Drugs List

Therapeutic Indications

Uses

Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone

Indicated in adult patients with type 2 diabetes mellitus to improve glycaemic control.

As monotherapy when diet and exercise do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate.

In combination with other glucose lowering medication including insulin where the existing regimen with diet and exercise does not provide adequate glycaemic control.

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance below 30ml/minute at baseline
Severe hepatic impairment

Precautions and Warnings

Acute illness
Major surgery
Patients over 65 years
Predisposition to hypotension
Cardiovascular disorder
Dehydration
Glucose-galactose malabsorption syndrome
History of alcohol abuse
Hypotension
Hypovolaemia
Lactose intolerance
New York Heart Association class III failure
New York Heart Association class IV failure
Polycythaemia
Renal impairment - creatinine clearance below 60ml/minute

Correct electrolyte disorders before treatment
Reduce dose in patients with creatinine clearance below 60ml/min
Advise ability to drive/operate machinery may be affected by side effects
Correct hypovolaemia prior to administration
Contains lactose
Monitor renal function prior to initiating treatment
Electrolyte & volume depletion may occur - interrupt treatment as necessary
Hospitalised patients: Monitor blood ketones before restart treatment
Monitor blood pressure
Monitor renal function 2-4 times a year in renal impairment
Monitor renal function annually in patients with normal renal function
Monitor renal function if concomitant drugs that impair renal function
Advise patient to report genital/perineal symptoms with fever or malaise
Advise patient to report symptoms of diabetic ketoacidosis immediately
Discontinue SGLT2 inhibitor if Fournier's gangrene is suspected
Increased risk of genital mycotic infection
Increased risk of urinary tract infection
Interrupt treatment temporarily in complicated urinary tract infections
Test results for urinary glucose will be positive
Advise patient to seek advice at first indications of pregnancy
Interrupt therapy if acute serious illness requiring hospitalisation occurs
Interrupt treatment in patients undergoing major surgery
Discontinue if diabetic ketoacidosis is suspected
Discontinue if foot infection, ulcer or gangrene occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid excess of alcohol
Advise patient on the need for adequate foot hygiene
Advise patient on the need for adequate hydration
Advise patient to report symptoms of volume depletion
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Clinical trials suggest there is an increased risk of lower limb amputation (primarily of the toe) in patients treated with canagliflozin. This risk is independent of predisposing factors, however the absolute risk is higher in patients with previous amputations, existing peripheral vascular disease or neuropathy. Patients with these risk factors should be carefully monitored and discontinuation or interruption of treatment can be considered in the event of any significant complication such as lower-extremity skin ulcer, osteomyelitis or gangrene.

Cases of diabetic ketoacidosis (DKA), including rare life-threatening and fatal cases, have been reported in patients taking SGLT2 inhibitors. The signs and symptoms of DKA are rapid weight loss; feeling or being sick; stomach pain; fast and deep breathing; sleepiness; a sweet smell to the breath; a sweet or metallic taste in the mouth; or a different odour to urine or sweat. Patients with moderate to severe renal impairment who require insulin appear to be at a greater risk of developing DKA. Other risk factors for DKA include low beta cell function reserve; conditions leading to restricted food intake or severe dehydration; sudden reduction in insulin; increased insulin requirements due to acute illness; surgery and alcohol abuse.

Cases of necrotising fasciitis of the perineum (Fournier's gangrene) have been reported in patients taking SGLT2 inhibitors. This a rare but serious event that requires urgent intervention and may be preceded by genital infection or penineal abscess. Patients should be advised to report a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise.

Patients with diabetic kidney disease with albuminuria using canagliflozin may have additional benefit from treatment.

Pregnancy and Lactation

Pregnancy

Canagliflozin is contraindicated in pregnancy.

At the time of writing there are no data from the use of canagliflozin in pregnant women. Animal studies have shown reproductive toxicity at high doses. The potential risk for humans is unknown.

Detailed guidance on the treatment of diabetes during pregnancy is available from the National Institute for Health and Clinical Excellence (NICE) at https://www.nice.org.uk/guidance/ng3 .

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Canagliflozin is contraindicated in breastfeeding.

It is unknown whether canagliflozin and/or its metabolites are excreted in human milk. Animal studies have shown excretion of canagliflozin/metabolites in milk. Therefore a risk to the nursing infant cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Anaphylactic reaction
Angioedema
Balanitis
Balanoposthitis
Constipation
Dehydration
Dyslipidaemia
Elevated serum potassium
Fournier's gangrene
Hypoglycaemia
Hypotension
Increase in blood urea or creatinine
Increase in haematocrit
Increased risk of fractures
Increased serum inorganic phosphate
Ketoacidosis
Lower limb amputation
Nausea
Orthostatic hypotension
Osmotic diuresis
Pollakiuria
Polyuria
Postural dizziness
Rash
Renal impairment
Syncope
Thirst
Urinary tract infections
Urticaria
Vaginal candidiasis

Presentation

Oral formulations of canagliflozin.

Drugs List

Therapeutic Indications

Uses

Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone

Indicated in adult patients with type 2 diabetes mellitus to improve glycaemic control.

As monotherapy when diet and exercise do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate.

In combination with other glucose lowering medication including insulin where the existing regimen with diet and exercise does not provide adequate glycaemic control.

