ATC Class:A11DA01
VA Class:VT105
Thiamine is a water-soluble, B complex vitamin.
Thiamine is used to prevent and to treat thiamine deficiency syndromes including beriberi, Wernicke's encephalopathy syndrome, delirium, and peripheral neuritis associated with pellagra or neuritis of pregnancy (if associated with severe vomiting). Wernicke's encephalopathy syndrome and high output heart failure secondary to beriberi are considered medical emergencies, and IV or IM thiamine should be administered immediately. Many clinicians recommend administration of at least one dose of IV or IM thiamine to all alcoholic patients with altered sensorium (e.g., delirium) who are admitted to the hospital. Whenever possible, poor dietary habits should be corrected, and many clinicians recommend administration of multivitamin preparations containing thiamine in patients with vitamin deficiencies since poor dietary habits often result in concurrent deficiencies. (See Multivitamins 88:28.) Thiamine is also used when IV dextrose is administered to patients with marginal thiamine status to avoid precipitation of heart failure.
Although an adequate amount of thiamine is usually obtained from dietary sources in patients with normal GI absorption, malabsorption of thiamine may occur in patients with alcoholism, cirrhosis, or GI diseases. Thiamine is useful in preventing deficiency in these patients; malabsorption syndromes should be corrected, if possible. Thiamine deficiency can also occur in patients with inadequate oral intake (e.g., patients with severe anorexia, nausea, vomiting). Increased thiamine requirements are associated with pregnancy, increased carbohydrate intake, increased physical activity, hyperthyroidism, infection, and hepatic disease; however, dietary thiamine deficiency is rarely associated with these conditions.
Because of the essential need for thiamine supplementation in certain patients and the risk of deficiency-associated lactic acidosis and, rarely, death,102, 103, 104, 105, 107, 108 if a national shortage of parenteral multivitamin preparations occurs,102, 107 it is recommended that pediatric IV multivitamins not be used for adults and that available supplies of parenteral multivitamin preparations be conserved for patients undergoing total parenteral nutrition or those with a medical need for IV multivitamins.107 During such shortages, conservation measures may include administering parenteral multivitamins less often than daily and attempting to increase the use of oral supplements, administering single-entity vitamin preparations if in greater supply.102 In addition, during such shortages, use of pediatric IV multivitamins should be reserved for neonates since adult multivitamin preparations (e.g., MVI®-12) may contain propylene glycol and polysorbate that may cause adverse effects in such neonates.107 Adult IV multivitamins may be used in infants weighing more than 1.5 kg and in children.107
The National Academy of Sciences (NAS) has issued a comprehensive set of Recommended Dietary Allowances (RDAs) as reference values for dietary nutrient intakes since 1941.109 In 1997, the NAS Food and Nutrition Board (part of the Institute of Medicine [IOM]) announced that they would begin issuing revised nutrient recommendations that would replace RDAs with Dietary Reference Intakes (DRIs).109 DRIs are reference values that can be used for planning and assessing diets for healthy populations and for many other purposes and that encompass the Estimated Average Requirement (EAR), the Recommended Dietary Allowance (RDA), the Adequate Intake (AI), and the Tolerable Upper Intake Level (UL).109
The NAS has established an EAR and RDA for thiamine for adults based on erythrocyte transketolase activity, urinary thiamine excretion, and other findings.109 The EAR and RDA for children and adolescents 1-18 years of age were established based on data in adults, since only limited data in children and adolescents 9-18 years of age are available.109 An AI has been set for infants up to 6 months of age based on the observed mean thiamine intake of infants fed principally human milk.109 An AI for infants 6-12 months of age has been set based on the AI for younger infants and data from adults.109 (For a definition of Estimated Average Intake, Recommended Dietary Allowance, Adequate Intake, and other reference values for dietary nutrient intakes, see Uses: Dietary Requirements in Folic Acid 88:08.)
The principal goal of maintaining an adequate intake of thiamine in the US and Canada is to prevent thiamine deficiency (beriberi).109 In industrialized countries, thiamine deficiency generally is associated with high alcohol consumption together with limited food consumption.109 Adequate intake of thiamine can be accomplished through consumption of foodstuffs.109 In the US, thiamine principally is obtained from enriched, fortified, or whole grain products; bread and bread products; mixed foods with grain as a main ingredient; and ready-to-eat cereals.109
For specific information on currently recommended AIs and RDAs of thiamine for various life-stage and gender groups, see Dosage: Dietary and Replacement Requirements, under Dosage and Administration.
Thiamine is useful in correcting (at least temporarily) the metabolic disorders associated with some genetic diseases including subacute necrotizing encephalomyelopathy (SNE, Leigh's disease), maple syrup urine disease (branched-chain aminoacidopathy), and lactic acidosis associated with pyruvate carboxylase deficiency and hyperalaninemia.
