1 Name of Medicine
Thiamine hydrochloride.
2 Qualitative and Quantitative Composition
Each 2 mL injection in ampoule contains 100 mg of thiamine hydrochloride.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Injection for intravenous use.
The pH of the solution is 2.5 to 4.5.
Aqueous, clear, colorless to slightly yellow solution, visible particle free.
4.1 Therapeutic Indications
Thiamine hydrochloride 100 mg in 2 mL injection is used for the prevention and treatment of vitamin B1 deficiency.
4.2 Dose and Method of Administration
Use in one patient on one occasion only and discard any residue.
Thiamine hydrochloride 100 mg in 2 mL injection is administered by slow IV injection over a period of at least 10 minutes.
Due to the potential for serious anaphylactic reactions, parenteral administration of thiamine is only indicated when oral administration of thiamine is not acceptable or possible. Facilities for treating anaphylaxis should be available when administering thiamine injection.
If the thiamine hydrochloride solution is cloudy or contains visually detectable particles, please contact the Quality Assurance Manager at Advanz Pharma.
Thiamine deficiency.
Simple thiamine deficiency is rare and as a result multiple vitamin deficiencies should be suspected either in those patients exhibiting signs consistent with thiamine deficiency, or those considered to be at risk of developing thiamine deficiency. Consideration should be given to administering other water-soluble vitamins in conjunction with thiamine.
In critically ill thiamine deficient adults and in patients with malabsorption syndromes, the usual IV dosage of thiamine hydrochloride is 5 to 100 mg three times daily. In patients with beriberi, the dose should then be reduced according to response and followed by oral therapy for one month.
In patients with Wernicke's encephalopathy, thiamine hydrochloride therapy is usually initiated with an IV dose of 100 mg over at least 30 minutes, followed by IV doses of 50-100 mg daily until the patient is consuming a regular, well-balanced diet. High carbohydrate diets or IV glucose solutions increase thiamine requirements and may worsen symptoms in thiamine deficient patients. Thiamine should be administered parentally before giving glucose solutions to the patient with Wernicke's encephalopathy.
In alcohol withdrawal syndrome to prevent Wernicke's encephalopathy, 100 mg of thiamine should be given through IV followed by 100 mg orally, IV for up to 5 days.
Dietary supplementation.
Dietary improvement is preferred over supplementation wherever possible. The Australian recommended daily intake (RDI) of thiamine for adults is shown in Table 1.
Use in infants and children.
Critically ill children who are thiamine deficient receive a usual IV dose of thiamine hydrochloride of 10-25 mg daily. The Australian recommended daily intake (RDI) of thiamine for children is shown in Table 2.
Compatibility.
Thiamine hydrochloride 100 mg in 2 mL injection is reported to be compatible with 100 mL of diluent; glucose 5%, glucose 10%, sodium chloride 0.9% or compound sodium lactate (Hartmann's solution).4.3 Contraindications
Known hypersensitivity to any of the ingredients.
There is only limited experience with therapy in children and in adolescents.
4.4 Special Warnings and Precautions for Use
Serious hypersensitivity reactions to thiamine have been reported following parenteral administration [see Section 4.8 Adverse Effects (Undesirable Effects)]. These reactions include feelings of warmth, tingling, pruritus, pain, urticaria, weakness, sweating, nausea, restlessness, tightness of the throat, angioedema, respiratory distress, cyanosis, pulmonary oedema, gastrointestinal bleeding, transient vasodilatation and hypotension, vascular collapse, and death.
A sensitivity history should be obtained from the patient prior to administration of thiamine.
An intradermal diluted test dose of thiamine should be administered to patients with suspected sensitivity (e.g. a history of an allergic response such as itching, sneezing, wheezing or frank anaphylactic shock with a previous injection) before parenteral administration.
Simple thiamine deficiency is rare. Multiple vitamin deficiencies should be suspected in any case of dietary inadequacy.
Intravenous glucose loading may precipitate or worsen the condition of Wernicke's encephalopathy in thiamine-deficient patients: Thiamine hydrochloride should be administered prior to glucose.
Use in the elderly.
Problems in geriatrics have not been documented with intake of normal daily recommended amounts.
The elderly may have impaired thiamine status, thereby requiring thiamine supplementation. Information on large doses is not available.
Paediatric use.
There is only limited experience with therapy in children and adolescents.
Information on large doses in children over 2 years is not available.
Effects on laboratory tests.
Thiamine reportedly causes false-positive results in the urine spot test with Erlich's reagent for urobilinogen and may also interfere with the phosphotungstate method for determination of uric acid concentrations. Large doses of thiamine have reportedly interfered with the Schack and Waxler spectrophotometric determination of serum theophylline concentrations, giving falsely raised results.4.5 Interactions with Other Medicines and Other Forms of Interactions
Although the clinical importance is unknown, thiamine reportedly may enhance the effect of neuromuscular blocking agents.
