Usage
- Benfotiamine + Metformin is primarily prescribed for the management of diabetic neuropathy (nerve damage due to diabetes) and to improve glycemic control in patients with type 2 diabetes mellitus when diet and exercise alone are insufficient. It is specifically beneficial in alleviating symptoms of diabetic neuropathy such as numbness, tingling, burning, and needle-like sensations in the extremities.
- Pharmacological Classification: Vitamin (Benfotiamine) and Biguanide Antidiabetic (Metformin).
- Mechanism of Action: Benfotiamine, a lipid-soluble form of thiamine (vitamin B1), increases thiamine levels in nerve tissues and inhibits pathways linked to nerve damage in diabetic neuropathy. Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity.
Alternate Names
- Benfotiamine + Metformin Hydrochloride
- Benfotiamine and Metformin
- Brand Names: Benforce-M, Cystop, Metben
How It Works
- Pharmacodynamics: Benfotiamine improves transketolase activity, reducing the accumulation of harmful metabolites that contribute to diabetic neuropathy. Metformin reduces hepatic glucose output and improves peripheral glucose utilization, which helps manage blood glucose levels.
- Pharmacokinetics: Benfotiamine is absorbed in the intestines, where it is dephosphorylated to S-benzoylthiamine, which is then hydrolyzed in the liver into thiamine. It offers better bioavailability compared to thiamine salts. Metformin is minimally metabolized and excreted primarily by the kidneys.
- Mode of Action: Benfotiamine inhibits three major metabolic pathways linked to hyperglycemia-induced damage. Metformin activates AMP-activated protein kinase (AMPK), which leads to suppressed hepatic gluconeogenesis.
- Elimination Pathways: Metformin is predominantly excreted unchanged through renal pathways. Benfotiamine is metabolized to thiamine and excreted.
Dosage
Standard Dosage
Adults:
- One tablet of 75 mg benfotiamine and 500 mg metformin, taken two to three times daily with meals.
- Maximum dosage is usually 2550mg of metformin a day, and 600mg of benfotiamine.
- Dosage may be adjusted according to individual patient requirements and glycemic control.
Children:
- Benfotiamine + Metformin is generally not recommended for patients under 18 years old, as its safety and effectiveness haven’t been established in this population.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate upwards gradually, closely monitoring renal function due to potential age-related decline.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (eGFR < 30 mL/min). Dose reduction is necessary for moderate impairment (eGFR 30-45 mL/min).
- Patients with Hepatic Dysfunction: Use with caution, coupled with close monitoring of liver function tests. Metformin should be avoided in patients with severe hepatic dysfunction, due to increase risk of lactic acidosis.
- Patients with Comorbid Conditions: Caution is advised for patients with heart failure due to the elevated risk of lactic acidosis with metformin. Temporary discontinuation of metformin is necessary for patients with severe infections, dehydration, or those undergoing radiologic procedures with iodinated contrast.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: In these scenarios, temporarily discontinue metformin due to increased risk of lactic acidosis under stress conditions, and adjust the dose if necessary after the situation has stabilized.
Dosage Adjustments
- Adjust dosages based on renal/hepatic function, other metabolic disorders, and genetic polymorphisms that might influence drug metabolism.
Side Effects
Common Side Effects
- Nausea
- Diarrhea
- Stomach pain
- Loss of appetite
- Taste changes
Rare but Serious Side Effects
- Lactic acidosis (a rare but serious metabolic complication characterized by excess lactic acid in the blood)
- Diabetic ketoacidosis (marked by the excessive production of ketones in the blood)
- Hypoglycaemia
Long-Term Effects
- Vitamin B12 deficiency (with long-term metformin use)
Adverse Drug Reactions (ADR)
- Severe hypoglycemia
- Lactic acidosis requiring immediate intervention
Contraindications
- Severe renal impairment (eGFR < 30 mL/min)
- Metabolic acidosis
- Heart failure
- Severe hepatic impairment
- Hypersensitivity to benfotiamine or metformin
Drug Interactions
- Alcohol: Avoid alcohol as it significantly increases the risk of lactic acidosis and hypoglycemia.
