ZOLIGET Pioglitazone Hydrochloride / Glimepiride 30mg / 2mg Tablet 14's
RXDRUG-DR-XY38657
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of pioglitazone HCl and a sulfonylurea or whose diabetes is not adequately controlled with sulfonylurea alone, or for those patients who have initially responded to pioglitazone HCl alone and require additional glycemic control.
Dosage/Direction for Use
General: The use of antihyperglycemic therapy in the management of type 2 diabetes should be individualized on the basis of effectiveness and tolerability. Failure to follow an appropriate dosage regimen may precipitate hypoglycemia.
Recommended Dose: Selecting the starting dose of Zoliget should be based on the patient's current regimen of pioglitazone and/or sulfonylurea. Those patients who may be more sensitive to antihyperglycemic drugs should be monitored carefully during dose adjustment. It is recommended that a single dose of Zoliget be administered once daily with the first main meal.
Patients Currently on Pioglitazone HCl Monotherapy: Usual Starting Dose: Glimepiride (1 or 2 mg once daily) and pioglitazone HCl 15 or 30 mg, Zoliget may be initiated at 15 mg/2 mg once daily and adjusted after assessing adequacy of therapeutic response.
Patients Currently on Glimepiride Monotherapy: Usual Starting Dose: Pioglitazone HCl (15 or 30 mg daily), Zoliget may be initiated at 15 mg/2 mg once daily, and adjusted after assessing adequacy of therapeutic response.
Patients Switching from Combination Therapy of Pioglitazone Plus Glimepiride as Separate Tablets: May be initiated with 15 mg/2 mg tablet based on the dose of pioglitazone HCl and glimepiride already being taken. Patients who are not controlled with pioglitazone HCl 15 mg in combination with glimepiride should be carefully monitored when switched to Zoliget.
Patients Currently on a Different Sulfonylurea Monotherapy or Switching from Combination Therapy of Pioglitazone Plus a Different Sulfonylurea: No exact dosage relationship exists between glimepiride and the other sulfonylurea agents. Therefore, based on the maximum starting dose of glimepiride 2 mg, Zoliget should be limited initially to a starting dose of 15 mg/2 mg once daily, and adjusted after assessing adequacy of therapeutic response. Any change in diabetic therapy should be undertaken with care and appropriate monitoring as change in glycemic control can occur. Patients should be observed carefully for hypoglycemia (1-2 weeks) when being transferred to Zoliget, especially from longer t½ sulfonylureas due to potential overlapping of drug effect.
Maximum Recommended Dose: The maximum recommended daily dose for pioglitazone is 15 mg plus glimepiride 2 mg or a pioglitazone 30 mg plus glimepiride 4 mg formulation for oral administration.
Maximum Recommended Daily Dose: Pioglitazone is 45 mg and glimepiride is 8 mg. Zoliget should therefore not be given more than once daily at any of the tablet strengths.
Elderly, Debilitated or Malnourished Patients, or in Patients with Renal or Hepatic Impairment: Initial dosing, dose increments, and maintenance dosage of Zoliget should be conservative to avoid hypoglycemic reactions. These patients should be started at glimepiride 1 mg prior to prescribing Zoliget. During initiation of Zoliget therapy and any subsequent dose adjustment, patients should be observed carefully for hypoglycemia. Therapy with Zoliget should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5 x ULN) at start of therapy. The lowest approved dose of Zoliget therapy should be prescribed to patients with type 2 diabetes and systolic dysfunction only after titration from pioglitazone HCl 15-30 mg has been safely tolerated. If subsequent dose adjustment is necessary, patients should be carefully monitored for weight gain, edema or signs and symptoms of congestive heart failure exacerbation.
Recommended Dose: Selecting the starting dose of Zoliget should be based on the patient's current regimen of pioglitazone and/or sulfonylurea. Those patients who may be more sensitive to antihyperglycemic drugs should be monitored carefully during dose adjustment. It is recommended that a single dose of Zoliget be administered once daily with the first main meal.
Patients Currently on Pioglitazone HCl Monotherapy: Usual Starting Dose: Glimepiride (1 or 2 mg once daily) and pioglitazone HCl 15 or 30 mg, Zoliget may be initiated at 15 mg/2 mg once daily and adjusted after assessing adequacy of therapeutic response.
