Consumer medicine information

HYDROXO-B12 Injection

Hydroxocobalamin chloride

BRAND INFORMATION

Brand name

Hydroxo-B12 Solution for injection

Active ingredient

Hydroxocobalamin chloride

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using HYDROXO-B12 Injection.

What is in this leaflet

This leaflet answers some common questions about HYDROXO-B12 Injection. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you being given this medicine against the benefits they expect it will have for you.

If you have any concerns about being given it, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What HYDROXO-B12 Injection is used for

HYDROXO-B12 Injection contains hydroxocobalamin as the active ingredient which is a form of vitamin B12.

It is used for the prevention and treatment of anaemias associated with vitamin B12 deficiency. It is also used to treat diseases of nerves in the eyes.

Ask your doctor if you have any questions about why HYDROXO-B12 Injection has been prescribed for you.

Your doctor may have prescribed this medicine for another reason.

This medicine is not addictive.

Before you are given it

When you must not be given it

You must not be given HYDROXO-B12 Injection if you have an allergy to:

  • hydroxocobalamin
  • cobalt
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; skin rash, itching or hives.

You must not be given it to treat megaloblastic anaemia of pregnancy.

This is a type of anaemia usually caused by the deficiency of another vitamin called folic acid.

You must not be given this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged return it to your pharmacist for disposal.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor or pharmacist if you are allergic to any other medicines or any foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions, including:

  • a disease of the spinal cord
  • folate-deficient megaloblastic anaemia (a type of anaemia caused by the deficiency of another vitamin called folic acid).

Tell your doctor or pharmacist if you are pregnant or plan to become pregnant or are breast-feeding.

Your doctor can discuss with you the possible risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you are given HYDROXO-B12 Injection.

Taking other medicines

Tell your doctor or pharmacist if you are using any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may be affected by HYDROXO-B12 or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines. These include:

  • chloramphenicol, a medicine used to treat infections
  • the contraceptive pill (birth control pill)
  • folic acid.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while being given this medicine.

How it is given

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight.

How it is given

HYDROXO-B12 Injection is given as an injection into a muscle.

It must only be given by a nurse or doctor.

If you receive too much (overdose)

As HYDROXO-B12 Injection is given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience severe side effects, tell your doctor immediately or go to the Accident and Emergency department of your nearest hospital.

Symptoms of an overdose may include the side effects listed in the 'Side effects' section, but are usually of a more severe nature.

Ask your doctor or pharmacist if you have any concerns.

While you are being given it

Things you must do

If you are to be started on any new medicine, remind your doctor and pharmacist that you are being given HYDROXO-B12 Injection.

Tell any other doctors, dentists, and pharmacists who treat you that you are being given this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine.

It may affect other medicines used during surgery.

If you become pregnant while you are being treated with this medicine tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are being given this medicine.

It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent any unwanted side effects.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being treated with HYDROXO-B12 Injection.

This medicine helps most people with vitamin B12 deficiency, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • diarrhoea
  • nausea
  • headache
  • vomiting
  • dizziness
  • acne
  • skin rash
  • pain or redness at the injection site. This side effect is usually mild.

If any of the following happen, tell your doctor immediately or go to the Accident and Emergency Department at your nearest hospital:

  • signs of an allergic reaction, which may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin
  • breathlessness, which may be very severe and usually worsens on lying down (due to a build-up of fluid in the lungs)
  • changes in heart rate (fast, slow or irregular)
  • chest tightness or pain.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell, even if you think the problems are not connected with this medicine and are not referred to in this leaflet.

Other side effects not listed above may also occur in some people.

Do not be alarmed by this list of side effects.

You may not experience and of them.

After being given it

Storage

HYDROXO-B12 Injection is usually stored in the doctor's surgery or clinic, or at the pharmacy. The injection is kept in a cool, dry place where the temperature stays below 25°C.

If you need to store HYDROXO-B12 Injection, keep it in the original pack until it is time for it to be given.

If you take the ampoules out of the pack, they may not keep as well.

Do not store this medicine or any other medicine in the bathroom or near a sink. Do not leave it in the car on hot days, or on window sills.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using HYDROXO-B12 Injection or it has passed its expiry date, ask your pharmacist what to do with any ampoules that are left over.