- Cationic drugs: These may compete with metformin for renal tubular transport, thus increasing metformin concentrations.
- Diuretics: May reduce renal function, increasing metformin levels and the risk of lactic acidosis.
- Other antidiabetic agents: Additive hypoglycemic effects may necessitate dosage adjustments.
- Drugs that affect CYP450 enzymes: Although metformin is minimally metabolized, monitor for interactions with strong CYP450 inducers or inhibitors, which may affect its renal excretion.
- Fluorouracil, metoprolol, propranolol, timolol: Potential for interaction, requiring monitoring and dosage adjustments.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Consult with a healthcare professional before taking during pregnancy or planning to become pregnant, as there are potential fetal risks.
- Benfotiamine + Metformin is excreted in breast milk. Consult with a healthcare professional before taking while breastfeeding.
Drug Profile Summary
- Mechanism of Action: Benfotiamine improves transketolase activity and inhibits pathways associated with nerve damage; Metformin reduces hepatic glucose production, intestinal glucose absorption, and increases insulin sensitivity.
- Side Effects: Nausea, diarrhea, stomach pain, lactic acidosis (rare), hypoglycaemia, vitamin B12 deficiency.
- Contraindications: Severe renal or hepatic impairment, metabolic acidosis, heart failure, hypersensitivity.
- Drug Interactions: Alcohol, cationic drugs, diuretics, other antidiabetic agents, drugs that affect CYP450 enzymes, fluorouracil, metoprolol, propranolol, timolol.
- Pregnancy & Breastfeeding: Use with caution; consult with a healthcare professional.
- Dosage: 75mg benfotiamine/500mg metformin tablet, 2-3 times daily with meals.
- Monitoring Parameters: Blood glucose, renal function (eGFR, creatinine), vitamin B12 levels (long-term metformin use), liver function (periodically).
Popular Combinations
- Other B vitamins (B6, B12) for enhanced efficacy in treating neuropathy.
Precautions
- Assess renal function, hepatic function, and cardiac function before initiating treatment.
- Monitor blood glucose regularly.
- In elderly patients, monitor renal function closely.
- Avoid excessive alcohol intake and maintain a healthy diet and exercise plan.
FAQs (Frequently Asked Questions)
A: The standard adult dose is one 75mg/500mg tablet, 2-3 times daily with meals. Dose adjustments may be needed for elderly patients or those with renal impairment. Not recommended for patients under 18.
Q2: How does this combination treat diabetic neuropathy?
A: Benfotiamine, a form of vitamin B1, aids in alleviating nerve damage by improving thiamine levels in nerve tissues. Metformin manages blood sugar levels, indirectly reducing nerve damage progression.
Q3: What are common side effects?
A: Common side effects include nausea, diarrhea, stomach pain, loss of appetite, and taste changes. Rare but serious side effects are lactic acidosis and hypoglycaemia.
Q4: What are the contraindications?
A: Contraindications include severe renal impairment, metabolic acidosis, heart failure, and hypersensitivity to either component.
Q5: Are there any drug interactions I should be aware of?
A: Yes, clinically significant drug interactions can occur with alcohol (increases risk of lactic acidosis), cationic drugs (compete with metformin for renal excretion), other antidiabetic agents (additive effects), and certain other medications like diuretics, fluorouracil, metoprolol, propranolol and timolol.
Q6: Can this combination be used during pregnancy or breastfeeding?
A: Consult with a healthcare professional before using during pregnancy or breastfeeding, as there are potential risks to the fetus and neonate.
Q7: What monitoring should be done for patients on this medication?
A: Regularly monitor blood glucose, renal function (eGFR, creatinine). Periodically check liver function and vitamin B12 levels, particularly with long-term metformin use.
Q8: What are the signs of lactic acidosis?
A: Signs of lactic acidosis include general feeling of being unwell, severe tiredness, fast or shallow breathing, feeling cold, slow heartbeat, nausea, vomiting, abdominal pain and muscle cramps. Seek immediate medical help if these symptoms manifest. It is a medical emergency.
Q9: What patient education is necessary?
A: Educate patients about potential side effects, drug interactions, adherence to prescribed dosage, diet, exercise, and the importance of avoiding excessive alcohol.
