Invokana

canagliflozin · Tablet, Film Coated · Oral

Prescription (Rx) Sodium-Glucose Cotransporter 2 Inhibitor

Uses

(canagliflozin) is indicated: as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD). to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. INVOKANA is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus ( 1 ). To reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease ( 1 ). To reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria ( 1 ). Limitations of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus ( 1 ). Not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 ( 1 ). Limitations of Use INVOKANA is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.1) ] . INVOKANA is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 . INVOKANA is likely to be ineffective in this setting based upon its mechanism of action.

Dosage and administration

Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating ( 2.1 ). The recommended starting dosage in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus is 100 mg orally once daily, taken before the first meal of the day to improve glycemic control. The dosage can be increased to 300 mg once daily in patients tolerating 100 mg once daily who have an eGFR of 60 mL/min/1.73 m 2 or greater and require additional glycemic control ( 2.2 ). For all other indications in adults, the recommended dosage of INVOKANA is 100 mg orally once daily ( 2.2 ). Dosage adjustments for patients with renal impairment may be required ( 2.3 ). See full prescribing information for INVOKANA dosage modifications due to drug interactions ( 2.4 ). Withhold INVOKANA at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting ( 2.5 ). 2.1 Prior to Initiation of INVOKANA Assess renal function before initiating INVOKANA and as clinically indicated [see Dosage and Administration (2.3) and Warnings and Precautions (5.3) ] . In patients with volume depletion, correct this condition before initiating INVOKANA [see Warnings and Precautions (5.3) and Use in Specific Populations (8.5 , 8.6) ] . 2.2 Recommended Dosage and Administration Recommended Dosage for Glycemic Control in Adults and Pediatric Patients Aged 10 Years and Older The recommended starting dosage of INVOKANA is 100 mg orally once daily to improve glycemic control, taken before the first meal of the day. For additional glycemic control, the dosage of INVOKANA may be increased to the maximum recommended dosage of 300 mg once daily. Recommended Dosage for Other Indications in Adults The recommended dosage of INVOKANA is 100 mg orally once daily for the following indications in adults: to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD). to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. 2.3 Recommended Dosage in Adults and Pediatric Patients Aged 10 Years and Older with Renal Impairment Table 1 provides dosage recommendations for adults and pediatric patients aged 10 years and older with renal impairment, based on estimated glomerular filtration rate (eGFR). Table 1: Recommended Dosage in Adults and Pediatric Patients Aged 10 Years and Older with Renal Impairment Estimated Glomerular Filtration Rate [eGFR (mL/min/1.73 m 2 )] Recommended Dosage eGFR 30 to less than 60 The maximum recommended dosage is 100 mg orally once daily. eGFR less than 30 Initiation is not recommended Adult patients taking INVOKANA with albuminuria greater than 300 mg/day may continue INVOKANA 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for heart failure [see Indications and Usage (1) and Use in Specific Populations (8.6) ]. 2.4 Concomitant Use with UDP-Glucuronosyl transferase (UGT) Enzyme Inducers When co-administering INVOKANA with an inducer of UGT (e.g., rifampin, phenytoin, phenobarbital, ritonavir), increase the dosage of INVOKANA based on renal function [see Drug Interactions (7) ]: In patients with eGFR 60 mL/min/1.73 m 2 or greater, increase the dosage to 200 mg orally once daily in patients currently tolerating INVOKANA 100 mg once daily. The maximum recommended dosage of INVOKANA is 300 mg once daily. In patients with eGFR less than 60 mL/min/1.73 m 2 , increase to a maximum recommended dosage of 200 mg orally once daily in patients currently tolerating INVOKANA 100 mg once daily. 2.5 Temporary Interruption for Surgery Withhold INVOKANA at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume INVOKANA when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ]. 2.6 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to take the dose as soon as possible. Advise patients not to double up the next dose.

