Thiamine Hydrochloride Injection, Solution

Dosage for Thiamine varies significantly based on the severity of the deficiency and the underlying medical condition. Healthcare providers typically follow these guidelines:

• Mild Chronic Deficiency: 5 mg to 30 mg orally per day, often as part of a B-complex vitamin.
• Severe Deficiency (Beriberi): 10 mg to 100 mg intramuscularly or intravenously three times daily for several days, followed by 5 mg to 10 mg orally daily for one month.
• Wernicke-Korsakoff Syndrome: This is a medical emergency. The standard protocol often involves 500 mg intravenously three times daily for two to three days, followed by 250 mg daily for several more days. Long-term oral maintenance of 100 mg daily is usually required.
• Alcohol Withdrawal/Prophylaxis: 100 mg daily, either orally or parenterally, to prevent the onset of Wernicke’s encephalopathy during glucose administration.

Thiamine is approved for use in children, but doses must be carefully calculated by a pediatrician.

• Infantile Beriberi: 10 mg to 25 mg intravenously or intramuscularly for acute symptoms, followed by oral maintenance.
• Daily Requirements: The Recommended Dietary Allowance (RDA) for children ranges from 0.2 mg/day in infants to 1.2 mg/day in adolescents.

Renal Impairment

No specific dose adjustments are typically required for patients with kidney disease, as Thiamine is generally non-toxic. However, patients on hemodialysis may require supplemental thiamine as the vitamin is cleared during the dialysis process.

Hepatic Impairment

Patients with liver disease, particularly cirrhosis, often have significantly impaired thiamine storage and conversion capabilities. Higher doses are frequently necessary in this population to achieve therapeutic levels.

Elderly Patients

Older adults may have reduced dietary intake and decreased intestinal absorption. While the standard adult dose is usually appropriate, healthcare providers should monitor for signs of subclinical deficiency.

• Oral Administration: Thiamine tablets can be taken with or without food. Taking it with a meal may reduce the risk of mild stomach upset.
• Swallowing: Tablets should be swallowed whole with a full glass of water. Do not crush or chew extended-release formulations if prescribed.
• Consistency: For best results, take the medication at the same time each day to maintain steady levels in the body.
• Storage: Store Thiamine at room temperature (68°F to 77°F or 20°C to 25°C). Keep it away from excessive heat, moisture, and direct light. Ensure the container is tightly closed.

If you miss a dose, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not 'double up' on doses to catch up.

Thiamine has a very high safety margin because it is water-soluble; excess amounts are usually excreted in the urine. However, extremely high doses (especially via IV) may lead to symptoms such as:

• Agitation
• Respiratory distress
• Nausea
• Skin irritation

In the event of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking Thiamine without medical guidance, especially if being treated for a severe deficiency.

Thiamine is generally exceptionally well-tolerated. Most patients do not experience significant side effects when taken orally at recommended doses. However, some may notice:

• Mild Nausea: A slight feeling of queasiness shortly after ingestion.
• Stomach Upset: Mild cramping or discomfort in the upper abdomen.
• Flushing: A temporary sensation of warmth or redness on the skin.

These effects are usually transient and disappear as the body adjusts to the supplement.

• Diarrhea: Loose stools may occur, particularly with higher oral doses.
• Restlessness: A mild feeling of being 'jittery' or unable to relax.
• Sweating: Increased perspiration (diaphoresis) may be noted in some individuals.

• Pruritus (Itching): A persistent itchy sensation on the skin without a visible rash.
• Urticaria (Hives): Small, raised, itchy bumps on the skin surface.
• Injection Site Reactions: For those receiving Thiamine via IM or IV, localized pain, swelling, or redness at the site of the needle insertion may occur.

While extremely rare, serious allergic reactions can occur, particularly after repeated intravenous doses.

> Warning: Stop taking Thiamine and call your doctor or emergency services immediately if you experience:

• Anaphylaxis: A severe, life-threatening allergic reaction characterized by a sudden drop in blood pressure and difficulty breathing.
• Angioedema: Swelling of the face, lips, tongue, or throat, which can obstruct the airway.
• Pulmonary Edema: Sudden shortness of breath or a feeling of 'suffocating,' which may indicate fluid in the lungs (reported in rare cases of thiamine toxicity).
• Cyanosis: A bluish tint to the skin or lips, indicating a lack of oxygen in the blood.
• Gastrointestinal Hemorrhage: While very rare, any signs of black, tarry stools or vomiting blood require immediate evaluation.

There are no well-documented adverse effects associated with long-term use of Thiamine at physiological doses. Because it is water-soluble, it does not accumulate in the body to toxic levels like fat-soluble vitamins (A, D, E, K). However, chronic high-dose supplementation should always be supervised by a healthcare provider to ensure it does not mask other B-vitamin deficiencies (such as B12 deficiency).

No FDA black box warnings exist for Thiamine. It is considered one of the safest medications in the clinical pharmacopeia. The primary risk is not toxicity, but rather the failure to treat a deficiency in time to prevent permanent neurological damage.

Report any unusual symptoms or persistent side effects to your healthcare provider. Even mild symptoms should be discussed if they interfere with your daily activities.

