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Pioglitazone Hydrochloride / Glimepiride
Pronunciation: PYE-oh-GLI-ta-zone HYE-droe-KLOR-ide/glye-MEP-ir-ide
Class: Antidiabetic combination
- Tablets, oral pioglitazone hydrochloride 30 mg (as base)/glimepiride 2 mg
- Tablets, oral pioglitazone hydrochloride 30 mg (as base)/glimepiride 4 mg
Increases insulin sensitivity; inhibits hepatic gluconeogenesis.Glimepiride
Stimulates insulin release from the pancreas; increases sensitivity to insulin.
Indications and Usage
Adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus who are already treated with a thiazolidinedione (eg, pioglitazone) plus a sulfonylurea or who have inadequate glycemic control on a thiazolidinedione or sulfonylurea alone.
Diabetic ketoacidosis with or without coma; hypersensitivity to any component of the product; patients with established New York Heart Association (NYHA) class III or IV heart failure.
Dosage and AdministrationElderly, Debilitated, or Malnourished Patients, or Patients With Renal or Hepatic Function Impairment
The initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. The initial dose should be started at glimepiride 1 mg prior to prescribing pioglitazone/glimepiride.Patients Currently on Glimepiride Monotherapy
PO Titrate the dose based on individual response to each component as monotherapy. Based on the usual starting dose of pioglitazone (15 or 30 mg daily), treatment may be started at 30 mg/2 mg or 30 mg/4 mg once daily and adjusted after assessing adequacy of therapeutic response.Patients Currently on Pioglitazone Monotherapy
PO Titrate the dose based on individual response to each component as monotherapy. Based on the usual starting dose of glimepiride (1 or 2 mg daily) and pioglitazone 15 or 30 mg, treatment may be started at 30 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
PO Treatment may be started at 30 mg/2 mg or 30 mg/4 mg once daily based on the dose of pioglitazone and glimepiride already being taken.Patients Currently on a Different Sulfonylurea Monotherapy or Switching From Combination Therapy of Pioglitazone Plus a Different Sulfonylurea
PO Based on the max starting dose of glimepiride 2 mg, treatment may be started at 30 mg/2 mg once daily and adjusted after assessing the adequacy of therapeutic response.
- The max recommended daily dose of pioglitazone and glimepiride is 45 and 8 mg, respectively.
- Do not give more than once daily at any of the tablet strengths.
- Administer once daily with the first main meal.
Store between 59° and 86°F. Protect from moisture and humidity.
Drug InteractionsACE inhibitors (eg, enalapril)
The risk of hypoglycemia may be increased. Closely monitor glycemic control when these agents are started or stopped.Alcohol
Alcohol inhibits gluconeogenesis, so hypoglycemia may occur whenever gluconeogenesis is required to maintain glucose levels. Avoid coadministration.Aspirin
Aspirin may decrease the glimepiride AUC. Blood glucose and C-peptide concentrations appear to be unaffected and no hypoglycemic symptoms are noted.Atorvastatin
Coadministration of pioglitazone and atorvastatin may decrease pioglitazone and atorvastatin serum concentrations.Azole antifungal agents (eg, ketoconazole), trimethoprim
Pioglitazone plasma levels may be elevated, increasing pharmacologic effect and adverse reactions. Monitor blood glucose and for clinical signs of hypoglycemia. Pioglitazone dosage reduction may be needed.Bosentan
Toxic effects may be increased with coadministration. In addition, the risk for liver enzyme elevations may be increased. Coadministration is contraindicated.Ciprofloxacin, gatifloxacin
Severe and persistent hypoglycemia may occur. Closely monitor for signs and symptoms of hypoglycemia.Clofibrate
Plasma concentrations of glimepiride may be elevated, increasing the hypoglycemic effect. Closely monitor for hypoglycemia.Contraceptives, hormonal
Ethinyl estradiol levels may be decreased slightly by pioglitazone; however, the clinical importance of this interaction has not been established.Drugs that may potentiate the hypoglycemic action of sulfonylureas (eg, glimepiride), such as chloramphenicol, MAOIs, NSAIDs, probenecid, salicylates, and sulfonamides
Closely monitor glycemic control when these agents are started, stopped, or coadministered with glimepiride.Drugs that tend to produce hyperglycemia (eg, beta-blockers [eg, propranolol], corticosteroids, diazoxide, estrogens, isoniazid, phenothiazines, phenytoin, sympathomimetics, thiazide diuretics, thyroid products)
Closely monitor glycemic control when these agents are started, stopped, or coadministered with glimepiride. Because some signs and symptoms of hypoglycemia may be attenuated in patients receiving beta-blockers, hypoglycemia may be difficult to recognize.Inducers of CYP2C8 (eg, rifampin)
May decrease pioglitazone exposure, reducing the pharmacologic effect. Closely monitor glycemic control when these agents are started or stopped.Inhibitors of CYP2C8 (eg, gemfibrozil, trimethoprim)
May increase pioglitazone exposure, increasing the pharmacologic effect and adverse reactions. Closely monitor glycemic control when these agents are started or stopped.Insulin
Incidence of edema may be increased, even after several months of combined therapy.Miconazole
Severe hypoglycemia has been reported when oral hypoglycemic agents are coadministered with oral miconazole. Whether this interaction occurs with IV, topical, or vaginal miconazole preparations is not known.Midazolam
Midazolam plasma levels may be reduced, decreasing the efficacy. Monitor the clinical response and adjust the midazolam dose as needed.Nifedipine ER
Concurrent use of pioglitazone and nifedipine ER may result in a decrease in nifedipine concentrations. The clinical importance is unknown.Rifamycins (eg, rifampin)
Glimepiride or pioglitazone plasma levels may be reduced, decreasing glycemic control. Close clinical and laboratory monitoring for signs of hypoglycemia is warranted, especially when a rifamycin is added to pioglitazone/glimepiride.Warfarin
Coadministration of glimepiride and warfarin may result in a slight, but statistically significant, decrease in the pharmacodynamic response to warfarin. The magnitude of this change is unlikely to be clinically important. However, pioglitazone may increase or decrease the anticoagulant effect of warfarin. Closely monitor anticoagulant activity and adjust the warfarin dose as needed.
