Glucophage Information

Generic Name: Metformin

Brand Name: Glucophage

Other Common Names: Glucopage

Glucophage (metformin hydrochloride tablets) and Glucophage XR (metformin hydrochloride extended-release tablets), as monotherapy, are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. Glucophage is indicated in patients 10 years of age and older, and Glucophage XR is indicated in patients 17 years of age and older. Glucophage or Glucophage XR may be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults (17 years of age and older).

In simple terms:

Glucophage and Glucophage XR - (metformin) are used to treat type 2 diabetes. This is also known as non-insulin-dependent diabetes mellitus.

Glucophage and Glucophage XR - (metformin) have the same active ingredient. However, Glucophage XR works longer in your body.

How Does Glucophage Work?

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Glucophage (Metformin) decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With Glucophage (metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

How To Take Glucophage and Glucophage Dosage and Administration

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with Glucophage or Glucophage XR or any other pharmacologic agent. Dosage of Glucophage or Glucophage XR must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of Glucophage is 2550 mg in adults and 2000 mg in pediatric patients (10-16 years of age); the maximum recommended daily dose of Glucophage XR in adults is 2000 mg.

Glucophage (metformin) should be given in divided doses with meals while Glucophage XR should generally be given once daily with the evening meal. Glucophage or Glucophage XR should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to Glucophage or Glucophage XR and identify the minimum effective dose for the patient. Thereafter, glycosylat-ed hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Glucophage or Glucophage XR, either when used as monotherapy or in combination with sulfonylurea or insulin.

Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.

Short-term administration of Glucophage or Glucophage XR may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Glucophage XR tablets must be swallowed whole and never crushed or chewed.

Occasionally, the inactive ingredients of Glucophage XR will be eliminated in the feces as a soft, hydrated mass.

Recommended Dosing Schedule for Adults

In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.

The usual starting dose of Glucophage (metformin hydrochloride tablets) is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, Glucophage may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.

The usual starting dose of Glucophage XR (metformin hydrochloride extended-release tablets) is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on Glucophage XR 2000 mg once daily, a trial of Glucophage XR 1000 mg twice daily should be considered. If higher doses of metformin are required, Glucophage should be used at total daily doses up to 2550 mg administered in divided daily doses, as described above. In a randomized trial, patients currently treated with Glucophage were switched to Glucophage XR. Results of this trial suggest that patients receiving Glucophage treatment may be safely switched to Glucophage XR once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from Glucophage to Glucophage XR, glycemic control should be closely monitored and dosage adjustments made accordingly.

Recommended Dosing Schedule in Pediatrics

The usual starting dose of Glucophage is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. Safety and effectiveness of Glucophage XR in pediatric patients have not been established.

If you suspect a Glucophage Overdose

Hypoglycemia has not been seen even with ingestion of up to 85 grams of Glucophage (metformin), although lactic acidosis has occurred in such circumstances. Glucophage (metformin) is dia-lyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated Glucophage (metformin) from patients in whom overdose is suspected.

Glucophage Side Effects

Glucophage Precautions and Contraindications

Glucophage (metformin) may cause lactic acidosis.

While taking Glucophage or Glucophage XR - (metformin), tell your doctor if you:

• have an illness that causes severe vomiting, diarrhea or fever, or if you drink a much lower amount of liquid than normal. These conditions can lead to severe dehydration (loss of water in your body). You may need to stop taking Glucophage or Glucophage XR - (metformin) for a short time.
• plan to have surgery or an x-ray procedure with injection of dye (contrast agent). You may need to stop taking Glucophage (metformin hydrochloride tablets) or Glucophage XR (metformin hydrochloride extended-release tablets) for a short time.
• start to take other medicines or change how you take a medicine. Glucophage and Glucophage XR - (metformin) can affect how well other drugs work, and some drugs can affect how well Glucophage or Glucophage XR - (metformin) work. Some medicines may cause high blood sugar.

Monitoring of renal function

Renal function should be monitored as Metformin is known to be substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive Glucophage (metformin hydrochloride tablets) or Glucophage XR (metformin hydrochloride extended-release tablets). In patients with advanced age, Glucophage and Glucophage XR should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those >80 years of age, renal function should be monitored regularly and, generally, Glucophage and Glucophage XR should not be titrated to the maximum dose

Glucophage and Glucophage XR - (metformin) are contraindicated in patients with:

1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels < 1.5 mg/dL [males], < 1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia
2. Congestive heart failure requiring pharmacologic treatment.
3. Known hypersensitivity to metformin hydrochloride.
4. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

Glucophage and Glucophage XR - (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.

Taking Glucophage during Pregnancy or Breast-feeding

Recent information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, Glucophage and Glucophage XR should not be used during pregnancy unless clearly needed.

There are no adequate and well-controlled studies in pregnant women with Glucophage or Glucophage XR. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about two and six times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin.

Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of Glucophage (metformin) to the mother. If Glucophage or Glucophage XR is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

Glucophage and Alcohol Interaction

Do not drink a lot of alcoholic drinks while taking Glucophage or Glucophage XR - (metformin). This means you should not binge drink for short periods, and you should not drink a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis.

Lactic Acidosis

In rare cases, Glucophage and Glucophage XR - (metformin) can cause a serious side effect called lactic acidosis. This is caused by a buildup of lactic acid in your blood. This build-up can cause serious damage. Lactic acidosis caused by Glucophage (metformin hydrochloride tablets) and Glucophage XR (metformin hydrochloride extended release tablets) is rare and has occurred mostly in people whose kidneys were not working normally. Lactic acidosis has been reported in about one in 33,000 patients taking Glucophage over the course of a year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the people who develop it.

It is also important for your liver to be working normally when you take Glucophage and Glucophage XR - (metformin). Your liver helps remove lactic acid from your blood.

Make sure you tell your doctor before you use Glucophage orGlucophage XR - (metformin) if you have kidney or liver problems. You should also stop using Glucophage and Glucophage XR - (metformin) and call your doctor right away if you have signs of lactic acidosis. Lactic acidosis is a medical emergency that must be treated in a hospital.

Signs of lactic acidosis are:

• feeling very weak, tired, or uncomfortable
• unusual muscle pain
• trouble breathing
• unusual or unexpected stomach discomfort
• feeling cold
• feeling dizzy or lightheaded
• suddenly developing a slow or irregular heartbeat

Storing Glucophage

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F).