Usual Adult Dose for Diabetes Type 2

Individualize dose based on safety, efficacy, and prior therapy; asses the risk versus benefit of initiating with combination therapy versus monotherapy

Initial dose: rosiglitazone 4 mg/glimepiride 1 mg orally once a day

• Patients receiving a sulfonylurea or rosiglitazone: May consider a starting dose of rosiglitazone 4 mg/glimepiride 2 mg orally once a day
• Patients receiving rosiglitazone and glimepiride as individual components: Initial dose is the combination product containing the same dose of each component

Dose Titration: Individualize based on glycemic response and safety concerns for each component.

• Patients switching from rosiglitazone: Titrate glimepiride after 1 to 2 weeks in increments of no more than 2 mg; following increase, rosiglitazone may be titrated after 1 to 2 weeks
• Patients switching from sulfonylurea: Titrate rosiglitazone after 8 to 12 weeks; allow 2 to 3 months to see full effect of increase before further titration

Maximum dose: rosiglitazone 8 mg/glimepiride 4 mg

Comments: Take with first meal of the day.

• Monitor closely for fluid related adverse events, particularly with rosiglitazone initiation and titration.
• If hypoglycemia occurs, dose reduction of the glimepiride component may be necessary.

Use: To improve glycemic control in adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise.

Renal Dose Adjustments

Initial dose: rosiglitazone 4 mg/glimepiride 1 mg orally once a day; titrate based on fasting glucose levels

Liver Dose Adjustments

Not recommended in patients with active liver disease or in patients with ALT elevations 2.5 times the upper limit of normal (2.5 x ULN).

• If ALT elevations greater than 3 x ULN develop during therapy, recheck liver enzymes as soon as possible; if ALT remains greater than 3 x ULN, treatment should be discontinued.
• If symptoms suggestive of liver dysfunction develop, liver enzymes should be checked; if jaundice develops, treatment should be discontinued.

Dose Adjustments

• Elderly, debilitated, or malnourished patients: Dose conservatively to avoid hypoglycemia
• Patients with adrenal insufficiency: Dose conservatively to avoid hypoglycemia

• For hypoglycemia: Dose reduction of glimepiride component should be considered

• If signs or symptoms of heart failure develop, dose reduction or drug discontinuation of rosiglitazone should be considered.

Precautions

US BOXED WARNING: Congestive Heart Failure

• Thiazolidinediones, including rosiglitazone, may cause or exacerbate congestive heart failure.
• After initiation of therapy and with any dosage increase, observe patients carefully for signs and symptoms of heart failure including excessive, rapid weight gain, dyspnea, and/or edema; if signs and symptoms of heart failure develop, manage in accordance to current standards of care.
• Drug discontinuation or dosage reduction should be considered in patients showing signs and symptoms of heart failure; this drug is not recommended in patients with symptomatic heart failure.
• Initiation in patients with established NYHA Class III or IV heart failure is contraindicated.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: Data not available
Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• Take with the first meal of the day
• When coadministered with colesevelam, this drug should be taken at least 4 hours prior

General:

• Coadministration with insulin is not recommended.
• This drug should not be used in patients with symptomatic heart failure.
• Hypoglycemia may occur, especially in the elderly, debilitated, or malnourished patient, and/or those with renal, hepatic or adrenal insufficiency; dose reduction of glimepiride may be necessary.
• This drug should not be used in patients with type 1 diabetes or diabetic ketoacidosis.
• Hemolytic anemia may occur in glucose 6-phosphate dehydrogenase (G6PD) deficient patients; consider a non-sulfonylurea alternative.

Monitoring:

• Observe closely for signs and symptoms of heart failure upon initiation and with each dose increase
• Hepatic: Monitor liver enzymes baseline and periodically
• Monitor glycemic control

Patient advice:

• This drug may cause edema; patients experiencing rapid weight gain, shortness of breath or other symptoms of heart failure should notify their health care professional promptly.
• Premenopausal anovulatory women may be at risk for pregnancy while on this drug; pregnancy risk should be discussed with patient and adequate contraception recommended if necessary.
• Patients with unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine should be advised to report these symptoms to their health care professional.
• Patients should be informed about the risks of hypoglycemia, its symptoms, the conditions that might predispose them to develop it, and treatment.
• Patients should speak with their health care provider during periods of stress such as fever, trauma, infection, or surgery, as their diabetes management may need to be changed.