Consumer medicine information

Draximage Macrosalb

Technetium(99mTc) macrosalb

BRAND INFORMATION

Brand name

Draximage Macrosalb

Active ingredient

Technetium(99mTc) macrosalb

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Draximage Macrosalb.

What is in this leaflet?

This leaflet answers some common questions about DRAXIMAGE MACROSALB®. It does not contain all the available information, nor does it take the place of talking to your doctor or treatment provider.

All medicines and diagnostic preparations have risks and benefits. Your doctor has weighed the risks of you receiving DRAXIMAGE MACROSALB® against the expected benefits.

If you have any concerns about being given DRAXIMAGE MACROSALB®, ask your doctor or treatment provider.

Keep this leaflet. You may need to refer to it again.

What DRAXIMAGE MACROSALB® is used for

DRAXIMAGE MACROSALB® is for diagnostic use only.

It is used in the preparation of a radiopharmaceutical, which is a medicinal product containing a small amount of radioactivity.

Such radiopharmaceuticals are given in small amounts to find or rule out a disease. The radiation your body receives is very low and is considered safe. After the radioactive liquid is given to you, it is taken up by the organs of interest or just passes through your body. The radiation is captured by a special camera and pictures are prepared. These pictures allow the nuclear medicine doctor to detect any problems.

DRAXIMAGE MACROSALB® can be used for lung scans. These scans provide information about the structure of the lungs and the blood flow through the lung tissue.

DRAXIMAGE MACROSALB® can also be used to show how the blood flows through the veins.

Your doctor will tell you which specific investigation DRAXIMAGE MACROSALB® will be used for in your case.

Before you are given DRAXIMAGE MACROSALB®

When you must not be given DRAXIMAGE MACROSALB®

Do not use DRAXIMAGE MACROSALB® if you are allergic (hypersensitive) to macroaggregated albumin or any of the ingredients of DRAXIMAGE MACROSALB® listed at the end of this leaflet, or if you have severe pulmonary hypertension (unusually high blood pressure in the arteries of the lungs). The literature contains reports of deaths after the administration of aggregated albumin to patients with preexisting severe pulmonary hypertension. In case of doubt, it is important to consult your doctor.

Before you are given DRAXIMAGE MACROSALB®

Your doctor must know about all of the following before you are given DRAXIMAGE MACROSALB®. Tell your doctor if you:

  1. Are pregnant:
The use of radiopharmaceuticals during pregnancy should be considered carefully. Your doctor will only administer this product during pregnancy if a benefit is expected which should outweigh the risks.
  1. Are breastfeeding:
Your doctor may advise you to interrupt breastfeeding after the procedure for a period of at least 12 hours and to discard expressed milk during that time. Breastfeeding may be resumed after the prescribed period.

Taking other medicines

Tell your doctor if you are taking any other medicines including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Your doctor or treatment provider has more information on medicines to be careful with or to avoid when you are given DRAXIMAGE MACROSALB®

If you have not told your doctor about any of the above, tell them before you are given any DRAXIMAGE MACROSALB®

About blood products

This product contains albumin, a derivative of human blood. When medicines are made from human blood or plasma, measures are put in place to prevent infection transmission. Despite this, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia specifications by established processes.

How DRAXIMAGE MACROSALB® is given

Your doctor may have special instructions for you to follow to get ready for your procedure.

DRAXIMAGE MACROSALB® is given as an injection into a vein.

DRAXIMAGE MACROSALB® must only be given by a doctor or nuclear medicine technologist. Your doctor is qualified in nuclear medicine and will decide what dose of DRAXIMAGE MACROSALB® you will receive, depending on your condition. The amount of radioactivity you will receive can vary from 37 to 148 MBq (Mega Becquerel, the unit used to express radioactivity).

DRAXIMAGE MACROSALB® is usually given as a single dose and, within minutes after it is given, diagnostic images will be taken.

If you have any questions about taking DRAXIMAGE MACROSALB® or about the diagnostic procedure, ask your doctor.

After being given DRAXIMAGE MACROSALB®

Your doctor may advise you to drink a lot to help the traces of radioactivity leave your body more quickly. This is normal when using diagnostic radiopharmaceuticals. Your doctor will also tell you about any other steps you may need to take following the use of this product.

