Kit for the Preparation of Technetium Tc 99m Albumin Aggregated

INDICATIONS AND USAGE PULMOTECH MAA, after radiolabeling with technetium-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 adults. PULMOTECH MAA, after radiolabeling with technetium-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 )

DOSAGE AND ADMINISTRATION For lung perfusion scintigraphy, the following recommended activity is administered by intravenous injection. • Adults : 37 MBq to 148 MBq (1 mCi to 4 mCi) and 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 peritoneovenous shunts scintigraphy in adults: 37 MBq to 111 MBq (1 mCi to 3 mCi) and 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 PULMOTECH 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 range of particle numbers per single injection should be 200,000 to 700,000 with the recommended number of 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 technetium-99m that has occurred. The number of particles in any dose and volume to be administrated may be calculated as follows: 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) Fr = fraction of Technetium-99m remaining after the time of calibration from Table 6 [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 the lot is located on the vial label. 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 dose for lung perfusion scintigraphy in this age 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 shown 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 Maximal recommended activity MBq 103.6 mCi 2.8 MBq 62.9 mCi 1.7 MBq 37 mCi 1 MBq 22.2 mCi 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. image description 2.4 Recommended Dosage for Peritoneo veno us 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 and the number of particles per single injection should be 200,000 to 700,000 with the recommended number of 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 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 Perform all transfer and vial stopper entries using aseptic techniques. Wear waterproof gloves during the entire preparation procedure and during subsequent patient dose withdrawals from the PULMOTECH MAA vial. Make all transfers of Sodium Pertechnetate Tc 99m Injection during the preparation procedure with an adequately shielded syringe. Keep the prepared Technetium Tc 99m Albumin Aggregated Injection in the dispensing vial shield described below (with cap in place) during the useful life of the radioactive preparation. Make all withdrawals and injections of the Technetium Tc 99m Albumin Aggregated Injection with an adequately shielded syringe. Procedure for the Preparation , Storage, and Handling of Technetium Tc 99m Albumin Aggregated Injection If PULMOTECH MAA reaction vials are stored in the refrigerator, remove a vial and allow the contents to come to room temperature for approximately 5 minutes. Remove the protective cap from the reaction vial and swab the rubber septum with an alcohol swab or a suitable bacteriostatic agent to disinfect the surface. Place the vial in a suitable dispensing vial shield fitted with a shielded cap. Calculate the amount of Sodium Pertechnetate Tc 99m Injection (2 mL to 13 mL) to be added to the reaction vial. In choosing the amount of Sodium Pertechnetate Tc 99m Injection to be used in the preparation of Technetium Tc 99m Albumin Aggregated Injection ensure that the radioactive dose will contain the desired number of macroaggregated albumin (MAA) particles, while taking into account the number of patients, administered activity, and radioactive decay. The recommended maximum activity of Sodium Pertechnetate Tc 99m Injection to be added to the reaction vial is 6.85 GBq (185 mCi). Calculate the amount of radioactivity per vial required to be added to maintain the number of particles per dose within a recommended range, for adults 200,000 to 700,000 and for pediatric patients as per Table 1 [see Dosage and Administration ( 2.3 , 2.4 ) ] . During or prior to addition of Sodium Pertechnetate Tc 99m Injection do not vent the reaction vial. After ad

WARNINGS AND PRECAUTIONS Patients with P ulmonary H ypertension : Administer the lowest number of particles possible and have emergency resuscitation equipment available. ( 5.1 ) Hypersensitivity Reactions : Have emergency resuscitation equipment and trained personnel available. Interrupt the administration if a reaction occurs during administration. Monitor patients. ( 5.2 ) Risk of Temporary Impediment to Blood Flow in Patients with Right-to-Left Heart Shunts : Administer the lowest possible number of particles. ( 5.3 ) Radiation Risks : Ensure safe handling to minimize radiation exposure to the patient and healthcare providers. ( 5.4 ) 5.1 Patients with Pulmonary Hypertension Deaths have been reported in patients with severe pulmonary hypertension after the administration of technetium Tc 99m albumin aggregated products [see Adverse Reactions ( 6 )] . Assess patients for history or signs of pulmonary hypertension. PULMOTECH MAA is contraindicated in patients with severe pulmonary hypertension [see Contraindications ( 4 )] . Administer the lowest number of particles possible, have emergency resuscitation equipment available, and monitor patients for adverse reactions . 5.2 Hypersensitivity Reactions Serious hypersensitivity reactions including anaphylaxis have been reported in patients treated with products containing albumin human, including PULMOTECH MAA [see Adverse Reactions ( 6 )] . Obtain a history of allergy or hypersensitivity reactions. PULMOTECH MAA is contraindicated in patients with a history of hypersensitivity to albumin human [see Contraindications ( 4 )] . Have emergency resuscitation equipment and trained personnel available prior to administration of Technetium Tc 99m Albumin Aggregated Injection. Monitor all patients for hypersensitivity reactions. 5.3 Risk of Temporary Impediment to Blood Flow in Patients with Right-to-Left Heart Shunts In patients with right-to-left heart shunts, risk for temporary mechanical impediment to blood flow may exist due to the rapid entry of aggregated albumin into the systemic circulation. Administer the lowest possible number of particles of Technetium Tc 99m Albumin Aggregated Injection in these patients. 5.4 Radiation Risks Technetium Tc 99m albumin aggregated contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration ( 2.2 )] .

CONTRAINDICATIONS PULMOTECH 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 )

ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in 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 PULMOTECH MAA have been 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 CURIUM US LLC at 1-866-789-2211 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Mechanism of Action Within 1 to 5 minutes of intravenous injection, over 90 percent of the technetium Tc 99m albumin aggregated particles are trapped in the arterioles and capillaries of the lung. Following intraperitoneal administration, technetium Tc 99m albumin aggregated mixes with the peritoneal fluid. Clearance from the peritoneal cavity varies from insignificant, which may occur with complete shunt blockage, to very rapid clearance with subsequent transfer into the systemic circulation when the shunt is patent.