nice [45:<60 mL/minute) which may result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia; unstable and/or insulin-dependent (type I) diabetes mellitus; acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma; history of lactic acidosis (regardless of precipitating factors); excessive alcohol intake (acute or chronic); severe hepatic dysfunction or clinical or laboratory evidence of hepatic disease; cardiovascular collapse and disease states associated with hypoxemia including cardiorespiratory insufficiency, which are often associated with hyperlactacidemia; stress conditions (eg, severe infection, trauma, surgery and postoperative recovery phase); severe dehydration; pregnancy; breast-feeding; period of time around administration of iodinated contrast materials Dosing: Adult Note: If present, correct volume depletion prior to initiation. Diabetes mellitus, type 2: Oral: Initial: Individualize dose based on patient's current antidiabetic regimen. May gradually increase dose based on effectiveness and tolerability. Patients naïve to canagliflozin or metformin : Initial: Canagliflozin 100 mg/metformin 1,000 mg per day in 2 divided doses (immediate release) or once daily (ER). Patients on metformin : Initial: Canagliflozin 100 mg/day plus similar total daily dose of metformin in 2 divided doses (immediate release) or once daily (ER). Patients taking an evening dose of metformin ER should skip their last dose before starting canagliflozin/metformin ER the following morning. Patients on canagliflozin : Initial: Metformin 1,000 mg/day plus same total daily dose of canagliflozin in 2 divided doses (immediate release) or once daily (ER). Patients switching from combination therapy of canagliflozin and metformin as separate tablets: Administer same total daily dose of canagliflozin plus similar total daily dose of metformin in 2 divided doses (immediate release) or once daily (ER). Patients switching from immediate release to ER : Use current total daily dose. Maximum: Canagliflozin 300 mg/metformin 2,000 mg per day Dosing adjustment for concomitant therapy with UDP-glucuronosyl transferase (UGT) inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): Consider increasing the dose of canagliflozin/metformin to canagliflozin 300 mg/day in patients currently tolerating canagliflozin 100 mg/day who have eGFR 60 mL/minute/1.73 m 2 and require additional glycemic control. If patient is receiving concurrent UGT enzyme inducers and has eGFR 45 to> <60 mL/minute/1.73 m 2 , consider alternate therapy. Dosing: Geriatric Refer to adult dosing. The initial and maintenance dosing should be conservative, due to the potential for decreased renal function (monitor). Dosing: Renal Impairment eGFR 60 mL/minute/1.73 m 2 : No dosage adjustment necessary. eGFR 45 to> <60 mL/minute/1.73 m 2 : Limit the dose of canagliflozin/metformin to canagliflozin 100 mg/day. If patient is receiving concurrent UGT enzyme inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir) and has eGFR 45 to> <60 mL/minute/1.73 m 2 , consider the use of another antidiabetic agent. eGFR> <45 mL/minute/1.73 m 2 : Use is contraindicated. End stage renal disease (ESRD) or hemodialysis: Use is contraindicated. Dosing: Hepatic Impairment The manufacturer recommends avoiding metformin because liver disease is considered a risk factor for the development of lactic acidosis during metformin therapy. However, continued use of metformin in patients with diabetes with liver dysfunction, including cirrhosis, has been used successfully and may be associated with a survival benefit in carefully selected patients; use cautiously in patients at risk for lactic acidosis (eg, renal impairment, alcohol use) (Brackett 2010; Zhang 2014). For canagliflozin, no dosage adjustment is necessary in patients with mild or moderate hepatic impairment according to the manufacturer's labeling; use of canagliflozin is not recommended in severe hepatic impairment. Administration Oral: Immediate release: Administer twice daily with meals. Extended release: Administer once daily with morning meal. Swallow tablets whole; do not crush, cut, or chew. Dietary Considerations Should be taken with meals. Avoid ethanol. Dietary modification based on ADA recommendations is a part of therapy. Storage Store between 20 C and 25 C (68 F and 77 F); excursions are permitted to 15 C to 30 C (59 F to 86 F). Store in original container. Drug Interactions Abemaciclib: May increase the serum concentration of MetFORMIN. Monitor therapy Alcohol (Ethyl): May enhance the adverse/toxic effect of MetFORMIN. Specifically, alcohol may potentiate the risk of lactic acidosis Avoid combination Aliskiren: Canagliflozin may enhance the hyperkalemic effect of Aliskiren. Canagliflozin may enhance the hypotensive effect of Aliskiren. Monitor therapy Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy Angiotensin II Receptor Blockers: Canagliflozin may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Canagliflozin may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Monitor therapy Angiotensin-Converting Enzyme Inhibitors: Canagliflozin may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Canagliflozin may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy CarBAMazepine: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR> 60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy Cephalexin: May increase the serum concentration of MetFORMIN. Monitor therapy Cimetidine: May increase the serum concentration of MetFORMIN. Management: Consider alternatives to cimetidine in patients receiving metformin due to a potential for increased metformin concentrations and toxicity (including lactic acidosis). Consider therapy modification Dalfampridine: MetFORMIN may increase the serum concentration of Dalfampridine. Dalfampridine