Metformin Hydrochloride
Pronouncation: (met-FORE-min HYE-droe-KLOR-ide)
Class: Biguanide
Trade Names:
Fortamet
- Tablets, extended-release 500 mg
- Tablets, extended-release 1,000 mg
Trade Names:
Glucophage
- Tablets 500 mg
- Tablets 850 mg
- Tablets 1,000 mg
Trade Names:
Glucophage XR
- Tablets, extended-release 500 mg
- Tablets, extended-release 750 mg
Trade Names:
Glumetza
- Tablets, extended-release 500 mg
Trade Names:
Riomet
- Oral solution 500 mg per 5 mL
Apo-Metformin (Canada)
Gen-Metformin (Canada)
Novo-Metformin (Canada)
Nu-Metformin (Canada)
PMS-Metformin (Canada)
ratio-Metformin (Canada)
Rhoxal-metformin (Canada)
Rhoxal-metformin FC (Canada)
Decreases blood glucose by decreasing hepatic glucose production. May also decrease intestinal absorption of glucose and increase response to insulin.
Pharmacokinetics
Absorption
Absolute bioavailability is approximately 50% to 60%. T max is 4 to 8 h; C max is approximately 0.6 to 1.8 mcg/mL (extended-release [ER]). Food decreases the extent of absorption and increases the T max (immediate-release [IR]).
Distribution
The apparent Vd is approximately 654 L; protein binding is negligible.
Elimination
The major route for excretion is renal via tubular secretion as unchanged. The plasma t ½ is 6.2 h; t ½ in blood is 17.6 h.
Indications and Usage
Adjunct to diet and exercise to lower blood glucose in patients with type 2 diabetes mellitus. Metformin IR tablets and oral solution are indicated in patients 10 yr of age and older. The ER tablets are indicated in patients 17 yr of age and older (18 yr of age and older for Glumetza ). In combination with a sulfonylurea or insulin to improve glycemic control, metformin is indicated in patients 17 yr of age and older (18 yr of age and older for Glumetza ).
Unlabeled Uses
Treatment of anovulation in women with polycystic ovary syndrome; treatment of antipsychotic-induced weight gain.
Contraindications
Renal disease or dysfunction as suggested by serum creatinine of 1.5 mg/dL or higher in men, or 1.4 mg/dL or higher in women, or abnormal CrCl; conditions that predispose to renal function impairment (eg, CV collapse, acute MI, septicemia); in patients undergoing radiologic studies involving parenteral administration of iodinated contrast material (potential to acutely alter renal function); acute or chronic metabolic acidosis, including diabetic ketoacidosis; CHF requiring pharmacologic treatment ( Fortamet and Glumetza ); hypersensitivity to any component of the product.
Dosage and Administration
Dosages of metformin must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose.
Concomitant Sulfonylurea Therapy
Adults
PO If patient has not responded to 4 wk of max metformin monotherapy, consider gradual addition of an oral sulfonylurea while continuing the max metformin dose. Attempts should be made to identify the minimum effective dose of each drug.
Concomitant Insulin Therapy
Adults
PO Initiate metformin IR or ER therapy at 500 mg once daily in patients receiving insulin therapy. The metformin dose may be increased 500 mg after 1 wk and by 500 mg every wk thereafter until adequate glycemic control is achieved (max, 2,500 mg/day of metformin IR and 2,000 mg/day of metformin ER [2,500 mg/day of Fortamet ]). It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose decreases to less than 120 mg/dL in patients receiving metformin IR or ER.
Transfer From Other Antidiabetic Therapy
PO When transferring patients from standard oral hypoglycemic agents other than chlorpropamide, no transition period generally is needed. When transferring from chlorpropamide, exercise care during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.
Glucophage, Riomet (Metformin IR)
Adults
PO Initial dose: 500 mg twice daily or 850 mg once daily given with meals, increase by 500 mg weekly or 850 mg every 2 wk (max, 2,000 mg/day) in divided doses. Patients can also be titrated from 500 mg twice daily to 850 mg twice daily after 2 weeks. For patients requiring additional glycemic control, Glucophage or Riomet may be given up to a max dose of 2,550 mg/day. Doses more than 2,000 mg may be better tolerated given 3 times daily with meals.
Fortamet (Metformin ER)
Adults
PO 1,000 mg once daily with evening meal, increase by 500 mg weekly (max, 2,500 mg once daily).
Glucophage XR (Metformin ER)
Adults
PO Initial dose: 500 mg once daily with evening meal, increase by 500 mg every wk (max, 2,000 mg once daily). If glycemic control is not achieved on Glucophage XR 2,000 mg once daily, consider a trial of Glucophage XR 1,000 mg twice daily. If higher doses of metformin are required, administer at total daily dose up to 2,550 mg in divided daily doses as previously described.