Do not hesitate to consult your doctor if you are not sure.

Side Effects

Like all medicines, DRAXIMAGE MACROSALB® may cause side effects, although not everybody gets them. Most people have no side effects.

A very small number of patients have experienced allergic reactions such as urticaria (hives or red raised itchy bumps on the skin), nausea and reddening of the face. Local injection site reactions in the form of redness, swelling and itching have also been observed.

Other side effects may include fever, shivering, seizures, sweating, as well as impairments of cardiorespiratory and circulatory functions in the form of changes in respiration, pulse, low blood pressure and fainting.

Importantly, if any side effects gets serious or when in doubt, seek prompt medical attention. If treated immediately, reactions were short-lived.

If you notice side effects not listed in this leaflet, it is important that you speak to your doctor or pharmacist.

Overdose

The dose of DRAXIMAGE MACROSALB® you will receive will be calculated by a qualified nuclear medicine doctor and given to you in a highly specialized setting. Therefore the possibility of overdose is minimal.

Storage

DRAXIMAGE MACROSALB® will be stored by the hospital or clinic.

The hospital or clinic will make sure that DRAXIMAGE MACROSALB® is not used if the expiry date printed on the pack has passed.

Further information

This is not all information that is available on DRAXIMAGE MACROSALB®. If you have any more questions or are not sure about anything, ask your doctor or nuclear medicine technologist.

Product description

What it looks like

DRAXIMAGE MACROSALB® is a white powder. It comes in a 10 mL glass vial.

Ingredients

The active substance is a natural protein from human blood: albumin aggregated.

Each reaction vial contains:

  • 2.5 mg of albumin aggregated
  • 5.0 mg of albumin
  • 0.1 mg of stannous chloride dehydrate
  • 1.2 mg of sodium chloride

Australian Registration Number

AUST R315902

Sponsor

DRAXIMAGE MACROSALB® is

Jubilant Pharma Australia PTY Limited
Freshwater Place
Level 13, 2 Southbank
Boulevard,
Southbank, VIC, 3006 Australia

DRAXIMAGE MACROSALB® is distributed in Australia by:

Distributor:
Australian Nuclear Science and Technology Organisation
New Illawarra Road, Lucas
Heights,
New South Wales 2234
Australia
+61 2 9717 3111

This leaflet was prepared in April 2020.

DRAXIMAGE MACROSALB® is a registered trademark of Jubilant DraxImage Inc.

Published by MIMS January 2021

BRAND INFORMATION

Brand name

Draximage Macrosalb

Active ingredient

Technetium(99mTc) macrosalb

Schedule

Unscheduled

 

Notes

Distributed by Australian Nuclear Science and Technology Organisation

1 Name of Medicine

Albumin Aggregated.

2 Qualitative and Quantitative Composition

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 mg of albumin, 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 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 the albumin in a heating and aggregation process. Each vial contains 3 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 a sterile isotonic sodium pertechnetate solution is added to the vial (The radioisotope is not part of the kit). 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 usage lifetime of the preparation (see Section 4.2 Dose and Method of Administration, Directions for preparation).

3 Pharmaceutical Form

Kit for the Preparation of Technetium Tc 99m Albumin Aggregated Injection - Diagnostic - For Intravenous and Intraperitoneal Use.

4 Clinical Particulars

4.1 Therapeutic Indications

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.

4.2 Dose and Method of Administration

Adult patients.

The recommended dose range for intravenous injection in the average (70 kg) adult patient for lung imaging is 37 to 148 MBq (1 to 4 mCi) of Technetium Tc 99m Albumin Aggregated Injection after reconstitution with oxidant-free Sodium Pertechnetate Tc 99m Injection.
The suggested dosage range for intraperitoneal injection used in the average patient (70 kg) for peritoneovenous (LeVeen) shunt patency evaluation is 37 to 111 MBq (1 to 3 mCi). 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 suggested percutaneous transtubal (efferent limb) dosage range for the average patient (70 kg) is 12 to 37 MBq (0.3 to 1 mCi) in a volume not to exceed 0.5 mL.
The number of particles is to be reduced between 100,000 and 200,000 for patients with severe cardiovascular disease, with pulmonary hypertension accompanied by respiratory insufficiency or with right-to-left shunt.