may increase the serum concentration of MetFORMIN. Monitor therapy Dofetilide: MetFORMIN may increase the serum concentration of Dofetilide. Monitor therapy Dolutegravir: May increase the serum concentration of MetFORMIN. Management: Limit the daily metformin dose to 1,000 mg when used together with dolutegravir. Metformin dose adjustments may also be needed upon discontinuation of dolutegravir. Monitor patient response to metformin closely. Consider therapy modification Efavirenz: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Eplerenone: Canagliflozin may enhance the hyperkalemic effect of Eplerenone. Canagliflozin may enhance the hypotensive effect of Eplerenone. Monitor therapy Fosphenytoin: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Glycopyrrolate (Systemic): May increase the serum concentration of MetFORMIN. Monitor therapy Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy Heparin: May enhance the hyperkalemic effect of Canagliflozin. Monitor therapy Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Canagliflozin. Monitor therapy Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy Insulins: Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification Iodinated Contrast Agents: May enhance the adverse/toxic effect of MetFORMIN. Renal dysfunction that may be caused by iodinated contrast agents may lead to metformin-associated lactic acidosis. Management: Management advice varies. Refer to the full drug interaction monograph content for details. Exceptions: Diatrizoate Meglumine; Diatrizoate Sodium; Ethiodized Oil. Consider therapy modification Isavuconazonium Sulfate: May increase the serum concentration of MetFORMIN. Monitor therapy LamoTRIgine: May increase the serum concentration of MetFORMIN. Management: The lamotrigine Canadian product monograph states that coadministration of these drugs is not recommended. Monitor therapy Loop Diuretics: Canagliflozin may enhance the hypotensive effect of Loop Diuretics. Management: If canagliflozin is combined with a loop diuretic, monitor for symptoms of intravascular volume depletion and hypotension. Canadian product labeling recommends avoiding the combination of canagliflozin and loop diuretics. Consider therapy modification Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy Ombitasvir, Paritaprevir, and Ritonavir: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. Monitor therapy Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. Monitor therapy Ondansetron: May increase the serum concentration of MetFORMIN. Monitor therapy Patiromer: May decrease the serum concentration of MetFORMIN. Management: Administer metformin at least 3 hours before or 3 hours after patiromer. Consider therapy modification Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy PHENobarbital: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Phenytoin: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Potassium-Sparing Diuretics: Canagliflozin may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Canagliflozin may enhance the hypotensive effect of Potassium-Sparing Diuretics. Monitor therapy Primidone: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy Ranolazine: May increase the serum concentration of MetFORMIN. Management: Limit the metformin dose to a maximum of 1700 mg/day when used together with ranolazine 1000 mg twice daily. Consider therapy modification RifAMPin: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Ritonavir: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy St John's Wort: May decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification Sulfonylureas: Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy Topiramate: May enhance the adverse/toxic effect of MetFORMIN. Monitor therapy Trimethoprim: May increase the serum concentration of MetFORMIN. Monitor therapy Trospium: MetFORMIN may decrease the serum concentration of Trospium. Monitor therapy Vandetanib: May increase the serum concentration of MetFORMIN. Monitor therapy Verapamil: May diminish the therapeutic effect of MetFORMIN. Monitor therapy Adverse Reactions See individual agents. ALERT: U.S. Boxed Warning Lactic acidosis: Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate:pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information. If metformin-associated lactic acidosis is suspected, immediately discontinue canagliflozin/metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Lower limb amputation: An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin use was observed in CANVAS and CANVAS-R, 2 large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD. Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs. Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Monitor patients receiving canagliflozin for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur. Warnings/Precautions Concerns related to adverse effects: Bone fracture: Increased incidence of bone fractures may occur as early as 12 weeks after treatment initiation. Consider patient's risk of fracture prior to initiation. Genital mycotic infections: Canagliflozin may increase the risk of genital mycotic infections (eg, vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis). Patients with a history of these infections or uncircumcised males are at greater risk. Hyperkalemia: Canagliflozin may cause hyperkalemia. Patients predisposed to hyperkalemia (including patients with renal impairment or taking potassium-sparing diuretics, ACE inhibitors, and ARBs) are more likely to develop hyperkalemia; monitor serum potassium after initiation in those who are predisposed. Hypersensitivity reactions: Hypersensitivity reactions (eg, angioedema, anaphylaxis), some serious, generally occurs within hours to days after therapy initiation. Discontinue therapy if hypersensitivity