thiamine
water-soluble vitamin· Brands: Benerva, Pabrinex, Betalin S, Vitamin B1IMIVPO
Mechanism of action
Thiamine (vitamin B1) is taken up by cells and phosphorylated to thiamine pyrophosphate (TPP), which acts as a coenzyme for several enzymes central to energy metabolism. TPP is required by pyruvate dehydrogenase for the oxidative decarboxylation of pyruvate to acetyl-CoA, by alpha-ketoglutarate dehydrogenase in the citric acid cycle, by branched-chain alpha-keto acid dehydrogenase in the catabolism of leucine, isoleucine and valine, and by transketolase in the pentose phosphate pathway, which supplies ribose-5-phosphate for nucleic acid synthesis and NADPH for reductive reactions. When thiamine is deficient, these reactions slow, oxidative metabolism of glucose and branched-chain amino acids is impaired, lactate accumulates, and cells with high energy demand such as neurons and cardiac myocytes are affected first. Thiamine also has non-coenzyme roles in nerve membranes and synaptic transmission, which may explain why high parenteral doses can produce rapid neurological improvement that is faster than enzyme repletion alone would predict. Body reserves are small, so deficiency develops within weeks of inadequate intake or increased loss.
Pharmacokinetics
Oral thiamine is absorbed from the small intestine by a saturable, sodium-dependent carrier mechanism at low doses, with passive diffusion contributing at higher doses. Absorption is therefore dose-limited, and the amount absorbed from a single oral dose does not rise proportionately once the carrier is saturated; oral bioavailability is low and falls as the dose increases. After absorption, thiamine is distributed widely to tissues, crosses the placenta and appears in breast milk; it is not stored in appreciable amounts and liver reserves are small. It is not significantly protein bound. Thiamine is metabolised in the liver to several metabolites, including thiochrome and pyrimidine and thiazole derivatives, and is excreted in urine both unchanged and as metabolites. Elimination is relatively rapid, so frequent dosing is needed in acute deficiency states. Cerebrospinal fluid concentrations are lower than plasma concentrations, which is one reason why high parenteral doses are used when central nervous system deficiency is suspected. Prolonged use of diuretics, alcohol and some other drugs increases thiamine loss.
Indications & dosing
Wernicke encephalopathy (treatment)
High-dose regimen; some guidelines recommend 100-250 mg IV three times daily. Continue for 3-5 days then review.
- adult · IV: 500 mg TID · High-dose regimen; some guidelines recommend 100-250 mg IV three times daily. Continue for 3-5 days then review.
Thiamine deficiency (beriberi)
For cardiac or neurological involvement. Switch to oral once improved.
- adult · IV: 10–30 mg TID · For cardiac or neurological involvement. Switch to oral once improved.
Prophylaxis of thiamine deficiency in alcohol misuse or malnutrition
Often given with other B vitamins. Higher doses may be used in some local protocols.
- adult · PO: 100 mg daily · Often given with other B vitamins. Higher doses may be used in some local protocols.
Maintenance after acute thiamine deficiency
Follow-up oral therapy after parenteral treatment.
- adult · PO: 10–30 mg daily · Follow-up oral therapy after parenteral treatment.
Thiamine deficiency (beriberi) in children
Doses may be given IM if IV access not available. Higher doses may be needed in severe cases.
- pediatric · IV: 10–25 mg daily · Doses may be given IM if IV access not available. Higher doses may be needed in severe cases.
Contraindications & precautions
- Hypersensitivity to thiamine or any component of the formulation · Thiamine should not be given to patients with a known allergy to thiamine or to excipients in the specific product.
- Previous anaphylactic reaction to thiamine · A history of anaphylaxis to thiamine, especially with parenteral administration, contraindicates further thiamine use.
- Give parenteral thiamine before glucose in suspected Wernicke's encephalopathy to avoid precipitating or worsening the condition.
- Have resuscitation facilities available when giving IV thiamine and observe the patient for at least 15 minutes after injection due to anaphylaxis risk.
- Use with caution in patients with asthma or a history of allergy; consider a test dose or slower administration if risk factors are present.
- Thiamine requirements are increased in pregnancy, lactation, dialysis and malabsorption states; dose adjustment may be needed.
