RiteMED Metformin Extended-Release Tablet 1 g

Adjunct to diet & exercise to improve glycemic control in patients w/ type 2 DM. Monotherapy or in combination w/ other oral antidiabetic agents or insulin.

Adult ≥17 yr Initially 500 mg once daily w/ evening meal, may be increased in increments of 500 mg wkly up to max 2,000 mg once daily w/ evening meal. May consider 1,000 mg bid if glycemic control w/ 2,000 mg once daily remains unsatisfactory. Max dose: 2,000 mg/day. Patient w/ renal impairment eGFR 45-<60 mL/min/1.73 m² Initially 500 mg once daily up to max dose 1,000 mg/day in 2 divided doses, 30-45 mL/min/1.73 m² Continuation of existing therapy: May continue at reduced dose up to max dose 1,000 mg/day in 2 divided doses. Concomitant insulin therapy Continue current insulin dose upon initiation of metformin therapy. Initial oral dose of metformin HCl tab: 500 mg once daily, may be increased by 500 mg after approx 1 wk & by 500 mg every wk thereafter until adequate glycemic control is achieved. Max recommended daily dose w/ insulin: 2,000 mg.

Should be taken with food: Swallow whole. Do not chew/crush.

Hypersensitivity. Unstable &/or type 1 (insulin-dependent) DM. History of lactic acidosis irrespective of precipitating factors. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, w/ or w/o coma. Acute conditions w/ potential to alter renal function eg, dehydration due to persistent or severe diarrhea, recurrent vomiting, severe infection, diagnostic exam (eg, IV urography, angiography) that would involve use of iodinated contrast agents/media. Acute or chronic disease which may cause tissue hypoxia eg, cardiac or resp failure, recent MI, shock. Acute or chronic alcoholism. Severe renal impairment (eGFR <30 mL/min/1.73 m²). Severe liver disease.

Immediately discontinue & institute general supportive measures in a hospital setting if metformin-associated lactic acidosis is suspected; prompt hemodialysis is recommended. Discontinue metformin at the time of, or prior to, an intravascular iodinated contrast imaging procedure in patients w/ eGFR between 30 & 60 mL/min/1.73 m²; in patients w/ history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hr after imaging procedure, & restart metformin if renal function is stable. Temporarily discontinue treatment while patients have restricted food & fluid intake during surgical or other procedures. Promptly discontinue treatment when CV collapse (shock), acute MI, sepsis, & other conditions associated w/ hypoxemia occur. Temporarily discontinue metformin & administer insulin in periods of stress eg, fever, trauma, infection, or surgery; reinstitute metformin after acute episode is resolved. Obtain eGFR before initiating therapy & determine at least annually. Assess renal function more frequently (eg, every 3-6 mth) in patients at risk for development of renal impairment (eg, elderly). Not recommended to initiate therapy in patients w/ eGFR 30-45 mL/min/1.73 m². Assess benefits & risks of continuing treatment in patients whose eGFR falls <45 mL/min/1.73 m². Discontinue if eGFR later falls <30 mL/min/1.73 m². Avoid excessive alcohol intake on acute or chronic basis. Avoid use in patients w/ clinical or lab evidence of hepatic disease. Increased risk of metformin accumulation & lactic acidosis w/ degree of renal impairment. May increase risk of metformin-associated lactic acidosis w/ drugs that impair renal function, result in significant hemodynamic change, interfere w/ acid-base balance, or increase metformin accumulation. Hypoglycemia could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use w/ other glucose-lowering agents (eg, sulfonylureas & insulin) or ethanol. Reports of impairment of vit B₁₂ absorption; reductions in vit B₁₂ serum levels w/ long-term metformin treatment; perform periodic measurements of serum vit B₁₂ levels in patients on long-term treatment, particularly in patients w/ anemia or neuropathy. Induces reduction in TSH levels in patients w/ treated or untreated hypothyroidism; regularly monitor TSH levels in patients w/ hypothyroidism. Patients should be warned about driving a vehicle or operating machinery under conditions where risk of hypoglycemia is present. If clinically needed, use of metformin can be considered during pregnancy & in periconceptional phase as addition or alternative to insulin. Breast-feeding is not recommended. Elderly, debilitated or malnourished patients, & those w/ adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemia. Greater risk of serious adverse reactions in patients w/ reduced/impaired renal function especially in elderly. Safety & efficacy have not been established in childn.

