Combination of two antidiabetic agents with different mechanisms of action to improve glycemic control in patients with type 2 diabetes: Rosiglitazone maleate, a member of the thiazolidinedione class, and Metformin hydrochloride, a member of the biguanide class. Thiazolidinediones are insulin sensitizing agents that act primarily by enhancing peripheral glucose utilization, whereas biguanides act primarily by decreasing endogenous hepatic glucose production.
Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator–activated receptor-gamma (PPARγ). Activation of PPARγ nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In addition, PPARγ-responsive genes also participate in the regulation of fatty acid metabolism.
The pharmacologic mechanism of action of Metformin is different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and increases peripheral glucose uptake and utilization. Unlike sulfonylureas, With Metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
This is used for an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus who are not adequately controlled on Metformin alone. Management of type 2 diabetes mellitus should include diet control. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient because they help improve insulin sensitivity. This is important not only in the primary treatment of type 2 diabetes but also in maintaining the efficacy of drug therapy.
|Generic||Rosiglitazone + Metformin|
|Weight||1 mg+500mg, 2mg+500mg|
|Therapeutic Class||Combination Oral hypoglycemic preparations|
|Last Updated:||June 23, 2021 at 11:25 am|
Table Of contents
The selection of the dose of Rosiglitazone and Metformin combination should be based on the patient’s current doses of Rosiglitazone and/or Metformin. The safety and efficacy of Rosiglitazone and Metformin combination as initial therapy for patients with type 2 diabetes mellitus have not been established.
The following recommendations regarding the use of Rosiglitazone and Metformin combination in patients inadequately controlled on Rosiglitazone and Metformin monotherapies are based on clinical practice experience with Rosiglitazone and Metformin combination therapy.
- The dosage of antidiabetic therapy with Rosiglitazone and Metformin combination should be individualized on the basis of effectiveness and tolerability while not exceeding the maximum recommended daily dose of 8 mg/2,000 mg.
- Rosiglitazone and Metformin combination should be given in divided doses with meals, with gradual dose escalation. This reduces GI side effects (largely due to Metformin) and permits determination of the minimum effective dose for the individual patient.
- Sufficient time should be given to assess adequacy of therapeutic response. Fasting plasma glucose (FPG) should be used to determine the therapeutic response to Rosiglitazone and Metformin combination . After an increase in Metformin dosage, dose titration is recommended if patients are not adequately controlled after 1 to 2 weeks. After an increase in Rosiglitazone dosage, dose titration is recommended if patients are not adequately controlled after 8 to 12 weeks.
For patients inadequately controlled on Metformin monotherapy: The usual starting dose of Rosiglitazone and Metformin combination is 4 mg Rosiglitazone (total daily dose) plus the dose of Metformin already being taken.
For patients inadequately controlled on Rosiglitazone monotherapy: The usual starting dose of Rosiglitazone and Metformin combination is 1,000 mg Metformin (total daily dose) plus the dose of Rosiglitazone already being taken.
The incidence and types of adverse events reported in clinical trials of Rosiglitazone as monotherapy are upper respiratory tract infection, headache, back pain, hyperglycemia, fatigue, sinusitis, diarrhea, and hypoglycemia. Adverse reactions reported in greater than 5% of the Metformin patients, and that were more common in Metformin- than placebo-treated patients are diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, headache.
When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold combination of Rosiglitazone and Metformin and temporarily administer insulin. Combination of Rosiglitazone and Metformin may be reinstituted after the acute episode is resolved. Combination of Rosiglitazone and Metformin should be used with caution in patients with edema.
If an inhibitor or an inducer of CYP2C8 (such as gemfibrozil or rifampin) is started or stopped during treatment with Rosiglitazone, changes in diabetes treatment may be needed based upon clinical response.
Although drug interactions with cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of combination of Rosiglitazone and Metformin and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
When drugs that produce hyperglycemia which may lead to loss of glycemic control are administered to a patient receiving combination of Rosiglitazone and Metformin, the patient should be closely observed to maintain adequate glycemic control.
Pregnancy & Breastfeeding use
Pregnancy Category C. Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies as well as increased neonatal morbidity and mortality, most experts recommend that insulin monotherapy be used during pregnancy to maintain blood glucose levels as close to normal as possible. Combination of Rosiglitazone and Metformin should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women with combination of Rosiglitazone and Metformin or its individual components.
It is not known whether Rosiglitazone and/or Metformin are excreted in human milk. Because many drugs are excreted in human milk, a combination of Rosiglitazone and Metformin should not be administered to a nursing woman.
Combination of Rosiglitazone and Metformin tablets arecontraindicated in patients with:
- Renal disease or renal dysfunction which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia
- Congestive heart failure requiring pharmacologic treatment.
- Known hypersensitivity to Rosiglitazone maleate or Metformin hydrochloride.
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.
Combination of Rosiglitazone and Metformin should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.
Pediatric Use: Safety and effectiveness of combination of Rosiglitazone and Metformin in pdiatric patients have not been established.
Geriatric Use: Because aging is associated with reduced renal function, combination of Rosi litazone and Metformin should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of combination of Rosiglitazone and Metformin.
Store in a cool dry place protected from light. Keep out of reach of children.