- Oral absorption is reduced by alcohol; use parenteral thiamine in severe deficiency or when malabsorption is suspected.
- Do not use thiamine to treat non-deficient states; it is not a general tonic or appetite stimulant.
Adverse effects
- Anaphylaxisserious
- Angioedemaserious
- Hypotension and cardiovascular collapseserious
- Bronchospasm and dyspnoeaserious
- Injection site pain or reaction
- Rash, pruritus or urticaria
- Nausea, vomiting or abdominal discomfort
- Sweating, tachycardia or restlessness
Monitoring, pregnancy & toxicity
- Clinical neurological response in suspected Wernicke encephalopathy (confusion, ophthalmoplegia, nystagmus, ataxia, gait) · Daily during acute parenteral treatment, then at each review
- Blood pressure and heart rate · Before and during each intravenous dose, particularly the first doses and with rapid infusion
- Magnesium and other electrolytes · At presentation and during treatment, as hypomagnesaemia impairs conversion of thiamine to its active coenzyme forms
- Blood glucose · At presentation where alcohol misuse, malnutrition or hyperemesis is suspected; give thiamine before or alongside glucose
- Thiamine status where the assay is available (whole-blood thiamine diphosphate, erythrocyte transketolase activity) · At baseline when the diagnosis is uncertain or deficiency is being confirmed
- Pregnancy: Thiamine is used in pregnancy when clinically indicated and is not associated with teratogenic risk at usual therapeutic doses. Treatment is not withheld or reduced in pregnancy: prolonged vomiting such as hyperemesis gravidarum, alcohol use disorder, bariatric surgery and malnutrition all increase the risk of Wernicke encephalopathy, and deficiency should be corrected promptly. Requirements rise modestly in pregnancy, so preventive oral doses are usually continued or increased. Practice varies by region and formulary, so confirm the dose and route against local guidance.
- Toxicity: Anaphylaxis or anaphylactoid reaction after parenteral thiamine, with urticaria, rash, angioedema, bronchospasm, hypotension or collapse. Rare but recognised, and more frequent with intravenous than intramuscular administration. · Stop the infusion immediately, maintain the airway and circulation, and treat as anaphylaxis according to local resuscitation protocol, including adrenaline where indicated. Record the reaction and avoid further parenteral thiamine unless the benefit clearly outweighs the risk.
- Toxicity: Transient hypotension, flushing, warmth, nausea or injection-site pain during or shortly after rapid intravenous injection. · Give parenteral thiamine by slow intravenous infusion rather than rapid bolus, or by the intramuscular route, and monitor blood pressure during administration. Symptoms usually resolve without specific treatment once the rate is reduced.
- Toxicity: Oral thiamine at usual therapeutic doses is not associated with clinically important toxicity. High oral doses may cause mild nausea, abdominal discomfort or diarrhoea. · Reduce the dose or divide it through the day; no specific antidote or decontamination is required. Oral dosing has no established maximum toxic dose in routine practice.
Clinical notes
Thiamine is used to treat and prevent thiamine deficiency, including beriberi (dry, wet and infantile forms), Wernicke encephalopathy and Korsakoff syndrome, and deficiency related to chronic alcohol misuse, malnutrition, malabsorption, bariatric surgery, prolonged vomiting such as hyperemesis gravidarum, dialysis and refeeding syndrome. Suspected Wernicke encephalopathy is a medical emergency requiring prompt parenteral treatment; oral thiamine is inadequate for this indication because of poor and dose-limited absorption. Where deficiency is suspected or the patient is at high risk, thiamine should be given before or alongside glucose-containing fluids, because a glucose load can precipitate or worsen Wernicke encephalopathy in a thiamine-depleted patient. Magnesium should be corrected, since hypomagnesaemia impairs the conversion of thiamine to its active coenzyme form and can reduce clinical response. Anaphylaxis and other hypersensitivity reactions are rare but recognised after parenteral administration, so resuscitation facilities should be available and the injection given where patients can be observed. Oral thiamine is generally well tolerated and has a wide margin of safety. Dosing regimens, product availability and the use of combination parenteral products vary between regions and formularies, and local guidance should be checked. Clinical response, neurological signs and electrolyte status guide monitoring.
Log in to read the full thiamine monograph
A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.
BNF; local formulary; manufacturer's prescribing information