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Diabetes & metabolic

Canagliflozin (canagliflozin)

Canagliflozin is a sglt2 inhibitor (sodium-glucose co-transporter 2 inhibitor) from Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma, marketed originally as Invokana. This monograph covers approved indications, mechanism, dosing, side effects and the manufacturer landscape.

Overview

Canagliflozin is an oral sodium-glucose co-transporter 2 (SGLT2) inhibitor marketed by Janssen Pharmaceuticals (Johnson & Johnson) under licence from Mitsubishi Tanabe Pharma. It is sold as Invokana - 怡可安 in Chinese-language markets - with Invokamet and Invokamet XR as the metformin combinations. It is approved as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes, and carries two outcome-based indications added in the United States: reducing the risk of major adverse cardiovascular events (heart attack, stroke or cardiovascular death) in adults with type 2 diabetes and established cardiovascular disease (30 October 2018), and reducing the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death and hospitalisation for heart failure in adults with type 2 diabetes and diabetic kidney disease (30 September 2019). It is not for type 1 diabetes or diabetic ketoacidosis and has not been established in children under 18 years. Dosing starts at 100 mg once daily before the first meal and may be increased to 300 mg once daily only in patients who tolerate 100 mg, have an eGFR of at least 60 mL/min/1. 73 m2 and need further glucose lowering; an eGFR of 45 to under 60 limits the dose to 100 mg, and treatment should not be started below an eGFR of 45 mL/min/1. 73 m2. The 2017 boxed warning for lower limb amputation was removed by the FDA on 26 August 2020, but the amputation risk remains in the warnings section of the label. 65, and no local 300 mg product was found.

How it works

Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease.

Reversible inhibitor of subtype 2 sodium-glucose co-transporter (SGLT2) in the renal proximal tubule, lowering the renal threshold for glucose and increasing urinary glucose excretion with an accompanying osmotic diuresis and natriuresis. It also transiently reduces renal hyperfiltration (described as an initial eGFR dip followed by slower eGFR decline). The CANVAS programme and CREDENCE trial provide the cardiovascular and renal outcome evidence; oral bioavailability is about 65% and protein binding is approximately 99%, mainly to albumin.

Approved indications

  • As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
  • To reduce the risk of major adverse cardiovascular events (heart attack, stroke or cardiovascular death) in adults with type 2 diabetes mellitus and established cardiovascular disease (US approval 30 October 2018)
  • 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 kidney disease (US approval 30 September 2019)
  • Not for patients with type 1 diabetes mellitus or diabetic ketoacidosis; not established in children under 18 years

Dosage & administration

Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

Dose adjustment

Assess renal function before starting; do not initiate if eGFR is below 45 mL/min/1. 73 m2. In patients with eGFR 45 to less than 60 mL/min/1. 73 m2 the dose is limited to 100 mg once daily. Correct volume depletion first and assess volume status. Ongoing use may continue at 100 mg once daily as eGFR falls below 45 in patients already tolerating it, to reduce the risk of ESKD, worsening kidney function, CV death and heart failure hospitalization (per the 2019 diabetic kidney disease indication). No dose adjustment for hepatic impairment is specified for mild to moderate impairment.

Side effects

Female genital mycotic (yeast) infections · Urinary tract infection · Increased urination, thirst, osmotic diuresis · Volume depletion - hypotension, dizziness, especially in elderly, renal impairment or diuretic use · Necrotizing fasciitis of the perineum (Fournier's gangrene) - rare · Hyperkalemia · Hypoglycemia when combined with insulin or an insulin secretagogue

Serious reactions to watch for
  • Lower limb amputation - risk remains and is described in Warnings and Precautions after the 2020 removal of the boxed warning
  • Bone fracture
  • Diabetic ketoacidosis - may occur with normal blood glucose; assess if metabolic acidosis is suspected

Monitoring

  • Renal function (eGFR) before starting and periodically during therapy
  • Volume status and blood pressure; correct volume depletion before initiation
  • Foot care - monitor for new pain, tenderness, sores, ulcers and infections of the legs and feet
  • Bone health and fracture risk
  • Ketones and acid-base status if the patient is unwell, dehydrated, fasting or post-surgery
  • Serum potassium
  • Signs of urinary tract / genital infection
  • Signs of hypoglycemia if on insulin or a sulfonylurea

Generic and biosimilar landscape

Invokana (Janssen) is the reference product for canagliflozin 100 mg and 300 mg tablets. A proprietary boxed warning for lower limb amputation was added in 2017 and removed by the FDA on 26 August 2020; the amputation risk remains in Warnings and Precautions, so any generic leaflet must carry that warning. Canagliflozin generics in South Asia are locally approved products; verify on the local regulator's registered list (e. g. DGDA Bangladesh) before claiming interchangeability with Invokana. Note that many Bangladeshi listings show only the 100 mg strength.

