Drugs: metFORMIN hydrochloride

SAFETY ALERT!

metFORMIN hydrochloride
met-FOR-min

Glucophage, , Glucophage XR, , Glumetza, , Riomet

Therapeutic class: Antidiabetics

Pharmacologic class: Biguanides

Available Forms
Oral solution: 500 mg/5 mL
Tablets: 500 mg; 850 mg; 1,000 mg
Tablets (extended-release) : 500 mg; 750 mg; 1,000 mg

Indications & Dosages

Adjust-a-dose (for all indications): Obtain patient’s eGFR before starting drug. Contraindicated in patients
with eGFR below 30 mL/minute/1.73 m2. Starting drug in patients with eGFR between 30 and 45
mL/minute/1.73 m2 isn’t recommended. If eGFR falls below 45 mL/minute/1.73 m2 in patients taking drug,
assess benefits and risks of continuing treatment. Discontinue if eGFR falls below 30 mL/minute/1.73 m2.
Obtain eGFR at least annually in all patients taking drug. In patients at increased risk for development of renal
impairment such as the elderly, assess renal function more frequently.
For elderly or debilitated patients, use conservative initial and maintenance dosage because of potential
decrease in renal function. Adjust dosage carefully. Don’t adjust to maximum dosage.
Adjunct to diet to lower glucose level in patients with type 2 diabetes
Adults: If using immediate-release tablets or oral solution, initially 500 mg PO b.i.d. given with morning and
evening meals, or 850 mg PO once daily given with morning meal. Titrate immediate-release forms in
increments of 500 mg weekly or 850 mg every other week to maximum dose of 2,550 mg PO daily in
divided doses. If using extended-release formulation, start therapy at 500 mg PO once daily with the
evening meal. May increase dose as tolerated weekly (every 1 to 2 weeks for Glumetza) in increments of
500 mg daily, up to a maximum dose of 2,000 mg once daily. If higher doses are required, consider a trial
of 1,000 mg b.i.d. or using the regular-release formulation up to its maximum dose.
Children ages 10 and older: 500 mg PO b.i.d. using the immediate-release formulation only. Increase
dosage in increments of 500 mg weekly up to a maximum of 2,000 mg daily in divided doses.
Prevention of type 2 diabetes in patients with prediabetes (impaired glucose tolerance,
impaired fasting glucose, or an HbA1c of 5.7% to 6.4%), especially those with BMI of more
than 35 kg/m2, those younger than age 60, and women with prior history of gestational
diabetes or polycystic ovary syndrome
Adults: 850 mg immediate-release tablets PO once daily for 1 month; then increase to 850 mg b.i.d., unless
GI adverse effects warrant a longer titration period.

Administration
PO
Give drug with meals. Maximum doses may be better tolerated if total dose is divided and given in three
doses with meals (immediate-release tablets only).
Don’t cut or crush extended-release tablets.
Action
Decreases hepatic glucose production and intestinal absorption of glucose and improves insulin sensitivity
(increases peripheral glucose uptake and use).

Route Onset Peak Duration

PO (conventional) Unknown 2–3 hr Unknown
PO (extended-release) Unknown 4–8 hr Unknown
PO (solution) Unknown 21/2 hr Unknown
Half-life: About 4 to 9 hours.

Adverse Reactions
CNS: asthenia, headache, dizziness, chills, light-headedness.
CV: chest discomfort, palpitations.
EENT: rhinitis.
GI: diarrhea, nausea, vomiting, abdominal bloating, flatulence, anorexia, taste disorder, abnormal stools,
constipation, dyspepsia, weight loss.
Metabolic: hypoglycemia.
Musculoskeletal: myalgia, limb pain.
Respiratory: URI.
Skin: flushing, nail disorder, diaphoresis.
Other: accidental injury, infection.

Interactions
Drug-drug
Beta blockers: Hypoglycemia may be difficult to recognize in patients using beta blockers. Monitor patient
and blood glucose.
Calcium channel blockers, corticosteroids, estrogens, fosphenytoin, hormonal contraceptives, isoniazid,
nicotinic acid, phenothiazines, phenytoin, sympathomimetics, thiazide and other diuretics, thyroid drugs:
May produce hyperglycemia. Monitor patient’s glycemic control. Metformin dosage may need to be
increased.
Cationic drugs (amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine,
triamterene, trimethoprim, vancomycin): May compete for common renal tubular transport systems, which
may increase metformin level. Monitor glucose level.
Dolutegravir: Increases metformin exposure. Total daily dose of metformin shouldn’t exceed 1,000 mg.
Closely monitor response to metformin.
Nifedipine: May increase metformin level. Monitor patient closely. Metformin dosage may need to be
decreased.
QT interval–prolonging drugs (such as antiarrhythmics, chlorpromazine, citalopram, dolasetron): May have
an additive effect on QT-interval prolongation. Coadminister with caution.
Black Box Warning: Radiologic contrast dye: May cause acute renal failure or lactic acidosis. Withhold
metformin at the time of or prior to the procedure and 48 hours after the procedure. Restart drug only
after renal function is evaluated and found to be normal.
Drug-herb
Guar gum: May decrease hypoglycemic effect. Discourage use together.
Drug-lifestyle
Black Box Warning: Alcohol use: May increase drug effects and potentiate metformin’s effect on lactate
metabolism. Discourage use together.

Effects on Lab Test Results

 May decrease vitamin B12 and Hb levels.