Dosage forms and strengths

100 mg tablets are yellow, capsule-shaped, tablets with "CFZ" on one side and "100" on the other side. INVOKANA 300 mg tablets are white, capsule-shaped, tablets with "CFZ" on one side and "300" on the other side. Tablets: 100 mg, 300 mg ( 3 )

Contraindications

4 CONTRAINDICATIONS INVOKANA is contraindicated in patients with a serious hypersensitivity reaction to INVOKANA, such as anaphylaxis or angioedema [see Warnings and Precautions (5.6) and Adverse Reactions (6.1 , 6.2) ] . Serious hypersensitivity reaction to INVOKANA ( 4 )

Warnings and precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis : Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue INVOKANA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting ( 5.1 ). Lower Limb Amputation : Monitor patients for infections or ulcers of lower limb and institute appropriate treatment ( 5.2 ). Volume Depletion : May result in acute kidney injury. Before initiating INVOKANA, assess and correct volume status in patients with renal impairment, elderly patients, or patients on loop diuretics. Monitor for signs and symptoms during therapy ( 5.3 ). Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections : Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated. Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis and if suspected, discontinue INVOKANA, and promptly institute appropriate medical and/or surgical intervention ( 5.4 ). Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues : Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with INVOKANA ( 5.5 ). Hypersensitivity Reactions : Discontinue INVOKANA and monitor until signs and symptoms resolve ( 5.6 ). Bone Fracture : Consider factors that contribute to fracture risk before initiating INVOKANA ( 5.7 ). 5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, INVOKANA significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose transporter 2 (SGLT2) inhibitors compared to patients who received placebo; this risk may be greater with higher doses of INVOKANA. INVOKANA is not indicated for glycemic control in patients with type 1 diabetes mellitus. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including INVOKANA. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuing INVOKANA [see Clinical Pharmacology (12.2) ]; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors. Consider ketone monitoring in patients at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue INVOKANA, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting INVOKANA. Withhold INVOKANA, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume INVOKANA when the patient is clinically stable and has resumed oral intake [see Dosage and Administration (2.5) ] . Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue INVOKANA and seek medical attention immediately if signs and symptoms occur. 5.2 Lower Limb Amputation An increased risk of lower limb amputations associated with INVOKANA use versus placebo was observed in CANVAS (5.9 vs 2.8 events per 1,000 patient-years) and CANVAS-R (7.5 vs 4.2 events per 1,000 patient-years), two randomized, placebo-controlled trials evaluating adult patients with type 2 diabetes mellitus who had either established cardiovascular disease or were at risk for cardiovascular disease [see Adverse Reactions (6.1) and Clinical Studies (14.3) ]. Amputations of the toe and midfoot (99 out of 140 patients with amputations receiving INVOKANA in the two trials) were the most frequent; however, amputations involving the leg, below and above the knee, were also observed (41 out of 140 patients with amputations receiving INVOKANA in the two trials). Some patients had multiple amputations, some involving both lower limbs. Lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy. Counsel patients about the importance of routine preventative foot care. Monitor patients receiving INVOKANA for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.

