Glucophage

Glucophage Overview

Glucophage, known generically as metformin hydrochloride, is an oral antihyperglycemic medication belonging to the biguanide class. Primarily prescribed for the treatment of type 2 diabetes mellitus, Glucophage is used to improve blood glucose control in adults and children over 10 years of age.

Therapeutic Mechanism of Action

Glucophage works by decreasing hepatic glucose production, reducing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, Glucophage does not induce hypoglycemia in either patients with type 2 diabetes or healthy subjects and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.

Pharmacokinetics

After an oral dose of Glucophage, maximum plasma concentration is reached in 2.5 hours. Absolute bioavailability of a 500 mg or 850 mg metformin tablet is approximately 50-60% in healthy subjects. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of roughly 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

Indications and Usage

Glucophage is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients age 10 years and older with type 2 diabetes mellitus. It is also used in combination with an insulin regimen in patients who are not adequately controlled on insulin alone and require additional glycemic control.

Dosage Forms and Strengths

Glucophage is available in tablet form and should be taken orally. Dosage strengths include 500 mg, 850 mg, and 1000 mg. The tablets are white and oval-shaped, biconvex, with “BMS” debossed on one side and “6060” on the other (for 500 mg tablets), “6070” on 850 mg tablets, and “1000” on 1000 mg tablets.

Recommended Dosage and Administration

The starting dose of Glucophage in adults is 500 mg orally 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, based upon the patient’s glycemic response. The maximum recommended daily dose is 2550 mg for adults. In pediatric patients (10-16 years of age), the starting dose is 500 mg twice a day, with a maximum recommended daily dose of 2000 mg.

Administration Instructions for Patients

Patients should be informed to swallow Glucophage tablets whole and not to crush, chew, or cut the tablets. Consistency in taking the medication with food will help reduce gastrointestinal symptoms. If a dose of Glucophage is missed, patients are advised to take it as soon as possible with food, but to skip the missed dose if it is almost time for the next scheduled dose, in order to prevent overcompensation.

Drug Interactions

Glucophage may interact with certain medications such as iodinated contrast materials, which could lead to acute alteration of renal function and increase the risk of lactic acidosis. Concomitant use with alcohol may also increase the risk for lactic acidosis. Caution should be taken when using with other drugs that affect blood glucose levels such as insulin or sulfonylureas. Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control; these drugs include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, and isoniazid.

Adverse Reactions and Side Effects

Glucophage is generally well-tolerated; however, the most common side effects encountered include gastrointestinal disturbances such as diarrhea, nausea, vomiting, flatulence, indigestion, abdominal discomfort, and anorexia. Vitamin B12 absorption may be decreased during long-term use. Inform the patient to report signs of lactic acidosis such as muscle pain, trouble breathing, stomach pain, dizziness, feeling cold, or feeling very weak or tired.

Use in Special Populations

The safety and effectiveness of Glucophage for the treatment of type 2 diabetes have been established in pediatric patients 10 years of age and older. No studies have been conducted specifically in elderly patients; however, since they are more likely to have decreased renal function, care should be taken in dose selection and monitoring renal function. Metformin is not recommended in patients below the age of 10 or for the treatment of type 1 diabetes. It should be used with caution in patients with renal impairment or hepatic insufficiency.

Monitoring and Laboratory Tests

It is recommended that the renal function is assessed before initiating treatment and periodically thereafter. Metformin should be temporarily discontinued prior to any radiologic study involving intravenous iodinated contrast materials and for any surgical procedure requiring general anesthesia. Serum vitamin B-12 measurements at 2- to 3-year intervals may be useful. Regular blood glucose and glycosylated hemoglobin (HbA1c) levels should be monitored to determine the patient’s response to Glucophage therapy.

Proper Storage and Handling

Glucophage should be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). Tablets should be kept in their original container, tightly closed, and out of reach of children. Dispose of any unused or expired medication properly according to the local regulations and guidelines.

Pregnancy and Nursing Mothers

There are no adequate and well-controlled studies in pregnant women with Glucophage. It is unknown whether Glucophage is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Glucophage is administered to a nursing woman. Consider the benefits of glycemic control with Glucophage against the potential risks to the infant.

Overdosage Management

In the event of an overdose, prompt supportive treatment is recommended. Overdosage of Glucophage can result in lactic acidosis, which is a medical emergency requiring immediate treatment in a hospital setting. Hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.