Avandamet

What is Avandamet?

How does Avandamet work?

Dosage

• 2 mg/500 mg
• 4 mg/500 mg
• 2 mg/1000 mg
• 4 mg/1000 mg

The dose should be started at 2 mg/500 mg once or twice a day, and increased per patient tolerance and individualization. If blood sugar is not well controlled after 4 weeks, the dosage can be increased by 2 mg/500 mg until adequate control is achieved. For metformin, it can take 1-2 weeks to assess the effects of a dose increase. For rosiglitazone, it can take up to 12 weeks to assess the effects of a dose increase. Gradual escalation is recommended to find the minimum effective dose.

The daily dose should not exceed 8 mg of rosiglitazone and 2000 mg of metformin.

Overdose

If immediate help is required, call 911. If overdose is suspected, call poison control at 800-222-1222.

Warnings & Precautions

Avandamet has not been studied or approved in children under 18 years old

Diabetic ketoacidosis

This medication should not be used for the treatment of diabetic ketoacidosis, a life-threatening condition evidenced by a blood sugar greater than 240 mg/dL and the presence of ketones in the blood. Early symptoms of DKA include severe thirst and frequent urination. Advanced symptoms include fast, deep breathing, fruity-smelling breath, headache, nausea, vomiting, lethargy, and dry skin and mouth. If you’re sick, experiencing any of the symptoms of DKA, or your blood sugar is greater than 240 mg/dL, you should test your urine or blood for ketones. If ketones are detected, you should call 911 or seek immediate medical attention.

Diabetes type-1

Avandamet is not approved for the treatment of type-1 diabetes.

Edema

Rosiglitazone is known to cause fluid retention and edema so Avandamet should be used cautiously in patients with existing swelling or edema. Increased fluid volume can lead to and/or worsen heart failure, so patients with heart failure should exercise extra caution when taking this medication.

Eye problems

Patients with diabetes are at an increased risk for developing eye problems and Avadamet can further increase this risk. Macular edema can be a complication of taking Avandamet, and seems to correlate with edema elsewhere in the body. A baseline eye exam should be performed before starting this medication, and eye exams should be performed regularly. If symptoms such as blurred vision or vision loss are noted, the patient should immediately be referred to an ophthalmologist.

Fractures

Avandamet can increase the risk of bone fractures, particularly in women. Fractures of the upper arm, hand, and foot are the most common fractures seen with this medication. Care should be taken to monitor and maintain bone health. Notify your doctor if you have, or are at increased risk of developing osteoporosis.

Heart problems

Avandamet can increase the risk of developing heart failure, and care should be taken to monitor for signs and symptoms of new or developing heart failure. Symptoms include increased edema, shortness of breath with activity, difficulty breathing while lying flat, weight gain, weakness, or cough.

For patients with existing heart failure, Avandamet can increase the number of cardiovascular events. While a decrease in heart function was not seen, Avandamet seemed to correspond with an increase in hospitalizations and cardiovascular deaths, as well as reports of worsening shortness of breath and edema. For patients with NYHA Class I and II heart failure, caution should be exercised when taking Avandamet. For patients with NYHA Class III and IV heart failure, taking Avandamet is not recommended.

Hematologic effects

Avandamet can decrease hemoglobin and hematocrit levels in the blood. Studies have shown a correlation between Avandamet dosage and blood count: the higher the dose of Avandamet, the lower the hemoglobin and hematocrit. It’s unclear if this decrease is due to dilution from fluid retention/edema or as a result of a vitamin B12 deficiency. Regular blood work should be performed to monitor blood counts.

Hypoglycemia

Hypoglycemia is rare with metformin but can occur after exercise or if calorie intake is insufficient. Hypoglycemia can be seen with rosiglitazone, especially if being taken in combination with other anti-diabetic medications.

Lactic Acidosis

Lactic acidosis is a metabolic condition defined by a low pH and a high level of blood lactate. While lactic acidosis has many potential causes, an overdose of metformin is known to be one of them. Factors that can cause an unsafe buildup of metformin in the body are kidney problems, liver problems, and advanced age. Regular blood work should be performed to monitor kidney and liver function.