Although thiamine has not been shown by well-controlled trials to have any therapeutic value, the drug has been used for the management of poor appetite, ulcerative colitis, chronic diarrhea, other GI disorders, and the cerebellar syndrome. Thiamine has also been used orally as an insect repellent, but there is a lack of adequate evidence to establish the efficacy of thiamine for this use.100, 101
Thiamine hydrochloride is usually administered orally. When oral administration is not feasible, when malabsorption is suspected, or in patients with Wernicke's encephalopathy syndrome or high-output heart failure secondary to beriberi, the drug may be administered IM or IV; most clinicians prefer IV administration of thiamine hydrochloride for the treatment of high-output heart failure.
Dietary and Replacement Requirements
The Adequate Intake (AI) (see Uses: Dietary Requirements) of thiamine currently recommended by the National Academy of Sciences (NAS) for healthy infants up to 6 months of age is 0.2 mg (0.03 mg/kg) daily and for those 6-12 months of age is 0.3 mg (0.03 mg/kg) daily.109 The Recommended Dietary Allowance (RDA) of thiamine currently recommended by NAS for healthy children 1-3, 4-8, or 9-13 years of age is 0.5, 0.6 or 0.9 mg of thiamine daily, respectively.109 In established the thiamine dietary requirement in individuals 14 years of age or older, the NAS considered the requirement to be lower in women than men, based on women's size and average energy utilization.109 The RDA of thiamine for boys 14-18 years of age is 1.2 mg daily, and the RDA for girls 14-18 years of age is 1 mg daily.109 The RDA for healthy men 19-50 years of age and 51 years of age and older is 1.2 mg of thiamine daily.109 The RDA for healthy women 19-50 years of age and 51 years of age or older is 1.1 mg of thiamine daily.109 These RDAs are not expected to be sufficient to meet the needs of individuals with malabsorption syndrome or those undergoing hemodialysis or peritoneal dialysis.109
During pregnancy, the need for thiamine is increased to cover increased energy utilization and growth in maternal and fetal compartments.109 The RDA of thiamine recommended by the NAS for pregnant women is 1.4 mg daily.109 To ensure an adequate concentration of thiamine in milk, the NAS recommends a RDA of 1.5 mg of thiamine daily for lactating women.109 Thiamine intake higher than these RDAs may be needed by women who are pregnant with more than one fetus and mothers nursing more than one infant.109
In critically ill thiamine-deficient adults and in patients with malabsorption syndromes, the usual IM or IV dosage of thiamine hydrochloride recommended by most clinicians is 5-100 mg 3 times daily; however, single doses greater than 30 mg are not likely to be utilized in vivo. In patients with Wernicke's encephalopathy, thiamine hydrochloride therapy usually is initiated with an IV dose of 100 mg, followed by IM or IV doses of 50-100 mg daily until the patient is consuming a regular, balanced diet. High carbohydrate diets or IV dextrose solutions increase thiamine requirements and may worsen symptoms in thiamine-deficient patients. Following improvement in clinical signs of deficiency in critically ill patients or to initiate therapy in noncritically ill thiamine-deficient patients, the usual oral dosage of thiamine hydrochloride is 5-30 mg daily, given in single or divided (3) doses, for 1 month. In noncritically ill thiamine-deficient children, the usual oral dosage of thiamine hydrochloride is 10-50 mg daily, given in divided doses. Critically ill children should receive 10-25 mg of thiamine hydrochloride IM or IV. Neuritis, ocular signs, ataxia, edema, and heart failure begin to respond within hours after thiamine administration and disappear in a few days. Confusion and psychosis respond more slowly and may not respond if nerve damage has occurred.
For the management of genetic enzyme deficiency diseases that are responsive to thiamine the usual oral dosage of thiamine hydrochloride is 10-20 mg daily; however, dosages up to 4 g daily, given in divided doses, have been used.
Thiamine is usually nontoxic even following parenteral administration of single large doses (100-500 mg); however, hypersensitivity and other adverse reactions to the drug, including feelings of warmth, tingling, pruritus, pain, urticaria, weakness, sweating, nausea, restlessness, tightness of the throat, angioedema, respiratory distress, cyanosis, pulmonary edema, GI bleeding, transient vasodilation and hypotension, vascular collapse, and death, have occurred occasionally, mainly following repeated IV administration of the drug. Tenderness and induration may occur following IM administration of thiamine. In animals, very large parenteral doses of thiamine have produced neuromuscular and ganglionic blockade.
Precautions and Contraindications
A sensitivity history should be obtained from the patient prior to administration of thiamine. Some manufacturers recommend that an intradermal test dose of thiamine be administered to patients with suspected sensitivity before parenteral administration of usual doses of the drug; manufacturers' labeling should be consulted for specific testing procedures. Thiamine is contraindicated in patients with a known sensitivity to the drug or any ingredient in commercially available thiamine preparations.