Elderly patients.

The dose for elderly is unknown. However, they have generally been treated with a similar dose as adult patients.

Pediatric patients.

In pediatric patients, the suggested intravenous dose to be employed for perfusion lung imaging is in the range of 0.925 to 1.85 MBq per kilogram (25 to 50 microCi/kg) of body weight; a usual dose is 1.11 MBq per kilogram (30 microCi/kg), except in newborns, in whom the administered dose should be 7.4 to 18.5 MBq (200 to 500 microCi). Not less than the minimum dose of 7.4 MBq (200 microCi) should be employed for this procedure. The number of particles will vary with age and weight of the pediatric patient as indicated in Table 1.
The number of particles available per dose of Technetium Tc 99m Albumin Aggregated Injection will vary depending on the physical decay of the technetium Tc-99m that has occurred. The number of particles in any dose and volume to be administered may be calculated as follows:
In pediatric patients, the suggested intravenous dose to be employed for perfusion lung imaging is in the range of 0.925 to 1.85 MBq per kilogram (25 to 50 microCi/kg) of body weight; a usual dose is 1.11 MBq per kilogram (30 microCi/kg), except in newborns, in whom the administered dose should be 7.4 to 18.5 MBq (200 to 500 microCi). Not less than the minimum dose of 7.4 MBq (200 microCi) should be employed for this procedure. The number of particles will vary with age and weight of the pediatric patient as indicated in Table 1.
Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit.
Using proper shielding, parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration.
The patient dose should be measured 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.
Gently 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 optimum results and because of rapid lung clearance of the radiopharmaceutical, it is suggested that the patient be positioned 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.

Radiation dosimetry.

The estimated absorbed radiation doses to an average adult patient (70 kg) from an intravenous injection of 148 MBq (4 mCi) of Technetium Tc 99m Albumin Aggregated Injection are shown in Table 2.
In pediatric patients, the radiation absorbed doses using the maximum recommended dose for lung imaging are based on 1.85 MBq (50 microCi) per kilogram of body weight [except in the newborn where the maximum recommended dose of 18.5 MBq (500 microCi) is used] and are shown in Table 1, which lists the maximum dose for pediatric patients from newborn to adults. Note the recommendations regarding number of particles to be administered.
Table 3 represents the absorbed radiation dose resulting from the intraperitoneal administration of 111 MBq (3 mCi) of Technetium Tc 99m Albumin Aggregated.

Directions for preparation.

Note.

Use aseptic procedures throughout and take precautions to minimize radiation exposure by use of suitable shielding. Waterproof gloves should be worn during the preparation procedure.
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 lost.
To prepare Technetium Tc 99m Albumin Aggregated Injection:
1. Remove the protective disc from a reaction vial and swab the rubber septum with either an alcohol swab or a suitable bacteriostatic agent to disinfect the surface.
2. Place the vial in a suitable lead vial shield which has a fitted cap. Obtain 2 to 8 mL of a sterile pyrogen-free Sodium Pertechnetate Tc 99m Injection using a shielded syringe. Sodium pertechnetate Tc 99m solutions containing an oxidizing agent are not suitable for use. The recommended maximum amount of Tc-99m to be added to a reaction vial varies with the number of particles per vial and is shown in Table 4. Other calculations for reconstitution are permitted provided that the patient dose remains within the range prescribed in this package insert (see Section 4.2 Dose and Method of Administration).
3. Using a shielded syringe, add the Sodium Pertechnetate Tc 99m Injection to the reaction vial aseptically.
4. 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. Avoid formation of foam. Using proper shielding, the vial should be visually inspected to ensure that the suspension is free of foreign matter before proceeding. Do not administer if foreign particulates are found in the preparation. To ensure maximum tagging, allow the preparation to stand for 15 minutes after mixing.
5. Assay the product in a suitable calibrator, record the radioassay information on the label with radiation warning symbol, and attach it to the vial shield.
6. The radiochemical purity of the finished preparation should be determined prior to patient administration. The radiochemical purity should not be less than 90%.
7. 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, replacement of the contents with air should be minimized.
8. Retain the reconstituted product in the lead vial shield with cap in place during its in-use shelf life. Store the reconstituted product at 2°C to 8°C (36°F to 46°F) when not in use and discard within 12 hours depending on the number of particles per vial, the activity added at reconstitution and the final dose to be administered to the patient (see Section 4.2 Dose and Method of Administration).