Product description

What it looks like

HYDROXO-B12 Injection is a clear, dark red solution in a glass ampoule. It is available in packs of 3 ampoules.

Ingredients

Active ingredient:

Each ampoule contains 1 mg/mL of hydroxocobalamin (as hydroxocobalamin chloride).

Inactive ingredients:

  • sodium chloride
  • water for injections.

BRAND INFORMATION

Brand name

Hydroxo-B12 Solution for injection

Active ingredient

Hydroxocobalamin chloride

Schedule

Unscheduled

 

1 Name of Medicine

Hydroxocobalamin chloride (vitamin B12).

6.7 Physicochemical Properties

Molecular formula: C62H90ClCoN13O15P.
Molecular weight is 1,383 g/mol.

Chemical structure.


CAS number.

58288-50-9.

2 Qualitative and Quantitative Composition

Hydroxocobalamin is a dark red, odourless crystalline powder or crystals. It is soluble in water and alcohol, sparingly soluble in methyl alcohol and practically insoluble in acetone, chloroform and ether.
Hydroxocobalamin (as chloride) and hydroxocobalamin chloride 1.027 mg/mL equivalent to 1.0 mg/mL hydroxocobalamin.
Hydroxo-B12 also contains sodium chloride 9.0 mg and hydrochloric acid for pH adjustment and water for injections. The pH of the solution is approximately 4.6.

3 Pharmaceutical Form

Solution for injection in ampoules, 1 mg/mL (1000 microgram/mL) (clear dark red solution) in a pack of 3 ampoules.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Several chemically related forms of vitamin B12, differing in slight modification of a side chain attached to the cobalamin nucleus have been isolated. Two such variants of vitamin B12are cyanocobalamin and hydroxocobalamin. Vitamin B12 is essential for normal growth, haemopoiesis, production of all epithelial cells and maintenance of myelin throughout the nervous system. Whenever nucleic acid synthesis occurs and therefore whenever cell reproduction occurs, vitamin B12 is required.
The amounts of vitamin B12 needed to maintain normal blood forming functions are small and low doses are sufficient to correct the usual symptoms of vitamin B12 deficiency. Vitamin B12 acts as an enzyme or coenzyme in a number of metabolic processes and is transformed in the body to at least two compounds which possess enzymatic properties.
i) Coenzyme B12 is required for conversion of propionate to succinate, thus involving vitamin B12 in both fat and carbohydrate metabolism.
ii) Methylcobalamin acts in a transmethylation process converting homocysteine to methionine, thus involving vitamin B12 in fat and protein metabolism. In some cases of vitamin B deficiency, severe neurological symptoms develop, as vitamin B12 is necessary for the formation of protein structures required for the integrity of the nerve cell and myelin sheath.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Hydroxocobalamin produces higher and more prolonged serum levels of vitamin B12 than cyanocobalamin when given by intramuscular injection in the same dosage. Hydroxocobalamin disperses more slowly from the site of injection than cyanocobalamin, is more strongly bound to plasma proteins and accumulates in the liver to a greater extent. Hydroxocobalamin is excreted in the bile and urine, but more slowly than cyanocobalamin. Hydroxocobalamin combines with cyanide and thus acts as a cyanide antagonist in vivo resulting in the formation of cyanocobalamin.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Prophylaxis and treatment of pernicious (Addisonian) anaemia and other macrocytic anaemias associated with vitamin B12 deficiency. Treatment of optic neuropathies such as tobacco amblyopia and Leber's optic atrophy.

4.3 Contraindications

Known sensitivity to hydroxocobalamin or any other ingredient in Hydroxo-B12. Known sensitivity to cobalt. Hydroxocobalamin should not be used for the treatment of megaloblastic anaemia of pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

