The following Structured Product Label (SPL) was submitted to the FDA by Curium Us Llc for the product Pulmotech Maa (NDC 69945-139). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2.1 recommended dosage and administration, 2.2 radiation dosimetry, 2.3 directions for preparation, 3 dosage forms and strengths, 4 contraindications, 5.1 pulmonary hypertension, 5.2 hypersensitivity reactions, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
Technetium Tc 99m Albumin Aggregated Injection is a radioactive diagnostic agent indicated for:
Adult Patients
The recommended intravenous dose range for adult patients for lung imaging is 37 MBq to 148 MBq (1 mCi to 4 mCi) and 200,000 to 700,000 particles of Technetium Tc 99m Albumin Aggregated Injection after preparation with oxidant-free Sodium Pertechnetate Tc 99m Injection.
The recommended intraperitoneal dosage range for adult patients for peritoneovenous shunt patency evaluation is 37 MBq to 111 MBq (1 mCi to 3 mCi) and 200,000 to 700,000 particles. Adequate measures should be taken to assure uniform mixing with peritoneal fluid. Serial images of both the shunt and target organ should be obtained and correlated with other clinical findings. Alternatively, the drug may be administered by percutaneous transtubal injection. The recommended percutaneous transtubal dosage range for adult patients is 12 MBq to 37 MBq (0.3 mCi to 1 mCi) in a volume not to exceed 0.5 mL.
The recommended range of particle numbers per single injection is 200,000 to 700,000 with the recommended number of approximately 350,000. Depending on the activity added and volume of the final reconstituted 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 Tc 99m that has occurred. The number of particles in any dose and volume to be administrated may be calculated as follows:
Where:
VTc = volume of solution added to reaction vial
D = desired dose to be administered in MBq (mCi)
C = concentration at calibration time of Sodium Pertechnetate solution to be added to the reaction vial in MBq/mL (mCi/mL)
Va = volume to be administered in mL
P = number of particles in dose to be administered
Fr = fraction of Technetium Tc 99m remaining after the time of calibration (Table 7)
N = number of particles per vial. The number of particles per vial for the lot is located on the vial label.
Pediatric Patients
In pediatric patients, the recommended intravenous dose for perfusion lung imaging is in the range of 0.925 MBq/kg to 1.85 MBq/kg (0.025 mCi/kg to 0.05 mCi/kg) of body weight; a usual dose is 1.11 MBq/kg (0.03 mCi/kg), except in newborns, in whom the administered dose should be 7.4 MBq to 18.5 MBq (0.2 mCi to 0.5 mCi). Not less than the minimum dose of 7.4 MBq (0.2 mCi) should be employed for this procedure. The number of particles varies with age and weight as shown in Table 1.
| Age | Newborn | 1 year | 5 years | 10 years | 15 years | |||||
| Weight (kg) | 3.5 | 12.1 | 20.3 | 33.5 | 55 | |||||
| Maximal recommended dose | MBq | mCi | MBq | mCi | MBq | mCi | MBq | mCi | MBq | mCi |
| 18.5 | 0.5 | 22.2 | 0.6 | 37 | 1 | 62.9 | 1.7 | 103.6 | 2.8 | |
| Range of particles | 10,000 to | 50,000 to | 200,000 to | 200,000 to | 200,000 to | |||||
| administered | 50,000 | 150,000 | 300,000 | 300,000 | 700,000 | |||||
Adults and Pediatric Patients
Visually inspect for particulate matter and discoloration prior to administration.
Measure the patient dose by a suitable radioactivity calibration system immediately prior to administration. Mix the contents of the vial by gentle inversion just prior to withdrawing a patient dose.
Mix the contents of the syringe just before injection. If blood is drawn into the syringe, any unnecessary delay prior to injection may lead to clot formation. For optimal results and because of rapid lung clearance of the radiopharmaceutical, position the patient under the imaging apparatus before administration. Slow injection is recommended. Lung imaging may begin immediately after intravenous injection of the radiopharmaceutical. Due to high kidney uptake, imaging later than one-half hour after administration will yield poor results.