Patients Currently on Glimepiride Monotherapy: Usual Starting Dose: Pioglitazone HCl (15 or 30 mg daily), Zoliget may be initiated at 15 mg/2 mg once daily, and adjusted after assessing adequacy of therapeutic response.
Patients Switching from Combination Therapy of Pioglitazone Plus Glimepiride as Separate Tablets: May be initiated with 15 mg/2 mg tablet based on the dose of pioglitazone HCl and glimepiride already being taken. Patients who are not controlled with pioglitazone HCl 15 mg in combination with glimepiride should be carefully monitored when switched to Zoliget.
Patients Currently on a Different Sulfonylurea Monotherapy or Switching from Combination Therapy of Pioglitazone Plus a Different Sulfonylurea: No exact dosage relationship exists between glimepiride and the other sulfonylurea agents. Therefore, based on the maximum starting dose of glimepiride 2 mg, Zoliget should be limited initially to a starting dose of 15 mg/2 mg once daily, and adjusted after assessing adequacy of therapeutic response. Any change in diabetic therapy should be undertaken with care and appropriate monitoring as change in glycemic control can occur. Patients should be observed carefully for hypoglycemia (1-2 weeks) when being transferred to Zoliget, especially from longer t½ sulfonylureas due to potential overlapping of drug effect.
Maximum Recommended Dose: The maximum recommended daily dose for pioglitazone is 15 mg plus glimepiride 2 mg or a pioglitazone 30 mg plus glimepiride 4 mg formulation for oral administration.
Maximum Recommended Daily Dose: Pioglitazone is 45 mg and glimepiride is 8 mg. Zoliget should therefore not be given more than once daily at any of the tablet strengths.
Elderly, Debilitated or Malnourished Patients, or in Patients with Renal or Hepatic Impairment: Initial dosing, dose increments, and maintenance dosage of Zoliget should be conservative to avoid hypoglycemic reactions. These patients should be started at glimepiride 1 mg prior to prescribing Zoliget. During initiation of Zoliget therapy and any subsequent dose adjustment, patients should be observed carefully for hypoglycemia. Therapy with Zoliget should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5 x ULN) at start of therapy. The lowest approved dose of Zoliget therapy should be prescribed to patients with type 2 diabetes and systolic dysfunction only after titration from pioglitazone HCl 15-30 mg has been safely tolerated. If subsequent dose adjustment is necessary, patients should be carefully monitored for weight gain, edema or signs and symptoms of congestive heart failure exacerbation.
Administration
Should be taken with food: Take w/ the 1st main meal.
Contraindications
Hypersensitivity to pioglitazone HCl, glimepiride or any of component of Zoliget.
Patients with diabetic ketoacidosis, with or without coma. This condition should be treated with insulin. Those with antihypertensive effect in the presence of insulin; therefore, Zoliget should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Patients with moderate to severe heart failure or liver problems.
Use in pregnancy & lactation. Children.
Zoliget is not recommended in patients with symptomatic heart failure.
Initiation of Zoliget in patients with established NYHA Class III or IV heart failure is contraindicated.
Patients with diabetic ketoacidosis, with or without coma. This condition should be treated with insulin. Those with antihypertensive effect in the presence of insulin; therefore, Zoliget should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Patients with moderate to severe heart failure or liver problems.
Use in pregnancy & lactation. Children.
Zoliget is not recommended in patients with symptomatic heart failure.
Initiation of Zoliget in patients with established NYHA Class III or IV heart failure is contraindicated.
Warnings
Congestive Heart Failure: Thiazolidinediones, including pioglitazone, which is a component of Zoliget, cause or exacerbate congestive heart failure in some patients. After initiation of Zoliget, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea and/or edema). If these signs and symptoms develop, the heart failure should be managed according to the current standards of care. Furthermore, discontinuation of Zoliget must be considered.
Do not use pioglitazone in patients with active bladder cancer.
Use pioglitazone with caution in patients with prior history of bladder cancer. The benefits of blood sugar control with pioglitazone should be weighed against the unknown risks of cancer recurrence.
