Thiamine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

Generic: 50 mg

Solution, Injection, as hydrochloride:

Generic: 100 mg/mL (2 mL)

Tablet, Oral, as hydrochloride:

Generic: 50 mg, 100 mg, 250 mg

Tablet, Oral, as hydrochloride [preservative free]:

Generic: 100 mg [DSC]

Tablet, Oral, as mononitrate:

Generic: 100 mg

Tablet, Oral, as mononitrate [preservative free]:

Generic: 100 mg

Pharmacology

Mechanism of Action

An essential coenzyme in carbohydrate metabolism by combining with adenosine triphosphate to form thiamine pyrophosphate.

When used for the treatment of ethylene glycol poisoning, thiamine is theorized to increase the formation of glycine, a nontoxic metabolite.

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: Adequate; IM: Rapid and complete

Distribution

Highest concentrations found in brain, heart, kidney, liver

Metabolism

In the liver

Excretion

Urine (as unchanged drug and as pyrimidine after body storage sites become saturated)

Use: Labeled Indications

Treatment of thiamine deficiency (including thiamine deficiency in pregnancy associated with neuropathy), beriberi (dry or wet variety), Wernicke encephalopathy, infantile beriberi with acute collapse, cardiovascular disease due to thiamine deficiency, or when giving IV dextrose to individuals with marginal thiamine status to avoid precipitation of heart failure; dietary supplement.

Use: Off Label

Alcohol withdrawal syndrome (adjunct)c

Data from a limited number of patients studied suggest that thiamine may be beneficial as an adjunct in the management of alcohol withdrawal syndrome to prevent Wernicke encephalopathy Cook 1998, Latt 2014, Sechi 2007, Thomson 2002. Additional data may be necessary to further define the role of thiamine in this condition.

Ethylene glycol poisoningc

The American Academy of Clinical Toxicology (AACT) guidelines recognize the lack of human clinical data for this use and consider it as a use in ethylene glycol poisoning without a formal or evidence-based recommendation, especially in patients who may have vitamin deficiencies (eg, patients with alcoholism) Barceloux 1999.

Sepsis (severe) or septic shockc

Data from one small retrospective before/after study suggest that IV thiamine in combination with IV ascorbic acid (vitamin C) and IV hydrocortisone in patients with severe sepsis or septic shock may be effective in decreasing mortality and preventing organ dysfunction Marik 2017.

Contraindications

Hypersensitivity to thiamine or any component of the formulation

Dosage and Administration

Dosing: Adult

Marginal thiamine status (to avoid precipitating heart failure): IV: 100 mg thiamine in each of the first few liters of IV fluid in patients with marginal thiamine status to whom dextrose is being administered.

Parenteral nutrition supplementation (Vanek 2012): IV: 6 mg/day

Thiamine deficiency (beriberi): 5 to 30 mg/dose IM or IV 3 times daily (if critically ill); then 5 to 30 mg orally daily in single or divided doses 3 times daily for 1 month.

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. 10 to 20 mg IM 3 times daily for as long as 2 weeks followed by an oral multivitamin preparation containing 5 to 10 mg thiamine administered daily for 1 month.

Alcohol withdrawal syndrome (adjunct) (off-label use): 100 to 250 mg IV or IM once daily for 3 to 5 days (Cook 1998; Latt 2014; Sechi 2007; Thomson 2002) followed by 100 mg orally 3 times daily for 1 to 2 weeks then 100 mg orally daily thereafter (Latt 2014). Additional data may be necessary to further define the role of thiamine in this condition.

Ethylene glycol poisoning (off-label use): IV: 100 mg per day until the intoxication has resolved (Hoffman 2015)

Sepsis (severe) or septic shock (off-label use): IV: 200 mg every 12 hours over 30 minutes for 4 days or until ICU discharge; administer in combination with IV ascorbic acid (vitamin C) and IV hydrocortisone (Marik 2017).

Wernicke encephalopathy:

Prophylaxis (off-label use): 100 to 250 mg IV or IM once daily for 3 to 5 days (Cook 1998; Latt 2014; Sechi 2007; Thomson 2002) followed by 100 mg orally three times daily for 1 to 2 weeks then 100 mg orally daily thereafter (Latt 2014).

Treatment: Initial: 200 to 500 mg IV 3 times daily for 2 to 7 days (Cook 1998; Latt 2014; Sechi 2007; Thomson 2002). If response to thiamine, continue with 250 mg IV or IM once daily for an additional 3 to 5 days (or until clinical improvement ceases) followed by 30 mg orally twice daily thereafter (Sechi 2007) or 100 mg orally 3 times daily for 1 to 2 weeks followed by 100 mg orally once daily thereafter (Latt 2014).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. Initial: 100 mg IV, then 50 to 100 mg IM daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing presented in mcg/kg, mg/kg, and mg/day; use precaution.

Parenteral nutrition, maintenance requirement (Vanek 2012): Limited data available: IV:

Infants: 0.35 to 0.5 mg/kg/day; maximum daily dose: 1.2 mg/day

Children: 1.2 mg/day

Thiamine deficiency (beriberi); treatment (critically ill):

Infants: Various regimens reported: Initial: IV: 25 to 50 mg once, followed by 10 mg IM once daily for a week then 3 to 5 mg orally once daily for at least 6 weeks (WHO 1999). Other regimens with higher initial doses have also been reported. One study used an oral dose of 100 mg/day given as 25 mg, 25 mg, and 50 mg doses administered 30 minutes apart for 3 days (Coats 2012). Another study administered 30 mg orally once daily for 20 days (Barennes 2015). Note: If patient is being breast-fed, the mother should also be considered for thiamine deficiency treatment (Bowman 2013).

