Vitamin B12a Other names: Hydroxocobalamin Hydroxycobalamin

Animal studies have shown teratogenic effects following daily exposure throughout organogenesis. There are no adequate data from the use of hydroxocobalamin in pregnant women and the potential risk for humans is unknown.

However, taken into account:

• that no more than two injections of hydroxocobalamin are to be administered,
• the potentially life threatening condition,
• the lack of alternative treatment, hydroxocobalamin may be given to a pregnant woman.

In case of known pregnancy at the time of treatment with hydroxocobalamin or in case that pregnancy becomes known after treatment with hydroxocobalamin, health care professionals are requested to promptly report the exposure during pregnancy to the Marketing Authorisation Holder and/or Health Authorities and to carefully follow-up on the pregnancy and its outcome.

Because hydroxocobalamin will be administered in potentially life-threatening situations, breast-feeding is not a contraindication to its use. In the absence of data in breast-fed infants, breast-feeding discontinuation is recommended after receiving hydroxocobalamin.

Fertility

No studies on fertility have been performed.

Not relevant.

Summary of the safety profile

A total of 347 subjects were exposed to hydroxocobalamin in clinical studies. Of these 347 subjects, 245 patients had suspected exposure to cyanide at the time of hydroxocobalamin administration. The remaining 102 subjects were healthy volunteers who had not been exposed to cyanide at the time of hydroxocobalamin administration.

List of adverse reactions

The following adverse reactions have been reported in association with hydroxocobalamin use. However, because of the limitations of the available data, it is not possible to apply frequency estimations:

Blood and lymphatic system disorders:

Decrease in the percentage of lymphocytes.

Immune system disorders:

Allergic reactions including angioneurotic oedema, skin eruption, urticaria and pruritus.

Psychiatric disorders:

Restlessness.

Nervous system disorders:

Memory impairment; dizziness.

Eye disorders:

Swelling, irritation, redness.

Cardiac disorders:

Ventricular extrasystoles. An increase in heart rate was observed in cyanide-poisoned patients.

Vascular disorders:

Transient increase in blood pressure, usually resolving within several hours; hot flush. A decrease in blood pressure was observed in cyanide-poisoned patients.

Respiratory, thoracic and mediastinal disorders:

Pleural effusion, dyspnoea, throat tightness, dry throat, chest discomfort.

Gastrointestinal disorders:

Abdominal discomfort, dyspepsia, diarrhoea, vomiting, nausea, dysphagia.

Skin and subcutaneous tissue disorders:

Reversible red colouration of the skin and mucous membranes: most patients will experience it up to 15 days after administration of hydroxocobalamin. Pustular rashes, which may last for several weeks, affecting mainly the face and the neck.

Renal and urinary disorders:

• Acute renal failure with acute tubular necrosis, renal impairment, urine calcium oxalate crystals present.
• Chromaturia: all patients will show a dark red colouration of the urine quite marked during the first three days following administration. Urine colouration may last up to 35 days after administration of hydroxocobalamin.

General disorders and administration site conditions:

Headache; injection site reaction; peripheral oedema.

Investigations:

Hydroxocobalamin may cause red discolouration of the plasma, which may cause artificial elevation or reduction in the levels of certain laboratory parameters.

Paediatric population

Limited data on children (0 to 18 years old) treated with hydroxocobalamin did not show any difference in the safety profile of hydroxocobalamin between adults and children.