tolazamide

Action and Spectrum

Actions and spectrum: 

Actions: 

• Stimulates insulin secretion: tolazamide works by binding to the ATP-sensitive potassium channels in pancreatic beta-cells, which results in the opening of calcium channels and the subsequent release of insulin. 
• Enhances insulin sensitivity: tolazamide can also increase the sensitivity of peripheral tissues, such as muscle and fat, to the effects of insulin. 

Spectrum: 

• Type 2 diabetes: tolazamide is used to treat type 2 diabetes, which is a condition in which the body is unable to produce enough insulin or cannot effectively use the insulin it produces. It is usually prescribed when exercise and diet alone are not able to control blood sugar levels. 
• Monotherapy or combination therapy: tolazamide can be used in combination or as monotherapy with other medications, such as metformin, in patients with type 2 diabetes to achieve glycemic control. 
• Maintenance therapy: tolazamide is used as a long-term maintenance therapy to help prevent complications of diabetes, such as kidney damage, nerve damage, and blindness. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Dermatologic reactions 

Dizziness 

Anorexia 

Nausea/vomiting 

Hypoglycemia 

Heartburn 

Vertigo 

Constipation 

Hepatitis and Cholestatic jaundice rarely which leads to liver failure 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: tolazamide is contraindicated in patients with a known hypersensitivity to sulfonylureas or any of the other ingredients in the medication. 
• Type 1 diabetes: tolazamide is not effective in the treatment of type 1 diabetes, as it requires the presence of functioning pancreatic beta-cells to stimulate insulin secretion. 
• Diabetic ketoacidosis: tolazamide should not be used in patients with diabetic ketoacidosis, a serious complication of uncontrolled diabetes that is characterized by high levels of ketones in the blood and urine. 
• Severe liver or kidney disease: tolazamide is primarily metabolized by the liver and excreted in the urine, so it should be used in patients with severe liver or kidney disease with caution. 
• Pregnancy: tolazamide is classified as a pregnancy category C drug, which means that its safety during pregnancy has not been established. It should be used in pregnant women with caution and only if the potential benefits outweigh the potential risks. 
• Breastfeeding: tolazamide is excreted in breast milk and may cause hypoglycemia in nursing infants. It should be used with caution in breastfeeding women, and alternative medications should be considered.

Caution: 

• Hypoglycemia: tolazamide can cause hypoglycemia (low blood sugar), especially in elderly patients, patients with liver or kidney disease, and those taking other medications that can lower blood sugar levels. Patients taking tolazamide should be monitored closely for signs and symptoms of hypoglycemia and should be advised to take precautions to prevent hypoglycemia, such as eating regular meals, avoiding excessive alcohol consumption, and checking their blood sugar levels regularly. 
• Hemolytic anemia: tolazamide can cause hemolytic anemia, a condition in which RBCs are destroyed faster than they can be produced. Patients taking tolazamide should be monitored for signs and symptoms of hemolytic anemia, such as fatigue, weakness, and yellowing of the skin and eyes. 
• Adrenal or pituitary insufficiency: tolazamide can interfere with the body’s ability to respond to stress, such as illness, injury, or surgery, in patients with adrenal or pituitary insufficiency. Patients with these conditions should be monitored closely for signs and symptoms of adrenal or pituitary insufficiency and should be advised to take precautions to prevent hypoglycemia during periods of stress. 
• Thyroid disease: tolazamide can interfere with the body’s ability to produce thyroid hormones in patients with thyroid disease. Patients with thyroid disease should be monitored closely for signs and symptoms of hypothyroidism and should have their thyroid hormone levels checked regularly. 
• Surgery: tolazamide should be discontinued prior to elective surgery, as it can interfere with the body’s ability to respond to stress during the perioperative period. Patients should be advised to monitor their blood sugar levels closely during the perioperative period and to resume tolazamide therapy as soon as possible after surgery. 
• Alcohol consumption: Alcohol consumption can increase the risk of hypoglycemia in patients taking tolazamide. Patients should be advised to avoid excessive alcohol consumption while taking tolazamide.

Comorbidities: 

tolazamide is generally well-tolerated in patients with type 2 diabetes and does not have any specific comorbidities associated with its use. However, it should be used in patients with certain comorbidities with caution, as described in the caution section. These include patients with liver or kidney disease, adrenal or pituitary insufficiency, thyroid disease, and a history of hemolytic anemia.