Macular edema with blurred vision or decreased visual acuity (postmarketing).
Diarrhea (6%); nausea (5%).
Anemia; hemolytic anemia (postmarketing).
Hepatic enzyme elevations, hepatitis (postmarketing).
Increased incidence of bone fractures in women (postmarketing).
Hypoglycemia (16%); weight gain (13%).
Upper respiratory tract infection (15%).
Lower limb edema (12%); limb pain (5%); edema and worsening of edema (postmarketing).
Pioglitazone may cause or exacerbate CHF. Carefully observe patients for signs and symptoms of heart failure. Not recommended for use in patients with symptomatic heart failure.
Monitor liver enzymes prior to the initiation of therapy and periodically thereafter; periodically perform fasting blood glucose and HbA 1c measurements to monitor glycemic control and therapeutic response. Observe patients for signs and symptoms of heart failure (eg, excessive rapid weight gain, dyspnea, edema). Assess bone health. Perform eye exams regularly. Observe patients carefully for hypoglycemia (for 1 to 2 wk) after initiation of the therapy.
Category C . Not recommended for use during pregnancy.
Undetermined. Not recommended for use during breast-feeding.
Safety and efficacy not established.
Use with caution.
Start with glimepiride 1 mg in patients with renal function impairment.
Do not initiate therapy in patients with clinical evidence of active liver disease or if the ALT levels exceed 2.5 times the ULN. Use caution in mildly elevated liver enzymes.
Do not use in patients with active bladder cancer.
Oral hypoglycemic agents have been associated with increased CV mortality compared with diet alone or diet plus insulin.
Use with caution; can cause fluid retention.
An increased incidence of bone fracture was noted in women taking pioglitazone.
Use with caution in patients with G6PD deficiency.
Decreases in Hgb (2% to 4%) have been reported in patients receiving pioglitazone. Hemolytic anemia has been reported with sulfonylurea agents.
The risk of hypoglycemia increases when used with other oral hypoglycemic agents or insulin; reduction in the dose of the concomitant agent may be necessary. Debilitated or malnourished patients, and those with adrenal, pituitary, or hepatic impairment are particularly susceptible to the hypoglycemic action of glucose-lowering drugs.
Loss of glucose control
Exposure to stress, such as fever, trauma, infection, or surgery, may result in loss of blood glucose control.
Patients with diabetes should have regular eye exams by an ophthalmologist.
May result in ovulation in premenopausal, anovulatory women; adequate contraception is recommended.
Type 1 diabetes
Do not use in these patients.
Dose-related weight gain has been seen alone and in combination with other hypoglycemic agents.
Coma, seizures, or other neurological impairment; hypoglycemia; loss of consciousness.
- Advise patients to read the Medication Guide before starting therapy and with each refill.
- Instruct patients to take this medication once daily with the first main meal.
- Instruct patients in signs, symptoms, and treatment of hypoglycemic reaction.
- Review dietary and exercise guidelines for diabetes with patients.
- Instruct patients to promptly seek medical advice during periods of stress, such as fever, trauma, infection, or surgery, because medication requirements may change.
- Instruct patients who experience an unusually rapid increase in weight or edema or who develop shortness of breath or other symptoms of heart failure to immediately report these symptoms to their health care provider.
- Instruct patients to seek immediate medical advice for abdominal pain, anorexia, dark urine, fatigue, unexplained nausea, or vomiting.
- Caution women that resumption of ovulation may occur in premenopausal, anovulatory women. Address adequate contraceptive measures.
- Advise patients to promptly report any sign of macroscopic hematuria or other symptoms such as dysuria or urinary urgency that develop or increase during treatment as these may be due to bladder cancer.
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