Schedule H

Oral

• Tablets: 100 mg, 300 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 2 Diabetes Mellitus

As adjunct to diet and exercise to improve glycaemic control; may be used as monotherapy or in combination with metformin, sulfonylureas, DPP-4 inhibitors, thiazolidinediones, or insulin.

Parameter Recommendation

Starting dose 100 mg orally once daily, before the first meal of the day

Titration May increase to 300 mg once daily after 4–12 weeks if additional glycaemic control needed and eGFR ≥60 mL/min/1.73 m²

Usual maintenance dose 100–300 mg once daily

Maximum dose 300 mg once daily

Clinical Notes:

• Not recommended as first-line agent where metformin is appropriate

• 300 mg dose not recommended if eGFR <60 mL/min/1.73 m²

• Ensure adequate hydration before initiation

• Correct volume depletion before starting therapy

• Provides modest weight loss (2–4 kg) and blood pressure reduction (3–5 mmHg systolic)

1. Reduction of Cardiovascular Risk in Type 2 Diabetes with Established Cardiovascular Disease

Parameter Recommendation

Starting dose 100 mg orally once daily

Titration May increase to 300 mg once daily if tolerated and eGFR ≥60 mL/min/1.73 m²

Usual maintenance dose 100–300 mg once daily

Maximum dose 300 mg once daily

Clinical Notes:

• Cardiovascular benefit demonstrated in CANVAS Program trial

• Consider in T2DM patients with established atherosclerotic cardiovascular disease

• Benefits include reduction in major adverse cardiovascular events (MACE)

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Diabetic Kidney Disease with Albuminuria 100 mg once daily Long-term OFF-LABEL in India; Specialist only (Nephrology/Endocrinology); Evidence: CREDENCE trial demonstrated significant reduction in renal composite endpoints and cardiovascular events in T2DM with CKD

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for use in children and adolescents below 18 years in India.

• Safety and efficacy not established in paediatric population

• Indian regulatory sources (CDSCO) do not list paediatric indications

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable.

• No off-label paediatric indications supported by Indian practice

• Use in paediatric populations remains investigational

Not recommended below age 18 years; do not use outside registered clinical trials or tertiary specialist settings.

ESRD / Haemodialysis Contraindicated

Peritoneal Dialysis Contraindicated

Note: Monitor renal function before initiation and periodically during therapy. Temporary discontinuation recommended during conditions predisposing to acute kidney injury.

• Type 1 diabetes mellitus (risk of diabetic ketoacidosis)

• Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis

• Known hypersensitivity to canagliflozin or any excipient

• History of serious hypersensitivity reactions (angioedema, anaphylaxis) to SGLT2 inhibitors

• Diabetic ketoacidosis (current or history of recurrent episodes)

• Volume depletion — elderly, patients on diuretics, those with low systolic blood pressure; correct hypovolaemia before initiation

• Recurrent urinary tract infections or genital mycotic infections

• Risk of euglycaemic diabetic ketoacidosis — especially during acute illness, surgery, prolonged fasting, excessive alcohol intake, or reduced carbohydrate intake

• Peripheral vascular disease or diabetic neuropathy — increased risk of lower-limb amputation (particularly toes and midfoot)

• Elderly patients (≥75 years) — increased susceptibility to volume-related adverse effects

• Risk of Fournier's gangrene (necrotising fasciitis of perineum) — rare but serious

• Patients on loop diuretics or with reduced oral intake

• History of hypotension or syncope

Parameter Details

Risk Category Not recommended during pregnancy

Known Risks Animal studies demonstrate adverse effects on renal development during 2nd and 3rd trimesters; human data insufficient

Preferred Alternatives Insulin is preferred for glycaemic control in pregnancy; Metformin may be acceptable in selected cases (ICMR, FOGSI guidelines)

When May Be Used Only if potential benefit clearly outweighs fetal risk; requires endocrinologist and obstetrician supervision

Monitoring If inadvertently exposed, monitor fetal growth, amniotic fluid volume, and renal development; neonatal renal function at birth

Parameter Details

Compatibility Not recommended during breastfeeding

Drug Levels in Milk Unknown in humans; excreted in milk in animal studies

Potential Infant Risks Theoretical concerns regarding effects on renal development and glucose homeostasis

Preferred Alternatives Insulin or metformin (better characterised safety profile during lactation)

Infant Monitoring If inadvertent exposure, monitor infant for signs of dehydration, poor feeding, and adequate weight gain

Parameter Recommendation

Starting dose 100 mg once daily

Titration Slower titration recommended; assess volume status and renal function before dose escalation

Special Risks Higher susceptibility to volume depletion, hypotension, orthostatic symptoms, falls, acute kidney injury; increased risk of genitourinary infections

Age ≥75 years Limited experience; use with particular caution; 300 mg dose generally not recommended

Monitoring Renal function, blood pressure, volume status, and symptoms of dehydration at each visit

Interacting Drug Mechanism / Effect Recommendation

Loop Diuretics (furosemide, torsemide) Additive volume depletion; risk of hypotension and AKI Assess volume status; consider dose reduction of diuretic; monitor BP and renal function closely

Insulin Additive hypoglycaemia risk Consider reducing insulin dose by 10–20% when initiating canagliflozin