4.3 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 albumin.

4.4 Special Warnings and Precautions for Use

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.

General precautions.

The contents of the kit before reconstitution are not radioactive. However, after the sodium pertechnetate Tc-99m is added, maintain adequate shielding of the reconstituted product.
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°C to 8°C and discarded 12 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 non-uniform 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.

Pathogen safety.

This product contains albumin, a derivative of human blood. When medicines are made from human blood or plasma, measures are put in place to prevent infection transmission. Despite this, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia specifications by established processes.
It is recommended that the name and batch number of the product be recorded in order to document the batches utilized.

Use in the elderly.

No data available.

Pediatric use.

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

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Changes in the biological distribution of Technetium Tc 99m Albumin Aggregated could be induced by different medicinal products.
Theoretical considerations should be given to toxicological interactions with various chemotherapeutics, heroin, busulfan, nitrofurantoin and methysergide.
Pharmacologic interaction may be expected with bronchodilators, heparin and chemotherapeutic agents. Interaction with chemotherapeutic agents could result in an increased bone marrow uptake.
Pharmaceutical interaction could result from the concomitant administration of cations, such as magnesium, leading to flocculation (aggregation) of Albumin Aggregated particles.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No long term animal studies have been performed to evaluate whether Technetium Tc 99m Albumin Aggregated Injection affects fertility in males or females.
(Category C)
Since adequate reproduction studies with technetium Tc 99m Albumin Aggregated Injection have not been performed in animals to determine whether this drug affects fertility in males and females, has teratogenic potential or has other adverse effects on the foetus, this radiopharmaceutical preparation should not be administered to pregnant or nursing women unless it is considered that the benefits to be gained outweigh the potential hazards to the foetus and safer alternative procedures are not available.
When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Where uncertainty exists it is important that radiation exposure should be minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation should be considered.
 Technetium-99m is excreted in human milk. Interruption to breast feeding is necessary after the administration of Technetium Tc 99m Albumin Aggregated Injection for a period of at least 12 h.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

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 Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Healthcare professionals should report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption and distribution.

The early use of radiolabelled Macrosalb in humans already gave initial data on the pharmacokinetic profile of this compound. As indicated above, after intravenous injection the lung capillary beds efficiently extract the particles from the bloodstream with (almost) no activity detectable in other organs. Distribution studies have confirmed these earlier data and showed that 87% of the dose will be trapped in the lungs of patients (Furth et al., 1965).
Some pathological conditions may lead to disturbances in this distribution pattern. A case report describes the extrapulmonary uptake in the spleen after lung scanning without any right-left shunting being present. Partial fragmentation of the particles and subsequent phagocytosis by leucocytes which then are trapped in splenic sinusoids is considered the only possible explanation (Hellin et al., 1992).
When used for venoscintigraphic purposes (vide infra) in the presence of circulatory defects, such as superior and inferior vena cava obstruction, hepatic localization of Macrosalb has been described as a consequence of alternate pathways of venous return (Kolla et al., 1989; Rieker et al., 1993).
Likewise, significant radioisotope uptake in the lungs, brain, spleen and both kidneys was demonstrated in 2 patients with liver cirrhosis associated with marked hypoxemia (Shijo et al., 1989). The increased passage of Macrosalb particles through widened pulmonary capillaries (pulmonary telangiectasia) rather than the occurrence of small pulmonary arterio-venous shunts is considered as the cause of this aberrant distribution pattern.
A number of reports exist which describe measurable concentrations of (assumed free pertechnetate) radioactivity in the expressed breast milk of mothers with babies (Cranage and Palmer, 1985; Ahlgren 1985; Rose 1997). Cranage showed that the fraction of the original dose which entered into the milk was 8 x 10-5/mL at 4 hours after administration, while at 24 hours post-injection this was decreased to 0.1-0.2 x 10-5/mL. Based on these data it was calculated that the cumulative absorbed dose for the baby varied from 6.1 mrad to 0.2 mrad when starting breastfeeding 4 hours after the injection or 24 hours after the injection respectively. The authors consider a 24-hour break in feeding ideal from a radiation-protection viewpoint as this reduces both the internal radiation caused by milk consumption and the external radiation received by the infant whilst being nursed by the mother. Others have suggested 12 hours is an adequate interval (Stabin 2000).