Thiamine is essential for health, but its administration requires clinical oversight, especially in patients with complex medical histories. The most critical safety consideration is the 'glucose-loading' phenomenon. In malnourished patients, administering intravenous glucose (sugar) before Thiamine can trigger acute Wernicke’s encephalopathy because the glucose metabolism rapidly consumes the body's remaining tiny stores of Thiamine. Healthcare providers should always administer Thiamine before or concurrently with glucose in at-risk patients.

No FDA black box warnings for Thiamine. It is widely recognized as safe (GRAS) by the FDA when used appropriately.

• Hypersensitivity/Anaphylaxis: Sensitivity to Thiamine can develop over time. Patients who have had a mild reaction in the past are at higher risk for a severe reaction with subsequent doses, particularly via the intravenous route. Skin testing may be considered if a sensitivity is suspected.
• Wernicke’s Encephalopathy Risk: Patients with chronic alcoholism, hyperemesis gravidarum (severe pregnancy morning sickness), or post-bariatric surgery must be monitored closely for neurological changes.
• Cardiovascular Stress: In patients with 'Wet Beriberi,' the initiation of Thiamine can cause a rapid shift in fluid dynamics as the heart begins to pump more effectively. This must be managed carefully to avoid temporary cardiovascular strain.

There is no routine 'blood test' that perfectly reflects thiamine status in all patients, but healthcare providers may use:

• Erythrocyte Transketolase Activity (ETKA): A functional test that measures the activity of a thiamine-dependent enzyme in red blood cells. An increase in activity after adding TPP in the lab indicates a deficiency.
• Blood Thiamine Levels: Direct measurement of thiamine or TPP in whole blood.
• Clinical Exam: Regular assessment of gait, eye movements, and mental status is the most important monitoring tool in high-risk patients.

Thiamine itself does not typically cause sedation or cognitive impairment. However, the conditions it treats (like Wernicke’s encephalopathy) can severely impair the ability to drive. Patients should not operate heavy machinery until their healthcare provider confirms their neurological function is stable.

Alcohol consumption is the leading cause of thiamine deficiency in developed countries. Alcohol interferes with thiamine in three ways: it decreases dietary intake, inhibits active transport from the gut, and impairs the liver's ability to convert thiamine into its active form. Patients taking Thiamine for deficiency must avoid alcohol to ensure the treatment is effective.

There is no 'withdrawal syndrome' associated with stopping Thiamine. However, if Thiamine is stopped in a patient with an ongoing deficiency (such as someone with a malabsorption disorder), the symptoms of beriberi or Wernicke’s will likely return. Tapering is generally not required.

> Important: Discuss all your medical conditions, especially any history of allergies or alcohol use, with your healthcare provider before starting Thiamine.

There are no absolute contraindications where Thiamine must never be used with another drug, as it is a necessary nutrient. However, certain drugs can render Thiamine therapy ineffective.

• 5-Fluorouracil (5-FU): This chemotherapy agent inhibits the enzyme thiamine pyrophosphokinase, which is responsible for converting thiamine into its active form (TPP). Patients on 5-FU may develop thiamine deficiency symptoms despite taking supplements.
• Loop Diuretics (e.g., Furosemide/Lasix): Long-term use of high-dose loop diuretics can increase the renal excretion of thiamine, potentially leading to a deficiency. This is particularly concerning in patients with congestive heart failure.

• Metformin: Some studies suggest that long-term metformin use may slightly alter B-vitamin absorption, though this is more commonly associated with B12 than B1.
• Phenytoin: This anti-seizure medication may lower plasma thiamine levels in some patients.

• Anti-thiamine Factors (ATFs): Certain foods contain substances that react with thiamine, making it inactive. These include:
• Raw Fish/Shellfish: Contain the enzyme thiaminase, which destroys thiamine. Cooking the fish inactivates this enzyme.
• Tea and Coffee: Contain tannins and chlorogenic acids that can oxidize thiamine.
• Betel Nuts: Consumption of betel nuts is a known risk factor for deficiency due to chemical antagonism.
• Carbohydrates: A high-carbohydrate diet increases the body's demand for thiamine. If intake is marginal, a sudden increase in sugar or starch can precipitate deficiency symptoms.

• Quercetin: Some laboratory studies suggest quercetin might interfere with thiamine transport, though the clinical significance in humans is likely low.
• Other B Vitamins: While usually taken together, high doses of one B vitamin can sometimes mask the deficiency of another. A balanced B-complex is often preferred.

• Theophylline Tests: Thiamine may cause false-positive results in certain spectrophotometric methods used to measure theophylline levels in the blood.
• Uric Acid: High doses of thiamine may interfere with the Schack and Waxler method for determining uric acid concentrations.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. Even 'natural' products can change how Thiamine works in your body.

• Known Hypersensitivity: Thiamine should never be administered to individuals with a documented, severe allergy to thiamine or any components of the injection (such as specific preservatives in multi-dose vials). The mechanism is an IgE-mediated hypersensitivity reaction which can lead to fatal anaphylaxis.