Adult Patients
The estimated absorbed radiation doses3 to an average adult patient (70 kg) from an intravenous administration of 148 MBq (4 mCi) of Technetium Tc 99m Albumin Aggregated Injection are shown in Table 2.
| Organs | mGy/148 MBq | rad/4 mCi |
| Total body | 0.6 | 0.06 |
| Lungs | 8.8 | 0.88 |
| Liver | 0.72 | 0.072 |
| Spleen | 0.68 | 0.068 |
| Kidneys | 0.44 | 0.044 |
| Bladder wall | ||
| 3.5 hr. void | 1.2 | 0.12 |
| 4.8 hr. void | 2.2 | 0.22 |
| Testes | ||
| 3.5 hr. void | 0.24 | 0.024 |
| 4.8 hr. void | 0.26 | 0.026 |
| Ovaries | ||
| 3.5 hr. void | 0.3 | 0.03 |
| 4.8 hr. void | 0.34 | 0.034 |
Table 3 shows the radiation absorbed dose resulting from the intraperitoneal administration of 111 MBq (3 mCi) of Technetium Tc 99m Albumin Aggregated.
| Organs | Shunt Patency | Shunt Patency | ||
| (Open) | (Closed) | |||
| mGy | Rad | mGy | Rad | |
| Lung | 6.9 | 0.69 | 1.68 | 0.168 |
| Ovaries & Testes | 0.18 to 0.3 | 0.018 to 0.03 | 1.68 | 0.168 |
| Organs in the peritoneal cavity | - | - | 1.68 | 0.168 |
| Total body | 0.36 | 0.036 | 0.57 | 0.057 |
Assumptions: calculations for the radiation absorbed dose are based upon an effective half-time of 3 hours for the open shunt and a physical half-life of 6 hours for the closed shunt and an even distribution of the radiopharmaceutical in the peritoneal cavity with no biological clearance.
Pediatric Patients
In pediatric patients, the radiation absorbed doses using the maximum recommended dose for lung imaging are based on 1.85 MBq (0.05 mCi) per kilogram of body weight (except in the newborns where the maximum recommended dose of 18.5 MBq (0.5 mCi) is used) and are shown in Table 4.
| Age | Newborn | 1 year | 5 years | 10 years | 15 years | |||||
| mGy | rad | mGy | Rad | mGy | rad | mGy | rad | mGy | Rad | |
| ORGANS | ||||||||||
| Total body | 0.6 | 0.06 | 0.3 | 0.03 | 0.31 | 0.031 | 0.48 | 0.048 | 0.41 | 0.041 |
| Lungs | 19 | 1.9 | 6.6 | 0.66 | 5.8 | 0.58 | 8.7 | 0.87 | 7.7 | 0.77 |
| Liver | 1.4 | 0.14 | 0.6 | 0.06 | 0.62 | 0.062 | 1.8 | 0.18 | 1.2 | 0.12 |
| Bladder wall | 2.1 | 0.21(1) | 1.5 | 0.15(1) | 3.1 | 0.31(2) | 3.9 | 0.39(2) | 4.1 | 0.41 |
| Ovaries | 0.38 | 0.038 | 0.2 | 0.02 | 0.19 | 0.019 | 0.44 | 0.044 | 0.41 | 0.041 |
| Testes | 0.31 | 0.031 | 0.13 | 0.013 | 0.19 | 0.019 | 0.2 | 0.02 | 0.36 | 0.036 |
(1) 2 hour voiding interval
(2) 4.8 hour voiding interval
Procedural Precautions
Procedure for the Preparation of Technetium Tc 99m Albumin Aggregated
1. If Pulmotech MAA vials are stored in the refrigerator, remove a vial and allow the contents to come to room temperature for approximately 5 minutes.
2. Remove the protective disc from the Pulmotech MAA vial and swab the rubber septum with an alcohol swab or a suitable bacteriostatic agent to disinfect the surface.
3. Place the vial in a suitable dispensing vial shield fitted with a shielded cap.
4. Calculate the amount of sodium pertechnetate Tc 99m injection solution (2 mL to 13 mL) to be added to the Pulmotech MAA vial. During or prior to addition of technetium Tc 99m solution do not vent the Pulmotech MAA vial. In choosing the amount of technetium Tc 99m radioactivity to be used in the preparation of technetium Tc 99m albumin aggregated ensure that the radioactive dose will contain the desired number of MAA particles, while taking into account the number of patients, administered radioactive dose, and radioactive decay. The recommended maximum amount of technetium Tc 99m to be added to the Pulmotech vial is 6.85 GBq (185 mCi). Calculate (see section 2.1) 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].