Although the clinical importance is unknown, thiamine reportedly may enhance the effect of neuromuscular blocking agents.
Thiamine reportedly causes false-positive results in the phosphotungstate method for determination of uric acid and in the urine spot test with Ehrlich's reagent for urobilinogen. Large doses of thiamine reportedly interfere with the Schack and Waxler spectrophotometric determination of serum theophylline concentrations.
In humans, an exogenous source of thiamine is required for carbohydrate metabolism. Thiamine combines with adenosine triphosphate (ATP) in the liver, kidneys, and leukocytes to form thiamine diphosphate (thiamine pyrophosphate). Thiamine diphosphate is a coenzyme in carbohydrate metabolism (in the decarboxylation of pyruvic and α-ketoglutaric acids) and in transketolation 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.102, 103 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.102, 103
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 GI tract. Administration of thiamine completely reverses the cardiovascular and GI symptoms of thiamine deficiency; however, the degree of improvement in neurologic 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.102, 103 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.102
Following oral administration of small doses, thiamine hydrochloride is readily absorbed; however, absorption is an active process and the total amount absorbed following 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 rapidly and completely absorbed following IM administration.
Thiamine is widely distributed into body tissues. Body stores of thiamine have been estimated to be about 30 mg with about a 1-mg daily turnover. About 100-200 mcg of thiamine is distributed daily into the milk of nursing women receiving a normal diet.
Thiamine is metabolized in the liver in animals. Several urinary metabolites of thiamine have been identified in humans. Little or no unchanged thiamine is excreted in urine following administration of physiologic doses; however, following administration of larger doses, both unchanged thiamine and metabolites are excreted after tissue stores become saturated.
Thiamine is a water-soluble, B complex vitamin which is present in many foods including yeast, cereal grains, legumes, nuts, and meat. Commercially available thiamine hydrochloride and thiamine mononitrate, which is available only as a component of combination products, are prepared synthetically. Thiamine hydrochloride occurs as small, white hygroscopic crystals or crystalline powder and is freely soluble in water and slightly soluble in alcohol. The drug has a characteristic, yeast-like odor and a bitter taste. Thiamine hydrochloride injection is a sterile solution of the drug in water for injection. Sodium hydroxide and/or hydrochloric acid may be added during manufacture of the injection to adjust the pH to 2.5-4.5. Thiamine has pKa values of 4.8 and 9.0.
Thiamine hydrochloride is incompatible with alkaline or neutral solutions and with oxidizing and reducing agents. The drug is not highly susceptible to atmospheric oxidation but should be protected from air and light. Thiamine hydrochloride tablets should be stored in tight, light-resistant containers at a temperature less than 40°C, preferably between 15-30°C. Thiamine hydrochloride injection should be protected from light and stored at a temperature less than 40°C, preferably between 15-30°C; freezing should be avoided.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Bulk | Powder* |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions December 1, 2003. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
100. Food and Drug Administration. Insect repellent drug products for over-the-counter oral human use. [21 CFR Part 310] Fed Regist . 1985; 50:25170-1.
101. Food and Drug Administration. Insect repellent drug products for over-the-counter oral human use. [21 CFR Part 310] Fed Regist . 1982; 47:424-7.
102. Food and Drug Administration and American Society for Parenteral and Enteral Nutrition. Deaths associated with thiamine-deficient total parenteral nutrition. MMWR Morb Mortal Wkly Rep . 1989; 38:43-6. [PubMed 2492074]
103. Velez RJ, Myers B, Guber MS. Severe acute metabolic acidosis (acute beriberi): an avoidable complication of total parenteral nutrition. J Parenter Enteral Nutr . 1985; 9:216-9.
104. Mattioli S, Miglioli M, Montagna P et al. Wernicke's encephalopathy during total parenteral nutrition: observation in one case. J Parenter Enteral Nutr . 1988; 12:626-7.
105. Reuler JB, Girard DE, Cooney TG. Wernicke's encephalopathy. N Engl J Med . 1985; 312:1035-8. [PubMed 3885034]
106. National Research Council Food and Nutrition Board Subcommittee on the Tenth Edition of the RDAs. Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press; 1989:125-32.
107. Lactic acidosis traced to thiamine deficiency related to nationwide shortage of multivitamins for total parenteral nutrition-United States, 1997. MMWR . 1997; 46:523-8. (Also published in JAMA . 1997; 278:109-11.)
108. American Society for Parenteral and Enteral Nutrition (ASPEN). Multivitamin shortage-Update #17: fatality reported. Press release. 1997 Jul 21.
109. Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998. (Prepublication copy uncorrected proofs.)
110. American Psychiatric Association. Practice guidelines for the treatment of patients with delirium. Am J Psychiatry . 1999; 156(Suppl 5):1-20.