Patients with these conditions should be monitored closely for signs and symptoms of adverse effects associated with tolazamide use, such as hypoglycemia and hemolytic anemia. In addition, tolazamide should be used with caution in elderly patients, who may be more susceptible to the effects of the medication, and in patients with a history of alcohol abuse, as alcohol consumption may increase the risk of hypoglycemia. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: C 

Lactation: tolazamide is excreted in human milk.  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

tolazamide is an oral hypoglycemic agent that belongs to the class of sulfonylureas. It acts by stimulating the insulin release from the beta cells of the pancreas, which lowers blood glucose levels. tolazamide binds to and inhibits the ATP-sensitive potassium channels in the beta cells of the pancreas, which may lead to the depolarization of the cell membrane and the subsequent opening of voltage-gated calcium channels. This results in an increase in intracellular calcium levels, which triggers the release of insulin. 

tolazamide is rapidly absorbed from the gastrointestinal tract and reaches peak plasma concentrations within 2-4 hours after oral administration. The medication is extensively metabolized in the liver by the cytochrome P450 system, primarily by the CYP2C9 isoenzyme, and is excreted in the urine as inactive metabolites.

The elimination half-life of tolazamide is approximately 4-6 hours. The therapeutic effect of tolazamide is dose-dependent and lasts for approximately 12-24 hours after a single dose. The medication is typically administered once or twice daily with meals to minimize gastrointestinal side effects and to optimize glucose control.  

Pharmacodynamics: 

The pharmacodynamics of tolazamide involves its ability to stimulate insulin release from the beta cells of the pancreas. The medication works by binding to and inhibiting the ATP-sensitive potassium channels on the beta cells, which leads to membrane depolarization and the subsequent opening of voltage-gated calcium channels. This results in an increase in intracellular calcium levels, which triggers the exocytosis of insulin-containing granules from the beta cells into the bloodstream. 

tolazamide is a sulfonylurea drug, and its pharmacodynamics is like other drugs in this class. The primary pharmacodynamic effect of tolazamide is a reduction in blood glucose levels by stimulating insulin release. The medication can lower fasting plasma glucose levels by up to 20-30% and can also reduce postprandial glucose levels. 

The therapeutic effect of tolazamide is dependent on several factors, including the dose, the timing of administration, and the patient’s overall metabolic state. The medication may be less effective in patients with advanced type 2 diabetes who have significant beta cell dysfunction or insulin resistance.

In addition, the efficacy of tolazamide may be reduced in patients who have previously been treated with sulfonylureas or have developed sulfonylurea resistance. The onset and duration of action of tolazamide can vary depending on the individual patient and the dose of the medication. Generally, the onset of action is within 1 hour of administration, and the duration of action lasts for approximately 12-24 hours.  

Pharmacokinetics: 

Absorption 

tolazamide is well absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations reached within 2-4 hours. Absorption is not affected by food, but it is recommended to take the medication with meals to reduce the risk of gastrointestinal side effects. 

Distribution 

tolazamide is extensively bound to plasma proteins (greater than 99%), particularly albumin. It has a relatively small volume of distribution, suggesting limited extravascular distribution. 

Metabolism 

tolazamide is metabolized extensively in the liver by the cytochrome P450 system, primarily by the CYP2C9 isoenzyme. The metabolites are inactive, and the parent drug and metabolites are eliminated primarily through the kidneys. 

Elimination and excretion 

tolazamide and its metabolites are excreted primarily in the urine, with only a small amount eliminated in the feces. The elimination half-life of tolazamide is approximately 4-6 hours, with a longer half-life observed in elderly patients. 

Adminstartion

Administration: 

tolazamide is an oral medication that is typically taken once or twice daily with meals to reduce the risk of gastrointestinal side effects. The recommended starting dose is 100-250 mg daily, and the maximum daily dose is 1000 mg. The dose may need to be adjusted based on the patient’s blood glucose levels, response to treatment, and any adverse effects. 

tolazamide should be taken exactly as prescribed by a healthcare provider, and the medication should not be stopped, or the dose changed without first consulting a healthcare provider. It is important to regularly monitor blood glucose levels while taking tolazamide to ensure that the medication is working effectively and to identify any potential side effects. 

tolazamide is available in immediate-release tablets that should be administered whole and not crushed or chewed. The tablets may be scored to allow for easy splitting to achieve the prescribed dose. The medication should be stored at room temperature, protected from light and moisture, and kept out of the reach of children. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tolazamide 

Pronounced: [ tole-AZ-a-mide ] 

Why do we use tolazamide? 

tolazamide is a medication used to treat type 2 diabetes in which the body does not produce or use insulin effectively, resulting in high blood glucose levels. tolazamide works by stimulating the release of insulin from the pancreas, which helps to lower blood glucose levels. It is often used in combination with diet and exercise to help manage type 2 diabetes. 

tolazamide is indicated for use in adults with type 2 diabetes who cannot control their blood glucose levels with diet and exercise alone. It is not indicated for the treatment of type 1 diabetes, in which the body is unable to produce insulin at all. 

tolazamide may be used alone or in combination with other medications used to treat diabetes, such as metformin, pioglitazone, or insulin. The use of tolazamide should be individualized based on the patient’s medical history, blood glucose levels, and response to treatment. It is important to monitor blood regularly.