4.4 Special Warnings and Precautions for Use

Do not use intravenously. A sensitivity history should be obtained from the patient prior to administration of vitamin B12. An intradermal test dose is recommended before vitamin B12 is administered to patients who may be sensitive to cobalamins.
Hypokalaemia and cardiac arrest have been reported when megaloblastic anaemia is treated intensively.
Serum potassium is to be carefully monitored during the initial phase of treatment in pernicious anaemia.
Diagnosis of vitamin B12 deficiency should be confirmed by laboratory investigation before institution of hydroxocobalamin (vitamin B12) therapy.
Do not use hydroxocobalamin until diagnosis is fully established, as it may mask symptoms of subacute degeneration of the spinal cord, or of the true diagnosis of pernicious anaemia. Folic acid may potentiate the neurological complications of vitamin B12 deficiency, so it should not be administered to patients with pernicious anaemia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Regular blood tests to determine vitamin B12 levels are advisable during treatment. Administration of hydroxocobalamin doses in excess of 10 microgram daily may improve folate deficient megaloblastic anaemia and obscure the true diagnosis.
The therapeutic response to hydroxocobalamin may be impaired by concurrent infection, uraemia, folic acid or iron deficiency, or by drugs with bone marrow suppressing effects, such as chloramphenicol (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Treatment with hydroxocobalamin may unmask polycythaemia vera, because vitamin B12 deficiency may suppress the symptoms of this condition.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

Most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B12 microbiological blood assays.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concurrent administration of chloramphenicol and hydroxocobalamin may impair the therapeutic response to hydroxocobalamin in vitamin B12 deficient patients. The haematological response should be carefully monitored in patients receiving both these drugs. Serum concentrations of hydroxocobalamin may be lowered by oral contraceptives. Vitamin B12 concentrations in the blood may be reduced following administration of large and continuous doses of folic acid. Folic acid administration may impair the therapeutic response to hydroxocobalamin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
Problems in humans have not been documented with intake of normal daily amounts. Vitamin B12 crosses the placental barrier. There are no studies establishing the safety of this drug during pregnancy. It is not recommended for pregnancy unless the expected benefits outweigh any potential risk to the infant. Megaloblastic anaemia occurring during pregnancy is usually due to folic acid deficiency rather than vitamin B12 deficiency.
Hydroxocobalamin should not be used for the treatment of megaloblastic anaemia of pregnancy caused by folic acid deficiency.
Hydroxocobalamin is distributed into breast milk. Therefore it is not recommended for breastfeeding mothers unless the expected benefits to the mother outweigh any potential risk to the infant.

4.8 Adverse Effects (Undesirable Effects)

Sensitisation to hydroxocobalamin is rare, but may manifest itself as itching exanthema and rarely, anaphylaxis. Antibodies to hydroxocobalamin transcobalamin II complex may develop during hydroxocobalamin therapy.
Other reported adverse effects include diarrhoea, nausea, vomiting, headache, dizziness, peripheral vascular thrombosis, chest pain/ discomfort, cardiac arrest, injection site reactions, sensation of heat and cold, malaise, urticaria or a feeling of swelling of the whole body, eczematous skin lesions, acne and folliculitis.
Pulmonary oedema and congestive heart failure have been reported during early vitamin B12 treatment, possibly as a result of an increase in blood volume induced by the drug.
Polycythaemia vera may occur (see Section 4.4 Special Warnings and Precautions for Use).
Arrhythmias secondary to hypokalaemia have appeared at the beginning of parenteral treatment with hydroxocobalamin.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

This product contains no antimicrobial agent. It is for single use in one patient only. Discard any residue. Hydroxo-B12 injection is to be administered intramuscularly.
The following dosage schemes are suitable for adults and children.

Addisonian pernicious anaemia and other macrocytic anaemias without neurological involvement.

Initially.

250 to 1,000 micrograms intramuscularly on alternate days for one to two weeks, then 250 micrograms weekly until the blood count is normal.

Maintenance.

1,000 micrograms every two or three months.

Addisonian pernicious anaemia and other macrocytic anaemias with neurological involvement.

Initially.

1,000 micrograms on alternate days for one to two weeks.

Maintenance.

1,000 micrograms every two months.

Prophylaxis of macrocytic anaemia associated with vitamin B12 deficiency resulting from gastrectomy, some malabsorption syndromes and nutritional deficiencies.

1,000 micrograms every two or three months.

Tobacco amblyopia and Leber's optic atrophy.

Initially.

1,000 microgram daily by intramuscular injection for two weeks then twice weekly for four weeks.

Maintenance.

1,000 microgram monthly.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

Unscheduled.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

2 years.

6.4 Special Precautions for Storage

Store below 25°C.
Protect from light.

6.5 Nature and Contents of Container

Coloured glass ampoule.
Pack size 3.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes