Wednesday, October 16, 2013

Metformin

Today's med: Metformin 
(brand names: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet)

Drug Class: Antidiabetic Agent, Biguanide


Action: Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization)

Indications: Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) when hyperglycemia cannot be managed with diet and exercise alone.

Gestational diabetes mellitus (GDM); polycystic ovary syndrome (PCOS); prevention of type 2 diabetes mellitus
Contraindications: Hypersensitivity to metformin or any component of the formulation; renal disease or renal dysfunction (serum creatinine ≥1.5 mg/dL in males or ≥1.4 mg/dL in females) or abnormal creatinine clearance from any cause, including shock, acute myocardial infarction, or septicemia; acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis)
Note: Temporarily discontinue in patients undergoing radiologic studies in which intravascular iodinated contrast media are utilized.

Adverse Effects: 
>10%: Gastrointestinal: Diarrhea (IR tablet: 12% to 53%; ER tablet: 10% to 17%), nausea/vomiting (IR tablet: 7% to 26%; ER tablet: 7% to 9%), flatulence (12%)
Neuromuscular & skeletal: Weakness (9%)
1% to 10%:
Cardiovascular: Chest discomfort, flushing, palpitation
Central nervous system: Headache (6%), chills, dizziness, lightheadedness
Dermatologic: Rash
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Indigestion (7%), abdominal discomfort (6%), abdominal distention, abnormal stools, constipation, dyspepsia/ heartburn, taste disorder
Neuromuscular & skeletal: Myalgia
Respiratory: Dyspnea, upper respiratory tract infection
Miscellaneous: Decreased vitamin B12 levels (7%), increased diaphoresis, flu-like syndrome, nail disorder
<1% (Limited to important or life-threatening): Lactic acidosis, leukocytoclastic vasculitis, megaloblastic anemia, pneumonitis
Concerns related to adverse effects:
• Cardiovascular mortality: Administration of oral antidiabetic drugs has been reported to be associated with increased cardiovascular mortality; metformin does not appear to share this risk.
• Lactic acidosis: [U.S. Boxed Warning]: Lactic acidosis is a rare, but potentially severe consequence of therapy with metformin. Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis. Discontinue metformin in clinical situations predisposing to hypoxemia, including conditions such as cardiovascular collapse, respiratory failure, acute myocardial infarction, acute congestive heart failure, and septicemia. The risk of accumulation and lactic acidosis increases with the degree of impairment of renal function.
• Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may potentiate metformin's effect on lactate metabolism.
• Iodinated contrast: Therapy should be temporarily discontinued prior to or at the time of intravascular administration of iodinated contrast media (potential for acute alteration in renal function). Metformin should be withheld for 48 hours after the radiologic study and restarted only after renal function has been confirmed as normal.
• Surgical procedures: Therapy should be suspended for any surgical procedures (resume only after normal oral intake resumed and normal renal function is verified).

Standard DosingType 2 diabetes management: Note: Allow 1-2 weeks between dose titrations: Generally, clinically significant responses are not seen at doses <1500 mg daily; however, a lower recommended starting dose and gradual increased dosage is recommended to minimize gastrointestinal symptoms.
Immediate release tablet or solution: Oral:
Children 10-16 years: Initial: 500 mg twice daily; increases in daily dosage should be made in increments of 500 mg at weekly intervals, given in divided doses, up to a maximum of 2000 mg daily
Children ≥17 years and Adults: Initial: 500 mg twice daily or 850 mg once daily; titrate in increments of 500 mg weekly or 850 mg every other week; may also titrate from 500 mg twice a day to 850 mg twice a day after 2 weeks
If a dose >2000 mg daily is required, it may be better tolerated in 3 divided doses. Maximum recommended dose 2550 mg daily.
Extended release tablet: Oral: Note: If glycemic control is not achieved at maximum dose, may divide dose and administer twice daily.
Children ≥17 years and Adults:
Fortamet®: Initial: 500-1000 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2500 mg once daily
Glucophage® XR: Initial: 500 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2000 mg once daily
Adults: Glumetza®: Initial: 1000 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2000 mg once daily
Elderly: The initial and maintenance dosing should be conservative, due to the potential for decreased renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin. Do not use in patients ≥80 years of age unless normal renal function has been established.
Transfer from other antidiabetic agents: No transition period is generally necessary except when transferring from chlorpropamide. When transferring from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.
Concomitant metformin and oral sulfonylurea therapy: If patients have not responded to 4 weeks of the maximum dose of metformin monotherapy, consider a gradual addition of an oral sulfonylurea, even if prior primary or secondary failure to a sulfonylurea has occurred. Continue metformin at the maximum dose. If adequate response has not occurred following 3 months of metformin and sulfonylurea combination therapy, consider switching to insulin with or without metformin.
Failed sulfonylurea therapy: Patients with prior failure on glyburide may be treated by gradual addition of metformin. Initiate with glyburide 20 mg and metformin 500 mg daily. Metformin dosage may be increased by 500 mg/day at weekly intervals, up to a maximum metformin dose (dosage of glyburide maintained at 20 mg daily).
Concomitant metformin and insulin therapy: Initial: 500 mg metformin once daily, continue current insulin dose; increase by 500 mg metformin weekly until adequate glycemic control is achieved
Maximum daily dose: Immediate release and solution: 2550 mg metformin; Extended release: 2000-2500 mg (varies by product)
Decrease insulin dose 10% to 25% when FPG <120 mg/dL; monitor and make further adjustments as needed
Type 2 diabetes prevention (unlabeled use): Immediate release tablet or solution: Oral: Adults: Initial: 850 mg once daily; Target: 850 mg twice daily (Knowler, 2002)
Administer with a meal (to decrease GI upset).



A total of 669 drugs (4617 brand and generic names) are known to interact with metformin.
  • 14 major drug interactions (82 brand and generic names)
  • 598 moderate drug interactions (4179 brand and generic names)
  • 57 minor drug interactions (356 brand and generic names)
Show all medications in the database that may interact with metformin

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