1 NAME OF THE MEDICINE
Solution for Injection; multicomponent
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 3 ml ampoule contains: Thiamine hydrochloride (Vitamin B1) 100,0 mg Pyridoxine hydrochloride (Vitamin B6) 100,0 mg Cyanocobalamin (Vitamin B12) 1,0 mg Sugar free For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Clear, red solution with no visible particles.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
NEUROBION AMPOULES are indicated for: • Restoring Vitamin B1, B6 and/or B12 levels. • The prevention and treatment of deficiencies in vitamin B1, B6 and B12. NEUROBION AMPOULES assist with the management of neuropathies.
4.2 Posology and method of administration
NEUROBION AMPOULES are preferably injected intramuscularly (deep intragluteal).
• Hypersensitivity to Vitamin B1, B6 and/or B12 or any of the excipients of NEUROBION AMPOULES (see section 6.1). • Children below the age of 14 years (due to the high doses of the active ingredients). NEUROBION AMPOULES should not be used in patients on Levodopa therapy.
4.4 Special warnings and precautions for use
NEUROBION AMPOULES should not be given for Vitamin B12 deficiency before a diagnosis has been fully established, because of the possibility of masking symptoms of subacute degeneration of the spinal cord. NEUROBION AMPOULES are not a suitable form of Vitamin B12 for the treatment of optic neuropathies associated with raised plasma concentrations of Vitamin B12. Neuropathies are described in the literature following long-term intake (6 - 12 months) of more than 50 mg mean daily dose of vitamin B6. Therefore, regular monitoring is recommended if NEUROBION AMPOULES are given over longer periods of time.
4.5 Interactions with other medicines and other forms of interaction
Vitamin B6 (pyridoxine) may decrease the effect of L-DOPA.
Pyridoxine antagonists such as isoniazide, cycloserine, penicillamine, or hydralazine may decrease the efficacy of Vitamin B6 (pyridoxine).
Long-term use of loop diuretics such as furosemide may accelerate the elimination and thus decrease the serum levels of Vitamin B1 (thiamine).
Long term use of acid-lowering agents may lead to Vitamin B12 deficiency.
4.6 Fertility, pregnancy and lactation
The safety of this preparation in pregnancy and lactation has not been established. Vitamins B1, B6 and B12 (the components of NEUROBION AMPOULES) are secreted into human breast milk, but risks of overdose for the infant are not known. High doses of Vitamin B6, i.e. > 600 mg daily, may inhibit the production of breast milk. Mothers on NEUROBION AMPOULES should not breastfeed their infants.
4.7 Effects on ability to drive and use machines
No effects of the product on the ability to drive or use machines are known.
4.8 Undesirable effects
As most undesirable effects are based on post-marketing spontaneous reporting, frequency estimation is not possible. Immune system disorders Frequency not known: Hypersensitivity reactions, such as sweating, tachycardia, and skin reactions with itching and urticaria. Gastrointestinal disorders Less frequent: Gastrointestinal complaints, such as nausea, vomiting, diarrhoea and abdominal pain. Skin and subcutaneous tissue disorders Less frequent: Cases of acne or eczema have been reported after high doses of Vitamin B12. General disorders and administration site conditions Frequency not known: Injection site reactions. Renal and urinary disorders Less frequent: Chromaturia (“reddish urine”, appeared during the first 8 hours after an administration and typically resolves within 48 hours). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications:
Sensorial neuropathy and other sensorial neuropathy syndromes which can be caused by long-term administration of high doses of pyridoxine improve gradually upon vitamin discontinuation.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
A.22.2 – Vitamins: Others Vitamins B1, B6 and B12 act as coenzymes and accordingly constitute substances essential for metabolism.
5.2 Pharmacokinetic properties
Combined administration of vitamins B1, B6 and B12 is not expected to have a negative effect on the pharmacokinetics of the individual vitamins. Thiamine (Vitamin B1) The biological half-life of thiamine in humans is about 9,5 to 18,5 days, with an elimination half-life of approximately 4 hours. The reserve capacity is 4 to 10 days. The high turnover rate and limited storage of thiamine (20 – 30 mg, mainly in the heart, brain, liver, and kidneys) require an adequate daily thiamine intake to meet requirements. Deficiency can present within 2 - 3 weeks of intake ceasing. Pyridoxine (Vitamin B6) Vitamin B6 is phosphorylated mainly in the liver, forming the biologically active pyridoxal phosphate. To cross cell membranes, phosphorylated Vitamin B6 must be hydrolysed by alkaline phosphatase to free Vitamin B6. Transport into the cells is by simple diffusion followed by rephosphorylation. Peak concentrations are reached after 3,5 to 4 hours. The biological half-life of pyridoxal phosphate is about 15 - 25 days with an elimination half-life of approximately 3 hours. Cyanocobalamin (Vitamin B12) About 90 % of plasma cobalamin is bound to proteins (transcobalamins). Most of the vitamin B12 not circulating in the plasma is stored in the liver. Vitamin B12 is predominantly excreted via the bile and is largely reabsorbed via the enterohepatic circulation. If the body’s storage capacity is exceeded as a result of high-dose and, in particular, parenteral administration, the portion not retained is excreted in the urine.
5.3 Preclinical safety data
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Potassium cyanide, Sodium hydroxide solution
6.3 Shelf life
6.4 Special precautions for storage
Store between 2 - 8 °C in a refrigerator. Keep out of reach and sight of children.
6.5 Nature and contents of container
Boxes of 3 ampoules of 3 ml each.
6.6 Special precautions for disposal and other handling
No special requirements.
7 HOLDER OF CERTIFICATE OF REGISTRATION
P&G South African Trading (Pty) Ltd 10th Floor, Alice Lane Towers, 15 Alice Lane, Sandton, 2196 South Africa
8 REFERENCE NUMBER
H2488 (Act 101/1965)
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11 March 1988
10 DATE OF REVISION OF THE TEXT