Avandamet (rosiglitazone/metformin)

Avandamet

Is rosiglitazone/metformin available as a generic drug?

Yes

Do I need a prescription for rosiglitazone/metformin?

Yes

Avandamet is used with diet and exercise to improve blood glucose control in adult patients with type 2 diabetes.

The most common side effects include

• nausea,
• vomiting,
• diarrhea, and
• upset stomach.

Taking Avandamet with food may help lessen some of these side effects. Other commonly reported side effects include

• headache,
• cold-like symptoms,
• joint aches, and
• dizziness.

Rare but serious side effects include new or

• worsening heart failure,
• heart attack,
• edema or swelling (water retention),
• weight gain,
• liver problems,
• macula edema (a diabetic eye disease with swelling in the back of the eye),
• bone fractures,
• low red blood cell count,
• low blood glucose (hypoglycemia), and
• ovulation (increasing the chance of pregnancy).

Metformin can cause a rare but serious condition known as lactic acidosis, a build-up of acid in the blood. Lactic acidosis can cause death and requires immediate treatment. Symptoms of lactic acidosis include

• tiredness,
• weakness,
• unusual muscle pain,
• pain in the stomach,
• difficulty breathing,
• dizziness, and
• slow or irregular heartbeat.

Patients suspected of have signs or symptoms of lactic acidosis must seek emergency medical help.

The dosage of Avandamet should be individualized based on patient response and tolerability. It is generally given in divided doses with meals.

For patients inadequately controlled on diet and exercise

• Generally, the recommended starting dose of Avandamet is 2/500 mg administered once or twice daily.
• A starting dose of 2/500 mg twice daily may be considered for patients with HbA1c >11% or fasting plasma glucose (FPG) >270 mg//dL.
• If patients are not adequately controlled after 4 weeks of treatment the dosage may be increased in increments of 2/500 mg as necessary.
• The maximum daily dose of Avandamet is 8/2,000 mg.

For patients inadequately controlled on rosiglitazone or metformin monotherapy

• The selection of the dose of Avandamet must be based on the patient's current doses of rosiglitazone and/or metformin.
• To switch to Avandamet for patients currently treated with metformin
• The usual starting dose of Avandamet is 4 mg rosiglitazone and base the metformin dose on the current dose of metformin.
• To switch to Avandamet for patients currently treated with rosiglitazone
• The usual starting dose of Avandamet is 1,000 mg metformin and the corresponding dose of rosiglitazone that the patient is taking.

The safety and efficacy of Avandamet has not been established in pediatric patients. Therefore, use of Avandamet in this patient population is not recommended.

Metformin-containing drugs may be safely used in patients with mild to moderate renal impairment. Renal function should be assessed before starting treatment and at least yearly.

Metformin should not be used by patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 and starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.

Metformin should be stopped at the time of or before administering iodinated contrast in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Kidney function should be evaluated 48 hours after receiving contrast and metformin may be restarted if kidney function is stable.

Rosiglitazone is extensively metabolized or broken down by a group of liver enzymes known as CYP2C8. Gemfibrozil (Lopid), a known inhibitor of CYP2C8 may increase blood levels of rosiglitazone and consequently increase the risk of side effects. Concomitant use of agents that also inhibit CYP2C8 requires a reduction in the dose of rosiglitazone.

Rifampin (Rimactane or Rifadin), a known inducer of CYP2C8, increases the breakdown of rosiglitazone. Therefore, concomitant use of agents that induce CYP2C8 may decrease the effectiveness of rosiglitazone.

Drugs which cause blood glucose levels to increase may diminish the effectiveness of Avandamet therapy. These drugs include

• thiazides,
• other diuretics,
• corticosteroids,
• phenothiazines,
• thyroid medications,
• estrogens,
• birth control pills,
• phenytoin (Dilantin),
• nicotinic acid,
• sympathomimetics,
• calcium channel blockers (CCBs), and
• isoniazid (Nydrazid).

• Avandamet has not been adequately evaluated in pregnant women. Due to the lack of conclusive safety data, Avandamet should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Avandamet is classified as FDA pregnancy risk category C.
• It is not known if Avandamet is excreted in breast milk. Due to the lack of safety data, Avandamet is not recommended for use in nursing mothers.

What preparations of rosiglitazone/metformin are available?

Oral tablets containing Avandamet: 2/500, 4/500, 2/1,000, and 4/1,000 mg.

How should I keep rosiglitazone/metformin stored?

• Tablets should be stored at room temperature, between 15 C and 30 C (59 F and 86 F).
• Tablets should be dispensed and stored in an air-tight, light-resistant container.