"פורמט עלון זה נקבע ע"י משרד הבריאות ותוכנו נבדק ואושר". עלון מאושר: מאי 2011. “This leaflet format has been determined by the Ministry of Health and the content thereof has been checked and approved.” Date of approval: May 2011.
עלון לרופא Physician's Package Insert ======בדודקה BEDODEKA ------להזרקה לתוך השריר או מתחת לעור Solution for I.M. or S.C. Injection
Composition Each ampoule of 1 ml contains:
Active Ingredient Cyanocobalamin (vitamin B12) 1000 micrograms/ml
Other Ingredients Sodium acetate anhydrous, acetic acid glacial, water for injection.
Mechanism of Action Vitamin B12 (cyanocobalamin) is essential for 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.
Indications Pernicious anemia and its neurological complication, subacute combined degeneration of the spinal cord. Treatment of vitamin B12 deficiency states and macrocytic anemias associated with nutritional deficiencies, gastrectomy and abnormalities of, or malabsorption from, the gastrointestinal tract such as celiac disease, sprue and accompanying folic acid deficiency. Bedodeka is also suitable for use as the flushing dose in the Schilling Test for pernicious anemia.
Contraindications Known hypersensitivity to vitamin B12, or to any other ingredient of the preparation. Bedodeka is not indicated for treatment of toxic amblyopias.
Warnings An intradermal sensitivity test may be performed in patients with suspected hypersensitivity to cobalamins. It is important to accurately diagnose anemias prior to treatment, to ensure that appropriate therapy is initiated. If folic acid is used to treat pernicious anemia, for example, hematologic improvement may occur while neurologic complications continue to progress. 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, 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 anemia to normal erythropoiesis with vitamin
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B12 as a result of increased erythrocyte potassium requirements. Hypokalaemia and cardiac arrest have been reported when megaloblastic anemia is treated intensively.
Patients' nutritional status, including folate deficiency, should be considered. Folic acid may potentiate the neurological complications of vitamin B12 deficiency, so it should not be administered to patients with pernicious anemia (see Precautions). 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.
Lack of therapeutic response may be due to infection, uremia, concomitant treatment with chloramphenicol or misdiagnosis.
Use in Pregnancy Cyanocobalamin should not be used for the treatment of megaloblastic anemia of pregnancy unless vitamin B12 deficiency has been demonstrated.
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.
Sodium content One ampoule contains less than 1 mmol sodium (23mg), i.e. essentially "sodium- free".
Adverse Reactions 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 mild transient diarrhea, peripheral vascular thrombosis, urticaria or a feeling of swelling of the whole body, anaphylaxis and death. Anaphylaxis, pulmonary oedema and congestive heart failure have all been reported during early vitamin B12 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 (see also Precautions).
Reporting suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form http://forms.gov.il/globaldata/getsequence/getsequence.aspx? BEDODEKA FW 10-2018 Minor Updates
Precautions For pernicious anemia, an adequate dose must be used and the blood picture must be examined regularly at least every 3 months for 18 months until stabilized, and then annually. 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 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.
Drug Interactions 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 with erythrocyte maturation.
Other Interactions Colchicine, aminoglycosides, certain anticonvulsants (e.g. phenytoin, phenobarbital, primidone), para-aminosalicylic acid and/or excessive alcohol intake for longer than 2 weeks may impair the absorption of vitamin B12. Long-term ingestion of metformin and antacids may also contribute to food-cobalamin malabsorption especially in elderly patients
Histamine2-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).
Diagnostic Interference Antimetabolites, most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays.
Laboratory Tests During the initial treatment of patients with pernicious anemia, serum potassium must be observed closely for the first 48 hours and potassium replaced if necessary.
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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.
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.
Dosage and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Bedodeka may be given by subcutaneous or intramuscular injection. Do not use intravenously.
Pernicious Anemia, Vitamin B12 Deficiency States and Macrocytic Anemias The usual initial dose is 250-1000 micrograms on alternate days for 1-2 weeks, followed by 250 micrograms weekly until the blood count is normal. Thereafter, the maintenance dose is 1000 micrograms monthly. If there are neurological complications, the initial dose of 1000 micrograms is recommended on alternate days while improvement is occurring.
Maintenance 1000 micrograms monthly.
Schilling Test The flushing dose is 1000 micrograms.
Overdosage 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.
Pharmaceutical Precautions Store below 25C. Store in the original package, in order to protect from light.
Nature and Contents of Container BEDODEKA FW 10-2018 Minor Updates
5 Carton boxes packed with 10 brown glass ampoules. Each ampoule contains 1 ml solution.
Drug Registration No.: 019 98 20254.
Manufacturer and License Holder Teva Pharmaceutical Industries Ltd., P.O.Box 3190, Petah-Tikva
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