Side effects

The following important adverse reactions are described below and elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes and Other Ketoacidosis [see Warnings and Precautions (5.1) ] Lower Limb Amputation [see Warnings and Precautions (5.2) ] Volume Depletion [see Warnings and Precautions (5.3) ] Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.4) ] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.5) ] Hypersensitivity Reactions [see Warnings and Precautions (5.6) ] Bone Fracture [see Warnings and Precautions (5.7) ] Most common adverse reactions (5% or greater incidence): female genital mycotic infections, urinary tract infection, and increased urination ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. INVOKANA has been evaluated in clinical trials in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. Additionally, INVOKANA has been studied in clinical trials in adult patients with type 2 diabetes mellitus who also have heart failure or chronic kidney disease. The overall safety profile of INVOKANA was consistent across the studied indications. Clinical Trials in Adult Patients with Type 2 Diabetes Mellitus Pool of Placebo-Controlled Trials for Glycemic Control The data in Table 2 are derived from four 26-week placebo-controlled trials where INVOKANA was used as monotherapy in one trial and as add-on therapy in three trials. These data reflect exposure of 1,667 adult patients to INVOKANA and a mean duration of exposure to INVOKANA of 24 weeks. Patients received INVOKANA 100 mg (N=833), INVOKANA 300 mg (N=834) or placebo (N=646) once daily. The mean age of the population was 56 years and 2% were older than 75 years of age. Fifty percent (50%) of the population was male and 72% were White, 12% were Asian, and 5% were Black or African American. At baseline the population had diabetes for an average of 7.3 years, had a mean HbA 1C of 8.0% and 20% had established microvascular complications of diabetes. Baseline renal function was normal or mildly impaired (mean eGFR 88 mL/min/1.73 m 2 ). Table 2 shows common adverse reactions associated with the use of INVOKANA. These adverse reactions were not present at baseline, occurred more commonly on INVOKANA than on placebo, and occurred in at least 2% of patients treated with either INVOKANA 100 mg or INVOKANA 300 mg. Table 2: Adverse Reactions from Pool of Four 26–Week Placebo-Controlled Trials Reported in ≥ 2% of INVOKANA-Treated Adult Patients The four placebo-controlled trials included one monotherapy trial and three add-on combination trials with metformin HCl, metformin HCl and sulfonylurea, or metformin HCl and pioglitazone. Note: Percentages were weighted by studies. Trial weights were proportional to the harmonic mean of the three treatment sample sizes. Adverse Reaction Placebo N=646 INVOKANA 100 mg N=833 INVOKANA 300 mg N=834 Urinary tract infections Urinary tract infections include the following adverse reactions: Urinary tract infection, Cystitis, Kidney infection, and Urosepsis. 3.8% 5.9% 4.4% Increased urination Increased urination includes the following adverse reactions: Polyuria, Pollakiuria, Urine output increased, Micturition urgency, and Nocturia. 0.7% 5.1% 4.6% Thirst Thirst includes the following adverse reactions: Thirst, Dry mouth, and Polydipsia. 0.1% 2.8% 2.4% Constipation 0.9% 1.8% 2.4% Nausea 1.6% 2.1% 2.3% N=312 N=425 N=430 Female genital mycotic infections Female genital mycotic infections include the following adverse reactions: Vulvovaginal candidiasis, Vulvovaginal mycotic infection, Vulvovaginitis, Vaginal infection, Vulvitis, and Genital infection fungal. 2.8% 10.6% 11.6% Vulvovaginal pruritus 0.0% 1.6% 3.2% N=334 N=408 N=404 Male genital mycotic infections Male genital mycotic infections include the following adverse reactions: Balanitis or Balanoposthitis, Balanitis candida, and Genital infection fungal. 0.7% 4.2% 3.8% Abdominal pain was also more commonly reported in patients taking INVOKANA 100 mg (1.8%), 300 mg (1.7%) than in patients taking placebo (0.8%). Placebo-Controlled Trial in Diabetic Nephropathy The occurrence of adverse reactions for INVOKANA was evaluated in patients participating in CREDENCE, a trial in adult patients with type 2 diabetes mellitus and diabetic nephropathy with albuminuria > 300 mg/day [see Clinical Studies (14.4) ] . These data reflect exposure of 2,201 adult patients to INVOKANA and a mean duration of exposure to INVOKANA of 137 weeks. The rate of lower limb amputations associated with the use of INVOKANA 100 mg relative to placebo was 12.3 vs 11.2 events per 1,000 patient-years, respectively, with 2.6 years mean duration of follow-up. The incidence of hypotension was 2.8% and 1.5% on INVOKANA 100 mg and placebo, respectively. Pool of Placebo- and Active-Controlled Trials for Glycemic Control and Cardiovascular Outcomes in Adult Patients The occurrence of adverse reactions for INVOKANA was evaluated in adult patients participating in placebo- and active-controlled trials and in an integrated analysis of two cardiovascular trials, CANVAS and CANVAS-R. The types and frequency of common adverse reactions observed in the pool of eight clinical trials (which reflect an exposure of 6,177 adult patients to INVOKANA) were consistent with those listed in Table 2. Percentages were weighted by trials.

