Cyanocobalamin Co 57 (Systemic)


VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): Dicopac; Rubratrope-57.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid, radioactive (cyanocobalamin malabsorption syndromes)—

Indications

Accepted

Anemia (diagnosis)—Cyanocobalamin Co 57 is indicated in the diagnosis of pernicious anemia. {01} {1a} {08} {14} {23}

Vitamin B 12 deficiency (diagnosis adjunct)—Cyanocobalamin Co 57 is indicated as an adjunct in diagnosing intestinal cyanocobalamin malabsorption syndromes due to lack of intrinsic factor (IF) or other defects in intestinal absorption (e.g., blind loop syndrome and diverticulitis, celiac disease, Crohn's disease, lesions in the small intestine, severe pancreatitis, tropical sprue). {01} {1a} {02} {08} {23}
—Cyanocobalamin Co 57 may be used either in fecal excretion determinations of unabsorbed cyanocobalamin or urinary excretion determinations (Schilling test) of absorbed cyanocobalamin. However, a normal Schilling test does not rule out the possibility of vitamin B 12 deficiency. {05} {06} {10} {13}


Physical Properties

Nuclear data:

{01}{1a}{02}{22}{23}

Radionuclide
(half-life)
Mode of
decay
Principal
emissions
(keV)
Mean number
of
emissions/
disintegration
Co 57
(270.9 days)
Electron
capture
Gamma (122)
0.86
Co 58
(71.3 days)

Electron
capture 85%

Gamma 99%
(810.5)


0.84

  Positron
emission 15%
Annihilation
200%
(511)

0.30


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

The action of cyanocobalamin Co 57 in the body is identical to that of dietary cyanocobalamin. In order to be readily absorbed from the gastrointestinal tract, it must form a complex with intrinsic factor (IF). The absorption or lack of absorption of radiolabeled cyanocobalamin is determined by the measurement of samples of urine or feces with scintillation counting devices. In patients with pernicious anemia, absorption of cyanocobalamin is less than normal, but it may be normalized by the concurrent administration of IF with cyanocobalamin. Thus, if normal absorption is not obtained, repeat studies may be performed administering IF along with the test dose of cyanocobalamin Co 57 to differentiate pernicious anemia from other causes of cyanocobalamin malabsorption. {01} {02} {08} {13} {14} {22}

Absorption:

Oral—30 to 97% of doses up to 2 micrograms of cyanocobalamin (complexed to IF) are absorbed from the gastrointestinal tract in the distal ileum. At doses greater than 2 micrograms, the IF-dependent absorption process becomes saturated, and the percentage absorbed significantly decreases. {1a} {06} {19} {22} {23}

Protein binding:

High (>90%, primarily to the specific transcobalamin II vitamin B 12-binding protein). {01} {16} {23}

Half-life:

For cyanocobalamin—Biological (in liver): Approximately 500 days. {19}

Time to peak concentration:

6 to 14 hours.

Radiation dosimetry:
{19}

Organ
Co 57
Estimated absorbed radiation dose
Without flushing
With flushing *
mGy/
MBq
rad/
microcurie
mGy/
MBq
rad/
microcurie
Liver
36
0.13
24
0.089
Adrenals
3.8
0.014
2.5
0.0093
Pancreas
3.8
0.014
2.6
0.0096
Kidneys
3.5
0.013
2.3
0.0085
Large intestine
(upper)
2.6
0.0096
1.8
0.0067
Lungs
2.4
0.0088
1.6
0.0059
Red marrow
2.3
0.0085
1.5
0.0055
Small
intestine
2.0
0.0074
1.4
0.0052
Stomach wall
2.0
0.0074
1.4
0.0052
Bone
surfaces
1.8
0.0067
1.2
0.0044
Breast
1.5
0.0055
0.98
0.0036
Spleen
1.4
0.0052
0.97
0.0036
Large intestine
(lower)
1.3
0.0048
0.97
0.0036
Ovaries
1.2
0.0044
0.83
0.0031
Uterus
1.2
0.0044
0.84
0.0031
Bladder wall
0.95
0.0035
0.64
0.0024
Testes
0.69
0.0025
0.46
0.0017
Thyroid
0.66
0.0024
0.44
0.0016
Other tissue
1.4
0.0052
0.95
0.0035
Effective dose


