This information is intended for use by health professionals

1. Name of the medicinal product

Cobalin-H

Hydroxocobalamin 1000 microgram/ml Injection

2. Qualitative and quantitative composition

Anhydrous hydroxocobalamin 1000microgram/ml.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Injection

4. Clinical particulars
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 Leber' 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.

4.3 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 available

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

The following undesirable effects may occur with the use of hydroxocobalamin in the following frequencies:

Very common (> 1/10)

Common (> 1/100, <1/10)

Uncommon (> 1/1,000, <1/100)

Rare (> 1/10,000, <1/1,000)

Very rare (<1/10,000), (cannot be estimated from the available data) are not known.

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 unknown”.

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. Pharmacological properties
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 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.

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. Pharmaceutical particulars
6.1 List of excipients

Sodium dihydrogen orthophosphate

Sodium chloride

Sodium Hydroxide (for pH adjustment)

Hydrochloric Acid (for pH adjustment)

Water for Injections

6.2 Incompatibilities

None stated.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Protect from light. Store below 25°C.

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

None stated.

7. Marketing authorisation holder

Amdipharm UK Limited

Capital House, 85 King William Street,

London EC4N 7BL, UK

8. Marketing authorisation number(s)

PL 20072/0217

9. Date of first authorisation/renewal of the authorisation

18th June 1993 / 6th November 1998

10. Date of revision of the text

26/02/2018