Children: Limited data available: IM, IV: 10 mg once daily for the first week (if critically ill), then 3 to 5 mg orally once daily for at least 6 weeks (Kliegman 2016)

Adolescents: Limited data available: IM, IV: 100 mg once daily for up to 7 days (if critically ill), then 10 mg orally once daily. Dosing based on several case reports (n=3, age 14 to 17 years) of beriberi treatment after gastric bypass surgery (Towbin 2004)

Extemporaneously Prepared

A 100 mg/mL oral suspension may be made with commercially available thiamine powder. Add 10 g of powder to a mortar. Add small portions of a 1:1 mixture of Ora-Sweet® and Ora-Plus® and mix to a uniform paste; mix while adding the vehicle in equal proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 100 mL. Label "shake well". Stable 91 days under refrigeration or at room temperature.

Ensom MH and Decarie D, "Stability of Thiamine in Extemporaneously Compounded Suspensions," Can J Hosp Pharm, 2005, 58(1):26-30.

Administration

IM, IV: Parenteral form may be administered by IM or IV injection. Various rates of administration have been reported (eg, 100 mg over 5 minutes). An extended infusion time is preferred for doses ≥100 mg. Local injection reactions may be minimized by slow administration (~30 minutes) into larger, more proximal veins. Thiamine should be administered prior to parenteral glucose solutions to prevent precipitation of acute symptoms of thiamine deficiency in the poorly nourished.

Dietary Considerations

Dietary sources include legumes, pork, beef, whole grains, yeast, and fresh vegetables. A deficiency state can occur in as little as 3 weeks following total dietary absence.

Dietary reference intake (IOM 1998):

0 to 6 months: Adequate intake: 0.2 mg/day

7 to 12 months: Adequate intake: 0.3 mg/day

1 to 3 years: RDA: 0.5 mg

4 to 8 years: RDA: 0.6 mg

9 to 13 years: RDA: 0.9 mg

14 to 18 years: RDA: Females: 1 mg; Males: 1.2 mg

≥19 years: RDA: Females: 1.1 mg; Males: 1.2 mg

Pregnancy, lactation: RDA: 1.4 mg

Storage

Injection: Store at 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Etamsylate: May diminish the therapeutic effect of Thiamine. Management: If a patient is to receive intravenous (IV) etamsylate and an IV infusion containing thiamine, administer etamsylate first to avoid thiamine degradation by sulfites contained in the etamsylate product. Consider therapy modification

Test Interactions

False-positive for uric acid using the phosphotungstate method and for urobilinogen using the Ehrlich's reagent; large doses may interfere with the spectrophotometric determination of serum theophylline concentration

Adverse Reactions

Adverse reactions reported with injection. Frequency not defined.

Central nervous system: Flushing sensation, restlessness

Dermatologic: Diaphoresis, pruritus, skin sclerosis (at the injection site following IM administration), urticaria

Gastrointestinal: Nausea

Hematologic & oncologic: Hemorrhage (into the gastrointestinal tract)

Hypersensitivity: Anaphylaxis (following IV administration), angioedema, hypersensitivity reaction (following IV administration)

Local: Tenderness at injection site (following IM administration)

Neuromuscular & skeletal: Weakness

Respiratory: Cyanosis, pharyngeal edema, pulmonary edema

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Have been reported following repeated parenteral doses; consider skin test in individuals with history of allergic reactions.

Concurrent drug therapy issues:

• Dextrose: Administration of dextrose may precipitate acute symptoms of thiamine deficiency; use caution when thiamine status is marginal or suspect.

Dosage form specific issues:

• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register 2002).

Other warnings/precautions:

• Parenteral administration: Use with caution with parenteral route (especially IV) of administration.
• Vitamin deficiency: Single vitamin deficiency is rare; evaluate for other deficiencies.

Pregnancy

Pregnancy Risk Factor

A

Pregnancy Considerations

Water soluble vitamins cross the placenta. Thiamine requirements are increased in during pregnancy (IOM 1998).

Pregnant females are at increased risk of thiamine deficiency when prolonged nausea and vomiting (including hyperemesis gravidarum) occurs; deficiency may present as a polyneuropathy or Wernicke encephalopathy (Chiossi 2006; Karjalainen 1965; WHO 1999).

Thiamine supplementation is recommended in pregnant females with prolonged vomiting. Initial treatment with IV thiamine is needed when Wernicke encephalopathy is suspected. Oral, IM, or IV therapy may be considered depending on severity of thiamine deficiency (Berdai 2016; Chiossi 2006; Palacios-Marqués 2012). When intravenous hydration is used in the management of hyperemesis gravidarum, thiamine should be administered prior to infusing dextrose to prevent Wernicke encephalopathy (ACOG 189 2018).

Patient Education

What is this drug used for?

• It is used to prevent or treat thiamine (vitamin B1) deficiency.

Frequently reported side effects of this drug

• Nausea
• Sensation of warmth
• Restlessness
• Sweating a lot
• Weakness
• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Blue/gray skin discoloration
• Black, tarry, or bloody stools
• Vomiting blood
• Severe abdominal pain
• Shortness of breath
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.