Metformin/Rosiglitazone

DEA Class; Rx

Common Brand Names; Avandamet

Hypersensitivity to rosiglitazone or metformin

Heart failure NYHA Class III-IV

Metabolic acidosis, including diabetic ketoacidosis with or without coma

Severe renal disease: eGFR <30 ml/min/1.73 m²

Nursing women

• Edema (6% to 25% )
• Upper respiratory infections (16-20%)
• Diarrhea (12.7% to 14%)
• Hypoglycemia (12% )
• Anemia (4% to 7%)
• Fatigue (6%)
• Headache (6%)
• Sinusitis (6%)
• Arthralgia (5%)
• Back pain (5%)
• Viral infection (5%)
• Angioedema (rare )
• Congestive heart failure
• Death, from cardiovascular causes
• Stevens-Johnson syndrome (rare )
• Lactic acidosis (rare )
• Hepatotoxicity (rare)
• Anaphylaxis (rare )
• Diabetic macular edema
• Pleural effusion
• Pulmonary edema

Metformin

• Cholestatic, hepatocellular, and mixed hepatocellular liver injury

Risk of severe hypoglycemia especially in elderly, debilitated or malnourished, adrenal or pituitary insufficiency, dehydration, heavy alcohol use, hypoxic states, hepatic/renal impairment, stress due to infection, fever, trauma, or surgery

Rare lactic acidosis may occur due to metformin accumulation; fatal in approx 50% of cases; risk increases with age, degree of renal dysfunction, and with unstable or acute CHF; if metformin-associated lactic acidosis suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of therapy; in patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to170 mL/minute under good hemodynamic conditions); hemodialysis has often resulted in reversal of symptoms and recovery

Edema; thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin; not recommended for use with insulin

Withholding of food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension, and renal impairment; therapy should be temporarily discontinued while patients have restricted food and fluid intake

Several of the postmarketing cases of metformin-associated lactic acidosis occurred in setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse (shock) acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; discontinue therapy when such events occur

Therapy with thiazolidinediones may result in ovulation in premenopausal anovulatory women

Rosiglitazone: Associated with rare cases of new onset or worsening of macular edema

Pregnancy Category: C

Lactation: not known if crosses into breast milk, avoid