tc 99m Albumin Aggregated Injection. Handle Technetium Tc 99m Albumin Aggregated Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5.4)]. Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Technetium Tc 99m Albumin Aggregated 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. 2.2 Patient Preparation Instruct patients to drink a sufficient amount of water to ensure adequate hydration prior to administration of Technetium Tc 99m Albumin Aggregated Injection and to continue to drink and void frequently following administration to reduce radiation exposure [see Warnings and Precautions (5.4)]. 2.3 Recommended Dosage for Lung Perfusion Scintigraphy Adult Patients The recommended activity for lung perfusion scintigraphy in adult patients is 37 MBq to 148 MBq (1 mCi to 4 mCi) by intravenous injection. The number of particles per single injection should be 200,000 to 700,000 with the recommended number being approximately 350,000. Depending on the activity added and volume of the final radiolabeled product, the volume of the dose may vary from 0.2 mL to 1.9 mL. The number of particles available per dose of Technetium Tc 99m Albumin Aggregated Injection will vary depending on the physical decay of the technetium-99m that has occurred. The number of particles in any dose and volume to be administered may be calculated as follows: V a = D and P = V a x N C x F r V Tc Where: V a = Volume to be administered in mL D = Desired activity to be administered in MBq (mCi) C = Concentration at calibration time of Sodium Pertechnetate Tc 99m Injection to be added to the reaction vial in MBq/mL (mCi/mL) F r = Fraction of technetium-99m remaining after the time of calibration from Table 7 [see Description (11.3)] P = Number of particles in dose to be administered V a = Volume to be administered in mL V Tc = Volume of Sodium Pertechnetate Tc 99m Injection added to reaction vial in mL N = Number of particles per vial. The number of particles per vial for each lot is shipped with the product. Pediatric Patients Aged 4 Weeks and Older The recommended activity for lung perfusion scintigraphy in pediatric patients aged 4 weeks and older by intravenous injection is based on body weight and ranges from 0.925 MBq/kg to 1.85 MBq/kg (0.025 mCi/kg to 0.05 mCi/kg). The minimum recommended activity for lung perfusion scintigraphy in this age group is 7.4 MBq (0.2 mCi). The number of particles will vary with age and body weight of the pediatric patient. Particle numbers administered in four different age and weight categories are provided in Table 1. Table 1. Particle Numbers Administered in Four Different Age and Weight Categories of Pediatric Patients Receiving Maximum Recommended Activity of Technetium Tc 99m Albumin Aggregated Injection for Lung Perfusion Scintigraphy Age 15 years 10 years 5 years 1 year Weight (kg) 55 33.5 20.3 12.1 Maximum recommended activity MBq mCi MBq mCi MBq mCi MBq mCi 103.6 2.8 62.9 1.7 37 1 22.2 0.6 Range of particles administered 200,000 to 700,000 200,000 to 300,000 200,000 to 300,000 50,000 to 150,000 Pediatric Patients Aged Less Than 4 Weeks (Neonates) The recommended activity for lung perfusion scintigraphy in neonates by intravenous injection is 7.4 MBq to 18.5 MBq (0.2 mCi to 0.5 mCi). The number of particles in neonates for lung perfusion scintigraphy ranges from 10,000 to 50,000. Use the lowest possible number of particles for neonates. 2.4 Recommended Dosage for Peritoneovenous Shunt Scintigraphy in Adults The recommended activity for peritoneovenous shunt scintigraphy in adult patients is 37 MBq to 111 MBq (1 mCi to 3 mCi) by intraperitoneal injection. The number of particles per single injection should be 200,000 to 700,000 with the recommended number being approximately 350,000. Depending on the activity added and volume of the final radiolabeled product, the volume of the dose may vary from 0.2 mL to 1.9 mL. For calculation of the number of particles to be administered, see Recommended Dosage for Lung Perfusion Scintigraphy in Adult Patients [see Dosage and Administration (2.3)] . Assure uniform mixing with peritoneal fluid. Alternatively, administer the drug by percutaneous transtubal injection. The recommended activity for percutaneous transtubal (efferent limb) administration in adult patients