Rubratope-57

Generic Name: cyanocobalamin CO-57
Dosage Form: Diagnostic capsules

RUBRATOPE®-57
Cyanocobalamin Co 57 Capsules USP
DIAGNOSTIC CAPSULES

Rubratope-57 Description

DESCRIPTION Rubratrope-57 diagnostic capsules for oral administration provide radioactive cyanocobalamin in which a portion of the molecules contain Co 57 in the molecular structure vitamin B12-57Co. The chemical structure of cyanocobalamin is given below:

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Each Rubratope-57 capsule contains approximately 18.5 to 37 kBq (0.5 to 1.0 microcurie) of cyanocobalamin Co 57; the cyanocobalamin content of each capsule will vary with the specific activity of the cyanocobalamin Co 57 used. Complete assay data are provided on the vial label.

PHYSICAL CHARACTERISTICS

Cobalt 57 decays by electron capture with a physical half-life of 270.9 days.1 Photons that are useful for detection and imaging studies are listed in Table 1.

TABLE I
Principal Radiation Emission Data

Radiation
Mean % per
Disintegration
Mean Energy
(keV)
Gamma-2 85.5 122.1
Gamma-3 10.6 136.5
1
Kocher, David C., “Radioactive Decay Data Tables”, DOE/TIC-11026, (1981) p.77.

External Radiation

The specific gamma ray constant for Co 57 is 0.96 R/hour-millicurie at 1 cm. The first half-value thickness of Pb (lead) for Co 57 is 0.006 cm. To facilitate control of the radiation exposure, a range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 2. For example, the use of 1.6 cm of Pb will decrease the external radiation exposure by a factor of about 1,000.

TABLE 2
Radiation Attenuation by Lead Shielding
Shield Thickness
(Pb) cm
Attenuation
Factor
To correct for physical decay of Co 57, the fractions that remain at selected intervals before and after calibration time are shown in Table 3.
   0.006 0.5
  0.05 10-1
  0.14 10-2
1.6 10-3
3.5 10-4
TABLE 3
Physical Decay Chart: Co 57 half-life 270.9 days
Days Fraction
Remaining
Days Fraction
Remaining
*Calibration time
0* 1.000   75 0.825
0.987   90 0.794
10  0.975 105 0.764
15  0.962 120  0.736
30  0.926 135 0.708
45  0.891 150 0.681
60  0.858 165 0.656
180 0.631

Rubratope-57 - Clinical Pharmacology

After oral administration, cyanocobalamin is normally bound by intrinsic factor and absorbed by the distal ileum. It is then bound to plasma proteins, stored in the liver, and slowly released when needed to carry out normal cellular metabolic functions. Absorbed cyanocobalamin is ultimately excreted in the urine; any cyanocobalamin not bound by intrinsic factor is excreted in the stool.

Indications and Usage for Rubratope-57

Rubratope-57 (Cyanocobalamin Co 57 Capsules) is intended for the diagnosis of pernicious anemia and as a diagnostic adjunct in other defects of intestinal vitamin B12 absorption.

Contraindications

None known.

Warnings

None.

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.

Because a large parenteral dose of vitamin B12 may temporarily affect subsequent intestinal absorption and excretion of the vitamin, tests employing radioactive vitamin B12 should not be performed for at least 24 hours after either a flushing dose for the Schilling test or a therapeutic injection (1000 micrograms) of vitamin B12.

Drug Interactions

Most antibiotics, methotrexate, pyrimethamine, colchicine, para-aminosalicylic acid, or excessive alcohol intake for longer than two weeks may result in malabsorption of vitamin B12.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed to evaluate carcinogenic potential or whether this agent affects fertility in males or females.

Pregnancy: Teratogenic Effects

Category C

Animal reproduction studies have not been conducted with Cyanocobalamin Co 57 Capsules. It is also not known whether this agent can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Since vitamin B12-57Co is taken up by the fetus, radiocyanocobalamin absorption tests in pregnant women should be postponed until after delivery unless the potential benefit justifies the potential risk to the fetus.