4.0
mSv/
MBq
0.015
rem/
microcurie
2.7
mSv/
MBq
0.010
rem/
microcurie
* The administration of a flushing dose of nonradioactive cyanocobalamin decreases the absorbed radiation dose. {22}


Organ
Co 58
Estimated absorbed radiation dose

Without flushing

With flushing *

mGy/
MBq
rad/
microcurie
mGy/
MBq
rad/
microcurie
Liver
54
0.20
36
0.13
Adrenals
10
0.037
6.7
0.025
Pancreas
9.1
0.034
6.1
0.023
Kidneys
7.9
0.029
5.3
0.020
Large intestine
(upper)
6.3
0.023
4.4
0.016
Lungs
5.5
0.020
3.6
0.013
Stomach wall
4.9
0.018
3.3
0.012
Small
intestine
4.7
0.017
3.2
0.012
Breast
3.7
0.014
2.5
0.0093
Spleen
3.5
0.013
2.4
0.0088
Large intestine
(lower)
3.4
0.013
2.7
0.010
Red marrow
3.3
0.012
2.2
0.0081
Uterus
2.8
0.010
1.9
0.0070
Bone
surfaces
2.6
0.0096
1.8
0.0067
Ovaries
2.5
0.0093
1.8
0.0067
Bladder wall
2.4
0.0088
1.6
0.0059
Testes
2.1
0.0078
1.4
0.0052
Thyroid
1.8
0.0067
1.2
0.0044
Other tissue
3.3
0.012
2.2
0.0081
Effective dose


7.5
mSv/
MBq
0.028
rem/
microcurie
5.1
mSv/
MBq
0.019
rem/
microcurie
* The administration of a flushing dose of nonradioactive cyanocobalamin decreases the absorbed radiation dose.

Elimination:
    In normal patients—Renal (7 to 10% or more); fecal (50% or less).
    In patients with reduced absorption—Renal (0 to 7%); fecal (70 to 100%). {01} {08} {15}

Note: Diagnosis of pernicious anemia in patients with reduced absorption is confirmed if abnormal results become normal when IF is administered with the test dose of cyanocobalamin Co 57.

    Cyanocobalamin Co 57 is also eliminated in breast milk. {01}


Precautions to Consider

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of cyanocobalamin Co 57 have not been performed. {01} {1a}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies have not been done in humans. Diagnostic testing should be postponed, if possible, until after delivery since cyanocobalamin Co 57 crosses the placenta and is taken up by the fetus. {01}

To avoid the possibility of radiation exposure to the fetus, in those circumstances where the patient's pregnancy status is uncertain, a pregnancy test will help to prevent inadvertent administration of this preparation during pregnancy. {06}

Studies have not been done in animals.

FDA Pregnancy Category C. {01}

Breast-feeding

Cyanocobalamin Co 57 is excreted in breast milk in very small concentrations. Although discontinuation of breast-feeding is not essential, because of the potential risk to the infant from radiation exposure, temporary discontinuation of nursing is recommended for a short period of time. {01} {08} {20} {22} {23}

Pediatrics

Although cyanocobalamin Co 57 is used in children, there have been no specific studies evaluating safety and efficacy. When used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation. {21}


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of cyanocobalamin Co 57 in the elderly. However, elderly patients are more likely to have age-related renal function impairment which may falsely depress Schilling test results; a 48-hour urine collection period (instead of the usual 24-hour period) is recommended in patients with impaired renal function. {09} {22} {23}

Also, in geriatric patients with gastric atrophy that is severe enough to cause a lack of gastric acid and enzymes, the splitting of vitamin B 12 from its peptide linkages in food cannot be accomplished, thus causing vitamin B 12 deficiency. However, the gastric atrophy may not be severe enough to cause a lack of gastric intrinsic factor and thus the results of the Schilling test may be normal, unless cyanocobalamin Co 57 is given after incubation with serum protein (e.g., chicken serum). {05} {06} {10} {13} {16}

Drug interactions and/or related problems
See Laboratory value alterations.