Contraindications & Cautions

Contraindicated in patients hypersensitive to drug and in those with hepatic disease or metabolic acidosis
or lactic acidosis, including diabetic ketoacidosis with or without coma.
Not indicated for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis.
Contraindicated in patients with eGFR below 30 mL/minute/1.73 m2. Not recommended in patients with
eGFR between 30 and 45 mL/minute/1.73 m2.
Black Box Warning: Metformin-associated lactic acidosis has resulted in death, hypothermia,
hypotension, and resistant bradyarrhythmias. Onset is often subtle, accompanied only by nonspecific
symptoms, such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. It’s
characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of
ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally
above 5 mcg/mL. Metformin decreases liver uptake of lactate, increasing lactate blood levels, which may
increase the risk of lactic acidosis, especially in patients at risk.
Black Box Warning: Risk factors for metformin-associated lactic acidosis include renal impairment,
concomitant use of certain drugs, age 65 and older, having a radiologic study with contrast, surgery and
other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment.
Black Box Warning: Discontinue drug in the setting of acute CHF (particularly when accompanied by
hypoperfusion and hypoxemia), CV collapse (shock), acute MI, sepsis, and other conditions associated
with hypoxemia that have been associated with lactic acidosis and may cause prerenal azotemia.
Black Box Warning: Avoid using drug in patients with clinical or lab evidence of hepatic disease.
Administration of Glumetza with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower
doses of the insulin secretagogue or insulin to reduce risk of hypoglycemia.
Use cautiously in elderly, debilitated, or malnourished patients and in those with adrenal or pituitary
insufficiency because of increased risk of hypoglycemia.
Dialyzable drug: Yes.
Overdose Signs & Symptoms: Hypoglycemia, lactic acidosis.

Pregnancy-Lactation-Reproduction
Abnormal blood glucose levels during pregnancy may cause fetal harm. Most experts recommend that
insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Use
metformin during pregnancy only if clearly needed.
Drug appears in human milk. Patient should discontinue breastfeeding or discontinue drug, taking into
account importance of drug to the mother and risk of hypoglycemia in the infant. Consider insulin
therapy.

Nursing Considerations
Before therapy begins and at least annually thereafter, assess patient’s renal function. Assess more
frequently in patients at risk for renal impairment.
Black Box Warning: If metformin-associated lactic acidosis is suspected, immediately discontinue drug
and promptly institute general supportive measures in a hospital setting. Prompt hemodialysis is
recommended, which has often resulted in reversal of symptoms and recovery.
Black Box Warning: Consider more frequent monitoring of patients taking drugs that may increase the
risk of metformin-associated lactic acidosis, including drugs that impair renal function, result in
significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation.

When switching patients from chlorpropamide to metformin, take care during the first 2 weeks of
metformin therapy because the prolonged retention of chlorpropamide increases the risk of
hypoglycemia during this time.
Monitor patient’s glucose level regularly to evaluate effectiveness of therapy. Notify prescriber if glucose
 level increases despite therapy.
If patient hasn’t responded to 4 weeks of therapy with maximum dosage, an oral sulfonylurea can be
added while keeping metformin at maximum dosage. If patient still doesn’t respond after several months
of therapy with both drugs at maximum dosage, prescriber may stop both and start insulin therapy.
Monitor patient closely during times of increased stress, such as infection, fever, surgery, or trauma.
Insulin therapy may be needed in these situations.
Black Box Warning: Stop drug at the time of, or before, an iodinated contrast imaging procedure in
patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of hepatic
impairment, alcoholism, or HF; or in patients who will be administered intra-arterial iodinated contrast.
Reevaluate eGFR 48 hours after the imaging procedure; restart drug if renal function is stable.
Black Box Warning: Temporarily discontinue drug in patients with restricted food and fluid intake due to
surgery or other procedures because of increased risk of volume depletion, hypotension, and renal
impairment.
Monitor patient’s hematologic status for evidence of megaloblastic anemia. Patients with inadequate
vitamin B12 or calcium intake or absorption appear to be predisposed to developing subnormal vitamin
B12 level. These patients should have routine vitamin B12 level determinations every 2 to 3 years.
Look alike-sound alike: Don’t confuse Glucophage with Glucovance or Glucotrol; don’t confuse
metformin with metronidazole.

Patient Teaching
Instruct patient about nature of diabetes and importance of following therapeutic regimen, adhering to
specific diet, losing weight, getting exercise, following personal hygiene programs, and avoiding
infection. Explain how and when to monitor glucose level. Teach evidence of low and high glucose levels.
Explain emergency measures.
Black Box Warning: Instruct patient to stop drug and immediately notify prescriber about unexplained
hyperventilation, muscle pain, malaise, dizziness, light-headedness, unusual sleepiness, unexplained
stomach pain, feeling of coldness, slow or irregular HR, or other nonspecific symptoms of early lactic
acidosis.
Black Box Warning: Warn patient against excessive alcohol intake while taking drug.
Tell patient not to change drug dosage without prescriber’s knowledge. Encourage patient to report
abnormal glucose level test results.
Alert: Advise patient not to cut, crush, or chew extended-release tablets; instruct patient to swallow
them whole.
Tell patient that inactive ingredients may be eliminated in the stool as a soft mass resembling the
original tablet.
Advise patient not to take other drugs, including OTC drugs, without first checking with prescriber.
Instruct patient to carry medical identification at all times.
Tell patient to report all adverse reactions and that diarrhea, nausea, and upset stomach generally
subside over time.