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*Calibration time
CLINICAL PHARMACOLOGY
Following intravenous injection, radioiodinated albumin human is
uniformly distributed throughout the intravascular pool within 10
minutes; extravascular distribution takes place more slowly. Iodinated I
131 albumin also can be detected in the lymph and in certain body
tissues within 10 minutes after injection, but maximum distribution of
radioactivity throughout the extravascular space does not occur until
two to four days after administration. The time at which extravascular
activity is maximal has been designated as the "equilibrium time." When
this point has been reached, the radioactivity remaining in the
intravascular and extravascular spaces decreases slowly and
exponentially in parallel fashion.The administered radioactivity is
eliminated almost entirely in the urine, only about 2 percent of the
total dose ultimately appearing in the feces. The biologic half-life of
iodinated I 131 albumin is dependent upon a number of factors, and
publish studies have varied considerably in their reporting of this
figure. It has ranged, in the literature, from below 10 days to over 20
days. One important factor affecting the biologic half-life is the
initial rate of excretion, and this depends in part on the quality of
the iodinated I 131 albumin. With Megatope, the biologic half-life in
normal individuals has been reported to be approximately 14 days.
INDICATIONS AND USAGE
Megatope (Iodinated I 131 Albumin Injection) is indicated for use in
determinations of total blood and plasma volumes, cardiac output,
cardiac and pulmonary blood volumes and circulation times, and in
protein turnover studies, heart and great vessel delineation,
localization of the placenta, and localization of cerebral neoplasms.
CONTRAINDICATIONS
None known.
WARNINGS
A few instances of hyperpyrexia and aseptic (chemical) meningeal
irritation have been reported with the use of iodinated I 131 albumin in
cisternography. Iodinated I 131 Albumin injection is not approved
for use in cisternography.
PRECAUTIONS
General
In the use of any radioactive material, care should be taken to
insure minimum radiation exposure to the patient and occupational
workers consistent with proper patient management.Radiophaemaceuticls
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.
Carcinogens, Mutagenesis, Impairment of Fertility
No long-term animal studies have been performed to evaluate
carcinogenic potential or whether iodinated I 131 albumin affects
fertility in males or females.
Pregnancy Category C
Animal reproduction studies have not been conducted with Iodinated I
131 Albumin Injection. It is also not known whether this agent can cause
fetal harm when administered to a pregnant woman or can affect
reproduction capacity. Iodinated I 131 Albumin injection should be
administered to a pregnant woman only if clearly needed.Ideally,
examinations using radiopahrmaceuticals, 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.
Nursing Mothers
Since iodine 131 is excreted in human milk during lactation ,
formula feedings should be substituted for breast feedings.
Pediatric Use
Safety and effectiveness in children have not been established.
ADVERSE REACTIONS
Although the immunological properties of albumin human are believed
to be virtually unaltered by the iodination process, there is a
theoretical possibility that allergic reactions may occur in patients
receiving additional doses a number of weeks after an initial dose.
DOSAGE AND ADMINISTRATION
Megatope (Iodinated 131 Albumin Injection) is administered
intravenously. Parental drug products should be inspected visually
for particulate matter and abnormal coloration prior to administration
whenever solution and container permit.Megatope (Iodinated 131 Albumin
Injection) may be colorless to very pale yellow. Solutions with
excessive coloration should not be used.When a procedure such as blood
volume or a circulation time determination is to be repeated, the total
dosage administered in any one week should not exceed 200 microcuries.To
minimize the uptake of radioactive iodine by the thyroid, prior
administration of Lugol 's Solution (Strong Iodine Solution USP)
may be used. Ten drops of Lugol's Solution three times daily,
beginning at least 24 hours before administration of Megatope and
continuing for one or two weeks thereafter, is a suitable dose.Complete
assay data for each vial are provided on the container.
Note: The expiration date given on the container pertains to the
biologic properties of the material and not to the radioactivity level.
It is important to make certain that the radioactivity in the dose at
the time of administration is sufficient for the intended use.The
patient dose should be measured by a suitable radioactivity calibration
system immediately prior to administration.
Note: A shielded syringe should be used for withdrawing and
injecting the iodinated I 131 albumin.
Total Blood and Plasma Volumes
Dosage may range from 5 to 50 microcuries.
Blood Volume Determination
A. Preparation of Reference Solution
Remove an aliquot of the contents of the vial to be used in the
procedure identical in volume to the dose to be administered to the
patient. Prepare a reference solution using normal saline as diluent.
The recommended dilution is 1:4000 [Dilution Factor (DF) = 4000].