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With result of this test

Due to other medications
Alcohol, excessive intake for longer than 2 weeks or{01}
Aminosalicylates or
Antibiotics, especially oral neomycin or{01}
Anticonvulsants, especially phenobarbital, phenytoin, and primidone or
Calcium-chelating agents, such as edetate disodium and penicillamine or
Cholestyramine, prolonged use or
Colchicine or{01}
Potassium, extended-release    (may impair absorption of radioactive cyanocobalamin {01} {23})


Cyanocobalamin, nonradioactive    (prior administration may impair absorption and excretion of cyanocobalamin Co 57; it is recommended that 24 hours elapse before the administration of cyanocobalamin Co 57 {01})


Due to medical problems or conditions
Renal function impairment    (Schilling test results may be falsely depressed {08} {23})

With results of other tests
Bone marrow studies and
Cyanocobalamin determinations, serum and
Reticulocyte counts    (values may be altered because of hematopoietic response resulting from administration of large parenteral doses of cyanocobalamin given in conjunction with Schilling test; it is recommended that these tests be done prior to Schilling test {1a} {23})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

See also Laboratory value alterations.

Risk-benefit should be considered when the following medical problem exists
Sensitivity to cyanocobalamin


Side/Adverse Effects

Note: Presently, there are no known side/adverse effects associated with cyanocobalamin Co 57 used orally as a diagnostic aid. However, side/adverse effects, such as anaphylactic shock, have been reported with the parenteral use of nonradioactive cyanocobalamin. {01} {23}




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Identical to dietary cyanocobalamin

Absorption of radioactive cyanocobalamin determined by measurement of radioactivity in urine or fecal samples

Small amounts used in diagnosis; radiation exposure is considered low {22}

Before having this test
»   Conditions affecting use, especially:
Sensitivity to cyanocobalamin

Pregnancy—Crosses the placenta; risk to fetus from radiation exposure as opposed to benefit derived from use should be considered {21}





Breast-feeding—Excreted in breast milk; temporary discontinuation of nursing recommended because of risk of radiation exposure to infant





Use in children—Risk of radiation exposure


Preparation for this test
Special preparatory instructions may be given; patient should inquire in advance:

Avoiding oral or parenteral cyanocobalamin for at least 24 hours prior to administration of cyanocobalamin Co 57

Fasting for at least 8 to 12 hours prior to administration of cyanocobalamin Co 57 {22}

Precautions after having this test
No special precautions when used for diagnosis


Side/adverse effects
No side effects reported with diagnostic doses


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radionuclides and who are approved by the appropriate State agency or, outside the U.S., the appropriate authority. {01}

Fasting is recommended for at least 8 to 12 hours prior to the administration of the test dose of cyanocobalamin Co 57. Two hours after the ingestion of the test dose, a light breakfast may be given. {01} {08}

Voiding is recommended immediately prior to the administration of the test dose of cyanocobalamin Co 57. {01} Also, radioactivity measurement of a pre-test urine sample should be obtained prior to starting the study to establish the absence of any potentially interfering radioisotope. {01} {06} {08}

To prevent interference with absorption and elimination, at least 24 hours should elapse prior to the administration of cyanocobalamin Co 57 if a flushing dose for the Schilling test or a therapeutic injection of cyanocobalamin has previously been administered. {01} {23}

In the Schilling test, a flushing dose of 1 mg of nonradioactive cyanocobalamin must be intramuscularly injected within 2 hours following the administration of cyanocobalamin Co 57. A second flushing dose may be injected 24 hours later to help reduce the amount of radioactivity retained by the body. {01} {08} {23}

Manufacturer's package insert or other appropriate literature should be consulted for specific test procedure.

Safety considerations for handling this radiopharmaceutical
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals. {24}


Oral Dosage Forms

CYANOCOBALAMIN Co 57 CAPSULES USP

Usual adult and adolescent administered activity
Diagnosis of cyanocobalamin malabsorption syndromes
Oral, 0.02 to 0.037 megabecquerel (0.5 to 1 microcurie). {01}

Note: If the test kit containing both the cyanocobalamin Co 57 (bound to intrinsic factor [IF]) and the cyanocobalamin Co 58 capsules is used, both capsules are administered simultaneously. The test is performed in a manner similar to the Schilling test, except that both vitamin B 1 2 absorption and response to IF are measured simultaneously. {01}



Usual pediatric administered activity
See Usual adult and adolescent administered activity. {22}

Usual geriatric administered activity
See Usual adult and adolescent administered activity .