Sulfonylureas (glimepiride, gliclazide) Additive hypoglycaemia risk Consider reducing sulfonylurea dose when initiating canagliflozin

Rifampicin UGT enzyme induction; reduces canagliflozin AUC by ~50% May reduce glycaemic efficacy; consider alternative or increase canagliflozin to 300 mg if eGFR permits

Phenytoin / Phenobarbital / Ritonavir UGT inducers; may reduce canagliflozin levels Monitor glycaemic response; dose adjustment may be needed

Digoxin Canagliflozin increases digoxin levels by ~20% Monitor digoxin levels; watch for toxicity signs

Interacting Drug Mechanism / Effect Recommendation

Thiazide Diuretics Additive volume depletion and electrolyte disturbances Monitor blood pressure, renal function, and electrolytes

ACE Inhibitors / ARBs Combined hypotensive effect; additive risk of AKI in volume-depleted states Monitor BP and renal function; ensure adequate hydration

NSAIDs May exacerbate volume depletion and increase AKI risk Avoid prolonged use; monitor renal function

Lithium Increased lithium levels due to altered renal handling Monitor lithium levels closely

DPP-4 Inhibitors Additive glycaemic lowering Generally safe combination; monitor for hypoglycaemia

Metformin Additive glycaemic effect Commonly combined; standard monitoring

• Genital mycotic infections (vulvovaginal candidiasis, balanitis) — more common in women

• Urinary tract infections

• Increased urination (polyuria, pollakiuria)

• Thirst and dry mouth

• Hypotension, orthostatic hypotension

• Dizziness

• Constipation

• Nausea

• Hypoglycaemia (when combined with insulin or sulfonylureas)

• Mild increase in LDL cholesterol

• Increased haematocrit (due to haemoconcentration)

Adverse Effect Clinical Action

Diabetic Ketoacidosis (may be euglycaemic with near-normal blood glucose) Discontinue immediately; hospitalisation required; IV fluids and insulin therapy

Acute Kidney Injury Discontinue; supportive management; assess for precipitating factors (dehydration, NSAIDs, contrast agents)

Fournier's Gangrene (necrotising fasciitis of perineum) Discontinue immediately; urgent surgical consultation; IV antibiotics

Lower-Limb Amputation (toes, midfoot) Risk factor assessment mandatory before initiation; enhanced foot care; discontinue if ulcers develop

Severe Hypersensitivity Reactions (angioedema, anaphylaxis) Discontinue permanently; supportive care

Severe Hypotension Discontinue; volume resuscitation; identify contributing factors

Urosepsis / Pyelonephritis Discontinue temporarily; appropriate antibiotic therapy

1–2 weeks post-initiation Blood pressure, symptoms of volume depletion, renal function (especially in at-risk patients)

Every 3 months HbA1c, fasting/postprandial glucose, symptoms of genital/urinary infections

Every 6–12 months Renal function (eGFR), lipid profile, comprehensive foot examination

Ongoing Signs of ketoacidosis (nausea, vomiting, abdominal pain, fatigue, dyspnoea); genital hygiene; foot care

Sick Day Rules: Temporarily discontinue during acute illness, surgery, prolonged fasting, or dehydration to reduce ketoacidosis and AKI risk.

Monotherapy:

• Invokana (Johnson & Johnson / Janssen)

• Sulisent (Sun Pharma)

• Canakinra (Mankind)

• Prominad (Micro Labs)

• Canaglu (Glenmark)

Fixed-Dose Combinations with Metformin:

• Invokamet (Janssen)

• Sulisent-M

• Canakinra-M

• Not included in current NLEM; pricing not NPPA-controlled

• Jan Aushadhi generics may be available at lower cost in some centres

• Cost varies across brands and regions

• Initiate at 100 mg in all patients; reserve 300 mg for younger, well-hydrated patients with preserved renal function (eGFR ≥60) who need additional glycaemic control

• Always correct hypovolaemia and ensure adequate hydration before initiating therapy — reduces risk of hypotension and acute kidney injury

• Implement "sick day rules": temporarily stop during acute illness, surgery, prolonged fasting, or significant dehydration to prevent euglycaemic DKA

• Genital mycotic infections are common (especially in women and uncircumcised men) — counsel on genital hygiene; most cases respond to standard antifungal therapy

• Unique among SGLT2 inhibitors for documented amputation risk — perform thorough foot examination before initiation and regularly thereafter; avoid in patients with active foot ulcers or significant peripheral vascular disease

• Provides cardiovascular and potential renal benefits beyond glycaemic control — consider preferentially in T2DM with established cardiovascular disease or albuminuric kidney disease

• Not effective for glycaemic control when eGFR <45; however, cardiorenal benefits may persist at lower eGFR levels

Canagliflozin; SGLT2 inhibitor; type 2 diabetes; oral antidiabetic; cardiovascular benefit; renal protection; weight loss; genital infections; ketoacidosis risk; amputation risk; renal-dose adjustment; pregnancy-contraindicated; Schedule H

RxIndia v1.0 — 10 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022 — referenced for inclusion status

• API Textbook of Medicine — Diabetes Mellitus chapter

• ICMR Guidelines for Management of Type 2 Diabetes (2023)

• AIIMS Endocrinology Treatment Protocols

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• CANVAS Program Trial (cardiovascular outcomes)

• CREDENCE Trial (for off-label renal indication reference)