5. After adding sodium pertechnetate Tc 99m injection solution to the Pulmotech MAA vial in the dispensing Vial shield (with cap in place), mix the contents by agitation and allow to stand for a minimum of 15 minutes at room temperature. Once prepared the product will have a turbid white appearance.
6. Assay the product in a suitable dose calibrator and record the activity of the technetium Tc 99m albumin aggregated, total suspension volume, number of Tc 99m MAA particles, radioactive concentration, time and date of preparation, onto the radioassay information label and attach it to the dispensing vial shield. 0.9% Sodium Chloride Injection, USP may be used as a diluent for the radiolabeled product to achieve the desired number of particles and radioactivity.
7. Prior to withdrawing a dose, gently agitate the contents of the radiolabeled Pulmotech MAA vial to resuspend any settled technetium Tc 99m albumin aggregated particles. Failure to mix the reaction vial contents adequately before use may result in a non-homogenous suspension with a resulting non-uniform distribution of radioactivity in the lung. Withdrawals for administration must be made aseptically using a sterile needle (18 to 21 gauge) and syringe. Since the vials contain nitrogen to prevent oxidation of the complex, the vials should not be vented. If repeated withdrawals are made from the vial, the contents should not be replaced with air.
8. Store the radiolabeled Pulmotech MAA vial in the dispensing vial shield in a refrigerator at 2° to 8°C (36° to 46°F). Use radiolabeled Pulmotech MAA within 18 hours from the time of preparation. Discard unused product.
Pulmotech MAA multiple-dose vial contains 2 mg of albumin aggregated as lyophilized powder. Radiolabeling with sodium pertechnetate Tc 99m injection solution provides an injectable suspension of technetium Tc 99m albumin aggregated. The radioactive dose for an adult is intended to contain 200,000 particles to 700,000 particles of technetium Tc 99m albumin aggregated with the target dose of approximately 350,000. Depending on the activity added and volume of the final reconstituted product, the volume of the dose may vary from 0.2 mL to 1.9 mL.
Serious adverse reactions have been reported in patients with pulmonary hypertension after Technetium Tc 99m Albumin Aggregated Injection. Assess patients for history or signs of pulmonary hypertension, administer the lowest number of particles possible, have emergency resuscitation equipment available and monitor patients for adverse reactions. [see Adverse Reactions (6)].
Serious reactions have been reported in patients with hypersensitivity to products containing human serum albumin, including Technetium Tc 99m Albumin Aggregated Injection. Obtain a history of allergy or hypersensitivity reactions and always have emergency resuscitation equipment and trained personnel available prior to administration of Technetium Tc 99m Albumin Aggregated Injection. Monitor all patients for hypersensitivity reactions.
The contents of the supplied Pulmotech MAA vials are not radioactive. However, after adding sodium pertechnetate Tc 99m injection solution to the vial, adequate shielding of the final preparation must be maintained.
As in the use of any radioactive material, care should be taken to minimize radiation exposure to the patient and to insure minimum radiation exposure to occupational workers.
Radiopharmaceuticals should be used only by physicians who are qualified by 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.
Deaths occurring after the administration of aggregated albumin to patients with severe pulmonary hypertension and serious hypersensitivity reactions to preparations of Technetium Tc 99m Albumin Aggregated Injection have been reported.
Risk Summary
Available data from case reports on Technetium Tc 99m Albumin Aggregated Injection are insufficient to evaluate drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies with technetium Tc 99m Albumin Aggregated Injection have not been conducted. 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 Albumin Aggregated Injection administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from Technetium Tc 99m Albumin Aggregated Injection and the gestational timing of exposure.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Risk Summary
Data available in the published literature demonstrate the presence of pertechnetate in human milk. There are no data available on the effects of Tc-99m Albumin Aggregated Injection on the breastfed infant or the effects on milk production. Exposure of pertechnetate to a breast fed infant can be minimized by temporary discontinuation of breastfeeding (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for a Technetium Tc 99m Albumin Aggregated Injection, any potential adverse effects on the breastfed child from radioactivity and from the underlying maternal condition.
