Thiamine - Drug Monograph

Introduction

Thiamine (vitamin B₁) is a water-soluble essential nutrient that serves as a critical cofactor in carbohydrate metabolism and neuronal function. As the first B vitamin discovered, thiamine plays a fundamental role in energy production and nervous system maintenance. Unlike fat-soluble vitamins, thiamine is not stored in significant quantities in the body, requiring regular dietary intake or supplementation to maintain adequate levels.

Mechanism of Action

Thiamine functions primarily as a coenzyme in several key metabolic processes. After phosphorylation to thiamine pyrophosphate (TPP), it serves as an essential cofactor for:

• Transketolase in the pentose phosphate pathway
• Pyruvate dehydrogenase complex in carbohydrate metabolism
• Alpha-ketoglutarate dehydrogenase in the Krebs cycle
• Branched-chain alpha-ketoacid dehydrogenase

These enzymatic reactions are crucial for glucose metabolism, neurotransmitter synthesis, and energy production. In neurological function, thiamine is essential for nerve conduction and maintenance of myelin sheaths.

Indications

• Treatment and prevention of thiamine deficiency syndromes
• Beriberi (wet and dry forms)
• Wernicke-Korsakoff syndrome
• Metabolic disorders requiring thiamine supplementation

• Prophylaxis in patients receiving total parenteral nutrition
• Management of thiamine-responsive inborn errors of metabolism
• Adjunctive therapy in congestive heart failure
• Prevention in high-risk populations (alcohol use disorder, malnutrition)

Dosage and Administration

• Adults: 5-30 mg daily for deficiency; 50-100 mg daily for severe deficiency
• Children: 10-50 mg daily depending on age and severity

• Wernicke's encephalopathy: 100 mg IV three times daily for 2-3 days, followed by 100 mg daily for 3-5 days
• Beriberi: 50-100 mg IV/IM daily for 2 weeks, then oral maintenance
• Prophylaxis: 10-20 mg IM daily for malnutrition

• Renal impairment: No dosage adjustment required
• Hepatic impairment: No dosage adjustment required
• Elderly: Standard adult dosing
• Pregnancy: Category A - recommended daily intake 1.4 mg

Pharmacokinetics

• Oral bioavailability is limited to 5-15 mg per dose due to saturable transport mechanisms
• Maximum absorption occurs in the jejunum and ileum
• Alcohol and folate deficiency impair absorption

• Widely distributed throughout body tissues
• Crosses placenta and enters breast milk
• Protein binding: minimal

• Phosphorylated in liver and other tissues to active metabolites
• Primary metabolites: thiamine monophosphate, thiamine pyrophosphate, thiamine triphosphate

• Renal excretion of unchanged drug and metabolites
• Half-life: approximately 3-5 hours
• No significant accumulation occurs

Contraindications

• Known hypersensitivity to thiamine or any component of the formulation
• No other absolute contraindications exist

Warnings and Precautions

• Anaphylactic reactions have occurred with IV administration
• Use with caution in patients with known alcohol intolerance (some formulations contain alcohol)
• Parenteral administration may cause vascular irritation
• Thiamine deficiency should be suspected in patients with unexplained lactic acidosis
• High doses may interfere with certain laboratory tests (urinary catecholamines, urobilinogen)

Drug Interactions

• Loop diuretics: May increase urinary thiamine excretion
• Phenytoin: Long-term use may decrease thiamine levels
• Fluorouracil: May inhibit thiamine phosphorylation
• Alcohol: Chronic use impairs thiamine absorption and storage
• Oral contraceptives: May slightly decrease thiamine levels

Adverse Effects

• Nausea
• Warmth/tingling sensation
• Urticaria
• Pruritus

• Anaphylaxis (particularly with IV administration)
• Angioedema
• Cardiovascular collapse
• Pulmonary edema

• Pain at injection site
• Induration with IM administration

Monitoring Parameters

• Clinical signs of deficiency resolution
• Nutritional status assessment
• Neurological examination in Wernicke-Korsakoff syndrome
• Electrolyte balance in patients receiving IV therapy
• Response indicators: improved appetite, weight gain, neurological improvement
• Laboratory monitoring not routinely required

Patient Education

• Take with food to minimize gastrointestinal upset
• Maintain consistent dietary intake of thiamine-rich foods (whole grains, legumes, pork, nuts)
• Alcohol consumption significantly increases thiamine requirements
• Report any signs of allergic reaction immediately
• Do not exceed recommended doses without medical supervision
• Store in a cool, dry place away from light

References

1. National Institutes of Health. Thiamine Fact Sheet for Health Professionals. 2021. 2. Frank LL. Thiamine in Clinical Practice. JPEN J Parenter Enteral Nutr. 2015;39(5):503-520. 3. Thomson AD, Cook CC, Guerrini I, et al. Wernicke's encephalopathy: 'plus ça change, plus c'est la même chose'. Alcohol Alcohol. 2008;43(2):180-186. 4. World Health Organization. Thiamine Deficiency and Its Prevention and Control in Major Emergencies. 1999. 5. Lonsdale D. A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives. Evid Based Complement Alternat Med. 2006;3(1):49-59. 6. American Society of Health-System Pharmacists. AHFS Drug Information. Thiamine Monograph. 2023. 7. FDA-approved prescribing information for thiamine products.