Metabolism and excretion.

The major mechanism of the clearance from the lungs of the particles is breakup of large aggregates into smaller ones capable of passing through the capillaries to enter the main bloodstream. Therefore the smaller the particle size, the more rapid the clearance. This aggregate breakup can be caused by hemodynamic pressure and pulsation as well as by vessel contraction (Davis, 1975). In commercial preparations of 131I-Macrosalb it was shown that the percent activity remaining in the lungs 24 hours after injection correlates well with the percentage of activity on particles greater than 50 microm in the initial dose.
Early clinical studies (Wagner et al., 1964) showed that in 4 patients the half-time of 131I-Macrosalb for the disappearance from the lungs varied from 5-10 hours. More detailed experiments followed shortly (Furth, 1965) and demonstrated that the disappearance of radioactivity from the lungs of 9 patients was multi-exponential with a mean biological half-time of the rapid initial component of 0.25 days and of the second component, of 3.2 days. Total serum and protein bound activity also disappeared in a multi-exponential fashion and half-time values for both types of activity were virtually identical in man with a mean value of 0.44 day for the initial phase and 4.0 days for the second phase. It could not be made clear whether the slower component represented a typical compartment in the body or the disappearance of a distinctly different material.
Urinary investigations also revealed that about 95% of the radioactivity was iodide and by seven days a total of 72 ± 9% had been accounted for in the urine. There was no significant foetal excretion in 2 patients studied for 72 hours.
In a study including 24 patients and various batches of a commercial product of 131I-Macrosalb, a significant variation between batches and between patients was observed (Spencer, 1972) with the retention half-time varying from 7-31 hours. It was postulated that this variability was related to the progress of the underlying disease. Altered hemodynamics, for example, could seriously influence both the fragmentation of the initial particles as well as the rate of removal of the particle fragments from the lungs.
Pharmacokinetic results obtained initially with 99mTc-Macrosalb showed that the switch from 131I-Macrosalb to 99mTc-Macrosalb did not significantly influence the elimination half-life in the lungs as this was established at approximately 11 hours, using the 2nd-generation preparation (including stannous chloride). However, due to the more rapid radioactive decay of 99mTc the effective half-life was calculated at 236 ± 26 min. in seven patients (Chandre et al., 1973). Equal to the results described above, urinary excretion proceeded only slowly with 33% of the injected dose excreted in the first 24 hours and 50-60% in 72 hours. The radioactivity detected in the blood at 15 min., 4 hours, and 24 hours did not reveal much variation and was always less than 0.015% of the injected dose.
After the initial fragmentation of the albumin particles, the fragments are transported by the bloodstream towards the liver where they are trapped by the reticuloendothelial cells and subsequently are catabolized following the regular pathway for protein metabolism (Bocci, 1990). This pathway includes the presence of various serine-, cysteine-, aspartic- and metallo-proteinases in body fluids that can potentially hydrolyze any protein, including albumin. Parallel to the presence of these enzymes proteinase inhibitors (acute phase proteins) occur and which modulate the activity of the proteinases. However, the most important aspect is intracellular catabolism following phagocytosis by the reticuloendothelial cells or after internalization of the albumin-receptor complex formed by individual albumin molecules. Subsequently intracellular proteinases will be responsible for the catabolism of the albumin molecules. Early studies have shown this catabolism to proceed very rapidly in man with a half-time of approximately 20 minutes for the albumin accumulated in the liver (Taplin et al., 1963). At the same time, this rapid rate of proteolytic digestion and radiomarker release from the liver can be slowed by a factor of 2 or more by the simultaneous administration of unlabeled aggregates.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Please see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

The finished preparation should be discarded 12 hours after reconstitution. Do not use the kit beyond the expiry date stamped on the box.