Clinical Considerations
To decrease radiation exposure to the breastfed infant, advise a lactating woman to pump and discard breast milk after the administration of Technetium Tc 99m Albumin Aggregated Injection for 13 hours, where the duration corresponds to the typical range of administered activity, 37 to 148 MBq (1 to 4 mCi). During the period of interruption, the breasts should be emptied regularly and completely. The milk that is pumped by the mother during the time of breastfeeding interruption can either be discarded or stored refrigerated and given to the infant after 10 physical half-lives, or about 60 hours, have elapsed.
Technetium Tc 99m Albumin Aggregated Injection is indicated for lung scintigraphy as an adjunct in the evaluation of pulmonary perfusion in pediatric patients [see Dosage and Administration (2)]. The safety profile of Technetium Tc99m Albumin Aggregated Injection is similar to the one in adults.
Pulmotech MAA (kit for the preparation of technetium Tc 99m albumin aggregated injection), when prepared with sodium pertechnetate Tc 99m injection, provides Technetium Tc 99m Albumin Aggregated Injection. Pulmotech MAA contains macroaggregates of U.S.-licensed human serum albumin (non- reactive when tested for hepatitis B antigen (HBsAg) by enzyme immunoassay). The macroaggregated albumin (MAA) is obtained by heat denaturation of stannous chloride treated human serum albumin under controlled conditions.
Upon radiolabeling with sodium pertechnetate Tc 99m injection solution, the stannous reduced Tc99m binds to the aggregated albumin to provide technetium Tc 99m albumin aggregated. The particle size distribution of the aggregated albumin is such that not less than 90 percent are 10 to 90 microns in size. There are no aggregated albumin particles greater than 150 microns in size as determined by circular equivalents.
Pulmotech MAA is provided as a 15 mL multiple-dose glass vial containing white lyophilized powder. The contents of the vial are under nitrogen. Each vial contains 2 mg of albumin aggregated, 7.1 mg of albumin human (soluble), 0.22 mg of maximum total tin (as SnCl2 · 2H2O), 0.1 mg (minimum) stannous chloride, and 9 mg of sodium chloride. Hydrochloric acid is added for pH adjustment and the pH of the reconstituted solution is between 5 and 7. The kit does not contain any bacteriostatic agent.
Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours. The principal photon that is useful for detection and imaging is listed in Table 5.
| Radiation | Mean % per Disintegration | Energy (keV) |
| Gamma-2 | 89.07 | 140.5 |
The specific gamma ray constant for Technetium Tc 99m is 0.78 R/mCi-hr at 1 cm. The first half-value thickness of lead (Pb) for Technetium Tc 99m is 0.017 cm. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 6. For example, the use of 0.25 cm of Pb will decrease the external radiation exposure by a factor of about 1000.
| 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 time intervals after the time of calibration are shown in Table 7.
| Hours | Fraction Remaining | Hours | Fraction Remaining |
| 0* | 1.000 | 7 | 0.447 |
| 1 | 0.891 | 8 | 0.398 |
| 2 | 0.794 | 9 | 0.355 |
| 3 | 0.708 | 10 | 0.316 |
| 4 | 0.631 | 11 | 0.282 |
| 5 | 0.562 | 12 | 0.251 |
| 6 | 0.501 |
*Calibration Time
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 of Technetium Tc 99m Albumin Aggregated Injection, the radiopharmaceutical 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.
Distribution
Organ selectivity is a direct result of particle size. At 10 microns and below, the albumin aggregates are taken up by the reticuloendothelial system. Above 10 to 15 microns, the aggregates become lodged in the lung capillaries by a purely mechanical process. Distribution of aggregated albumin in the lungs is a function of regional pulmonary blood flow.
The albumin aggregated is sufficiently fragile for the capillary micro-occlusion to be temporary. Erosion and fragmentation reduce the particle size, allowing passage of the aggregates through the pulmonary alveolar capillary bed. The fragments then accumulate in the reticuloendothelial system.
Elimination
Elimination of the Technetium Tc 99m Albumin Aggregates from the normal and abnormal human lungs occurs with a biological half-life of 10.8 hours (range 6.9 to 19 hours, n=5).