Do not use pioglitazone in patients with active bladder cancer.
Use pioglitazone with caution in patients with prior history of bladder cancer. The benefits of blood sugar control with pioglitazone should be weighed against the unknown risks of cancer recurrence.
Special Precautions
Pioglitazone HCl, like other thiazolidinediones, can cause fluid retention when used alone or in combination with other antidiabetic agents, including insulin. Fluid retention may lead to or exacerbate heart failure. Patients should be observed for signs and symptoms of heart failure. If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of pioglitazone HCl must be considered.
All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage and instructions are important to avoid hypoglycemic episodes. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of glimepiride. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking β-adrenergic blocking drugs or other sympatholytic agents. Patients who are debilitated, malnourished and with adrenal, pituitary, renal or hepatic insufficiency are particularly susceptible to the hypoglycemic action of sulfonylureas and should therefore be carefully monitored. The dosage of glimepiride should be carefully adjusted in these patients.
Pioglitazone HCl may cause decline in hematocrit value along with the decline in mean hemoglobin values by 2-4% causing anemia. These changes primarily occurred within the first 4-12 weeks of therapy and remained relatively constant thereafter. These changes may be related to increased plasma volume and have rarely been associated with any significant hematological clinical effects.
In patients with type 2 diabetes (mean duration of diabetes 9.5 years), an increased incidence of bone fracture in female patients taking pioglitazone is observed. The risk of fracture should be considered in the care of patients, especially female patients, treated with pioglitazone HCl and attention should be given to assessing and maintaining bone health according to current standards of care.
Alcohol ingestion, severe or prolonged exercise, deficient caloric intake or use of >1 antidiabetic agent may predispose patients to the development of hypoglycemia.
When a patient stabilized on any diabetic regimen is exposed to stress eg, fever, trauma, infection or surgery, a loss of control may occur. At such times, it may be necessary to add insulin in combination with glimepiride or even use insulin monotherapy.
The patient's fasting blood glucose and HbA1c must be measured periodically to determine the minimum effective dose of pioglitazone plus glimepiride for the patient.
Liver enzyme monitoring is recommended prior to initiation of therapy with pioglitazone plus glimepiride in all patients and periodically thereafter per clinical judgment of the healthcare professional.
All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage and instructions are important to avoid hypoglycemic episodes. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of glimepiride. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking β-adrenergic blocking drugs or other sympatholytic agents. Patients who are debilitated, malnourished and with adrenal, pituitary, renal or hepatic insufficiency are particularly susceptible to the hypoglycemic action of sulfonylureas and should therefore be carefully monitored. The dosage of glimepiride should be carefully adjusted in these patients.
Pioglitazone HCl may cause decline in hematocrit value along with the decline in mean hemoglobin values by 2-4% causing anemia. These changes primarily occurred within the first 4-12 weeks of therapy and remained relatively constant thereafter. These changes may be related to increased plasma volume and have rarely been associated with any significant hematological clinical effects.
In patients with type 2 diabetes (mean duration of diabetes 9.5 years), an increased incidence of bone fracture in female patients taking pioglitazone is observed. The risk of fracture should be considered in the care of patients, especially female patients, treated with pioglitazone HCl and attention should be given to assessing and maintaining bone health according to current standards of care.
Alcohol ingestion, severe or prolonged exercise, deficient caloric intake or use of >1 antidiabetic agent may predispose patients to the development of hypoglycemia.
When a patient stabilized on any diabetic regimen is exposed to stress eg, fever, trauma, infection or surgery, a loss of control may occur. At such times, it may be necessary to add insulin in combination with glimepiride or even use insulin monotherapy.
The patient's fasting blood glucose and HbA1c must be measured periodically to determine the minimum effective dose of pioglitazone plus glimepiride for the patient.
Liver enzyme monitoring is recommended prior to initiation of therapy with pioglitazone plus glimepiride in all patients and periodically thereafter per clinical judgment of the healthcare professional.
Use In Pregnancy & Lactation
Zoliget is contraindicated in pregnancy & lactation.
