identical [1%:<30 mL/minute/1.73 m 2 ); end-stage renal disease or patients on dialysis. Canadian labeling: Additional contraindications (not in US labeling): eGFR> <45 mL/minute/1.73 m 2 Dosing: Adult Note: If present, correct volume depletion prior to initiation. Diabetes mellitus, type 2: Oral: Initial: 100 mg once daily prior to first meal of the day; may increase to 300 mg once daily ( only in patients with eGFR 60 mL/minute/1.73 m 2 ) Dosing adjustment for concomitant therapy with UDP-glucuronosyl transferase (UGT) inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): Consider increasing the canagliflozin dose to 300 mg once daily in patients currently tolerating canagliflozin 100 mg once daily 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 antihyperglycemic therapy. Dosing: Geriatric Refer to adult dosing. 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 : Maximum dose: 100 mg once daily. If patient receiving concurrent UDP-glucuronosyl transferase (UGT) enzyme inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir) and eGFR 45 to> <60 mL/minute/1.73 m 2 at baseline, consider the use of another antidiabetic agent. eGFR 30 to> <45 mL/minute/1.73 m 2 : Use not recommended for initiation of therapy or when eGFR is persistently> <45 mL/minute/1.73 m 2 . eGFR> <30 mL/minute/1.73 m 2 : Use is contraindicated. End-stage renal disease (ESRD): Use is contraindicated. Hemodialysis: Use is contraindicated. Dosing: Hepatic Impairment Mild-to-moderate impairment (Child-Pugh class A, B): No dosage adjustment necessary. Severe impairment (Child-Pugh class C): Use not recommended (has not been studied). Administration May be administered with or without food. It is recommended to take before the first meal of the day (may reduce postprandial hyperglycemia via delayed intestinal glucose absorption). Dietary Considerations Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy. Storage Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F). Drug Interactions 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 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 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 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 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 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 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 Test Interactions Positive test for glucosuria; may interfere with 1,5-anhydroglucitol (1,5-AG) assay; use alternative methods to monitor glycemic control. Adverse Reactions >10%: Endocrine & metabolic: Increased serum potassium (>5.4 mEq/mL: 9% to 27%, 6.5 mEq/mL: 1% to 2%; dose-related; more risk in patients with moderate renal impairment) Genitourinary: Genitourinary infection (females: 11% to 12%; including vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginitis, vaginal infection, vulvitis; males: 4%; including balanitis/balanoposthitis, balanitis candida, fungal genital infection) 1% to 10%: Central nervous system: Falling (1% to 2%), fatigue (2%) Endocrine & metabolic: Hypoglycemia (4%; monotherapy), increased thirst (2% to 3%) Gastrointestinal: Abdominal pain (2%), constipation (2%), nausea (2%) Genitourinary: Urinary tract infection (6%), increased urine output (5%), vulvovaginal pruritus (2% to 3%) Hypersensitivity: Hypersensitivity reaction (4%) Neuromuscular & skeletal: Amputation (2% to 4%), weakness ( 1%) Renal: Renal insufficiency (2% to 4%; 18% to 23% in patients with baseline eGFR 30 to <50 mL/minute/1.73 m 2 ) Frequency not defined: Endocrine & metabolic: Hypermagnesemia, increased LDL cholesterol, increased serum cholesterol (non-HDL), increased serum phosphate Hematologic & oncologic: Increased hemoglobin Neuromuscular & skeletal: Bone fracture, decreased bone mineral density Renal: Impaired renal function> <1%, postmarketing, and/or case reports: Acute renal failure, anaphylaxis, angioedema, ketoacidosis, pancreatitis, pyelonephritis, skin photosensitivity, urosepsis ALERT: U.S. Boxed Warning 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 fractures: 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: 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. Hypersensitivity reactions: Hypersensitivity reactions (eg, angioedema, anaphylaxis) may occur; generally occurs within hours to days after therapy initiation. Discontinue therapy if hypersensitivity occurs and treat as appropriate. Hypotension: 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. Hyperkalemia: 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. 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) (Handelsman 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. Lipid abnormality: 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 two 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. 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; treatment with SGLT2 inhibitors increase the risk for urinary tract infections (UTI); monitor for signs and symptoms of UTI and treat as needed. Disease-related concerns: Hepatic impairment: Not recommended for use in severe hepatic impairment (has not been studied). Dose adjustment is not necessary in mild or moderate hepatic impairment. Renal impairment: Glycemic efficacy may be decreased in renal impairment. Assess renal function prior to initiation and periodically during treatment. Dosage adjustment recommended if eGFR> <60 mL/minute/1.73m 2 ; use is contraindicated in patients with an eGFR> <30 mL/minute/1.73 m 2 , end stage renal disease, or maintained on dialysis. 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: Elderly patients ( 65 years) may have an increased risk of symptoms related to intravascular volume depletion (eg, hypotension, orthostatic hypotension, dizziness, syncope, and dehydration) during therapy, especially with the 300 mg dose; elderly patients 75 years may experience a more pronounced risk. HbA 1c reductions may be less in patients> 65 years compared to younger patients. Other warnings/precautions: Appropriate use: Not for use in patients with diabetic ketoacidosis (DKA) or patients with type 1 diabetes mellitus (insulin-dependent, IDDM). Monitoring Parameters Blood glucose, HbA 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); renal function (baseline and periodically during treatment); volume status (eg, blood pressure, hematocrit, electrolytes); serum potassium (periodically after initiation in renal impairment and those predisposed to hyperkalemia); serum magnesium and phosphate; LDL-C; genital mycotic infections and UTI; hypersensitivity reactions; blood pressure; signs and symptoms of metabolic acidosis; lower limb and feet (sores, ulcers, infection) Pregnancy Considerations Based on animal data, adverse fetal effects on renal development may occur in humans following in utero exposure during the second and third trimesters. In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2017c; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA 1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2017c; Blumer 2013; Kitzmiller 2008). Agents other than canagliflozin are currently recommended to treat diabetes in pregnant women (ADA 2017c). 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?) Have patient report immediately to prescriber 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 acidosis (confusion, fast breathing, tachycardia, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy); signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain); signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain); signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating); vaginal yeast infection; penile yeast infection; pain, sores, ulcers, or signs of infection in the legs or feet; or bone 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 Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 220 Reviews Add your own review/rating Drug class: SGLT-2 inhibitors Consumer resources Canagliflozin Canagliflozin (Advanced Reading) Professional resources Canagliflozin (AHFS Monograph) Other brands: Invokana 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 Rating 220 User Reviews 6.3 /10 220 User Reviews 6.3 Rate it! Drug Class SGLT-2 inhibitors Related Drugs SGLT-2 inhibitors Invokana , Jardiance , Farxiga , empagliflozin , dapagliflozin 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 , Tresiba , Glucotrol , Bydureon , More...} } many differing types
pictures in most cases Canagliflozin out of the blue
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