Uses of Glucovance 500mg/5mg

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1. Uses of Glucovance 500mg/5mg

Glucovance 500mg/5mg contains 500mg of Metformin and 5mg of Glibenclamide. Metformin is a biguanide that reduces glucose production and increases peripheral glucose uptake without stimulating insulin secretion. Glibenclamide is a second-generation sulfonylurea that stimulates insulin release from the pancreas to induce acute hypoglycemic effects by stimulating insulin release from the pancreas.

The combination of Metformin and Glibenclamide provides synergistic effects. Glibenclamide stimulates insulin secretion from the pancreas, while Metformin reduces insulin resistance in cells. This results in a more comprehensive benefit.

Glucovance 500mg/5mg is indicated for the treatment of type 2 diabetes mellitus in adults:

• As second-line therapy when diet, exercise, and initial treatment with Metformin or Glibenclamide alone do not achieve adequate glycemic control.
• As a replacement for previous combination therapy of Metformin and Glibenclamide in patients with stable and well-controlled blood glucose levels.

Glucovance 500mg/5mg is contraindicated in the following:

• Type 1 diabetes, diabetic precoma;
• Hypersensitivity to Metformin, Glibenclamide, sulfonylureas, sulfonamides, or any excipients;
• Acute metabolic acidosis;
• Severe renal impairment (eGFR < 30ml/min/1.73m2);
• Acute conditions affecting renal function: shock, severe infection, dehydration;
• Conditions that may cause tissue hypoxia: respiratory failure, decompensated heart failure, shock, recent myocardial infarction;
• Alcoholism, hepatic insufficiency, acute alcohol intoxication;
• Porphyria;
• Breastfeeding;
• Concomitant use with miconazole.

2. Dosage and administration of Glucovance 500mg/5mg

Administration: The patient takes Glucovance 500mg/5mg orally with a glass of water and should ingest it with meals. The medicine adjusts the dosing frequency according to the patient's meal schedule. If co-administered with bile acid sequestrants, take Glucovance 500mg/5mg at least 4 hours before the sequestrant to avoid malabsorption.

Dosage:

• Dosage in adults with normal renal function: The initial dose is one tablet of Glucovance 500mg/2.5mg or Glucovance 500mg/5mg once daily. To avoid hypoglycemia, the initial dose should not exceed the previous daily dose of Metformin or Glibenclamide. Then, the dose is adjusted every 2 weeks or more, with increments no greater than one tablet, based on the blood glucose test. Maximum daily dose: 2000mg Metformin hydrochloride/20mg Glibenclamide.
• Patients with renal impairment: It is essential to evaluate renal function before initiating Glucovance and periodically thereafter. Metformin dose reduction may be considered in patients with eGFR 50-89 ml/min/1.73m². Glucovance can be indicated in patients with eGFR 30-59 ml/min/1.73m² (in the absence of risk factors for lactic acidosis) with a maximum daily dose of 1000mg Metformin hydrochloride/10mg Glibenclamide.
• Elderly patients: Glucovance dosage should be adjusted based on renal function. The patients were initiated with Glucovance 500mg/2.5mg. In patients aged 65 and older, Glibenclamide initial and maintenance doses require careful titration to minimize hypoglycemia risk. The medicine should start with the lowest available dose and titrate gradually as needed.
• Children: Glucovance is contraindicated in children.

Overdose: If Glucovance overdoses, lactic acidosis may occur. Hemodialysis is the treatment of choice to remove lactate and Metformin from the bloodstream. Due to its strong protein binding, Glibenclamide is not effectively removed by hemodialysis.

Missed dose: If a dose of Glucovance 500mg/5mg is missed, it should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped and the regular schedule resumed.  

3. Adverse effects of Glucovance 500mg/5mg

When taking Glucovance 500mg/5mg, patients may experience some adverse effects, including:

• Common: Dysgeusia
• Uncommon: Mild to moderate increase in serum creatinine and urea levels, episodes of hepatic porphyria, cutaneous porphyria

If you experience any adverse effects while taking Glucovance, stop taking the medication and inform your doctor immediately or seek medical attention at the nearest hospital.