Drug interactions

Table 7: Clinically Significant Drug Interactions with INVOKANA UGT Enzyme Inducers Clinical Impact: UGT enzyme inducers decrease canagliflozin exposure which may reduce the effectiveness of INVOKANA. Intervention: For patients with eGFR 60 mL/min/1.73 m 2 or greater, if an inducer of UGTs is administered with INVOKANA, increase the dosage to 200 mg daily in patients currently tolerating INVOKANA 100 mg daily. The total daily dosage may be increased to 300 mg daily in patients currently tolerating INVOKANA 200 mg daily who require additional glycemic control. For patients with eGFR less than 60 mL/min/1.73 m 2 , if an inducer of UGTs is administered with INVOKANA, increase the dosage to 200 mg daily in patients currently tolerating INVOKANA 100 mg daily. Consider adding another antihyperglycemic agent in patients who require additional glycemic control [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ] . Examples: Rifampin, phenytoin, phenobarbital, ritonavir Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when INVOKANA is used concomitantly with insulin secretagogues (e.g., sulfonylurea) or insulin. Intervention: Concomitant use may require a lower dosage of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. Digoxin Clinical Impact: Canagliflozin increases digoxin exposure [see Clinical Pharmacology (12.3) ] . Intervention: Monitor patients taking INVOKANA with concomitant digoxin for a need to adjust the dosage of digoxin. Lithium Clinical Impact: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during INVOKANA initiation and dosage changes. Drug/Laboratory Test Interference Positive Urine Glucose Test Clinical Impact: SGLT2 inhibitors increase urinary glucose excretion which will lead to positive urine glucose tests. Intervention: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. Interference with 1,5-anhydroglucitol (1,5-AG) Assay Clinical Impact: Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Intervention: Monitoring glycemic control with 1,5-AG assay is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. See full prescribing information for information on drug interactions and interference of INVOKANA with laboratory tests ( 7 ).

Use in specific populations

Pregnancy : Advise females of the potential risk to a fetus especially during the second and third trimesters ( 8.1 ). Lactation : Not recommended when breastfeeding ( 8.2 ). Geriatrics : Higher incidence of adverse reactions related to reduced intravascular volume ( 8.5 ). Renal Impairment : Higher incidence of adverse reactions related to hypotension and renal function ( 8.6 ). Hepatic Impairment : Not recommended in patients with severe hepatic impairment ( 8.7 ). 8.1 Pregnancy Risk Summary Based on juvenile animal data showing adverse renal effects, INVOKANA is not recommended during the second and third trimesters of pregnancy. Limited data with INVOKANA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations ]. In juvenile animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on AUC. The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a HbA 1C >7 and has been reported to be as high as 20–25% in women with a HbA 1C >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Animal Data Canagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 4, 20, 65, or 100 mg/kg increased kidney weights and dose dependently increased the incidence and severity of renal pelvic and tubular dilatation at all doses tested. Exposure at the lowest dose was greater than or equal to 0.5-times the 300 mg clinical dose, based on AUC. These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development. The renal pelvic dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. In embryo-fetal development studies in rats and rabbits, canagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. No developmental toxicities independent of maternal toxicity were observed when canagliflozin was administered at doses up to 100 mg/kg in pregnant rats and 160 mg/kg in pregnant rabbits during embryonic organogenesis or during a study in which maternal rats were dosed from gestation day (GD) 6 through PND 21, yielding exposures up to approximately 19-times the 300 mg clinical dose, based on AUC. 8.2 Lactation Risk Summary There is no information regarding the presence of INVOKANA in human milk, the effects on the breastfed infant, or the effects on milk production. Canagliflozin is present in the milk of lactating rats [see Data ] . Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. Because of the potential for serious adverse reactions in a breastfed infant, advise women that use of INVOKANA is not recommended while breastfeeding. Data Animal Data Radiolabeled canagliflozin administered to lactating rats on day 13 post-partum was present at a milk/plasma ratio of 1.40, indicating that canagliflozin and its metabolites are transferred into milk at a concentration comparable to that in plasma. Juvenile rats directly exposed to canagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. 8.4 Pediatric Use The safety and effectiveness of INVOKANA as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients aged 10 years and older. Use of INVOKANA for this indication is supported by evidence from a 52-week double-blind, placebo-controlled trial in 171 pediatric patients aged 10 to 17 years with type 2 diabetes mellitus and in a pediatric pharmacokinetic study [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] . The safety profile of pediatric patients treated with INVOKANA was similar to that observed in adults with type 2 diabetes mellitus. The safety and effectiveness of INVOKANA for glycemic control in patients with type 2 diabetes have not been established in pediatric patients under 10 years of age. The safety and effectiveness of INVOKANA have not been established in pediatric patients to reduce the risk of: major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in patients with type 2 diabetes mellitus and established cardiovascular disease (CVD). end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in patients with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. 8.5 Geriatric Use In 13 clinical trials of INVOKANA, 2,294 patients 65 years and older, and 351 patients 75 years and older were exposed to INVOKANA [see Clinical Studies (14.1) ] .