Adverse Reactions
The more common side effects for the combination are anxiety, bladder pain, bloody or cloudy urine, blurred vision, chills, cold sweats, coma, confusion, cool pale skin, depression, difficult/burning or painful urination, fast heartbeat, frequent urge to urinate, headache, increased hunger, increased weight, lower back or side pain, nausea, nervousness, nightmares, seizures, shakiness, slurred speech, swelling of feet or lower legs, unusual tiredness or weakness, cough, ear congestion, hoarseness, joint pain, loss of voice, nasal congestion, tooth disorder, voice changes.
The less common side effects for the combination include accidental injury, loss of appetite, pain or swelling in arms or legs without any injury, pale skin, stomach pain, troubled breathing with exertion, unusual bleeding or bruising, vomiting, weight loss, yellow eyes or skin, allergic skin reactions.
Other side effects include upper respiratory tract infection, myalgia, aggravated diabetes, asthenia. In isolated cases, impairment of liver function (eg, with cholestasis and jaundice) as well as hepatitis, which may also lead to liver failure have been reported. Cases of hyponatremia have been reported most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The hematologic adverse reactions include leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia and pancytopenia.
The less common side effects for the combination include accidental injury, loss of appetite, pain or swelling in arms or legs without any injury, pale skin, stomach pain, troubled breathing with exertion, unusual bleeding or bruising, vomiting, weight loss, yellow eyes or skin, allergic skin reactions.
Other side effects include upper respiratory tract infection, myalgia, aggravated diabetes, asthenia. In isolated cases, impairment of liver function (eg, with cholestasis and jaundice) as well as hepatitis, which may also lead to liver failure have been reported. Cases of hyponatremia have been reported most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The hematologic adverse reactions include leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia and pancytopenia.
Drug Interactions
Ciprofloxacin and Gatifloxacin: Severe and persistent hypoglycemia may occur.
Pioglitazone HCl: Gemfibrozil and Rifampin: An enzyme inhibitor of CYP2C8 (eg, gemfibrozil) may significantly increase the AUC of pioglitazone HCl and an enzyme inducer of CYP2C8 (eg, rifampin) may significantly decrease the AUC of pioglitazone HCl. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with pioglitazone, changes in diabetes treatment may be needed based on clinical response.
Ketoconazole: Co-administration of pioglitazone HCl for 7 days with ketoconazole 200 mg administered twice daily resulted in a ratio of least square mean (90% Cl) values for unchanged pioglitazone HCl of 1.14 (1.06-1.23) for Cmax, 1.34 (1.26-1.41) for AUC and 1.87 (1.71-2.04) for Cmin.
Atorvastatin Calcium: Co-administration of pioglitazone HCl for 7 days with atorvastatin calcium 80 mg once daily resulted in a ratio of least square mean (90% Cl) values for unchanged pioglitazone HCl of 0.69 (0.57-0.85) for Cmax, 0.76 (0.65-0.88) for AUC and 0.96 (0.87-1.05) for Cmin. For unchanged atorvastatin, the ratio of least square mean (90% Cl) values were 0.77 (0.66-0.9) for Cmax, 0.86 (0.78-0.94) for AUC and 0.92 (0.82-1.02) for Cmin.
Midazolam: Administration of pioglitazone HCl for 15 days followed by a single 7.5-mg dose of midazolam syrup resulted in a 26% reduction in midazolam Cmax and AUC.
Glimepiride: General: The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory drugs and other drugs that are highly protein bound eg, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors and β-adrenergic blocking agents. Due to the potential drug interaction between these drugs and glimepiride, the patient should be observed closely for hypoglycemia when these drugs are co-administered. Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics and isoniazid. Due to the potential drug interaction between these drugs and glimepiride, the patient should be observed closely for loss of glycemic control when these drugs are co-administered.
Propranolol: Concomitant administration of propranolol (40 mg 3 times daily) and glimepiride significantly increased Cmax, AUC and t½ of glimepiride by 23%, 22% and 15%, respectively, and it decreased apparent clearance (CL/f) by 18%. If β-blockers are used, caution should be exercised and patients should be warned about the potential for hypoglycemia.
Miconazole: A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. There is a potential interaction of glimepiride with inhibitors (eg, fluconazole) and inducers (eg, rifampicin) of cytochrome P450 2C9.
