)‫בטיחות‬
)‫מידע בטיחות‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
___February 24, 2008____________________ ‫תאריך‬
___BEDODEKA INJECTION ____________‫שם תכשיר באנגלית‬
____019 98 20254 00 ________‫מספר רישום‬
Teva pharmaceutical Industries Ltd., P.O.Box 3190, Petach Tikva_‫שם בעל הרישום‬
‫השינויים בעלון מסומנים על רקע צהוב‬
‫רופא‬
‫בעלון ללרופא‬
‫בעלון‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
‫טקסט נוכחי‬
Vitamin B12 (cyanocobalamin) is essential to growth, cell
reproduction, hematopoiesis, and nucleoprotein and
myelin
synthesis.
It
has
many
metabolic
interrelationships with the basic nutrients. Its
physiological role is associated with methylation,
participating in nucleic acid and protein synthesis.
Vitamin B12 (cyanocobalamin) is essential for folate
utilization with functional folate deficiency resulting
from its absence.
Vitamin B12 (cyanocobalamin) is
essential
to
growth,
cell
reproduction, hematopoiesis, and
nucleoprotein and myelin synthesis.
It
has
many
metabolic
interrelationships with the basic
nutrients. Its physiological role is
associated
with
methylation,
participating in nucleic acid and
protein synthesis.
Patients who have early Leber's disease (hereditary optic
nerve atrophy) have been found to suffer severe and swift
optic atrophy when treated with vitamin B 12, and its use
should be avoided in these patients..
Serum potassium concentrations should be monitored
during early vitamin B12 therapy and potassium
administered if necessary, since fatal hypokalaemia could
occur upon conversion of megaloblastic anaemia to
normal erythropoiesis with vitamin B12 as a result of
increased
erythrocyte
potassium
requirements.
Hypokalaemia and cardiac arrest have been reported
when megaloblastic anaemia is treated intensively.
Hypokalemia may occur when severe megaloblastic
anemia is treated intensively.
Patients'nutritional status, including folate deficiency,
should be considered. Folic acid may potentiate the
neurological complications of vitamin B 12 deficiency, so
it should not be administered to patients with pernicious
anaemia (see Interactions).
Treatment with cyanocobalamin injection may
unmask polycythaemia vera, because vitamin B12
deficiency may suppress the symptoms of this
condition.
The increase in nucleic acid degradation produced
by administration of cyanocobalamin injection to
vitamin B12 deficient patients could lead to gout in
susceptible patients.
Cyanocobalamin injection should not be given
before a diagnosis has been fully established
because of the possibility of subacute degeneration
of the spinal cord.
‫פרק בעלון‬
Mechanism of
Action
Patients who have early Leber's
disease (hereditary optic nerve
atrophy) have been found to suffer
severe and swift optic atrophy
when treated with vitamin B12
Hypokalemia may occur when
severe megaloblastic anemia is
treated intensively.
Warnings
Use in Breastfeeding
Safety of use in breastfeeding has not been established.
Vitamin B12 is secreted into breast milk during lactation
in concentrations that approximate the maternal blood
vitamin B12 concentration. No adverse effects have been
reported with intake of normal daily requirements during
lactation.
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.
Anaphylactic shock and death have been reported after
parenteral
vitamin
B12
administration
Before
administering Bedodeka, an intradermal test dose is
recommended for patients known to be sensitive to
cobalamins.
Diagnosis of vitamin B12 deficiency should be
confirmed by laboratory investigation before institution
of cyanocobalamin (vitamin B12) therapy. Do not use
until diagnosis is fully established, because of the
possibility of masking symptoms of subacute
degeneration of the spinal cord, or of the true diagnosis of
pernicious anaemia.
Use in Breastfeeding
Safety of use in breastfeeding has
not been established. Vitamin B12 is
secreted into breast milk during
lactation
Before administering Bedodeka, an
intradermal
test
dose
is
recommended for patients known
to be sensitive to cobalamins.
Serum
potassium
must
be
monitored closely and potassium
supplement
administered
if
necessary,
since
cardiac
arrhythmias
secondary
to
hypokalemia have been reported
with intensive vitamin B12
treatment.