Pregnancy

8.1 Pregnancy Risk Summary Based on juvenile animal data showing adverse renal effects, INVOKANA is not recommended during the second and third trimesters of pregnancy. Limited data with INVOKANA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations ]. In juvenile animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on AUC. The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a HbA 1C >7 and has been reported to be as high as 20–25% in women with a HbA 1C >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Animal Data Canagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 4, 20, 65, or 100 mg/kg increased kidney weights and dose dependently increased the incidence and severity of renal pelvic and tubular dilatation at all doses tested. Exposure at the lowest dose was greater than or equal to 0.5-times the 300 mg clinical dose, based on AUC. These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development. The renal pelvic dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. In embryo-fetal development studies in rats and rabbits, canagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. No developmental toxicities independent of maternal toxicity were observed when canagliflozin was administered at doses up to 100 mg/kg in pregnant rats and 160 mg/kg in pregnant rabbits during embryonic organogenesis or during a study in which maternal rats were dosed from gestation day (GD) 6 through PND 21, yielding exposures up to approximately 19-times the 300 mg clinical dose, based on AUC.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of INVOKANA as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients aged 10 years and older. Use of INVOKANA for this indication is supported by evidence from a 52-week double-blind, placebo-controlled trial in 171 pediatric patients aged 10 to 17 years with type 2 diabetes mellitus and in a pediatric pharmacokinetic study [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] . The safety profile of pediatric patients treated with INVOKANA was similar to that observed in adults with type 2 diabetes mellitus. The safety and effectiveness of INVOKANA for glycemic control in patients with type 2 diabetes have not been established in pediatric patients under 10 years of age. The safety and effectiveness of INVOKANA have not been established in pediatric patients to reduce the risk of: major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in patients with type 2 diabetes mellitus and established cardiovascular disease (CVD). end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in patients with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day.

Geriatric use

8.5 Geriatric Use In 13 clinical trials of INVOKANA, 2,294 patients 65 years and older, and 351 patients 75 years and older were exposed to INVOKANA [see Clinical Studies (14.1) ] . Patients 65 years and older had a higher incidence of adverse reactions related to reduced intravascular volume with INVOKANA (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300 mg daily dose, compared to younger patients; a more prominent increase in the incidence was seen in patients who were 75 years and older [see Dosage and Administration (2.1) and Adverse Reactions (6.1) ]. Smaller reductions in HbA 1C with INVOKANA relative to placebo were seen in older (65 years and older; -0.61% with INVOKANA 100 mg and -0.74% with INVOKANA 300 mg relative to placebo) compared to younger patients (-0.72% with INVOKANA 100 mg and -0.87% with INVOKANA 300 mg relative to placebo).

Overdosage

In the event of an overdose, contact the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. It is also reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive treatment as dictated by the patient's clinical status. Canagliflozin was negligibly removed during a 4-hour hemodialysis session. Canagliflozin is not expected to be dialyzable by peritoneal dialysis.

Description

11 DESCRIPTION INVOKANA ® (canagliflozin) contains canagliflozin, an inhibitor of SGLT2, the transporter responsible for reabsorbing the majority of glucose filtered by the kidney. Canagliflozin, the active ingredient of INVOKANA, is chemically known as (1 S )-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hemihydrate and its molecular formula and weight are C 24 H 25 FO 5 S∙1/2 H 2 O and 453.53, respectively. The structural formula for canagliflozin is: Canagliflozin is practically insoluble in aqueous media from pH 1.1 to 12.9. INVOKANA is supplied as film-coated tablets for oral administration, containing 102 and 306 mg of canagliflozin in each tablet strength, corresponding to 100 mg and 300 mg of canagliflozin (anhydrous), respectively. Inactive ingredients of the core tablet are croscarmellose sodium (E468), hydroxypropyl cellulose (E463), lactose anhydrous, magnesium stearate (E572), and microcrystalline cellulose (E460[i]). The magnesium stearate is vegetable-sourced. The tablets are finished with a commercially available film-coating consisting of the following excipients: iron oxide yellow (E172) (100 mg tablet only), macrogol/PEG3350 (E1521), polyvinyl alcohol (E1203) (partially hydrolyzed), talc (E553b), and titanium dioxide (E171). Chemical Structure

