Cobalin-H 1000 microgram/ml Injection

Injection

4.1 Therapeutic indications Treatment of Addisonian pernicious anaemia. Prophylaxis and treatment of other macrocytic anaemias due to vitamin B12 deficiency. Treatment of tobacco amblyopia. Treatment of Lieber's atrophy.4.2 Posology and method of administration Posology The following dosages are suitable for children and adults. *Addisonian pernicious anaemia and other macrocytic anaemias without neurological involvement:* | | | | --- | --- | | Initially: | 250 micrograms to 1000 micrograms intramuscularly on alternate days for one or two weeks then 250 micrograms weekly until blood count is normal. | | Maintenance: | 1000 micrograms every two or three months. | *Addisonian pernicious anaemia and other macrocytic anaemias with neurological involvement:* | | | | --- | --- | | Initially: | 1000 micrograms on alternate days as long as improvement continues. | | Maintenance: | 1000 micrograms every two months. | *Prophylaxis of macrocytic anaemias associated with vitamin B12 deficiency resulting from gastrectomy, ileal resection, certain ma/absorption states and vegetarianism:* 1000 micrograms every two or three months. *Tobacco amblyopia and Leber's optic atrophy:* | | | | --- | --- | | Initially: | 1000 micrograms daily by intramuscular injection for two weeks then twice weekly as long as improvement is maintained. | | Maintenance: | 1000 micrograms every three months or as required. | Method of Administration Intramuscular injection4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.4.4 Special warnings and precautions for use It is advisable to confirm the diagnosis of Vitamin B12 deficiency before giving hydroxocobalamin; regular monitoring of the blood is recommended. If megaloblastic anaemia fails to respond, folate metabolism should be investigated. Doses in excess of 10 micrograms daily may produce a haematological response in patients with folate deficiency. Indiscriminate administration may mask the true diagnosis. Cardiac arrhythmias secondary to hypokalaemia during initial therapy have been reported. Plasma potassium should therefore be monitored during this period.4.5 Interaction with other medicinal products and other forms of interaction *Chloramphenicol* Parenteral chloramphenicol may attenuate the effect of hydroxocobalamin in anaemia. *Oral contraceptives* The serum concentration of hydroxocobalamin may be lowered. The above interactions are unlikely to be of clinical significance but should be taken into account when performing assays for blood concentrations. Vitamin B12 assays by microbiological techniques are invalidated by antimetabolites and most antibiotics.4.6 Fertility, pregnancy and lactation Pregnancy Hydroxocobalamin injection should not be used for the treatment of megaloblastic anaemia of pregnancy. Breast-feeding Hydroxocobalamin is secreted into breast milk but is unlikely to harm the infant. Fertility No data available4.7 Effects on ability to drive and use machines Not relevant.4.8 Undesirable effects The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: Not known (cannot be estimated from the available data) There are no modern clinical studies available that can be used to determine the frequency of undesirable effects. Therefore, all the undesirable effects listed are classed as “frequency Not known”. The following effects have been reported and are listed below by body system: | | | | | --- | --- | --- | | System organ class | Frequency | Undesirable effects | | Blood and lymphatic system disorders | Not Known | Reactive thrombocytosis can occur during the first weeks of use in megaloblastic anaemia. | | Immune system disorders | Not Known | Hypersensitivity reactions including rash; itching; exanthema. Antibodies to hydroxocobalamin-transcobalamin II complex have developed during hydroxocobalamin therapy. Anaphylaxis | | Metabolism and nutrition disorders | Not Known | Initial hypokalaemia | | Nervous system disorders | Not Known | Headache, paraesthesia, tremor. | | Cardiac disorders | Not Known | Arrhythmias secondary to hypokalaemia. | | Gastrointestinal disorders | Not Known | Nausea, vomiting, diarrhoea. | | General disorders and administration site conditions | Not Known | Fever, chills, hot flushes; dizziness; malaise; pain; Injection site reactions including injection site pain, injection site erythema, injection site pruritus, injection site` induration, and injection site swelling. | | Skin and subcutaneous tissue disorders | Not known | Acneiform and bullous eruptions | | Renal and urinary disorders | Not Known | Chromaturia | Reporting of 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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website : www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose Treatment is unlikely to be needed in case of overdose.

5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antianaemic preparations -Vitamin B12 ATC code: B03BA03 Hydroxocobalamin is used in the treatment and prevention of Vitamin B12 deficiency. For adults, the daily requirement of Vitamin B12 is probably about 1 to 2 micrograms and this amount is present in most normal diets. However, Vitamin B12 only occurs in animal products, not in vegetables, and therefore strict vegetarian or vegan diets that exclude dairy products may provide an inadequate amount, although a deficiency may not be apparent for many years. Deficiency is more likely in patients with malabsorption syndromes or metabolic disorders, nitrous-oxide induced megalobastosis, or following gastrectomy or extensive ileal resection. Deficiency leads to megaloblastic anaemias and demyelination and other neurological damage. On oral intake, Vitamin B12 substances bind to intrinsic factor, a glycoprotein secreted by the gastric mucosa, and are then actively absorbed from the gastrointestinal tract. A specific anaemia known as pernicious anaemia develops in patients with an absence of intrinsic factor. Absorption is also impaired in patients with disease or abnormality of the gut. Treatment usually results in rapid haematological improvement and a striking clinical response. However, neurological symptoms respond more slowly.5.2 Pharmacokinetic properties Distribution Hydroxocobalamin is extensively bound to specific plasma proteins (transcobalamins); transcobalamin II appears to be involved in the rapid transport of the cobalamins to tissues. Elimination Hydroxocobalamin is stored in the liver, excreted in the bile, and undergoes extensive enterohepatic recycling; part of the dose is excreted in the urine, most of it in the first 8 hours. It is stored in the liver, excreted in the bile, and undergoes enterohepatic recycling; part of a dose is excreted in the urine, most of it in the first 8 hours. Hydroxocobalamin diffuses across the placenta and also appears in breast milk. Hydroxocobalamin is better retained than cyanocobalamin; 90% of a 100 microgram dose and 30% of a 1000 microgram dose are retained, a range believed to be sufficient for body requirements for 2 to 10 months.5.3 Preclinical safety data There is no additional information relevant to the prescriber.

6.1 List of excipients Sodium dihydrogen orthophosphate Sodium chloride Sodium Hydroxide (for pH adjustment) Hydrochloric Acid (for pH adjustment) Water for Injections6.2 Incompatibilities Not Applicable6.3 Shelf life 2 years6.4 Special precautions for storage Protect from light. Store below 25ºC.6.5 Nature and contents of container This medicine is supplied in clear 1ml Type I glass ampoules in cartons of 5 or 10.6.6 Special precautions for disposal and other handling No special requirements