No long-term animal studies have been performed to evaluate carcinogenic or mutagenic potential or whether technetium Tc 99m albumin aggregated affects fertility in males or females.
Pulmotech MAA (kit for the preparation of technetium Tc 99m albumin aggregated injection) is supplied either as a 5 vial clam shell (NDC 69945-139-20) or as a carton of 30 vials (NDC 69945-139-40).
Each 5 vial kit contains 5 multiple dose Pulmotech MAA vials, 1 prescribing information and 5 radioassay information labels. Each 30 vial carton contains 30 multiple dose Pulmotech MAA vials, 1 prescribing information and 30 radioassay information labels.
Store Pulmotech MAA (kit for the preparation of Tc 99m albumin aggregated injection) at 2° to 25°C (36° to 77°F) before preparation (radiolabeling).
After preparation with sodium pertechnetate Tc 99m injection, store radiolabeled technetium Tc 99m albumin aggregated Injection in a refrigerator at 2° to 8°C (36° to 46°F).
Do not use and discard radiolabeled Pulmotech MAA at 18 hours after preparation.
Adequate Hydration
Advise patients to drink a sufficient amount of water to ensure adequate hydration before their study and urge them to drink and urinate as often as possible during the first hours following the administration of Technetium Tc 99m Albumin Aggregated Injection in order to reduce radiation exposure.
Pregnancy
Advise pregnant women of the risk of fetal exposure to radiation doses if they undergo a radionucleotide procedure [see Use in Specific Populations (8.1)].
Lactation
Advise a lactating woman to interrupt breastfeeding and pump and discard breast milk for 13 hours after Technetium Tc 99m Albumin Aggregated Injection administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations (8.2)].
Pulmotech is a trademark of a Curium company.
©2020 Curium US LLC. All Rights Reserved.
A139I0
Manufactured by:
CIS bio International for
Curium US LLC
2703 Wagner Place
Maryland Heights, MO 63043
Issued: R03/2020
CURIUM™
NDC 69945-139-40
Pulmotech™ MAA
(kit for the preparation of technetium Tc 99m albumin aggregated injection)
For intravenous and intraperitoneal use after radiolabeling with sodium pertechnetate Tc 99m.
Rx only
Before radiolabeling, store at 2° to 25°C (36° to 77°F). After radiolabeling, store shielded in refrigerator at 2° to 8°C (36° to 46°F). Use within 18 hours of radiolabeling.
CURIUM™
30 Vial Multiple-dose Carton
PINCH AT CORNERS / PULL OUT
Dosage: See prescribing information.
CARTON CONTAINS:
30 sterile, multiple-dose Pulmotech MAA vials
30 radioassay information labels
1 Prescribing Information
Each Pulmotech MAA vial contains:
2 mg Albumin Aggregated
7.1 mg Albumin Human
0.22 mg (maximum) stannous chloride
0.1 mg (minimum) stannous chloride
9 mg sodium chloride
Hydrochloric acid for pH adjustment
Sealed under nitrogen
Manufactured for:
Curium US LLC
2703 Wagner Place
Maryland Heights, MO 63043
Convenient Reorder Point
Maximum Six Vials Remaining
Open Flap For Package Insert and Radioassay Information Labels
A139DK
R03/2020
NDC 69945-139-10 Pulmotech™ MAA Sterile, Multiple-Dose Vial
(kit for the preparation of technetium Tc 99m albumin aggregated injection)
For intravenous and intraperitoneal use after radiolabeling with sodium pertechnetate Tc 99m.
Vial contains: 2 mg Albumin Aggregated, 7.1 mg Albumin Human, 0.1 mg (minimum) Stannous Chloride and 9 mg Sodium Chloride. HCl used for pH adjustment. Sealed under nitrogen.
Before radiolabeling, store at 2° to 25°C (36° to 77°F). After radiolabeling, store shielded in refrigerator at 2° to 8°C (36° to 46°F). Use within 18 hours.
Dosage: See prescribing information.
Rx only
Manufactured for: Curium US LLC, Maryland Heights, MO 63043
A139VO
R03/2020
* Please review the disclaimer below.
