Addisonian pernicious anaemia. Prophylaxis and treatment of other macrocytic anaemias associated with vitamin B12 deficiency. Tobacco amblyopia and Leber's optic atrophy.

Posology
Adults and Paediatric population
The following doses are suitable for adults and children.
Addisonian pernicious anaemias and other macrocytic anaemias without neurological involvement:
Initially 250 to 1000 micrograms intramuscularly on alternate days for one or two weeks, then 250 micrograms weekly until the blood count is normal

Maintenance: 1000 micrograms every two to three months
Addisonian pernicious anaemia and other macrocytic anaemias with neurological involvement:
Initially:1000 micrograms on alternate days as long as improvement is occurring.
Maintenance:1000 micrograms every two of three months.
Prophylaxis of macrocytic anaemia associated with vitamin B12 deficiency resulting from gastrectomy, some malabsorption syndromes and strict 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 occurring.
Maintenance: 1000 micrograms every one to three months as required.
Method of Administration:
Intramuscular injection.

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.

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.
Paediatric population
Interaction studies have only been performed in adults.

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.

Not relevant.

The following undesirable effects may occur with the use of Hydroxocobalamin Acetate in the following frequencies:
Very common (> 1/10)
Common (> 1/100, <1/10)

The following undesirable effects may occur with the use of Hydroxocobalamin Acetate in the following frequencies:
Very common (> 1/10)
Common (> 1/100, <1/10)

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.

Treatment is unlikely to be required in the case of overdose.

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 malabasorption 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.

Distribution: Transcobalamin II appears to be involved in the rapid transport of the cobalamins to tissues. Hydroxocobalamin is extensively bound to specific plasma proteins (transcobalamins). 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.
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.

There is no additional information relevant to the prescriber.

Sodium dihydrogen phosphate dihydrate.
Water for injection.

None.

Store below 25ºC, away from light

A Carton box contains 2 amber glass ampoules (type 1) each of 1ml solution with insert leaflet.

None Stated.