Adult: As monotherapy or in combination with other antidiabetic agents: As an adjunct to diet and exercise: To reduce the risk of major CV adverse events in patients with established CV disease or reduce the risk of end-stage kidney disease, doubling of serum creatinine and CV death in patients with diabetic nephropathy with albuminuria (>300 mg/day or >33.9 mg/mmol): Initially, 100 mg once daily; may increase dose to 300 mg once daily according to patient's response and tolerability. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
What are the brands available for Canagliflozin in Malaysia?
Patients taking concurrent UGT enzyme inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, efavirenz, ritonavir) and with eGFR ≥60 mL/min/1.73 m2: May increase dose to 300 mg once daily.
Renal Impairment
eGFR <30 mL/min/1.73 m2: In patients with urinary albumin/creatinine ratio >300 mg/g: Not recommended to initiate therapy or may continue 100 mg daily in patients already taking canagliflozin. eGFR 30-<60 mL/min/1.73 m2: 100 mg once daily.
Hepatic Impairment
Severe: Not recommended.
Administration
Canagliflozin May be taken with or without food.
Special Precautions
Patient with CV disease, history of hypotension; intercurrent conditions that may lead to volume depletion (e.g. gastrointestinal illness); risk factors for diabetic ketoacidosis (e.g. low β-cell function reserve, history of pancreatitis or pancreatic surgery, conditions leading to restricted food intake or severe dehydration, reduction in insulin dose, increased insulin requirements due to acute illness, surgery or alcohol abuse); risk factors for acute kidney injury (e.g. heart failure, hypovolaemia); history of infections. Patients taking concurrent UGT enzyme inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, efavirenz, ritonavir). Not indicated for the treatment of diabetic ketoacidosis or type 1 diabetes mellitus. Consider treatment interruption for at least 3 days before scheduled surgery. Renal and severe hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Acute kidney injury, genitourinary fungal infection (e.g. balanoposthitis, candida balanitis, vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis), UTI (including urosepsis and pyelonephritis), hypovolaemia (including symptomatic hypotension, syncope and dehydration), hypersensitivity reactions (e.g. angioedema, urticaria, anaphylaxis), increased serum K, elevated haematocrit, lower limb amputation (particularly of the toe or midfoot). Gastrointestinal disorders: Abdominal pain, constipation, nausea. Metabolism and nutrition disorders: Thirst, dyslipidaemia. Nervous system disorders: Postural dizziness, syncope. Renal and urinary disorders: Polyuria, pollakiuria. Potentially Fatal: Rarely, diabetic ketoacidosis, necrotising fasciitis of the perineum (Fournier's gangrene).
PO: Z (Embryo-foetal death and congenital anomaly have been reported. Not recommended especially during second and third trimesters due to possible adverse renal effects in infants.)
Monitoring Parameters
Correct volume depletion prior to treatment initiation. Obtain renal function at baseline and as clinically needed. Monitor blood glucose, HbA1c (at least twice yearly in patients who have stable glycaemic control; quarterly in patients not meeting treatment goals or with therapy change) and volume status (e.g. blood pressure, haematocrit, electrolytes). Assess for signs and symptoms of genital mycotic infections, UTI, necrotising fasciitis and ketoacidosis.
Drug Interactions
Increased risk of hypoglycaemia with insulin and insulin secretagogues (e.g. sulfonylureas). May decrease serum concentration with UGT enzyme inducers (e.g. rifampicin, phenytoin, barbiturates, carbamazepine, efavirenz, ritonavir). Increased risk of dehydration and hypotension with diuretics. May increase the serum concentration of digoxin. May decrease the serum concentration of lithium. Reduced exposure with colestyramine.
Food Interaction
May decrease serum concentration with St. John's wort.
Lab Interference
May interfere with 1,5-anhydroglucitol (1,5-AG) assay. May result in false-positive result for urine glucose test.
Action
Description: Mechanism of Action: Canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, decreases the reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose. This action results in increased urinary glucose excretion, thereby reducing plasma glucose concentrations. Additionally, it increases sodium delivery to the distal tubules which leads to increased tubuloglomerular feedback and reduced intraglomerular pressure. Onset: Within 24 hours. Duration: 24 hours (suppression of renal threshold for glucose). Pharmacokinetics: Absorption: Absorbed from the gastrointestinal tract. Bioavailability: Approx 65%. Time to peak plasma concentration: 1-2 hours. Distribution: Plasma protein binding: 99%, mainly to albumin. Metabolism: Mainly metabolised via O-glucuronidation by UGT1A9 and UGT2B4 into 2 inactive metabolites; undergoes minimal oxidative metabolism by CYP3A4 isoenzyme. Excretion: Via faeces (41.5% as unchanged drug, 7% as hydroxylated metabolite, 3.2% as O-glucuronide metabolite); urine (approx 33%; 30.5% as O-glucuronide metabolites, <1% as unchanged drug). Terminal elimination half-life: Approx 10-13 hours.
Chemical Structure
Canagliflozin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 24812758, Canagliflozin. https://pubchem.ncbi.nlm.nih.gov/compound/Canagliflozin. Accessed Oct. 28, 2024.
A10BK02 - canagliflozin ; Belongs to the class of sodium-glucose co-transporter 2 (SGLT2) inhibitors. Used in the treatment of diabetes.
References
Anon. Canagliflozin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 13/09/2024.Brayfield A, Cadart C (eds). Canagliflozin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/09/2024.Canagliflozin. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 13/09/2024.Invokana 100 mg and 300 mg Film-coated Tablets (Johnson & Johnson Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 13/09/2024.Invokana 100 mg Film-coated Tablets (Janssen-Cilag Limited). MHRA. https://products.mhra.gov.uk. Accessed 13/09/2024.Invokana Tablet, Film Coated (Janssen Pharmaceuticals, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 13/09/2024.Joint Formulary Committee. Canagliflozin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/09/2024.
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