Who makes it

ManufacturerCountryBrandStrengthNotes
Incepta Pharmaceuticals Ltd. Bangladesh Glicana 100 mg Listed on MedEx with the data
Drug International Ltd. Bangladesh Canarol 100 mg Listed on MedEx with the data
Square Pharmaceuticals PLC Bangladesh Canaglif 100 mg Lowest-the datad Bangladeshi brand found on MedEx
NIPRO JMI Pharma Ltd. Bangladesh Diacana 100 mg Listed on MedEx with the data
Steris Healthcare India 100 mg Sold through an international exporter listing; product identity not verified against CDSCO records - treat as unconfirmed
Cipla Ltd. India No Cipla canagliflozin brand confirmed from the sources reviewed in this pass - canagliflozin is a low-volume molecule in India because of the 2017-2020 amputation warning; verify

Availability in Southeast Asia

CountryStatusNotes
MalaysiaApproved and marketed (Invokana 100 mg and 300 mg)Manufacturer Janssen, distributor Zuellig Pharma, listed in MIMS Malaysia including pack sizes
BangladeshAvailable - originator Invokana plus four local 100 mg genericsMedEx lists Invokana and Canaglif/Canarol/Diacana/Glicana, all 100 mg; no 300 mg local product found
PhilippinesNot verified in this passCheck FDA Philippines registered products before publishing
IndonesiaNot verified in this passCheck BPOM registration database
VietnamNot verified in this passCheck DAV registration database
ThailandNot verified in this passCheck Thai FDA registration database

Frequently asked questions

What is the difference between Invokana and Farxiga or Jardiance?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

What is the recommended dose of canagliflozin for type 2 diabetes?

Standard dosing for canagliflozin: Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control. Dose adjustments: Assess renal function before starting; do not initiate if eGFR is below 45 mL/min/1. 73 m2. In patients with eGFR 45 to less than 60 mL/min/1. 73 m2 the dose is limited to 100 mg once daily. Correct volume depletion first and assess volume status. Ongoing use may continue at 100 mg once daily as eGFR falls below 45 in patients already tolerating it, to reduce the risk of ESKD, worsening kidney function, CV death and heart failure hospitalization (per the 2019 diabetic kidney disease indication). No dose adjustment for hepatic impairment is specified for mild to moderate impairment.

Does Invokana still have a boxed warning for amputation?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

Can canagliflozin be used in chronic kidney disease?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

Which patients should not take canagliflozin?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

Can canagliflozin cause bone fractures?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

Is there a generic version of Invokana?

Invokana (Janssen) is the reference product for canagliflozin 100 mg and 300 mg tablets. A proprietary boxed warning for lower limb amputation was added in 2017 and removed by the FDA on 26 August 2020; the amputation risk remains in Warnings and Precautions, so any generic leaflet must carry that warning. Canagliflozin generics in South Asia are locally approved products; verify on the local regulator's registered list (e. g. DGDA Bangladesh) before claiming interchangeability with Invokana. Note that many Bangladeshi listings show only the 100 mg strength. Manufacturers supplying canagliflozin generic versions include Cipla Ltd. , Drug International Ltd. , Incepta Pharmaceuticals Ltd. , NIPRO JMI Pharma Ltd. , Square Pharmaceuticals PLC, Steris Healthcare. Brands registered in Bangladesh include Canaglif, Canarol, Diacana, Glicana, Invokana.

Does canagliflozin lower the risk of heart attack or stroke?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

What is the safest dose of canagliflozin if my eGFR is between 45 and 60?

Standard dosing for canagliflozin: Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control. Dose adjustments: Assess renal function before starting; do not initiate if eGFR is below 45 mL/min/1. 73 m2. In patients with eGFR 45 to less than 60 mL/min/1. 73 m2 the dose is limited to 100 mg once daily. Correct volume depletion first and assess volume status. Ongoing use may continue at 100 mg once daily as eGFR falls below 45 in patients already tolerating it, to reduce the risk of ESKD, worsening kidney function, CV death and heart failure hospitalization (per the 2019 diabetic kidney disease indication). No dose adjustment for hepatic impairment is specified for mild to moderate impairment.

Can canagliflozin be taken with metformin?

Canagliflozin (SGLT2 inhibitor (sodium-glucose co-transporter 2 inhibitor), originally Invokana (怡可安 in Chinese-language markets); Invokamet and Invokamet XR are the metformin combinations by Janssen Pharmaceuticals (Johnson & Johnson), licensed from Mitsubishi Tanabe Pharma) Canagliflozin blocks the SGLT2 protein in the kidney, so less glucose is taken back into the bloodstream and more is passed out in the urine, lowering blood sugar without relying on insulin. It also increases salt and water loss, which lowers the workload on the heart and slows the loss of kidney function in people with diabetic kidney disease. Start 100 mg orally once daily, taken before the first meal of the day. The dose may be increased to 300 mg once daily in patients who tolerate 100 mg, have an eGFR of 60 mL/min/1. 73 m2 or greater, and need additional glycemic control.

Sources

  1. https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin
  2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204042s011lbl.pdf
  3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204042s036lbl.pdf
  4. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/INVOKANA-pi.pdf
  5. https://www.ema.europa.eu/en/documents/product-information/invokana-epar-product-information_en.pdf
  6. https://www.jnjmedicalconnect.com/products/invokana/medical-content/pharmacokinetics-of-invokana
  7. https://www.invokanahcp.com/medical-information-center-professional-product-sites
  8. https://www.drugs.com/history/invokana.html
  9. https://medex.com.bd/generics/245/canagliflozin-hemihydrate/brand-names
  10. https://www.mims.com/malaysia/drug/info/invokana/dosage
  11. https://www.mims.com/malaysia/company/info/janssen
  12. https://www.truemeds.in/medicine/invokana-100-mg-tablet-10-tm-tacr1-019647
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