Glumetza (Metformin ER)
Adults
PO Initial dose: 1,000 mg once daily with food, preferably in the evening. The dose may be increased in increments of 500 mg weekly (max, 2,000 mg once daily with evening meal). If glycemic control is not achieved with 2,000 mg once daily, consider a trial of 1,000 mg twice daily.
Glucophage , Riomet (Metformin IR)
Children 10 yr of age and older IR tablet or oral solution
PO 500 mg twice daily with meals. Dosage may be increased in weekly 500 mg increments to a max of 2,000 mg/day in divided doses.
Storage/Stability
Store tablets and oral solution at controlled room temperature (59° to 86°F).
Fortamet
Protect from moisture and light. Avoid excessive heat and humidity.
Glucophage
Protect from light.
Drug Interactions
Alcohol
Potentiates effect of metformin on lactate metabolism.
Cationic drugs (eg, amiloride, digoxin, quinidine)
May increase metformin serum concentration by competing for tubular secretion.
Cimetidine
Increases metformin serum concentration.
Drugs tending to produce hyperglycemia (eg, calcium channel blockers, diuretics, oral contraceptives, phenytoin, sympathomimetics)
Closely monitor blood glucose control when starting or stopping these agents.
Furosemide
May increase metformin serum concentration; metformin may reduce furosemide serum concentration.
Glyburide
Glyburide blood levels may be decreased.
Iodinated contrast material
May cause acute renal failure and has been associated with lactic acidosis in patients receiving metformin.
Nifedipine
Increases metformin serum concentration.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Palpitation (1% to 5%).
CNS
Asthenia (9%); headache (6%); light-headedness (1% to 5%).
Dermatologic
Increased sweating, nail disorder, rash, taste disorder (1% to 5%).
EENT
Rhinitis (5%).
GI
Diarrhea (53%); nausea/vomiting (26%); flatulence (12%); indigestion (7%); abdominal discomfort (6%); dyspepsia (5%); abdominal pain (3%); abnormal stools (1% to 5%).
Metabolic-Nutritional
Hypoglycemia (1% to 5%).
Musculoskeletal
Myalgia (1% to 5%).
Respiratory
Dyspnea (1% to 5%).
Miscellaneous
Infection (21%); accidental injury (7%); chest discomfort, chills, flu syndrome, flushing (1% to 5%).
Precautions
Warnings
Lactic acidosis
Can occur as a result of metformin accumulation (eg, renal function impairment) or with pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. When it occurs, it is fatal in approximately 50% of cases. The risk of lactic acidosis increases with the degree of renal function impairment and the patient's age.
Monitor
Monitor renal function before starting therapy and at least annually thereafter. Regularly monitor renal function in elderly patients, especially patients 80 yr of age and older.
Pregnancy
Category B . Insulin is recommended to maintain blood glucose levels during pregnancy.
Lactation
Undetermined.
Children
Fortamet , Glucophage XR (Metformin ER)
Safety and efficacy not established in patients younger than 17 yr of age.
Glumetza ER
Safety and efficacy not established in patients younger than 18 yr of age.
Glucophage , Riomet (Metformin IR)
Safety and efficacy not established in children younger than 10 yr of age.
Elderly
Use with caution. Max doses are generally not used because of age-related decreases in renal function.
Renal Function
Decreased renal function results in decreased renal Cl and prolongation of the metformin t 1/ 2 in patients with renal function impairment. Comedications that affect renal function result in significant hemodynamic changes or interfere with disposition of metformin (eg, cationic drugs eliminated by renal tubular secretion) should be used with caution.
Hepatic Function
Avoid using metformin in patients with clinical or laboratory evidence of hepatic disease.
GI symptoms
GI symptoms occurring after a patient is stabilized on metformin are unlikely to be drug related, but could be because of lactic acidosis or other serious disease.
Iodinated contrast media
Withhold metformin therapy at the time of or prior to the procedure; withhold for 48 h subsequent to the procedure and reinstate only after renal function has been reevaluated and found to be healthy.
Surgery
Hold therapy in patients undergoing surgical procedure until oral intake has resumed and renal function has been documented to be healthy.
Vitamin B 12
A decrease in vitamin B 12 levels to subnormal may occur. Supplementation may be necessary.
Overdosage
Symptoms
Lactic acidosis
Abdominal distress, increased somnolence, malaise, myalgia, respiratory distress
Hope this suffice :p