• Renal Failure: While not a reason to avoid thiamine, the presence of end-stage renal disease requires careful monitoring because the kidneys are the primary route of excretion for excess vitamin.
• Critical Illness with Metabolic Acidosis: In very rare cases of 'Shoshin Beriberi' (a fulminant form of wet beriberi), the rapid administration of thiamine can cause a massive shift in metabolic pathways. While thiamine is the treatment, it must be done in an Intensive Care Unit (ICU) setting with hemodynamic monitoring.

There is no significant cross-sensitivity between Thiamine and other B vitamins. However, patients who are sensitive to 'B-Complex' injections should be tested for sensitivity to the individual components, as the reaction is often due to the Thiamine or the preservative (like benzyl alcohol) rather than the other vitamins.

> Important: Your healthcare provider will evaluate your complete medical history, including any previous reactions to vitamin injections, before prescribing Thiamine.

FDA Pregnancy Category A (when used at RDA levels). Thiamine is a naturally occurring nutrient essential for fetal development. During pregnancy, the demand for thiamine increases due to the metabolic needs of the fetus and the mother's increased caloric intake.

• Risks: Severe thiamine deficiency during pregnancy (often caused by Hyperemesis Gravidarum) can lead to Wernicke’s encephalopathy in the mother and has been linked to poor fetal outcomes.
• Safety: High-dose thiamine (Category C for doses above RDA) should only be used if clearly needed, but it is generally considered safe and necessary if a deficiency is suspected.

Thiamine is actively secreted into breast milk. It is essential for the nursing infant, especially during the first six months of life.

• Infantile Beriberi: If a nursing mother is thiamine-deficient, her breast milk will also be deficient, which can lead to 'Infantile Beriberi' in the baby—a condition that can cause sudden heart failure. Supplementation for the mother is the standard treatment.

Thiamine is safe and effective for use in children when dosed appropriately. It is used to treat genetic metabolic disorders and nutritional deficiencies. There are no known negative effects on growth when used at recommended levels.

Elderly patients are at a higher risk for subclinical thiamine deficiency due to factors like:

• Reduced appetite (anorexia of aging)
• Decreased gastric acid, which may slightly affect absorption
• Higher prevalence of heart failure and loop diuretic use
• Cognitive decline, which may lead to poor dietary choices

Healthcare providers should have a low threshold for recommending thiamine supplements in the elderly.

As previously noted, Thiamine is cleared by the kidneys. While toxicity is rare, patients with significantly impaired GFR (Glomerular Filtration Rate) should be monitored. Patients on peritoneal dialysis or hemodialysis are at high risk for thiamine depletion and usually require daily supplementation.

In patients with severe liver disease (Child-Pugh Class C), the ability to store thiamine and convert it to its active TPP form is compromised. These patients may require parenteral (IV/IM) administration even if they are eating, as their internal 'processing' of the vitamin is dysfunctional.

> Important: Special populations, particularly pregnant women and the elderly, require individualized medical assessment to determine the correct dose of Thiamine.

Thiamine's primary molecular role is as a cofactor for the Pyruvate Dehydrogenase Complex. In the cytosol, glucose is broken down into pyruvate. For that pyruvate to enter the mitochondria and be converted into energy (ATP) via the Krebs cycle, it must be transformed into Acetyl-CoA. This transformation is entirely dependent on Thiamine Pyrophosphate (TPP).

Furthermore, Thiamine plays a non-coenzymatic role in nerve impulse transmission. It is concentrated in the membranes of neurons and is thought to regulate sodium channels and acetylcholine receptors, explaining why deficiency leads so rapidly to neurological 'short-circuiting' (ataxia and confusion).

• Dose-Response: The body’s response to thiamine is rapid. In cases of 'Wet Beriberi,' heart failure symptoms can begin to improve within hours of an IV dose.
• Duration of Effect: Because it is water-soluble and not highly protein-bound, the effects of a single dose last for less than 24 hours, necessitating daily intake or administration in deficient states.
• Tolerance: There is no known physiological tolerance to thiamine; the body does not 'get used to' it in a way that requires higher doses for the same effect.

| Parameter | Value |

|---|---|

| Bioavailability | Low to Moderate (Rate-limited active transport) |

| Protein Binding | Minimal (Mostly carried by erythrocytes) |

| Half-life | 1 to 12 hours |

| Tmax (Oral) | 1 to 2 hours |

| Metabolism | Hepatic (Phosphorylation to TPP) |

| Excretion | Renal (100% as metabolites or unchanged drug) |

• Molecular Formula: C12H17ClN4OS·HCl (Thiamine Hydrochloride)
• Molecular Weight: 337.27 g/mol
• Solubility: Highly soluble in water; slightly soluble in alcohol; insoluble in ether.
• Structure: Consists of a substituted pyrimidine ring and a substituted thiazole ring connected by a methylene bridge.

Thiamine belongs to the Vitamin B Complex Member [EPC] class. It is often grouped with other water-soluble vitamins like Riboflavin (B2), Niacin (B3), and Pyridoxine (B6). Unlike fat-soluble vitamins, it must be replenished frequently because the body cannot store it in significant amounts.