Rosiglitazone Maleate/Metformin Hydrochloride

A to Z Drug Facts

 Action Rosiglitazone: Increases insulin sensitivity; metformin: decreases blood glucose by reducing hepatic glucose production and may decrease intestinal absorption of glucose and increase response to insulin.

 Indications As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus who are already treated with combination rosiglitazone and metformin or who are not adequately controlled on metformin alone.

 Contraindications Patients with renal disease or renal dysfunction, that may also result from conditions such as cardiovascular collapse, acute MI, and septicemia; CHF requiring pharmacologic treatment; acute or chronic metabolic acidosis, with or without coma; known hypersensitivity to any component of the product.

 Route/Dosage

Base dosage selection of rosiglitazone and metformin on the patient's current doses of rosiglitazone or metformin (max, 8 mg rosiglitazone/2000 mg metformin/day).

Patients Inadequately Controlled on Metformin Monotherapy

Adults PO Start with 4 mg rosiglitazone daily plus the metformin dose already being taken. If prior therapy consists of 1000 mg/day of metformin, start with 2 mg/500 mg and administer 1 tablet bid. If prior therapy consists of 2000 mg/day of metformin, start with 1 mg/500 mg and administer 2 tablets bid.

Patients Inadequately Controlled on Rosiglitazone Monotherapy

Adults PO Start with 1000 mg metformin daily plus the rosiglitazone dose already being taken. If prior therapy consists of 4 mg/day of rosiglitazone, start with 2 mg/500 mg and administer 1 tablet bid. If prior therapy consists of 8 mg/day of rosiglitazone, start with 4 mg/500 mg and administer 1 tablet bid.

Switching From Separate Doses of Rosiglitazone and Metformin To Combination Therapy

Adults PO Start with the doses of rosiglitazone and metformin already being taken. Increase the dose in increments of 4 mg rosiglitazone and/or 500 mg metformin up to the maximum recommended total daily dose of 8 mg/2000 mg.

 Interactions

Alcohol The effects of metformin on lactate metabolism may be potentiated. Calcium channel blocking agents, corticosteroids, estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thiazides and other diuretics, thyroid products: These agents tend to produce hyperglycemia and may lead to loss of blood glucose control. Furosemide Metformin plasma levels may be elevated while furosemide levels may be decreased. Nifedipine Metformin plasma levels may be increased.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Cardiac failure. CNS: Headache; fatigue. EENT: Sinusitis. GI: Diarrhea. HEMATOLOGIC: Anemia. RESPIRATORY: Upper respiratory tract infection; pulmonary edema; pleural effusions. OTHER: Injury; back pain; viral infection; arthralgia; edema.

 Precautions

Pregnancy Category C. Lactation Undetermined. Children Safety and efficacy not established. Elderly In general, elderly patients are not titrated to the maximum dose because of age-related decreases in renal function. Cardiac failure Fluid retention, which may exacerbate or lead to heart failure, may occur. Hepatic disease Avoid metformin in patients with clinical or laboratory evidence of hepatic disease. Iodinated contrast materials Metformin therapy should be withheld at the time of or prior to parenteral contrast studies with iodinate materials. Reinstitute therapy 48 hr after the study and after renal function has been determined to be normal. Lactic acidosis Can occur as a result of metformin accumulation (eg, renal impairment) or in pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. The risk of lactic acidosis increases with the degree of renal dysfunction and the age of the patient. Renal disease Decreased renal function results in decreased renal clearance and prolongation of the metformin t_1/2. Concomitant medications that affect renal function may result in hemodynamic changes or interfere with disposition of metformin (eg, cationic drugs) and should be used with caution. Avoid metformin in patients whose serum creatinine levels exceed the upper limit of normal for their age. Special risk patients Use with caution in patients with edema; avoid use in patients with type 1 diabetes.

 Administration/Storage

• Do not administer to patients with renal impairment, clinical evidence of active liver disease, or elevated liver enzymes (ALT greater than 2.5 × upper limit of normal), or to patients with type 1 diabetes mellitus.
• Refer to manufacturer's dosing chart when converting patients from rosiglitazone or metformin monotherapy to combination therapy.
• Administer dose bid as prescribed.
• Administer each dose with food to prevent GI distress.
• Store at controlled room temperature (59° to 86°F).

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note history of renal disease, liver disease, CHF or edema, chronic metabolic acidosis, acute metabolic acidosis (eg, diabetic ketoacidosis), jaundice while taking troglitazone.
• Ensure that renal function, hemoglobin, hematocrit, and RBC indices have been assessed prior to starting therapy and at least annually during therapy.
• Ensure that creatinine clearance has been determined in patients greater than 80 yr before initiating therapy.
• Ensure that liver enzymes are determined before starting therapy, every 2 mo during therapy for the first year, and then periodically thereafter.
• Ensure that medication is discontinued in patient who develops symptoms of hepatic dysfunction or whose liver enzymes increase to 3 × upper limit of normal.
• Check blood sugars frequently and observe for signs of hypoglycemia. Inform health care provider if blood sugar readings are outside target range or if hypoglycemic events are noted.
• Monitor patient for fluid retention (eg, edema, rapid weight gain) or other symptoms or signs of heart failure. Inform health care provider if noted.
• Ensure that medication is withheld before, and for 48 hr after, undergoing a radiologic study with intravascular administration of iodinated contrast material and is not restarted until renal function has been documented to be normal.
• Hold therapy in patient undergoing surgical procedure until oral intake has resumed and renal function has been documented to be normal.
• Ensure that premenopausal anovulatory patient is on an effective contraception regimen.

 Patient/Family Education

• Explain name, dose, action, and potential side effects of drug.
• Advise patient to take prescribed dose bid and to take with food to decrease GI distress.
• Advise patient that dose may be gradually increased every 2 wk until maximum benefit is obtained.
• Educate patient, family, and caregiver regarding type 2 diabetes and its management, including target ranges for blood sugar control.
• Instruct patient that this drug is not a substitute for diet and exercise and that patient should continue to follow prescribed regimens.
• Emphasize the importance of regular daily blood glucose monitoring and periodic hemoglobin A_1c (HbA_1c) tests.
• Advise patient to keep a log of measured blood sugars and to take to each visit with their health care provider.
• Advise patient to carry medical identification that they are diabetic (eg, Medi-Alert).
• Caution patient to avoid excessive alcohol intake to reduce risk of metabolic acidosis.
• Instruct patient to report any of the following to the health care provider immediately: general body discomfort, muscle aches, unexplained rapid breathing or shortness of breath, unexplained drowsiness, nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, yellowing of the skin or eyes, rapid weight gain.
• Review symptoms of hypoglycemia and hyperglycemia and action plans to undertake in the event either occur.
• Instruct patient to notify health care provider if experiencing hypoglycemic episodes or if measured blood sugars are outside target range.
• Caution premenopausal women that drug can cause resumption of ovulation in premenopausal anovulatory women with insulin resistance. Address adequate contraceptive measures for these women.
• Advise women to contact their health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Instruct patient not to take prescription or OTC drugs or dietary supplements without consulting the health care provider.
• Advise patient that follow-up visits and lab tests will be necessary to monitor therapy and to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts