Glucophage

Action

Increases insulin sensitivity by decreasing glucose production and absorption in liver and intestines and enhancing glucose uptake and utilization

Availability

Oral solution: 100 mg/ml, 500 mg/5 ml

Tablets: 500 mg, 850 mg, 1,000 mg

Tablets (extended-release): 500 mg, 750 mg

Indications and dosages

➣ Adjunct to diet and exercise to improve glycemic control in type 2 (non-insulin-dependent) diabetes mellitus

Adults and children ages 17 and older: Initially, 500 mg P.O. b.i.d.; may increase by 500 mg/week, up to 2,000 mg/day. If patient needs more than 2,000 mg/day, give in three divided doses (not to exceed 2,500 mg/day). Alternatively, 850 mg P.O. daily, increased by 850 mg q 2 weeks, up to 2,550 mg/day in divided doses (850 mg t.i.d.). Extended-release tablets-500 mg/day P.O. with evening meal; may increase by 500 mg weekly, up to 2,000 mg/day. If 2,000 mg once daily is inadequate, 1,000 mg may be given b.i.d.

Children ages 10 to 16: 500 mg P.O. b.i.d. Increase in increments of 500 mg weekly to a maximum of 2,000 mg daily in divided doses.

➣ Concurrent use with sulfonylurea or insulin in type 2 diabetes mellitus

Adults and children ages 17 and older: If patient hasn't responded to maximum metformin dosage of 2,000 mg/day in 4 weeks, sulfonylurea may be added while metformin therapy continues at highest dosage (even if patient experienced primary or secondary failure on sulfonylurea). Adjust dosages of both drugs until glycemic control adequate. If response inadequate within 1 to 3 months of concurrent therapy, consider alternatives.

➣ Concurrent use with insulin in type 2 diabetes mellitus

Adults ages 17 and older: Continue current insulin dosage while starting metformin at 500 mg P.O. once daily. If response inadequate, increase metformin dosage by 500 mg after approximately 1 week and then by 500 mg weekly until glycemic control is achieved. Maximum metformin dosage is 2,500 mg. Optimally, decrease insulin dosage 10% to 25% when fasting plasma glucose level is below 120 mg/dl. Individualize dosage adjustments based on glycemic response.

Dosage adjustment

• Elderly or debilitated patients

Contraindications

• Hypersensitivity to drug

• Acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma

• Underlying renal dysfunction

• Heart failure requiring drug therapy

Precautions

Use cautiously in:

• renal impairment, myocardial infarction, cerebrovascular accident, hypoxia, sepsis, pituitary deficiency or hyperthyroidism, dehydration, hypoxemia, chronic alcohol use

• elderly or debilitated patients

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• Administer with a meal.

• Make sure patient swallows extended-release tablets whole without crushing or chewing.

• Don't administer extended-release tablets to children.

• Know that drug is given with diet therapy, sulfonylureas, or both.

Adverse reactions

GI: diarrhea, nausea, vomiting, abdominal bloating

Metabolic: lactic acidosis

Other: unpleasant metallic taste, decreased vitamin B₁₂ level

Interactions

Drug-drug. Amiloride, calcium channel blockers, digoxin, morphine, procainamide, quinidine, ranitidine, triamterene, trimethoprim, vancomycin: altered response to metformin

Cimetidine, furosemide, nifedipine: increased metformin effects

Iodinated contrast media: increased risk of lactic acidosis

Drug-diagnostic tests. Urine ketones: false-positive results

Drug-herbs. Glucosamine: decreased glycemic control

Chromium, coenzyme Q10, fenugreek: additive hypoglycemic effects

Drug-behaviors. Alcohol use: increased metformin effects

Patient monitoring

• When switching from chlorpropamide, stay alert for hypoglycemia during first 2 weeks of metformin therapy; chlorpropamide may stay in body for prolonged time. Conversion from other standard oral hypoglycemics requires no transition period.

• Monitor blood glucose level closely. If it isn't controlled after 4 weeks at maximum dosage, oral sulfonylurea may be added.

• Monitor kidney and liver function tests, particularly in elderly patients.

• Assess hematologic parameters and vitamin B₁₂ levels at start of therapy and periodically thereafter.

☞ Watch for signs and symptoms of lactic acidosis. Stop drug if acidosis occurs. To aid differential diagnosis, check electrolyte, ketone, glucose, blood pH, lactate, and metformin blood levels.

• Periodically monitor glucose and glycosylated hemoglobin levels to evaluate drug efficacy.

Patient teaching

• Teach patient about diabetes and importance of proper diet, exercise, weight control, and blood glucose monitoring.

• Inform patient that drug may cause diarrhea, nausea, and upset stomach. Advise him to take it with meals to reduce these effects, and tell him that adverse effects often subside over time.

☞ Teach patient to recognize and immediately report signs and symptoms of acidosis, such as weakness, fatigue, muscle pain, dyspnea, abdominal pain, dizziness, light-headedness, and slow or irregular heartbeat.

• Advise patient to report changes in health status (such as infection, persistent vomiting and diarrhea, or need for surgery). These may warrant dosage decrease or drug withdrawal.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.