Strength(s) usually available
U.S.—


0.02 megabecquerel (0.5 microcurie), with a specific activity ranging from 0.02 to 0.037 megabecquerel (0.5 to 1 microcurie) per microgram of cyanocobalamin, per capsule, at time of calibration (Rx)[Generic]


0.02 to 0.037 megabecquerel (0.5 to 1 microcurie), nominal activity per capsule, at time of calibration (Rx) [Rubratrope-57]


0.02 megabecquerel (0.5 microcurie), nominal activity per capsule, at time of calibration (Rx) [Dicopac]

Note: The Dicopac test kit also contains a capsule of cyanocobalamin Co 58 with 0.03 megabecquerel (0.8 microcurie), nominal activity at time of calibration.


Canada—


0.02 megabecquerel (0.5 microcurie) per capsule, at time of calibration (Rx)[Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Note: The Dicopac test kit should be stored between 2 and 4 °C (36 and 40 °F). {1a}


Stability:
Deteriorates in presence of strong light, traces of reducing agents, or microorganisms. Decomposes when autoclaved at 115 °C (239 °F) for 30 minutes. {22} {23}

Note: Caution—Radioactive material.




Revised: 08/02/1994



References
  1. Package insert (Rubratope-57 rev. 3/85, recv'd 1/88; Mallinckrodt rev. 8/90, recv'd 2/92).
  1. Dicopac package insert (rev. 1990)
  1. Chilton HM, Witcofski RL. Nuclear Pharmacy—An introduction to the clinical application of radiopharmaceuticals. Philadelphia: Lea and Febiger, 1986.
  1. NCRP 70.
  1. Loevinger R, Budinger T, Watson E. MIRD primer for absorbed dose calculations. New York: The Society of Nuclear Medicine, 1988: 34.
  1. Herbert, Victor: Laboratory Diagnosis of Pernicious Anemia.
  1. Panel comment.
  1. Maynard CD. Clinical nuclear medicine. Philadelphia: Lea & Febiger 1971: 63.
  1. Maisey MN, Britton KE, Gilday DL. Clinical nuclear medicine. 2nd ed. Philadelphia: J.B. Lippincott, 1991: 354-5.
  1. Nilsson-Ehle H, Jagenburg R, Landhal S, et al. Cyanocobalamin absorption in the elderly. Clin Chem 1986; 32(7): 1368-71.
  1. Dawson BW, Sawers AH, Sharma RK. Malabsorption of protein bound vitamin B 12. Br Med J 1984; 288(6418): 675-8.
  1. Zuckier LS, Chervu LR. Schilling evaluation of pernicious anemia: current status. J Nucl Med 1984; 25(9): 1032-9.
  1. Doscherholmen A, Silvis S, McMahon J. Dual isotope Schilling test for measuring absorption of food-bound and free vitamin B 12 simultaneously. Am J Clin Pathol 1983; 80(4): 490-5.
  1. Domstad PA, Choy YC, Kim EE. Reliability of the dual-isotope Schilling test for the diagnosis of pernicious anemia or malabsorption syndrome. Am J Clin Pathol 1981; 75(5): 723-6.
  1. Celada A, Herreros V, Donath A. Clinical evaluation of simultaneously administered Co 58 labelled vitamin B 12 and Co 57 labelled vitamin B 12 bound to intrinsic factor in patients with pernicious anemia. Blut 1981; 42(2): 87-93.
  1. Amin S, Spinks T, Ranicar A, et al. Long-term clearance of Co 57 cyanocobalamin in vegans and pernicious anemia. Clin Sci 1980; 58(1): 101-3.
  1. Panel comments as of 6/90.
  1. Int'l Committee for Standardization in Hematology. Recommended methods for the measurement of vitamin B 1 2 absorption. J Nucl Med 1981; 22: 1091-3.
  1. Ponto JA: Radiopharmaceuticals for hematological applications. II. Schilling test. In: Swanson DP, Chilton HM, Thrall JH. Pharmaceuticals in Medical Imaging. MacMillan Publishing Co. New York 1990. p 621-8.
  1. Task group of Committee 2 of the International Commission on Radiological Protection: ICRP Publication 53. New York: Pergamon Press, 1988: 131-4.
  1. Panel meeting 1/88.
  1. Panel meeting 5/91.
  1. Reviewers' responses to monograph revision of 6/92.
  1. Swanson DP, Chilton HM, Thrall JH (eds). Pharmaceuticals in medical imaging. New York: Macmillan Publishing Company, 1990: 623.
  1. Reviewers' responses to Ballot of 5/11/94.
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