4. Precautions for taking Glucovance 500mg/5mg

Important considerations for patients before and while taking Glucovance:

• If lactic acidosis is suspected to be associated with Metformin use, Glucovance administration must be stopped immediately. The patient requires urgent hospitalization for further evaluation and treatment. Prompt hemodialysis is indicated to correct the metabolic acidosis and facilitate the removal of Metformin, which may have accumulated in the body.
• Before initiating Glucovance 500mg/5mg, the estimated glomerular filtration rate (eGFR) should be measured. Treatment initiation is not contraindicated in patients with eGFR 30-44ml/min/1.73m². Before continuing the treatment regimen, a risk-benefit assessment is required in patients currently taking Glucovance with eGFR decreasing below 45ml/min/1.73m². 
  The risk of Metformin-associated lactic acidosis increases with age. Renal function should be assessed more frequently in elderly patients.
• Discontinue Glucovance 500mg/5mg before or at the time of iodinated contrast imaging in patients with eGFR 30-60ml/min/1.73m², a history of alcoholism, hepatic impairment, heart failure, or those undergoing intra-arterial iodinated contrast administration.
• Stop taking Glucovance 500mg/5mg if the patient is having surgery that requires general anesthesia, spinal anesthesia, or epidural anesthesia.
• Acute myocardial infarction, circulatory shock, septicemia, and conditions associated with hypoxemia can increase the risk of lactic acidosis and prerenal azotemia. If these adverse events occur, the patient needs to discontinue Glucovance 500mg/5mg
• Patients should not consume alcohol while taking Glucovance 500mg/5mg.
• Patients with hepatic impairment may have an increased risk of developing Metformin-associated lactic acidosis. Glucovance is contraindicated in patients with liver disease.
• Glucovance 500mg/5mg should only be prescribed if the patient adheres to a regular meal schedule. Consistent carbohydrate intake is important (due to increased hypoglycemia risk with late meals, unbalanced or insufficient carbohydrate intake).
• Heart failure patients taking Glucovance are at risk of reduced cardiac oxygenation and renal impairment. In stable chronic heart failure patients, Glucovance 500mg/5mg may be prescribed with regular monitoring of cardiac and renal function.
• Patients should inform their doctor before taking Glucovance if they have a urinary tract infection, influenza, or a respiratory tract infection.
• Patients taking Glucovance 500mg/5mg should adhere to a proper diet with regular carbohydrate distribution throughout the day.
• Regular testing to monitor diabetes should be performed: blood glucose levels, HbA1c.
• Caution is advised when taking Glucovance 500mg/5mg in patients with G6PD deficiency; an alternative non-sulfonylurea medication may be considered.
• Glucovance contains lactose and is therefore contraindicated in patients with glucose-galactose malabsorption syndrome or lactase deficiency.
• Patients should be warned about the symptoms of hypoglycemia when taking Glucovance 500mg/5mg and should be caution when driving or operating machinery.
• Inform the doctor if you are pregnant, suspect you are pregnant, or are planning to become pregnant if Glucovance use is considered. During pregnancy, diabetic patients should be treated with insulin instead of Glucovance. If pregnancy is detected while taking Glucovance 500mg/5mg, inform thedoctor for appropriate adjustments.
• Glucovance is contraindicated for breastfeeding mothers.

5. Drug interactions of Glucovance 500mg/5mg

Taking Glucovance 500mg/5mg with other medicines may increase the risk of adverse effects or alter the therapeutic efficacy of either drug. Some known drug interactions with Glucovance include:

• The co-administration of Glucovance and Miconazole is contraindicated due to the increased risk of hypoglycemia (with manifestations of hypoglycemia or coma).
• The concurrent use of Glucovance 500mg/5mg with beta-blockers is generally discouraged due to beta-blockers can mask the symptoms of hypoglycemia.  Furthermore, non-cardioselective beta-blockers increase the incidence and severity of hypoglycemia.
• The concurrent administration of Glucovance 500mg/5mg with angiotensin-converting enzyme (ACE) inhibitors, such as captopril and enalapril, is generally not recommended due to the potential for hypoglycemia.
• The combined use of Glucovance and Fluconazole is not advised as Fluconazole may prolong the elimination half-life of sulfonylureas, leading to hypoglycemia.
• The concurrent use of Glucovance 500mg/5mg with Bosentan is not recommended due to the risk of reduced hypoglycemic effect of Glibenclamide and increased risk of elevated liver enzymes.
• The concurrent administration of Glucovance with bile acid sequestrants is not recommended as it reduces plasma Glibenclamide concentrations, resulting in decreased hypoglycemic efficacy.
• Caution is advised when combining Glucovance with Desmopressin due to the potential for reduced antidiuretic effect.

During Glucovance 500mg/5mg treatment, patients should adhere to their physician's prescribed dosage and not adjust the dose without permission. If any adverse effects occur, patients should immediately inform their physician for appropriate intervention to minimize the risk of serious health consequences.

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