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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 syringecontaining
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 postinjection 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
postinjection 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 |
