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Technetium Tc 99m Albumin Aggregated Injection Kit

DIAGNOSTIC – For Intravenous Use

TABLE OF CONTENTS

1. DESCRIPTION 7. WARNINGS AND PRECAUTIONS
2. INDICATIONS AND USAGE 8. ADVERSE REACTIONS
3. DOSAGE AND ADMINISTRATION 9. OVERDOSAGE
4. CONTRAINDICATIONS 10. DRUG INTERACTIONS
5. MECHANISM OF ACTION 11. PHARMACOKINETICS
6. USE IN SPECIFIC POPULATIONS 12. HOW SUPPLIED/STORAGE AND HANDLING

 

1. DESCRIPTION

The kit consists of reaction vials which contain the sterile, non-pyrogenic, non-radioactive ingredients necessary to produce Technetium Tc 99m Albumin Aggregated Injection for diagnostic use by intravenous injection.

Each 10 mL reaction vial contains 2.5 mg of albumin aggregated, 5.0 mg of albumin human, 0.06 mg (minimum) stannous chloride (maximum stannous and stannic chloride 0.11 mg) and 1.2 mg of sodium chloride; the contents are in a lyophilized form under an atmosphere of nitrogen. Sodium hydroxide or hydrochloric acid has been used for pH adjustment. No bacteriostatic preservative is present.

The albumin human was non-reactive when tested for Hepatitis B Surface Antigen (HBsAg), antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2), antibody to Hepatitis C Virus (anti-HCV) and Antigen to Human Immunodeficiency Virus (HIV-1). The aggregated particles are formed by denaturation of albumin human in a heating and aggregation process. Each vial contains 4 to 8 million 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.

Technetium Tc 99m Albumin Aggregated Injection for intravenous use is in its final dosage form when sterile isotonic sodium pertechnetate solution is added to each vial. No less than 90% of the pertechnetate Tc-99m added to a reaction vial is bound to aggregate at preparation time and remains bound throughout the 6 hour lifetime of the preparation.

PHYSICAL CHARACTERISTICS

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 studies is listed in Table 1.

Table 1: PRINCIPAL RADIATION EMISSION DATA

EXTERNAL RADIATION

The specific gamma ray constant for Tc-99m is 0.78 R/mCi-hr at 1 cm.

The first half value layer is 0.017 cm of lead. To facilitate control of the radiation exposure from millicurie amounts of this radionuclide, the use of a 0.25 cm thickness of lead will attenuate the radiation emitted by a factor of about 1,000. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of lead is shown in Table 2.

Table 2: RADIATION ATTENUATION BY LEAD SHIELDING

To correct for physical decay of this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 3.

Table 3: PHYSICAL DECAY CHART: Tc-99m, half-life 6.02 hours

* Calibration time

2. INDICATIONS AND USAGE

Technetium Tc 99m Albumin Aggregated Injection is a lung imaging agent which may be used as an adjunct in the evaluation of pulmonary perfusion in adults and pediatric patients.

Technetium Tc 99m Albumin Aggregated Injection may be used in adults as an imaging agent to aid in the evaluation of peritoneovenous (LeVeen) shunt patency.

3. DOSAGE AND ADMINISTRATION

The recommended adult dose, after reconstitution with oxidant-free sodium pertechnetate Tc 99m, is 370 to 740 megabecquerels (10 to 20 millicuries [200 μCi/kg]) by slow intravenous injection over a period of 30 seconds. Optimum scanning time is 1 to 4 hours post-injection.

To minimize the contribution of the bladder content to the image, the patient should void immediately before imaging is started.

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. The solution should not be used if cloudy.

RADIATION DOSIMETRY

The estimated absorbed radiation doses to an average patient (70 kg) from an intravenous injection of a maximum dose of 740 megabecquerels (20 millicuries) of Technetium Tc 99m Medronate are shown in Table 4. The effective half-life was assumed to be the physical half-life for all calculated values.

Table 4: RADIATION DOSES

DIRECTIONS

NOTE:

Use aseptic procedures throughout and take precautions to minimize radiation exposure by use of suitable shielding. Use waterproof gloves during the following preparation procedure.

MDP-25 reaction vials are intended for the preparation of multiple doses of technetium Tc-99m medronate and the entire contents of the vial should not be used as a single dose.

Before reconstituting a vial, it should be inspected for cracks and/or a melted plug or any other indication that the integrity of the vacuum seal has been compromised.

To prepare Technetium Tc 99m Medronate:

1. Remove the central metal disc from a reaction vial and swab the closure with either an alcohol swab or a suitable bacteriostatic agent.