Early symptoms of lactic acidosis are quite nonspecific and include fatigue, lethargy, muscle pain, and respiratory distress. Advanced symptoms of lactic acidosis include low blood pressure, hypothermia, heart arrhythmias, and bradycardia. Lactic acidosis must be managed in a hospital setting, and Avandamet should be discontinued until the patient is stabilized.

In general, caution is advised when administering Avandamet in a hospital setting. Avandamet should promptly be discontinued if the patient is septic, dehydrated, or hypoxemic. Avandamet should not be administered before any diagnostic procedure involving radiocontrast or before surgery.

Insulin

Avandamet should not be taken concurrently with insulin as this increases the risk of cardiovascular side effects.

Liver problems

Avandamet can be dangerous for patients with severe liver dysfunction. For patients with a history of mild liver dysfunction, the use of Avandamet should be accompanied by routine checks of liver enzymes. Monitor for signs and symptoms of liver dysfunction which include nausea, vomiting, abdominal pain, fatigue, loss of appetite, and dark urine.

Pregnancy and Breastfeeding

Do not take Avandamet if you are pregnant or breastfeeding as no studies have been performed to test the safety and efficacy in these patients.

Vitamin B12 levels

Avandamet can decrease vitamin B12 levels in some patients. No symptoms have been noted with this decrease, but vitamin B12 supplementation could be recommended for some patient populations. Levels of vitamin B12 appear to rapidly increase upon discontinuation of the medication.

Weight gain

While Avandamet has not been linked to weight gain, a weight increase has been noted with rosiglitazone therapy alone. The mechanism of action is unclear but fluid retention and edema may be the cause of weight gain.

Drug Interactions

It’s important to note that this is not a complete list of drug interactions. Notify your doctor of all medications you’re taking, including vitamins and over-the-counter supplements.

Cationic drugs

Caution should be exercised when taking Avandamet in combination with cationic drugs that are excreted by the proximal renal tubule. Because metformin is excreted by the same system, competition can arise. This has been seen with cimetidine in particular, but it’s possible with other cationic drugs such as digoxin, morphine, procainamide, quinidine, quinine, ranitidine, and vancomycin.

Furosemide

With this diuretic in particular, one study showed an increase in the concentration of metformin when these drugs were administered concurrently. No studies have been done with long-term use of both medications so caution should be exercised when taking both.

Inhibitors and inducers of CYP2C8

These drugs can increase or decrease the concentration of rosiglitazone. E.g. Gemfibrozil, Rifampin

Nifedipine

Nifedipine is a calcium-channel blocker that has been shown to increase the absorption of metformin. Caution should be exercised when taking both medications.

Alternative Medications

Notify your doctor of all medications you are prescribed. Do not take Avandamet in addition to insulin.

Alpha-glucosidase inhibitors

• These drugs lower blood glucose by reducing glucose uptake in the small intestine and slowing the breakdown of carbohydrates
  • Precose (acarbose)
  • Glyset (miglitol)

Biguanides

• Metformin (one of the drugs in Avandamet) is a biguanide. These drugs reduce the amount of glucose produced by the liver and slow the breakdown of carbohydrates. These should not be taken in combination with Avandamet.
  • Glucophage, Glumetza, Fortamet (metformin)

Dopamine agonists

• These drugs decrease the amount of glucose excreted by the liver
  • Cyclocet (bromocriptine)

DPP-4 Inhibitors

• These drugs work with the pancreas to secrete more insulin and decrease the amount of glucose released by the liver
  • Januvia (sitagliptin)
  • Onglyza (saxagliptin)

Meglitinide

• These drugs work with the pancreas to secrete more insulin
  • Prandin (repaglinide)
  • Starlix (nateglinide)

SGLT2 inhibitors

• These drugs work with the kidneys to remove extra glucose
  • Invokana (canagliflozin)
  • Jardiance (empagliflozin)

Sulfonylureas

• These drugs work with the pancreas to secrete more insulin
  • Glucotrol (glipizide)
  • Amaryl (glimepiride)

Thiazolidinediones

• Rosiglitazone (one of the medications in Avandamet) is a thiazolidinedione. These medications allow more glucose to enter fat, muscles, and the liver. These should not be taken in combination with Avandamet.
  • Actos (pioglitazone)
  • Avandia (rosiglitazone)