Mechanism of action

12.1 Mechanism of Action SGLT2, expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RT G ), and thereby increases urinary glucose excretion (UGE). Canagliflozin increases the delivery of sodium to the distal tubule by blocking SGLT2-dependent glucose and sodium reabsorption. This is believed to increase tubuloglomerular feedback and reduce intraglomerular pressure.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING INVOKANA ® (canagliflozin) tablets are available in the strengths and packages listed below: 100 mg tablets are yellow, capsule-shaped, film-coated tablets with "CFZ" on one side and "100" on the other side. NDC 50458-140-30 Bottle of 30 NDC 50458-140-90 Bottle of 90 NDC 50458-140-50 Bottle of 500 300 mg tablets are white, capsule-shaped, film-coated tablets with "CFZ" on one side and "300" on the other side. NDC 50458-141-30 Bottle of 30 NDC 50458-141-90 Bottle of 90 NDC 50458-141-50 Bottle of 500 Storage and Handling Keep out of reach of children. Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted between 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] .

Storage

Storage and Handling Keep out of reach of children. Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted between 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] .

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Inform patients that INVOKANA can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors. Educate all patients on precipitating factors (such as insulin dose reduction or missed doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis. Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue INVOKANA and seek medical attention immediately [see Warnings and Precautions (5.1) ]. Lower Limb Amputation Counsel patients about the importance of routine preventative foot care. Instruct patients to monitor for new pain or tenderness, sores or ulcers, or infections involving the leg or foot and to seek medical advice immediately if such signs or symptoms develop [see Warnings and Precautions (5.2) ] . Volume Depletion Inform patients that symptomatic hypotension may occur with INVOKANA and advise them to contact their doctor if they experience such symptoms [see Warnings and Precautions (5.3) ] . Inform patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake. Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections Counsel patients that genitourinary infections may occur when taking INVOKANA and may become serious. Educate patients on the symptoms and advise them to seek medical advice if symptoms occur. Specifically, advise patients to promptly seek medical attention if they develop pain or tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, along with a fever above 100.4 °F or malaise [see Warnings and Precautions (5.4) ] . Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Inform patients that hypoglycemia has been reported when INVOKANA is used with insulin or insulin secretagogues. Educate patients or caregivers on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.5) ] . Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions, such as urticaria, rash, anaphylaxis, and angioedema, have been reported with INVOKANA. Advise patients to report immediately any signs or symptoms suggesting allergic reaction, and to discontinue drug until they have consulted prescribing physicians [see Warnings and Precautions (5.6) ] . Bone Fracture Inform patients that bone fractures have been reported in adult patients taking INVOKANA. Provide them with information on factors that may contribute to fracture risk [see Warnings and Precautions (5.7) ] . Pregnancy Advise pregnant women, and females of reproductive potential of the potential risk to a fetus with treatment with INVOKANA [see Use in Specific Populations (8.1) ] . Instruct females of reproductive potential to report pregnancies to their physicians as soon as possible. Lactation Advise women that breastfeeding is not recommended during treatment with INVOKANA [see Use in Specific Populations (8.2) ]. Laboratory Tests Inform patients that due to its mechanism of action, patients taking INVOKANA will test positive for glucose in their urine [see Drug Interactions (7) ] . Missed Dose Instruct patients to take INVOKANA only as prescribed. If a dose is missed, it should be taken as soon as possible. Advise patients not to double their next dose [see Dosage and Administration (2.6) ] .

Label text from the FDA structured product label by Janssen Pharmaceuticals, Inc. (revised Jun 11, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Canagliflozin in 7 products

Invokana NDC products (7)

NDC	Strength & form	Labeler	Type
50090-4364	Canagliflozin 300 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
50090-5029	Canagliflozin 300 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
50090-5034	Canagliflozin 100 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
55154-1425	Canagliflozin 100 mg/1 Tablet, Film Coated	Cardinal Health 107, LLC	NDA
55154-1426	Canagliflozin 300 mg/1 Tablet, Film Coated	Cardinal Health 107, LLC	NDA
50458-140	Canagliflozin 100 mg/1 Tablet, Film Coated	Janssen Pharmaceuticals, Inc.	NDA
50458-141	Canagliflozin 300 mg/1 Tablet, Film Coated	Janssen Pharmaceuticals, Inc.	NDA

Frequently asked questions

What is Invokana used for?

What are the side effects of Invokana?

Who makes Invokana?

Invokana is listed by 3 labelers in the FDA NDC directory, including A-S Medication Solutions, Cardinal Health 107, LLC, Janssen Pharmaceuticals, Inc..