2. Place the reaction vial in a suitable lead vial shield (minimum wall thickness 1/8 inch) which has a fitted lead cap. Obtain 2 to 10 mL of sterile, non-pyrogenic sodium pertechnetate Tc-99m, using a shielded syringe.

The recommended maximum amount of Technetium Tc-99m to be added to a reaction vial is 37.0 gigabecquerels (1000 mCi). Sufficient sodium pertechnetate is to be used for the reconstitution of a reaction vial to ensure that the dose of medronate administered does not exceed 10 mg. Sodium pertechnetate Tc-99m solutions containing an oxidizing agent are not suitable for use.

3. Using a shielded syringe, add the sodium pertechnetate Tc-99m solution to the reaction vial aseptically.

4. Place the lead cap on the reaction vial shield and agitate the shielded reaction vial until the contents are completely dissolved. The solution must be clear and free of particulate matter before proceeding.

5. Assay the product in a suitable calibrator, record the radioassay information on the label with radiation warning symbol, and apply it to the reaction vial.

6. Withdrawals for administration must be made aseptically using a shielded sterile syringe and needle. Since the reaction vials contain nitrogen to prevent oxidation of the complex, they should not be vented. If repeated withdrawals are made, minimize the replacement of contents with room air.


The following steps should be followed to ensure that each reconstituted of technetium Tc 99m Medronate contains between 1 and 10 mg of medronic acid.

Where:

Vr = Final volume of in the vial in mL after reconstitution.

C = Concentration of Medronic Acid in mg/mL.

Max. V = Maximum volume to be used for one dose in mL.

Min. V =Minimum volume to be used for one dose in mL.

a) Prior to reconstitution, determine the radioactive concentration of the sodium pertechnetate Tc-99m.

b) Note the volume and activity added to the vial. It should be between 1.85 – 37.0 GBq (50 – 1000 mCi) in 1 to 10 mL.

c) Calculate the concentration (C) of Medronic acid in the vial after reconstitution.

C (mg/mL) = 25 mg ÷ Vr (mL)

d) To ensure that the dose contains a maximum of 10 mg, the following formula should be used to calculate the maximum volume (Max. V) to be dispensed as one dose.

Max. V (mL) = 10 mg ÷ C (mg/mL)

e) To ensure that a minimum dose of 1 mg is dispensed, the following formula should be used to calculate the minimum volume (Min. V) to be dispensed as one dose.

Min. V = 1 mg ÷ C (mg/mL)


7. The finished preparation should be stored at 25ºC (77ºF); excursions permitted between 15° and 30ºC (59° to 86ºF) when not in use and discarded after 12 hours. It should also be stored during its life in a suitable lead shield.

4. CONTRAINDICATIONS

Technetium Tc 99m Albumin Aggregated Injection should not be administered to patients with severe pulmonary hypertension.

The use of Technetium Tc 99m Albumin Aggregated Injection is contraindicated in persons with a history of hypersensitivity reactions to products containing human serum albumin.

5. MECHANISM OF ACTION

Immediately following intravenous injection, more than 80% of the albumin aggregated is trapped in the pulmonary alveolar capillary bed. The imaging procedure can thus be started as soon as the injection is complete. Assuming that a sufficient number of radioactive particles has been used, the distribution of radioactive aggregated particles in the normally perfused lung is uniform throughout the vascular bed, and will produce a uniform image. Areas of reduced perfusion will be revealed by a corresponding decreased accumulation of the radioactive particles, and are imaged as areas of reduced photon density.

Organ selectivity is a direct result of particle size. Below 1 to 10 micrometers, the material is taken up by the reticuloendothelial system. Above 10 micrometers, the aggregates become lodged in the lung by a purely mechanical process. Distribution of particles 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 are then accumulated by the reticuloendothelial system.

Lung to liver ratios greater than 20:1 are obtained in the first few minutes post-injection. Elimination of the Technetium Tc 99m Aggregated Albumin from the lungs occurs with a half-life of about 2 to 3 hours. Cumulative urinary excretion studies show an average of 20% elimination of the injected technetium Tc 99m dose 24 hours post-administration.

Following administration of Technetium Tc 99m Albumin Aggregated by intraperitoneal 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.

Serial images should be obtained of both the shunt and lung (target organ). However, an adequate evaluation of the difference between total blockage of the shunt and partial blockage may not be feasible in all cases.

6. USE IN SPECIFIC POPULATIONS

6.1 Usage in Pregnancy

Pregnancy Category C

Animal reproduction and teratogenicity studies have not been conducted with Technetium Tc 99m Albumin Aggregated Injection. It is also not known whether Technetium Tc 99m Albumin Aggregated Injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. There have been no studies in pregnant women. Technetium Tc 99m Albumin Aggregated Injection should be given to a pregnant woman only if clearly needed.