Pioglitazone HCl: Gemfibrozil and Rifampin: An enzyme inhibitor of CYP2C8 (eg, gemfibrozil) may significantly increase the AUC of pioglitazone HCl and an enzyme inducer of CYP2C8 (eg, rifampin) may significantly decrease the AUC of pioglitazone HCl. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with pioglitazone, changes in diabetes treatment may be needed based on clinical response.
Ketoconazole: Co-administration of pioglitazone HCl for 7 days with ketoconazole 200 mg administered twice daily resulted in a ratio of least square mean (90% Cl) values for unchanged pioglitazone HCl of 1.14 (1.06-1.23) for Cmax, 1.34 (1.26-1.41) for AUC and 1.87 (1.71-2.04) for Cmin.
Atorvastatin Calcium: Co-administration of pioglitazone HCl for 7 days with atorvastatin calcium 80 mg once daily resulted in a ratio of least square mean (90% Cl) values for unchanged pioglitazone HCl of 0.69 (0.57-0.85) for Cmax, 0.76 (0.65-0.88) for AUC and 0.96 (0.87-1.05) for Cmin. For unchanged atorvastatin, the ratio of least square mean (90% Cl) values were 0.77 (0.66-0.9) for Cmax, 0.86 (0.78-0.94) for AUC and 0.92 (0.82-1.02) for Cmin.
Midazolam: Administration of pioglitazone HCl for 15 days followed by a single 7.5-mg dose of midazolam syrup resulted in a 26% reduction in midazolam Cmax and AUC.
Glimepiride: General: The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory drugs and other drugs that are highly protein bound eg, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors and β-adrenergic blocking agents. Due to the potential drug interaction between these drugs and glimepiride, the patient should be observed closely for hypoglycemia when these drugs are co-administered. Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics and isoniazid. Due to the potential drug interaction between these drugs and glimepiride, the patient should be observed closely for loss of glycemic control when these drugs are co-administered.
Propranolol: Concomitant administration of propranolol (40 mg 3 times daily) and glimepiride significantly increased Cmax, AUC and t½ of glimepiride by 23%, 22% and 15%, respectively, and it decreased apparent clearance (CL/f) by 18%. If β-blockers are used, caution should be exercised and patients should be warned about the potential for hypoglycemia.
Miconazole: A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. There is a potential interaction of glimepiride with inhibitors (eg, fluconazole) and inducers (eg, rifampicin) of cytochrome P450 2C9.
Storage
Store at temperatures not exceeding 30°C. Protect from sunlight and moisture.
Action
Pharmacology: Mechanism of Action: Zoliget is a combination of 2 antihyperglycemic agents to improve glycemic control in patients with type 2 diabetes.
Pioglitazone: Pioglitazone HCl is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its mechanism of action. Pioglitazone HCl decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Unlike sulfonylureas, pioglitazone is not an insulin secretagogue. Pioglitazone HCl is a potent and highly selective agonist for peroxisome proliferator-activated receptor-γ (PPARγ). PPAR receptors are found in tissues important for insulin action eg, adipose tissue, skeletal muscle and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.
Glimepiride: The primary mechanism of action of glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic β-cells. In addition, extrapancreatic effects (eg, reduction of basal hepatic glucose production and increased peripheral tissue sensitivity to insulin and glucose uptake) may also play a role in the activity of glimepiride. However, as with other sulfonylureas, the mechanism by which glimepiride lowers blood glucose during long-term administration has not been clearly established.
Pharmacokinetics: Pioglitazone: Pioglitazone HCl is rapidly absorbed after oral doses. Peak plasma concentrations are obtained within 2 hrs and bioavailability exceeds 80%. Pioglitazone HCl is >99% bound to plasma proteins. It is extensively metabolized by cytochrome P450 isoenzymes CYP3A4 and CYP2C9 to both active and inactive metabolites. It is excreted in urine and feces and has a plasma half-life (t½) of up to 7 hrs. The active metabolites have a t½ of up to 24 hrs.
Glimepiride: After oral administration, glimepiride is completely absorbed from the gastrointestinal tract. The oral bioavailability is approximately 100%. Peak plasma concentrations occur in 2-3 hrs. More than 99% of the drug is bound to plasma proteins. Glimepiride is completely metabolized by oxidative biotransformation into 2 main metabolites, a hydroxy and a carboxy derivative.