In vitro thiamine hydrochloride at a concentration of 0.1% significantly reduces the activity of kanamycin sulfate and streptomycin sulfate at 25°C.
Please see Section 6.2 Incompatibilities.
4.6 Fertility, Pregnancy and Lactation
Effects on fertility.
There is no information available on the effects of thiamine injection on fertility.
Exempt from classification in the Australian categorisation system for prescribing medicines in pregnancy.
There is an increasing demand for thiamine throughout pregnancy due to the increased energy requirement plus the amount needed to meet the foetal requirement. Thiamine is required by the newborn for normal growth and development. Problems in humans have not been documented with intake of normal daily recommended amounts.
There is limited information in humans that large doses in the second or third trimester have no apparent effect.
Embryonic and foetal death have been reported in pregnant women who have severe thiamine deficiency as a result of hyperemesis gravidarum.
There is an increasing metabolic requirement for thiamine to produce milk, and additional thiamine is also needed to compensate for that lost in the milk and also for the increased maternal energy requirement. About 100-200 micrograms of thiamine is distributed daily into the milk of lactating women receiving a normal diet (see Section 5.2 Pharmacokinetic Properties). Problems in humans have not been documented with intake of normal daily recommended amounts.
Information on large doses is not available.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.
4.8 Adverse Effects (Undesirable Effects)
Anaphylactic reactions.
Rare: these reactions can be preceded by sneezing or transient pruritus.
Symptoms and signs of hypersensitivity and other adverse reactions to thiamine may include any one or more of the following: feelings of warmth, tingling, pruritus, pain, urticaria, erythema, scaling of the facial skin, severe rash, weakness, sweating, nausea, vomiting, restlessness, tightness of the throat, angioedema, respiratory distress, cyanosis, pulmonary oedema, dyspnoea, respiratory failure, gastrointestinal bleeding, abdominal pain, precordial pain, palpitations, tachycardia, transient vasodilation and hypotension, shock, vascular collapse, semi-comatose state and death have occurred (see Section 4.4 Special Warnings and Precautions for Use).
Metabolic and nutritional disorders.
Very rare: fatty degeneration of the liver resulting in hyaline necrosis and ascites.
Rare: contact dermatitis, chronic pigment purpura.
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 www.tga.gov.au/reporting-problems.4.9 Overdose
In animals, very large parenteral doses have produced neuromuscular and ganglionic blockade. Parenteral doses of 100 mg to 500 mg, as single or repeated doses have been administered without toxic effects. In cases of overdose, withdraw thiamine and give supportive treatment for symptoms and respiratory and cardiac function.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
5 Pharmacological Properties
5.1 Pharmacodynamic Properties
Mechanism of action.
In humans, an exogenous source of thiamine (or vitamin B1) is required for carbohydrate metabolism. Thiamine combines with adenosine triphosphate (ATP) in the liver, kidneys, and leukocytes to form thiamine diphosphate (thiamine pyrophosphate) also known as cocarboxylase. Thiamine diphosphate is a coenzyme in carbohydrate metabolism (in the decarboxylation of pyruvic acid and α-ketoglutaric acids) and in transketolase reactions. Thiamine diphosphate is also a coenzyme in the utilization of pentose in the hexose monophosphate shunt. Even large doses of thiamine have no effect on blood glucose concentrations. Thiamine deficiency leads to decreased transketolase activity in erythrocytes and to increased pyruvic acid concentration in the blood. In the absence of thiamine as thiamine pyrophosphate, pyruvic acid is not converted to acetyl-COA and therefore is unable to enter the usual aerobic oxidative pathway (Krebs citric acid cycle), resulting in accumulation of pyruvic acid and subsequent conversion to lactic acid. In addition, the resultant decreased production of NADH within the Krebs cycle stimulates anaerobic glycolysis and further lactic acid production. Therefore, lactic acidosis may occur in thiamine deficiency.
The normal mean level of thiamine in whole blood is 28 micrograms/L, and of free thiamine is 6.5 to 11.4 micrograms/L.
Thiamine is used in the prevention or treatment of vitamin B1 deficiency syndromes including beriberi, Wernicke's encephalopathy and peripheral neuritis associated with pellagra or neuritis of pregnancy (if associated with severe vomiting). Dietary improvement is preferred over supplementation whenever possible to the administration of vitamin supplements.