Ideally, examinations using radiopharmaceuticals, especially those elective in nature, of a woman of childbearing capability, should be performed during the first few (approximately 10) days following the onset of menses.

6.2 Nursing Mothers

Technetium Tc-99m is excreted in human milk during lactation. Therefore, formula feedings should be substituted for breast feedings.

6.3 Pediatric Use

The lowest possible number of particles should be used in right-to-left shunting, in neonates, and in severe pulmonary disease.

7. WARNINGS AND PRECAUTIONS

WARNINGS

Although adverse reactions specifically attributable to Technetium Tc 99m Albumin Aggregated Injection have not been noted, the literature contains reports of deaths occurring after the administration of albumin aggregated to patients with pre-existing severe pulmonary hypertension. Instances of hemodynamic or idiosyncratic reactions to preparations of Technetium Tc 99m Albumin Aggregated have been reported.

PRECAUTIONS

The contents of the kit before preparation are not radioactive. However, after the sodium pertechnetate Tc-99m is added, adequate shielding of the final preparation must be maintained.

In patients with right-to-left heart shunts, additional risk may exist due to the rapid entry of albumin aggregated into the systemic circulation. The safety of this agent in such patients has not been established. Hypersensitivity reactions are possible whenever protein-containing materials such as pertechnetate labeled albumin aggregated are used in man. Epinephrine, antihistamines, and corticosteroids should be available for immediate use.

The intravenous administration of any particulate materials such as albumin aggregated imposes a temporary small mechanical impediment to blood flow. While this effect is probably physiologically insignificant in most patients, the administration of albumin aggregated is possibly hazardous in acute cor pulmonale and other states of severely impaired pulmonary blood flow.

The components of the kit are sterile and non-pyrogenic. It is essential to follow directions carefully and to adhere to strict aseptic procedures during preparation.

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.

The technetium Tc-99m labeling reactions involved depend on maintaining the stannous ion in the reduced state. Hence, sodium pertechnetate Tc-99m containing oxidants should not be employed.

The preparation contains no bacteriostatic preservative. Technetium Tc 99m Albumin Aggregated Injection should be stored at 2 to 8 ºC (36 to 46 ºF) and discarded 6 hours after reconstitution.

Technetium Tc 99m Albumin Aggregated Injection is physically unstable and consequently the particles settle with time. Failure to agitate the vial adequately before use may result in nonuniform distribution of radioactive particles.

If blood is drawn into the syringe, unnecessary delay prior to injection may result in clot formation in situ.

Do not use if clumping of the contents is observed.

Technetium Tc 99m Albumin Aggregated Injection, as well as other radioactive drugs, must be handled with care. Once sodium pertechnetate Tc-99m is added to the vial, appropriate safety measures must be used to minimize radiation exposure to clinical personnel. Care must also be taken to minimize the radiation exposure to patients in a manner consistent with proper patient management.

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 government agency authorized to license the use of radionuclides.

8. ADVERSE REACTIONS

The literature contains reports of deaths occurring after the administration of albumin aggregated to patients with pre-existing severe pulmonary hypertension. Instances of hemodynamic or idiosyncratic reactions to preparations of Technetium Tc 99m Albumin Aggregated have been reported (see WARNINGS).

9. OVERDOSAGE

No overdosage information is available.

10. DRUG INTERACTIONS

No drug interaction information is available.

11. PHARMACOKINETICS

No pharmacokinetics information is available.

12. HOW SUPPLIED/STORAGE AND HANDLING

1) How Available:

a) Brand name: DRAXIMAGE M A A, by Draximage.

b) Generic drugs: None.

2) How Supplied:

Kit for the Preparation of Technetium Tc 99m Albumin Aggregated Injection

Each kit contains 30 reaction vials, each vial containing in lyophilized form, sterile and non-pyrogenic:

Albumin aggregated 2.5 mg

Albumin human 5.0 mg

Stannous Chloride (minimum) 0.06 mg

(Maximum stannous and stannic chloride 0.11 mg)

Sodium chloride 1.2 mg

HCl and/or NaOH has been used for pH adjustment. The vials are sealed under an atmosphere of nitrogen.

Thirty labels with radiation warning symbol and a package insert are supplied in each carton.

3) Storage and Handling:

Store the unreconstituted reaction vials at 2 to 25 ºC (36 to 77 ºF). After labeling with Technetium Tc-99m, store the solution at 2 to 8 ºC (36 to 46 ºF) in a suitable lead shield and discard after 6 hours.

Rx only

Rev 09/11