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

Nursing Mothers

Since vitamin B12-57Co 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

No adverse reactions specifically attributable to Cyanocobalamin Co 57 Capsules have been reported.

The following adverse reactions have been reported with nonradioactive cyanocobalamin: mild transient diarrhea, polycythemia vera, peripheral vascular thrombosis, itching, transitory exanthema, feeling of swelling of the entire body, congestive heart failure and pulmonary edema, anaphylactic shock, and death.

Rubratope-57 Dosage and Administration

The suggested oral dose range for the average patient (70 kg) when performing a Schilling urinary excretion test is between 18.5 to 37 kBq (0.5 to 1 microcurie) of cyanocobalamin Co 57.

The patient dose in each Cyanocobalamin Co 57 Capsule should be measured by a suitable radioacttivity calibration system immediately prior to administration.

Schilling Urinary Excretion Test1,2

Test Procedure

The patient should be instructed to fast (patient may have water) for 12 hours prior to the test. Vitamin B12 should not be administered orally or parenterally during the preceding 24 hours. It is important to establish the absence of any potentially interfering gamma-emitting radioisotopes in the patient’s urine prior to starting the study.

After the patient voids, administer one Rubratope- 57 (Cyanocobalamin Co 57) capsule. Inject 1000 µg non-radioactive Cyanocobalamin Injection USP intramuscularly as a flushing dose two hours following administration of the capsule. Collect and pool all urine for 24 hours and mix thoroughly. Collect an additional 24 hour sample separately if renal function is impaired or if urinary excretion is delayed.

Determine 10-minute net radioactivity counts for a 4 mL sample of urine from each excretion period, and a 4 mL sample of diluted Cobatope-57 (Cobaltous Chloride Co 57 Reference Standard Solution). The working standard is prepared by diluting 0.5 mL Cobatope-57, which contains the equivalent of 1 percent of the total radioactivity in the oral dose, with 3.5 mL of water. Calculate as follows:

                          counts per                    volume
                             minute             x       of urine
                     per mL of urine(a)            collected                              of
                   ————————————————    x 100 = %    administered
                          counts per                                                               dose
                             minute             x          100(c)
                        of standard(b)

(a)
The measurement of radioactivity of the urine sample was a 10-minute count on a 4 mL sample. To convert to counts per minute per mL, divide by 40 (10 minutes x 4 mL).
(b)
The count rate of the 4 mL standard is divided by 10 in order to obtain the counts per minute.
(c)
1% standard, so dilution factor is 100.

Results

Values of 9 percent or more for samples excreted during either the first 24 hour period or first and second 24 hour periods combined, are generally considered to represent a normal state for vitamin B12 absorption. The test should be repeated if a lower result is obtained.

Retest Procedure

The need for repeating a test should be carefully evaluated, especially in younger patients. A retest can be conducted four or five days following the primary test. Administer one Intrinsic Factor Concentrate capsule with a Rubratope-57 (Cyanocobalamin Co 57) capsule. Repeat all other steps of the primary procedure. Retest values greater than 9 percent are indicative of pernicious anemia; values of less than 9 percent are indicative of bacterial interference, malabsorption or ileal lesion.

An additional retest can be conducted to determine malabsorption or bacterial interference. Administer antibiotics, in lieu of Intrinsic Factor, 10 to 14 days prior to the second retest. Repeat all other steps of the primary procedure. Values greater than 9 percent are indicactive of bacterial interference; values of less than 9 percent are indicative of lack of ileal absorption sites.

Radiation Dosimetry

The estimated absorbed radiation doses to an average patient (70 kg) from an oral dose of 37 kBq (1 microcurie) of vitamin B12-57 Co are shown in Table 4.