Thiamine deficiency results in beriberi and Wernicke's encephalopathy syndrome. Clinical signs of thiamine deficiency become evident after 2-3 weeks of inadequate thiamine intake. The organ systems principally affected by thiamine deficiency are the peripheral nervous system, cardiovascular system and the gastrointestinal tract. Administration of thiamine completely reverses the cardiovascular and gastrointestinal symptoms of thiamine deficiency, however the degree of improvement in neurological symptoms depends on the duration and severity of the lesions. Fatal deficiency can develop as rapidly as within 3-4 weeks in the absence of thiamine intake. Several cases of fatal, acute beriberi developed within 5 weeks in patients receiving thiamine deficient total parenteral nutrition solutions during a US shortage of parenteral multivitamin preparations.
Thiamine supplementation is useful in preventing deficiency in malabsorption syndromes such as alcoholism, cirrhosis and gastrointestinal diseases. Increased thiamine requirements are also associated with pregnancy, increased carbohydrate intake, increased physical activity, hyperthyroidism, infection and hepatic disease. Dietary improvement is preferred over supplementation whenever possible to the administration of vitamin supplements.
Thiamine requirement is directly related to the carbohydrate content of the diet. The minimum daily requirement is estimated to be 0.33 mg/4,200 kJ (1,000 kcal). Vitamin B1 depletion can occur after approximately 3 weeks of total absence of thiamine in the diet. Deficiency may occur in alcoholics and food faddists or in special situations such as haemodialysis or chronic peritoneal dialysis. Requirements may be increased due to burns, chronic fever, gastrectomy, intestinal disease, liver disease and hyperthyroidism. Symptoms of deficiency include mental confusion, anorexia, muscle wasting, oedema and heart failure.
Clinical trials.
No data available.
5.2 Pharmacokinetic Properties
Absorption.
Following oral administration of small doses, thiamine hydrochloride is readily absorbed; however absorption is an active process and the total amount absorbed after oral administration of a large dose is limited to about 4 - 8 mg.
GI absorption of thiamine is decreased in alcoholics and in patients with cirrhosis or malabsorption. The rate, but not the extent, of GI absorption of thiamine is decreased when the drug is administered with meals.
Thiamine is completely and rapidly absorbed after IV administration.
In chronic alcohol misusers, malnutrition can reduce intestinal thiamine absorption by ~70%, decreasing serum levels from 30 to 98% below the lower level established for normal subjects. Alcohol itself alone can also decrease absorption by 50% in one third of patients who are not malnourished.
Distribution.
Thiamine is widely distributed into body tissues, including the brain, liver, heart, kidneys, muscle, cerebrospinal fluid and blood cells. Thiamine is not stored to any appreciable extent in the body. Body stores of thiamine have been estimated to be about 30 mg with about a 1 mg daily turnover. About 100 - 200 micrograms of thiamine is distributed daily into the milk of nursing women receiving a normal diet.
Metabolism.
Thiamine is metabolised in the liver in animals. Several urinary metabolites of thiamine have been identified in humans.
Excretion.
Little or no unchanged thiamine is excreted in urine following administration of physiologic doses; however, dosages exceeding 30 mg three times daily are not utilised effectively. When the body tissues are saturated with thiamine, it is excreted in the urine - as pyrimidine. As the intake of thiamine is further increased, thiamine appears unchanged in the urine in amounts exceeding 100 micrograms/24 hours.
5.3 Preclinical Safety Data
Genotoxicity.
No data available.
Carcinogenicity.
No data available.6 Pharmaceutical Particulars
6.1 List of Excipients
Thiamine Sterop contains sodium hydroxide and water for injection.
6.2 Incompatibilities
Thiamine is unstable in neutral or alkaline solutions; therefore, administration with carbonates, citrates, barbiturates, or copper ions is not recommended. In addition, stability is poor in intravenous solutions containing sodium bisulfite as an antioxidant or preservative; if these solutions must be given, they should be given separately from a thiamine hydrochloride injection.
Oxidation of thiamine hydrochloride results in the formation of the highly blue-coloured and biologically inactive compound - thiochrome.
Please see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.
6.3 Shelf Life
In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
6.4 Special Precautions for Storage
Store below 25°C. Protect from light.
Keep out of reach of children.
6.5 Nature and Contents of Container
Container type.
Type I colorless glass ampoule.
Pack sizes.
Thiamine hydrochloride 100 mg/2 mL injection has below mentioned pack size 10 x 2 mL ampoule per carton.
6.6 Special Precautions for Disposal
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.
6.7 Physicochemical Properties
Chemical structure.
Molecular formula: C12H17ClN4OS, HCl.
Molecular weight: 337.3.
CAS number.
67-03-8.
Thiamine hydrochloride occurs as a white or almost white, crystalline powder or colourless crystals. It is freely soluble in water, slightly soluble in ethanol 96%.7 Medicine Schedule (Poisons Standard)
Not scheduled.
