WARNINGS
Patients with early Leber’s disease (hereditary
optic nerve atrophy) who were treated with cyanocobalamin
suffered severe and swift optic atrophy.
Hypokalemia and sudden death may occur in severe megaloblastic
anemia which is treated intensely. Anaphylactic shock
and death have been reported after parenteral vitamin
B12 administration. An intradermal test dose is recommended
before cyanocobalamin injection is administered to patients
suspected of being sensitive to this drug.
This product contains benzyl alcohol. Benzyl alcohol
has been reported to be associated with a fatal “Gasping
Syndrome” in premature infants.
PRECAUTIONS
General Precautions
Vitamin B12 deficiency that is allowed to progress for
longer than 3 months may produce permanent degenerative
lesions of the spinal cord. Doses of folic acid greater
than 0.1 mg per day may result in hematologic remission
in patients with vitamin B12 deficiency. Neurologic manifestations
will not be prevented with folic acid, and if not treated
with vitamin B12, irreversible damage will result. Doses
of cyanocobalamin exceeding 10 mcg daily may produce hematologic
response in patients with folate deficiency. Indiscriminate
administration may mask the true diagnosis.
Information for Patients
Patients with pernicious anemia should be informed that
they will require monthly injections of vitamin B12 for
the remainder of their lives. Failure to do so will result
in return of the anemia and in development of incapacitating
and irreversible damage to the nerves of the spinal cord.
Also, patients should be warned about the danger of taking
folic acid in place of vitamin B12, because the former
may prevent anemia but allow progression of subacute combined
degeneration. A vegetarian diet which contains no animal
products (including milk products or eggs) does not supply
any vitamin B12. Patients following such a diet, should
be advised to take oral vitamin B12 regularly. The need
for vitamin B12 is increased by pregnancy and lactation.
Deficiency has been recognized in infants of vegetarian
mothers who were breast fed, even though the mothers had
no symptoms of deficiency at the time.
Laboratory Tests
During the initial treatment of patients with pernicious
anemia, serum potassium must be observed closely the first
48 hours and potassium replaced if necessary. Hematocrit,
reticulocyte count, vitamin B12, folate and iron levels
should be obtained prior to treatment. Hematocrit and
reticulocyte counts should be repeated daily from the
fifth to seventh days of therapy and then frequently until
the hematocrit is normal. If folate levels are low, folic
acid should also be administered. If reticulocytes have
not increased after treatment or if reticulocyte counts
do not continue at least twice normal as long as the hematocrit
is less than 35%, diagnosis or treatment should be reevaluated.
Repeat determinations of iron and folic acid may reveal
a complicating illness that might inhibit the response
of the marrow. Patients with pernicious anemia have about
3 times the incidence of carcinoma of the stomach as the
general population, so appropriate tests for this condition
should be carried out when indicated.
Drug/Laboratory Test Interactions
Persons taking most antibiotics, methotrexate and pyrimethamine
invalidate folic acid and vitamin B12 diagnostic blood
assays. Colchicine para-aminosalicylic acid and heavy
alcohol intake for longer than 2 weeks may produce malabsorption
of vitamin B12.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies in animals to evaluate carcinogenic
potential have not been done. There is no evidence from
long-term use in patients with pernicious anemia that
cyanocobalamin is carcinogenic. Pernicious anemia is associated
with an increased incidence of carcinoma of the stomach,
but this is believed to be related to the underlying pathology
and not to treatment with cyanocobalamin.
Pregnancy
Teratogenic Effects: Pregnancy Category C: Adequate and
well-controlled studies have not been done in pregnant
women. However, vitamin B12 is an essential vitamin and
requirements are increased during pregnancy. Amounts of
vitamin B12 that are recommended by the Food and Nutrition
Board, National Academy of Science-National Research Council
for pregnant women (4 mcg daily) should be consumed during
pregnancy.
Nursing Mothers
Vitamin B12 is known to be excreted in human milk. Amounts
of vitamin B12 that are recommended by the Food and Nutrition
Board, National Academy of Science-National Research Council
for lactating women (4 mcg daily) should be consumed during
lactation.
Pediatric Use
Intake in children should be in the amount (0.5 to 3
mcg daily) recommended by the Food and Nutrition Board,
National Academy of Science-National Research Council.
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