TABLE 4
Estimated Absorbed Radiation Doses
Tissue mGy/37kBq Co57 (rads/uCi)
Normal Pernicious
Anemia
Liver 1.3* (0.13*) 0.26 (0.026)
Stomach 0.00081 (0.000081) 0.0011 (0.00011)
Small Intestine 0.0013 (0.00013) 0.0040 (0.00040)
Upper Large
   Intestine
0.0025 (0.00025) 0.0076 (0.00076)
Lower Large
   Intestine
0.0060 (0.00060) 0.018 (0.0018)
Testes 0.052 (0.0052) 0.0012 (0.00012)
Ovaries 0.065 (0.0065) 0.0057 (0.00057)
Whole-body 0.099 (0.0099) 0.013 (0.0013)

Method of Calculation: “S” Absorbed Dose per Unit Cumulated Activity for Selected Radionuclides and Organs, MIRD Pamphlet No. 11 (1975).

*The administration of a flushing dose of nonradioactive vitamin B12 will decrease the dose to the liver, gonads, and whole-body from Co 57 by about 30 percent.

How is Rubratope-57 Supplied

Rubratope-57 (Cyanocobalamin Co 57 Capsules) is available in bottles of 5 and 10 capsules. Each two-piece blue/red capsule contains approximately 18.5 to 37 kBq (0.5 to 1 microcurie) at the time of calibration. Complete assay data are provided on the container.

Also Available

Cobatope-57 (Cobaltous Chloride Co 57 Reference Standard Solution), supplied in 10 mL vials, is manufactured in companion lots to the diagnostic capsules. Cobatope-57 is intended for laboratory use only as a standard of comparison to the diagnostic capsules. Each mL of aqueous solution provides activity equivalent to 2 percent of the total radioactivity in each capsule bearing the same lot number as the reference standard solution. No decay corrections are necessary when the capsules are used with a companion vial of Cobatope-57 (Cobaltous Chloride Co 57 Reference Standard Solution).

Rubratope-57 Diagnostic Kit (Cyanocobalamin Co 57 Diagnostic Kit) provides material for primary and initial retesting (Schilling test) for two patients.

Storage

Rubratope-57 (Cyanocobalamin Co 57) capsules should be stored at 20-25°C (68-77°F) [See USP].

REFERENCES

  1. McIntyre PA: “Use of Radioisotope Techniques in the Clinical Evaluation of Patients with Megaloblastic Anemia”, Semin in Nucl. Med. 5:1 (1975), 79-94.
  2. Nickoloff EL: “Alternatives to Vitamin B12 Radioassays: The Schilling Test”, The Ligand Quart 2: (1979), 27-29.

“This package conforms to the conditions and limitations specified in 49 CFR 173.421 for exempted radioactive material, limited quantity, N.O.S. UN 2910”.

Receipt, transfer, handling, possession or use of this product is subject to the radioactive materials regulations and licensing requirements of the U.S. Nuclear Regulatory Commission, Agreements States or Licensing States as appropriate.

Manufactured for
Bracco Diagnostics Inc.
Princeton, NJ 08543
by Amersham plc Little Chalfont England

L/4734/04/04
Revised April 2004

Rubratope-57 
cyanocobalamin, co-57 capsule, gelatin coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) 0270-3866
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cyanocobalamin, CO-57 (cyanocobalamin, CO-57) cyanocobalamin, CO-57 1 uCi
Product Characteristics
Color RED (scarlet) , BLUE (blue) Score no score
Shape CAPSULE Size 18mm
Flavor Imprint Code
Contains         
Coating false Symbol false
Packaging
# Item Code Package Description
1 NDC:0270-3866-10 5 CAPSULE, GELATIN COATED (5 CAPSULE) in 1 BOTTLE
2 NDC:0270-3866-20 10 CAPSULE, GELATIN COATED (10 CAPSULE) in 1 BOTTLE
Labeler - Bracco Diagnostics Inc.
Revised: 03/2007
 
Bracco Diagnostics Inc.

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