FDA Label for Megatope

Caution

Federal (USA) law prohibits dispensing without prescription

Description

Megatope (Iodinated I 131 Albumin Injection) is a diagonostic radiopharmaceutical
containing iodinated I 131 albumin for intravenous use. Each mL of sterile, nonpyro-
genic, aqueous, colorless to very pale yellow solution provides approximate 10 mg
protein (albumin human), 16 mg dibasic sodium phosphate, 1.6 mg monobasic
sodium phosphate, not more than 0.4 guanidine hydrochloride, sodium chloride
for isotonicity, and 9 mg benzyl alcohol as a preservative. The pH has been adjusted
to 7.2 to 7.8 with sodium hydroxide or hydrochloric acid.
Megatope was prepared from blood that was nonreactive when tested for hepatitis
B surface antigen (HBsAg).
The structure of the complex is unknown.

Physical Characteristics

Iodine 131 decays by beta and gamma emissions with a physical half-life of 8.08 days.¹

Photons that are useful for detection and imaging studies are listed in Table 1.

External Radiation

The specific gamma ray constant for iodine 131 is 2.2 R/hour-millicurie at 1 cm. The 

first half-value layer is 0.24 cm lead (Pb). A range of values for the relative attenuation

of the radiation emitted by this radionuclide that result from interposition of various

thicknesses of Pb is shown in Table 2. To facilitate control of the radiation exposure

from this radionuclide, the use of a 2.55 cm thickness of Pb will attenuate the radiation

emitted by a factor of about 1,000.

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 can also 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 published 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 biological 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

dilineation, localization of the placenta, and localization of celebral neospasms.

Contraindications

None Known.

Warnings

A few instances of hyperpyrexia and aseptic (chemical) meningeal irritation have 

been reported with the use of iodinated I 131 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. 

    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.

Carcinogenesis, Mutagenesis,

Impairment of Fertility

No long-term animal studies have been performed to evaluate carcinogenic potential 

or whether iodinate I 131 albumin affects fertility in males and 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 adminis-

tered 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 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.

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 I 131 Albumin Injection) is administered intravenously. Parenteral 

drug products should be inspected visually for particulate matter and abnormal 

coloration prior to administration whenever solution and container permit.

Megatope (Iodinated I 131 Albumin Injection) may be colorless to very pale yellow. 

Solutions with excessive colorations 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 a 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.

A. 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 the 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 other arm with a sterile heparinized syringe.

B. 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 to zero time. The x ordinate iof the graph is the sample

    withdrawal time and the logarithmic y ordinate is radioconcentration in

    net cpm/mL.

3. Calculate the patient's blood volume (in mL) using the following formula:

      Net cpm/mL reference solution               ×    DF = blood volume (in mL)

   Net cpm/mL patient's blood sample

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 x 4000 = 4360 mL
                                                 48,100

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 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           ×  DF    =        blood
Net cpm/mL                       Net cpm/mL                       volume
postinjection     minus         background
blood sample                     blood sample                      (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                ×     DF    =   plasma volume
  Net cpm/mL patient's plasma sample                                   (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 the dose.

Heart and Great Vessel Delineation

The suggested dosage is 5 microcuries per kg of body weight, although doses up to

750 microcuries have been used, depending on the instrumentation available and the

scanning technique employed.

Localization of the Placenta

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 this hazard.

Localization of Celebral Neospasms

The suggested dosage is 5 microcuries per kg of body weight. Although doses as

large as 500 microcuries of Iodinated I 131 Albumin Injection 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.

How Supplied

Megatope (Iodinated I 131 Albumin Injection USP) is available in multiple dose vials

containing the following amounts of activity on the date of calibration: 500

microcuries and 1.0 millicurie. Complete assay data for each vial are provided on the 

container.

   The maximum concentration of Iodinated I 131 Albumin Injection does not exceed 

one millicurie per milliliter at a time of calibration.

Storage

Store between 2° and 8° C.

Other

This radiopharmaceutical is licensed by the Texas Department of Health, Bureau of Radiation Control for distribution to persons licensed

pursuant to 41.26(b) and Appendix 41-C, Group I and Group II, "Texas Regulations for Control of Radiation," or under equivalent licenses of

the U.S. Nuclear Regulatory Commission, an Agreement State, or a Licensing State.

Iso-Tex Diagnostics, Inc.

P.O. Box 909 . Friendswood, Texas 77546 . USA . (713) 482-1231
Telex (ITT) 499-8324 ITDI UI . FAX: (713) 482-1070