Cyanocobalamin has no effect on
ability to drive and use machines
Precautions
Indiscriminate administration of vitamin B12 may mask
the true diagnosis of pernicious anemia.
Serum potassium must be monitored closely and
potassium supplement administered if necessary, since
cardiac arrhythmias secondary to hypokalemia have been
reported with intensive vitamin B12 treatment.
Cyanocobalamin has no effect on ability to drive and
use machines.
Contraindications
Various reactions are occasionally reported and some
allergic reactions have been reported after injection.
These have included: abdominal pain, bullous eruption,
depression, emotional lability, injection site reactions
such as pain, myalgia, nausea, nervousness, palpitation,
personality disorders, photosensitivity reaction, pruritus,
maculopapular rash, syncope and thinking abnormally.
Other reported adverse effects include diarrhoea,
peripheral vascular thrombosis, urticaria or a feeling of
swelling of the whole body, anaphylaxis and death.
Hypersensitivity reactions have
been reported including skin
reactions (e.g. rash, itching) and
exceptionally anaphylaxis. Other
symptoms reported include: fever,
chills, hot flushing, dizziness,
malaise, nausea, acneiform and
bullous eruptions.
Adverse events
Anaphylaxis, pulmonary oedema and congestive heart
failure have all been reported during early vitamin B 12
treatment, possibly as a result of an increase in blood
volume induced by the drug.
Accelerated optic nerve atrophy has been reported
following administration of cyanocobalamin to patients
with early Leber's disease (see Warnings).
Administration of cyanocobalamin doses greater than 10
micrograms daily, may produce a haematological
response in patients with folate deficiency (se also
Precautinos).
Hypersensitivity reactions have been reported including
skin reactions (e.g. rash, itching) and exceptionally
anaphylaxis. Other symptoms reported include: fever,
chills, hot flushing, dizziness, malaise, nausea, acneiform
and bullous eruptions.
Vitamin B12/ Chloramphenicol: Chloramphenicol and
other drugs with bone marrow suppressant properties
may cause a lack of therapeutic response to vitamin B 12.
This effect may be due to interference with erythrocyte
maturation.
Other Interactions
Colchicine, aminoglycosides, certain anticonvulsants
(e.g. phenytoin, phenobarbital, primidone), paraaminosalicylic acid and/or excessive alcohol intake for
longer than 2 weeks may impair the absorption of vitamin
B12. Long-term ingestion of meformin and antacids may
also contribute to food-cobalamin malabsorption
especially in elderly patients
Vitamin B12/ Chloramphenicol:
Chloramphenicol and other drugs
with bone marrow suppressant
properties may cause a lack of
therapeutic response to vitamin
B12. This effect may be due to
interference
maturation.
with
erythrocyte
Histmaine2-receptor antagonists
(e.g. cimetidine,
ranitidine, nizatidine, famotidine) and proton pump
inhibitors (e.g. omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole) may potentially cause vitamin
B12 deficiency by decreasing gastric acid cleavage of
vitamin B12 from food sources. This may be important in
patients with low stores of vitamin B12 or in patients
taking H2-antagonists or proton pump inhibitors for
extended periods of time (more than 2 years).
Drug Interactions
Diagnostic Interference
Antimetabolites, most antibiotics, methotrexate and
pyrimethamine invalidate folic acid and vitamin B12
diagnostic blood assays
Antimetabolites and most antibiotics invalidate vitamin
B12 assays by microbiological techniques.
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.
Diagnostic Interference
Antimetabolites
and
most
antibiotics invalidate vitamin B12
assays
by
techniques.
microbiological
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
Information for Patients:
Patients with pernicious anemia should be informed that
they will require monthly injections of vitamin B 12 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 B 12, 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.
Information
Patients
Dosage
and
Administration
Do not use intravenously.
Since large amounts of the drug are routinely
administered as a treatment, no case of acute overdosage
in humans has been described.
Treatment is symptomatic and supportive.
Treatment is unlikely to be needed in cases of
overdosage.
for
Treatment is unlikely to be needed
in cases of overdosage.
OverDosage