is 12 MBq to 37 MBq (0.3 mCi to 1 mCi) in a volume not to exceed 0.5 mL. 2.5 Directions for Drug Preparation and Handling Procedural Precautions Before radiolabeling, the contents of the kit are not radioactive. Contents of the vials are intended only for use in the preparation of Technetium Tc 99m Albumin Aggregated Injection and are NOT to be administered directly to the patient. After the Sodium Pertechnetate Tc 99m Injection is added, maintain adequate shielding of the radiolabeled product. Use aseptic procedures throughout and take precautions to minimize radiation exposure by use of suitable shielding. Wear waterproof gloves during the preparation procedure. Before radiolabeling a vial, inspect the vial for cracks and/or a melted plug or any other indication that the integrity of the vacuum seal has been lost. Use only oxidant-free Sodium Pertechnetate Tc 99m Injection to maintain the stannous ion in the reduced state. Procedure for the Preparation of Technetium Tc 99m Albumin Aggregated Injection Remove the protective cap from a reaction vial and swab the rubber septum with either an alcohol swab or a suitable bacteriostatic agent to disinfect the surface. Place the vial in a suitable lead vial shield which has a fitted cap. The maximum activity of Sodium Pertechnetate Tc 99m Injection to be added to a reaction vial varies with the number of particles per vial and is shown in Table 2. The number of particles per vial for each lot is shipped with the product. Calculate the amount of radioactivity per vial required to maintain the number of particles per dose within a recommended range while taking into account administered activity, radioactive decay and the number of patients [see Dosage and Administration (2.3, 2.4)]. Other calculations for radiolabeling are permitted provided that the patient dose remains within the recommended range. Table 2. Maximum Activity of Sodium Pertechnetate Tc 99m Injection to be Added Based on Vial Particle Number Particles per vial Maximum Activity of Sodium Pertechnetate Tc 99m Injection to be added per vial 3 million to 4 million 3.7 GBq (100 mCi) 5 million 4.44 GBq (120 mCi) 6 million to 8 million 6.85 GBq (185 mCi) Using a shielded syringe, add the calculated amount of Sodium Pertechnetate Tc 99m Injection to the reaction vial aseptically. Place the lead cap on the vial shield and mix the contents of the shielded vial by repeated gentle inversion until all the material is suspended. Do not shake to avoid formation of foam. To ensure maximum tagging, allow the preparation to stand for 15 minutes after mixing. Using proper shielding, visually inspect the vial to ensure that the suspension is free of foreign matter before proceeding. Do not administer if foreign particulates are found in the preparation. Assay the product in a suitable dose calibrator, record the radioassay information on the label with radiation warning symbol, and attach it to the vial shield. No less than 90% of the sodium pertechnetate Tc 99m added to the reaction vial is bound to albumin aggregated at the time of preparation and remain bound throughout the usage lifetime of the preparation. Storage and Handling of Technetium Tc 99m Albumin Aggregated Injection Store the radiolabeled product in the lead vial shield with cap in place during its in-use shelf life. Store the radiolabeled product refrigerated at 2 ºC to 8 ºC (36 ºF to 46 ºF) when not in use and use within 12 hours from the time of radiolabeling depending on the number of particles per vial, the activity added at radiolabeling and the final dose to be administered to the patient [see Dosage and Administration (2.3, 2.4)] . Technetium Tc 99m Albumin Aggregated Injection is physically unstable and consequently the particles settle with time. Failure to agitate the vial adequately before administration may result in non-uniform distribution of radioactive particles. Do not use if clumping of the contents is observed. Since the vials are sealed under an atmosphere of nitrogen to prevent oxidation of the complex, do not vent the vials. If repeated withdrawals are made from the vial, minimize replacement of the contents with air. Dispose unused Technetium Tc 99m Albumin Aggregated Injection in compliance with appropriate regulations. 