occurs and treat as appropriate. Hypotension: Canagliflozin may cause symptomatic hypotension due to intravascular volume depletion especially in patients with renal impairment (ie, eGFR <60 mL/minute/1.73 m 2 ), elderly, patients on other antihypertensives (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]), or those with low systolic blood pressure. Assess volume status prior to initiation in patients at risk of hypotension and correct if depleted; monitor for signs and symptoms of hypotension after initiation. Ketoacidosis: Cases of ketoacidosis, a serious and life-threatening condition resulting in urgent hospitalization, have been reported in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose cotransporter-2 (SGLT2) inhibitors; in some cases, patients have presented with normal or only modestly elevated blood glucose (> <250 mg/dL) (Bobart 2016; FDA 2015; Handelsman 2016). Before initiating treatment, consider risk factors that may predispose to ketoacidosis (eg, pancreatic insulin deficiency, dose decreases or discontinuation of insulin, caloric restriction, alcohol abuse, extensive exercise, MI, stroke, severe infection, surgery, any other extreme stress event) (Handlelsman 2016). The American Association of Clinical Endocrinologists and American College of Endocrinology recommend considering withholding of SGLT2 inhibitors for at least 24 hours prior to events that may precipitate diabetic ketoacidosis (Handelsman 2016), while others have suggested withholding for 3 to 5 days (Bobart 2016). Patients presenting with nausea/vomiting, abdominal pain, generalized malaise, and/or shortness of breath should be assessed immediately for ketoacidosis; if indicated, consider interruption or discontinuation of therapy. Lactic acidosis: [US Boxed Warning]: Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset is often subtle, accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain); elevated blood lactate levels (> 5 mmol/L); anion gap acidosis (without evidence of ketonuria or ketonemia); increased lactate:pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Risk factors for lactic acidosis include patients with renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), 65 years, having a radiologic study with contrast, surgery and other procedures, hypoxic states (eg, acute heart failure), excessive alcohol intake, and hepatic impairment. Discontinue immediately if lactic acidosis is suspected; prompt hemodialysis is recommended. Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis. Discontinue use in patients with conditions associated with dehydration, hypoperfusion, sepsis, or hypoxemia. Temporarily discontinue therapy in patients with restricted food and fluid intake. The risk of accumulation and lactic acidosis increases with the degree of impairment of renal function. Lipid abnormality: Canagliflozin may cause dose-related LDL-cholesterol (C) elevation; monitor LDL-C and treat as needed. Lower limb amputation: [US Boxed Warning]: An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin use was observed in 2 large, randomized, placebo-controlled trials evaluating patients with type 2 diabetes who had either established cardiovascular disease or were at risk for cardiovascular disease. Amputations involved the toe, midfoot, or less frequently the leg (above or below the knee). Lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating factors. Prior to initiation consider risk factors for amputation including prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients about the importance of preventative foot care. Discontinue therapy if any of the following occur: signs and symptoms of new infection (including osteomyelitis), new pain or tenderness, or sores/ulcers involving the lower limbs. Renal effects: Acute kidney injury has been reported with canagliflozin. Prior to initiation, consider risk factors for acute kidney injury (eg, hypovolemia, chronic renal insufficiency, heart failure, use of concomitant medications [eg, diuretics, ACE inhibitors, angiotensin receptor blockers, or NSAIDs]). Temporarily discontinue use with reduced oral intake or fluid losses; discontinue use if acute kidney injury occurs. Additional abnormalities in renal function (decreased eGFR, increased serum creatinine) and adverse effects related to renal function may occur. Assess renal function prior to initiation and periodically during treatment. Urinary tract infection: Serious urinary infections including urosepsis and pyelonephritis requiring hospitalization have been reported with canagliflozin; treatment increases the risk for urinary tract infections (UTI); monitor for signs and symptoms of UTI and treat as needed. Vitamin B 12 concentrations: Long-term metformin use is associated with vitamin B 12 deficiency; monitor vitamin B 12 serum concentrations periodically with long-term therapy. Monitoring of B 12 serum concentrations should be considered in all patients receiving metformin and in particular those with peripheral neuropathy or anemia (ADA 2017c). Disease-related concerns: Heart failure: Use caution in patients with congestive heart failure requiring pharmacologic management, particularly in patients with unstable or acute heart failure; risk of lactic acidosis may be increased secondary to hypoperfusion. In addition, discontinue use in patients who develop hypoxic states (eg, cardiovascular collapse [shock], acute heart failure, acute myocardial infarction, other conditions with hypoxemia) due to risk of lactic acidosis. In a scientific statement from the AHA, metformin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). Hepatic impairment: Use metformin with caution in patients with impaired liver function due to potential for lactic acidosis. Renal impairment: Metformin is