Nausea, vomiting, diarrhea, abdominal pain & loss of appetite. Decreased serum vit B₁₂, hemolytic anemia; hyperglycemia, hypoglycemia (may occur when given concomitantly w/ sulfonylureas &/or alcohol), hypomagnesemia, lactic acidosis, decreased wt; agitation, dizziness, encephalopathy, headache, lightheadedness, peripheral neuropathy (in patients w/ vit B₁₂ deficiency); chest discomfort, palpitations; flushing, HTN; dyspnea, flu syndrome, pneumonitis w/ vasculitis, rhinitis, upper resp infection; abdominal discomfort (eg, bloating, cramps), abdominal distention, abnormal/loose stools, anorexia, constipation, dry mouth, dyspepsia/heartburn, epigastric discomfort, flatulence, gastric disorder & ulcer, GI disorder, indigestion, taste disturbance specifically metallic taste in the mouth; abnormal LFTs, autoimmune hepatitis, cholestasis, cholestatic, hepatocellular, & mixed hepatocellular liver injury, hepatitis, pancreatitis; dermatitis, erythema, nail disorder, photosensitivity, pruritus, rash, skin lesion, urticaria; asthenia, chills, musculoskeletal pain, myalgia; UTI; fatigue, increased sweating; increased blood lactic acid, decreased thyrotropin level (in patients w/ treated or untreated hypothyroidism).

Risk for lactic acidosis may be increased w/ carbonic anhydrase inhibitors (eg, topiramate, zonisamide, acetazolamide or dichlorphenamide); drugs that interfere w/ common renal tubular transport systems (eg, OCT2/MATE inhibitors). Efficacy may be reduced w/ OCT1 inhibitors (eg, verapamil). GI absorption & efficacy may be increased w/ OCT1 inducers (eg, rifampicin). Renal elimination may be decreased leading to increased plasma conc w/ OCT2 inhibitors (eg, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole). Efficacy & renal elimination may be altered w/ both OCT1 & OCT2 inhibitors (eg, crizotinib, olaparib). Hypoglycemia may occur w/ other antidiabetic agents eg, sulfonylureas, meglitinides, glitazones, or insulin. Thiazide diuretics may exacerbate DM & result in increased requirements of oral antidiabetic agents including metformin. Plasma conc & blood conc & AUC may be increased w/o significantly affecting renal clearance w/ furosemide. Increased absorption, C_max, AUC, & excretion in the urine w/ nifedipine. β-adrenergic blocking agents (eg, propranolol, nadolol) may impair glucose tolerance & mask the true frequency or severity of hypoglycemia, block hypoglycemia-induced tachycardia but not hypoglycemic sweating, delay the rate of recovery of blood glucose conc following drug-induced hypoglycemia, & impair peripheral circulation. ACE inhibitors (eg, captopril, enalapril) may reduce fasting blood glucose conc. Increased risk of hypoglycemia & lactic acidosis w/ alcohol. Increased ovulatory response w/ clomifene in premenopausal patients w/ PCOS. May affect pharmacokinetic properties of coumarin anticoagulants. May lead to renal failure, resulting in metformin accumulation w/ risk of lactic acidosis w/ intravascular administration of iodinated contrast media. Decreased C_max & blood AUC of glibenclamide. Hypoglycemic effect may be reduced w/ levothyroxine. Concomitant use w/ drugs that may cause hyperglycemia & may exacerbate loss of glycemic control including thiazides & other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, OCs, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers, & INH; drugs that may adversely affect renal function & increase risk of lactic acidosis including NSAIDs, selective COX-II inhibitors, ACE inhibitors, AIIA, aldosterone inhibitors, direct renin inhibitors, diuretics (particularly loop diuretics).

Antidiabetic Agents

A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.

Rx