6.4 Special Precautions for Storage

The vials are sealed under an atmosphere of nitrogen. The unreconstituted reaction vials should be stored at 2°C to 25°C.
After labeling with technetium Tc-99m, store the reconstituted product at 2°C to 8°C when not in use and discard within 12 hours (see Directions for preparation).
The reconstituted product should be stored during its in-use shelf life in a lead vial shield with cap in place.

6.5 Nature and Contents of Container

Draximage Macrosalb (ARTG # 315902) comprises:
10 multi-dose glass vials. Each vial contains a non-radioactive sterile, non-pyrogenic lyophilized mixture of: albumin aggregated 2.5 mg, albumin 5.0 mg, sodium chloride 1.2 mg, stannous chloride dihydrate 0.1 mg.
2 x 5 Radiation Labels.
1 Package Insert.
HCl and/or NaOH has been used for pH adjustment. The vials are sealed under an atmosphere of nitrogen.

6.6 Special Precautions for Disposal

The residual materials may be discarded in the ordinary trash, provided the radioactivity in the vials and syringes measures no more than background with an appropriate low-range survey meter. All identifying labels should be destroyed before discarding.

6.7 Physicochemical Properties

Chemical Structure and CAS Number are unidentified.
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 5.

External radiation.

The specific gamma ray constant for technetium Tc-99m is 0.78 R/mCi-hr at 1 cm.
The first half value layer is 0.017 cm of lead. 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.
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.

References

1. Kocher David C., "Radioactive Decay Data Tables", DOE/TIC-11026, 108 (1981).
2. Absorbed Dose per Unit Cumulated Activity for Selected Radionuclides and Organs, MIRD Pamphlet No. 11 (1975).
3. Kaul A., Oeff K., Roedler H.D. and Vogelsang T., Die Strahlenbelastung von Patienten bei der Nucklearmedizinischen Anwendung Offener Radioaktiver Stoffe. Informationsdienst fur Nuklearmedizin. Klinikum Steglitz der Freien Universitat 1000 Berlin 45, Hindenburgdamm 30, Herausgerber : Prof. Dr. Med. Karl Oeff, Berlin, 1973.
4. Henrichs K., Kaul A. and Krause M., Altersabhangige Werte der Spezifischen Organdosis. Klinikum Steglitz, Physik und Strahlenschutz (Biophysik), Freie Universitat Berlin, Berlin, 1980.
5. Parker J.A., Coleman R.E., Grady E., Royal H.D., Siegel B.A., Stabin M.G., Sostman H.D., Hilson A.J., Society of Nuclear Medicine. SNM practice guideline for lung scintigraphy 4.0. J Nucl Med Technol. 2012.
6. Bajc M., Neilly J.B., Miniati M., Schuemichen C., Meignan M., Jonson B., EANM Committee. EANM guidelines for ventilation/perfusion scintigraphy: Part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging 2009; 36(8):1356.
7. Stabin M.G.1, Breitz H.B., Breast milk excretion of radiopharmaceuticals: mechanisms, findings, and radiation dosimetry. J Nucl Med. 2000 May; 41(5):863-73.
8. Cranage R., Palmer M., Breast-milk radioactivity after 99mTc-MAA lung studies. Eur J Nucl Med. 1985; 11(6-7):257-9.
9. Howe D.B., Beardsley M., Bakhsh S.R., Office of Federal and State Materials and Environmental Management Programs U.S. Nuclear Regulatory Commission Washington, DC. Consolidated Guidance About Materials Licenses Program-Specific Guidance About Medical Use Licenses. NUREG - 14556 2008; 9(2).
10. Michael A. Davis, Particulate Radiopharmaceuticals for Pulmonary Studies, 1975; IV-00311 (267-281).

7 Medicine Schedule (Poisons Standard)

Not scheduled.