substantially excreted by the kidney; assess renal function prior to initiation of therapy and periodically thereafter using estimated glomerular filtration rate (eGFR); the risk of metformin accumulation and lactic acidosis increase with degree of renal impairment. Dosage adjustment recommended if eGFR <60 mL/minute/1.73m 2 ; use of combination product is contraindicated in patients with an eGFR> <45 mL/minute/1.73 m 2 , end stage renal disease, or maintained on dialysis. Use of concomitant medications that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition. Metformin should be withheld in patients with dehydration and/or prerenal azotemia. Glycemic efficacy of canagliflozin may be decreased in renal impairment. Concurrent drug therapy issues: Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations: Elderly: Use with caution; risk of metformin associated lactic acidosis increases with age. Elderly patients ( 65 years) may have an increased risk of symptoms related to intravascular volume depletion (eg, hypotension, orthostatic hypotension, postural dizziness, syncope, and dehydration) during canagliflozin therapy. Other warnings/precautions: Appropriate use: Not for use in patients with diabetic ketoacidosis (DKA) or patients with type 1 diabetes mellitus (insulin-dependent, IDDM). Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may potentiate metformin's effect on lactate metabolism. Iodinated contrast: Temporarily discontinue metformin at the time of or before iodinated contrast imaging procedures in patients with an eGFR 45 to 60 mL/minute/1.73 m 2 ; or with a history of hepatic disease, alcoholism, or heart failure; or in patients who will receive intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after imaging procedure; restart if renal function is stable. Alternatively, the American College of Radiology (ACR) guidelines recommend that metformin may be used prior to or following administration of iodinated contrast media in patients with no evidence of acute kidney injury (AKI) and with an eGFR 30 mL/minute/1.73 m 2 ; ACR guidelines recommend temporary discontinuation of metformin in patients with known AKI or severe chronic kidney disease ([stage IV or V [ie, eGFR> <30 mL/minute/1.73 m 2 ]) or who are undergoing arterial catheter studies (ACR 2015). Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy. Stress-related states: It may be necessary to discontinue metformin and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery). Surgical procedures: Metformin should be withheld 24 hours before surgery (all other oral hypoglycemic agents should be withheld the morning of surgery or procedure) (ADA 2017d). Monitoring Parameters Urine (glucose and ketones), fasting blood glucose, hemoglobin A 1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2017a]); serum glucose, fructosamine; hematologic parameters (eg, hemoglobin/hematocrit and red blood cell indices); renal function (baseline then annually or when clinically indicated); volume status (eg blood pressure, hematocrit, electrolytes); hematologic parameters (annually); vitamin B 12 (periodically with long-term treatment) and folate (if megaloblastic anemia is suspected); blood pressure; LDL-C; serum potassium; signs and symptoms of genital mycotic infections and UTI; signs and symptoms of metabolic acidosis; lower limb and feet (sores, ulcers, infection). Pregnancy Considerations Animal reproduction studies have not been conducted with this combination. Metformin crosses the placenta. The manufacturer recommends that alternative therapies be used in pregnant women, especially during the second and third trimesters. Refer to individual agents. Patient Education Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) Patient may experience polyuria, diarrhea, flatulence, nausea, vomiting, loss of strength and energy, or headache. Have patient report immediately to prescriber signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps); signs of acidosis (confusion, fast breathing, tachycardia, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy); signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness or passing out, tachycardia, increased thirst, seizures, loss of strength and energy, lack of appetite, urinary retention or change in the amount of urine passed, dry mouth, dry eyes, or nausea or vomiting); signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain); signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain); signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating); pain, sores, ulcers, or signs of infection in the legs or feet; vaginal yeast infection; penile yeast infection; bone pain; or severe abdominal pain (HCAHPS). Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients. Next Interactions Print this page Add to My Med List More about canagliflozin/metformin Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: antidiabetic combinations Consumer resources Canagliflozin and metformin ... +3 more Professional resources Other brands: Invokamet , Invokamet XR Related treatment guides Diabetes, Type 2> ]} Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Canagliflozin / metformin Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first! Drug Class Antidiabetic combinations Related Drugs antidiabetic combinations Janumet , Kombiglyze XR , Jentadueto , Invokamet , Glucovance , ActoPlus Met Diabetes, Type 2 metformin , insulin aspart , glipizide , glimepiride , Januvia , pioglitazone , Victoza , Actos , Tradjenta , Glucophage , glyburide , Janumet , Invokana , Amaryl , Welchol , Onglyza , sitagliptin , Trulicity , Jardiance , Lantus , Farxiga , Levemir , Tres make money working from home
an inexpensive Canagliflozin and Metformin at risk of
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