The elimination t½ after multiple doses is about 9 hrs. Approximately 60% of the dose is eliminated in the urine and 40% in the feces.
Special Populations: Glimepiride: Renal Insufficiency: A single-dose clinical study of glimepiride showed that glimepiride serum levels decreased with the decrease in renal function. However, metabolites serum levels (mean AUC values) increased. The apparent terminal t½ for glimepiride does not change, while the t½ for metabolites increased as renal function decreased. Mean urinary excretion of metabolites as percent of dose, however, decreased.
Pioglitazone HCl: Hepatic Insufficiency: Impaired hepatic function (Child-Pugh grade B or C) have an approximate 45% reduction in pioglitazone HCl and total pioglitazone HCl peak concentrations but no change in the mean area under the concentration-time curve (AUC) values. Therapy should not be initiated if the patient exhibits clinical evidence of active liver disease or serum transaminase levels (ALT) exceeds 2.5 times the upper limit of the normal (ULN).
Pioglitazone: Pioglitazone HCl is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its mechanism of action. Pioglitazone HCl decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Unlike sulfonylureas, pioglitazone is not an insulin secretagogue. Pioglitazone HCl is a potent and highly selective agonist for peroxisome proliferator-activated receptor-γ (PPARγ). PPAR receptors are found in tissues important for insulin action eg, adipose tissue, skeletal muscle and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.
Glimepiride: The primary mechanism of action of glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic β-cells. In addition, extrapancreatic effects (eg, reduction of basal hepatic glucose production and increased peripheral tissue sensitivity to insulin and glucose uptake) may also play a role in the activity of glimepiride. However, as with other sulfonylureas, the mechanism by which glimepiride lowers blood glucose during long-term administration has not been clearly established.
Pharmacokinetics: Pioglitazone: Pioglitazone HCl is rapidly absorbed after oral doses. Peak plasma concentrations are obtained within 2 hrs and bioavailability exceeds 80%. Pioglitazone HCl is >99% bound to plasma proteins. It is extensively metabolized by cytochrome P450 isoenzymes CYP3A4 and CYP2C9 to both active and inactive metabolites. It is excreted in urine and feces and has a plasma half-life (t½) of up to 7 hrs. The active metabolites have a t½ of up to 24 hrs.
Glimepiride: After oral administration, glimepiride is completely absorbed from the gastrointestinal tract. The oral bioavailability is approximately 100%. Peak plasma concentrations occur in 2-3 hrs. More than 99% of the drug is bound to plasma proteins. Glimepiride is completely metabolized by oxidative biotransformation into 2 main metabolites, a hydroxy and a carboxy derivative.
The elimination t½ after multiple doses is about 9 hrs. Approximately 60% of the dose is eliminated in the urine and 40% in the feces.
Special Populations: Glimepiride: Renal Insufficiency: A single-dose clinical study of glimepiride showed that glimepiride serum levels decreased with the decrease in renal function. However, metabolites serum levels (mean AUC values) increased. The apparent terminal t½ for glimepiride does not change, while the t½ for metabolites increased as renal function decreased. Mean urinary excretion of metabolites as percent of dose, however, decreased.
Pioglitazone HCl: Hepatic Insufficiency: Impaired hepatic function (Child-Pugh grade B or C) have an approximate 45% reduction in pioglitazone HCl and total pioglitazone HCl peak concentrations but no change in the mean area under the concentration-time curve (AUC) values. Therapy should not be initiated if the patient exhibits clinical evidence of active liver disease or serum transaminase levels (ALT) exceeds 2.5 times the upper limit of the normal (ULN).
MedsGo Class
Antidiabetic Agents
Features
Brand
Zoliget
Full Details
Dosage Strength
30mg / 2mg
Drug Ingredients
- Glimepiride
- Pioglitazone
Drug Packaging
Tablet 14's
Generic Name
Pioglitazone Hydrochloride / Glimepiride
Dosage Form
Tablet
Registration Number
DR-XY38657
Drug Classification
Prescription Drug (RX)
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