Hydroxocobalamin 1mg/ml Solution for Injection

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 dosage 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

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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.

Fertility

No data available

Not relevant.

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:

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

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.

Glacial acetic acid Ph Eur

Sodium chloride Ph Eur

Water for injection Ph Eur

Not applicable.

2 years

Store at or below 25ºC. Protect from light.

Type I glass ampoules in cardboard box.

5 ampoules per pack.

No special requirements.