2.6 Administration and Imaging Instructions Position the patient under the imaging apparatus before administration of Technetium Tc 99m Albumin Aggregated Injection because of rapid lung clearance of technetium Tc 99m albumin aggregated. Using proper shielding, visually inspect for foreign particulate matter and discoloration prior to administration. Do not administer if foreign particulates are found in the preparation. Mix the contents of the vial by gentle inversion just prior to withdrawing a patient dose. Withdraw the patient dose aseptically using a sterile needle (18 gauge to 21 gauge) and a shielded syringe. Measure the patient dose by a suitable radioactivity calibration system immediately prior to administration. Mix the contents of the syringe just before injection. Slow injection is recommended. If blood is drawn into the syringe, any unnecessary delay prior to injection may lead to clot formation. Begin lung imaging immediately after intravenous administration of Technetium Tc 99m Albumin Aggregated Injection. Due to high kidney uptake, imaging later than one-half hour after administration is not recommended. For peritoneovenous shunt imaging, obtain serial images of both the shunt and target organ. 2.7 Radiation Dosimetry Intravenous Administration Estimated radiation absorbed doses from intravenous administration are shown in Table 3. Table 3. Estimated Radiation Absorbed Doses From Intravenous Administration of Technetium Tc 99m Albumin Aggregated Injection for Lung Perfusion Scintigraphy Absorbed Dose per Activity Administered (microGy/MBq) Organs Adults 15 years 10 years 5 years 1 year Neonates Total body 4.05 3.96 7.63 8.38 13.5 32.4 Lungs 59.5 74.3 138 157 297 1027 Liver 4.86 11.6 28.6 16.8 27 75.7 Spleen 4.59 *-- -- -- -- -- Kidneys 2.97 -- -- -- -- -- Bladder Wall 2 hour void 4.8 hour void No voiding intervals 8.11 14.9 -- -- -- 39.6 -- 62 -- -- 83.8 -- 67.6 -- -- 114 -- -- Testes 2 hour void 4.8 hour void No voiding intervals 1.62 1.76 -- -- -- 3.47 -- -- 3.18 -- -- 5.14 -- -- 5.86 -- -- 16.8 Ovaries 2 hour void 4.8 hour void No voiding intervals 2.03 2.3 -- -- -- 3.96 -- -- 7 -- -- 5.14 -- -- 9.01 -- -- 20.5 *--: Not available Intraperitoneal Administration Estimated radiation absorbed doses from intraperitoneal administration are shown in Table 4. Table 4. Estimated Radiation Absorbed Doses From Intraperitoneal Administration of Technetium Tc 99m Albumin Aggregated Injection for Peritoneovenous Shunt Scintigraphy in Adults Absorbed Dose per Activity Administered (microGy/MBq) Organs Shunt Patency (Open) Shunt Patency (Closed) Lung 62.2 15.1 Ovaries or Testes 1.62 to 2.7 15.1 Organ in the Peritoneal Cavity *-- 15.1 Total Body 3.24 5.14 *--: Not available

DRAXIMAGE MAA is contraindicated in patients with: Severe pulmonary hypertension [see Warnings and Precautions (5.1)]. A history of hypersensitivity to albumin human.Reactions have included anaphylaxis [see Warnings and Precautions (5.2)] . Severe pulmonary hypertension. (4) A history of hypersensitivity reactions to albumin human. (4)

The following clinically significant adverse reactions are described elsewhere in the labeling: Patients with Pulmonary hypertension [see Warnings and Precautions (5.1)]. Hypersensitivity Reactions [see Warnings and Precautions (5.2)]. The following adverse reactions associated with the use of technetium Tc 99m albumin aggregated products including DRAXIMAGE MAA were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular Disorders : Deaths in patients with severe pulmonary hypertension Immune System Disorders : Hypersensitivity reactions such as anaphylaxis, impairment of cardiac and circulatory functions in the form of changes in respiration, pulse, and blood pressure, chest pain and syncope, urticaria, reddening of the face, sweating, and nausea Skin and Subcutaneous Tissue Disorders : Injection site reactions The following adverse reactions have been reported: Death in patients with severe pulmonary hypertension, anaphylaxis, impairment of cardiac and circulatory functions in the form of changes in respiration, pulse, and blood pressure, chest pain, and possible syncope, urticaria, reddening of the face, sweating, nausea, and injection site reaction. (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 .