Determine the radioactivity concentration (net cpm/mL) of the reference
solution. Care must be taken to assure that the reference solution and
the blood samples (Step B3) are assayed using the same geometric
configuration.
B. Administration of Dose
1. Inject the dose into a large vein in patient 's arm.
Measure the residual radioactivity in the syringe and needle.
2. Destroy syringe after injecting. Do not attempt to
resterilize.CAUTION: The syringe should be disposed of in accordance
with the US Nuclear Regulatory Commission or Agreement State regulations
pertaining to the disposal of radioactive waste.
3. At 5 and 15 minutes after injecting the dose, withdraw blood samples
from the patient's arm with a sterile haparinized syringe.
C. Calculation of Blood Volume
1. Take a known aliquot from each blood sample and determine
radioconcentration in net cpm/mL.
2. Plot the 5- and 15- minute sample counts (net cpm/mL) on semilog
graph paper using the average count value of each sample and determine
the radioconcentration at injection time (zero time) by drawing a
straight line through the 15- and 5- minute points at zero time. The x
ordinate of the graph is the sample withdrawal time and the logarithmic
y ordinate is radioconcentration in net cpm/mL.
3. Calculate patient's blood volume (in mL) using the following
formula:
(Net cpm/mL reference solution / Net cpm/mL patient's blood
sample) x DF = blood volume (in mL)
Sample Blood Volume Calculations
Volume of blood sample aliquot = 1.0 mL
Volume of reference solution aliquot = 1.0 mL
Net counts at zero time =
48,100
Net counts obtained from reference solution aliquot = 52,430
Using the formula above gives (52,430 / 48,100) x 4000 = 4360 mL
Serial Blood Volume Determinations
Iodinated I 131 Albumin Injection is administered in sufficiently
low dosage to permit repetitions as often as required by clinical
circumstances. It must be remembered that it is always necessary to
correct for background radioactivity remaining in the blood from former
determinations. Therefore, for each determination after the first one, a
background blood sample must be taken just before the iodinated I
131 albumin is injected.
Background Blood Sample
1. Withdraw background blood sample from large vein in patient's
arm with a sterile heparinized syringe.
2. Leaving needle in patient's vein, detach syringe containing
blood sample.
3. Attach syringe containing the dose of Megatope to the indwelling
needle and administer (see instructions under Blood Volume
Determination, Administration of Dose).
4. Determine radioconcentration in net cpm/mL of aliquots taken from
background and post injection blood samples, and from the reference
solution. The radioconcentration (net cpm/mL) per aliquot of the
background blood sample must be subtracted from the radioconcentration
per aliquot of the blood sample obtained after the injection of
iodinated I 131 albumin. The formula for calculating each blood volume
determination after the first one thus becomes:
[Net cpm/mL reference solution / (Net cpm/mL post injection blood sample
- net cpm/mL background blood sample)] x DF = blood volume (in mL)
Plasma Volume Determination
The procedure is essentially the same as that for blood volume
determination, except that the blood sample drawn from the patient is
centrifuged, the red blood cells are removed, and net cpm/mL of the
plasma is determined. The formula for calculation of plasma volume,
therefore, is:
(Net cpm/mL reference solution / Net cpm/mL patient's plasma
sample) x DF = plasma volume (in mL)
Cardiac Output
Dosage generally ranges from 3 to 50 microcuries.
Cardiac and Pulmonary Blood Volumes; Circulation Times
Dosages used have generally been 75 to 130 microcuries.
Protein Turnover Studies
Dosages used have ranged from 10 to 150 microcuries. After
injection, a period of seven days should be allowed before
determinations are made to permit the elimination of any degraded
protein in dose.
Heart and Great Vessel Delineation
For localization of the placenta in the differential diagnosis of
placenta praevia, a 3 to 5 microcurie dose is recommended; this dose has
proved adequate for excellent localization, and the fetal total body
radiation is a fraction of that received during x-ray placentography.
While fetal thyroid irradiation is higher with iodinated I 131 Albumin
Injection than with x-ray placentography, the administration of Lugol's
Solution is reported to eliminate hazard.
Localization of Cerebral Neoplasma
The suggested dosage is 5 microcuries per kg of body weight.
Although doses as large as 500 microcuries of Iodinated I 131 Albumin
have been used, the dose should be kept as small as possible. Dosage is
administered six hours before the initial examination, and scans are
repeated at periodic intervals.
Radiation Dosimetry
The estimated absorbed radiation doses to an average patient (70 kg)
from an intravenous injection of 50 microcuries of Iodinated I 131
Albumin Injection USP are shown in Table 4.
TABLE 4
Estimated Absorbed Radiation Doses |