Dosage

Adults

Patients with Renal Impairment

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance below 30ml/minute at baseline
Severe hepatic impairment

Precautions and Warnings

Acute illness
Major surgery
Patients over 65 years
Predisposition to hypotension
Cardiovascular disorder
Dehydration
Glucose-galactose malabsorption syndrome
History of alcohol abuse
Hypotension
Hypovolaemia
Lactose intolerance
New York Heart Association class III failure
New York Heart Association class IV failure
Polycythaemia
Renal impairment - creatinine clearance below 60ml/minute

Correct electrolyte disorders before treatment
Reduce dose in patients with creatinine clearance below 60ml/min
Advise ability to drive/operate machinery may be affected by side effects
Correct hypovolaemia prior to administration
Contains lactose
Monitor renal function prior to initiating treatment
Electrolyte & volume depletion may occur - interrupt treatment as necessary
Hospitalised patients: Monitor blood ketones before restart treatment
Monitor blood pressure
Monitor renal function 2-4 times a year in renal impairment
Monitor renal function annually in patients with normal renal function
Monitor renal function if concomitant drugs that impair renal function
Advise patient to report genital/perineal symptoms with fever or malaise
Advise patient to report symptoms of diabetic ketoacidosis immediately
Discontinue SGLT2 inhibitor if Fournier's gangrene is suspected
Increased risk of genital mycotic infection
Increased risk of urinary tract infection
Interrupt treatment temporarily in complicated urinary tract infections
Test results for urinary glucose will be positive
Advise patient to seek advice at first indications of pregnancy
Interrupt therapy if acute serious illness requiring hospitalisation occurs
Interrupt treatment in patients undergoing major surgery
Discontinue if diabetic ketoacidosis is suspected
Discontinue if foot infection, ulcer or gangrene occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid excess of alcohol
Advise patient on the need for adequate foot hygiene
Advise patient on the need for adequate hydration
Advise patient to report symptoms of volume depletion
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Clinical trials suggest there is an increased risk of lower limb amputation (primarily of the toe) in patients treated with canagliflozin. This risk is independent of predisposing factors, however the absolute risk is higher in patients with previous amputations, existing peripheral vascular disease or neuropathy. Patients with these risk factors should be carefully monitored and discontinuation or interruption of treatment can be considered in the event of any significant complication such as lower-extremity skin ulcer, osteomyelitis or gangrene.

Cases of diabetic ketoacidosis (DKA), including rare life-threatening and fatal cases, have been reported in patients taking SGLT2 inhibitors. The signs and symptoms of DKA are rapid weight loss; feeling or being sick; stomach pain; fast and deep breathing; sleepiness; a sweet smell to the breath; a sweet or metallic taste in the mouth; or a different odour to urine or sweat. Patients with moderate to severe renal impairment who require insulin appear to be at a greater risk of developing DKA. Other risk factors for DKA include low beta cell function reserve; conditions leading to restricted food intake or severe dehydration; sudden reduction in insulin; increased insulin requirements due to acute illness; surgery and alcohol abuse.

Cases of necrotising fasciitis of the perineum (Fournier's gangrene) have been reported in patients taking SGLT2 inhibitors. This a rare but serious event that requires urgent intervention and may be preceded by genital infection or penineal abscess. Patients should be advised to report a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise.

Patients with diabetic kidney disease with albuminuria using canagliflozin may have additional benefit from treatment.

Pregnancy and Lactation

Pregnancy

Canagliflozin is contraindicated in pregnancy.

At the time of writing there are no data from the use of canagliflozin in pregnant women. Animal studies have shown reproductive toxicity at high doses. The potential risk for humans is unknown.

Detailed guidance on the treatment of diabetes during pregnancy is available from the National Institute for Health and Clinical Excellence (NICE) at https://www.nice.org.uk/guidance/ng3 .

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Canagliflozin is contraindicated in breastfeeding.

It is unknown whether canagliflozin and/or its metabolites are excreted in human milk. Animal studies have shown excretion of canagliflozin/metabolites in milk. Therefore a risk to the nursing infant cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise the patient of the signs and symptoms of diabetic ketoacidosis (DKA) and to seek medical advice if they occur. The risk factors of DKA should be discussed with the patient.

Patients should be advised to report symptoms of volume depletion.

Advise patient on the need for adequate hydration.

Advise patient to seek advice at first signs of pregnancy.

Advise patient on the need for adequate foot hygiene.

Advise patient to report symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise.

Advise patient not to take St John's wort concurrently.

Advise patient to avoid excess consumption of alcohol.

Advise patient that their ability to drive or operate machinery may be impaired.

Advise patient to report to DVLA if there is a risk of hypoglycaemia, or if fitness to drive may be impaired due to diabetes complications. Guidance can be found by accessing Gov.uk website.

Side Effects

Anaphylactic reaction
Angioedema
Balanitis
Balanoposthitis
Constipation
Dehydration
Dyslipidaemia
Elevated serum potassium
Fournier's gangrene
Hypoglycaemia
Hypotension
Increase in blood urea or creatinine
Increase in haematocrit
Increased risk of fractures
Increased serum inorganic phosphate
Ketoacidosis
Lower limb amputation
Nausea
Orthostatic hypotension
Osmotic diuresis
Pollakiuria
Polyuria
Postural dizziness
Rash
Renal impairment
Syncope
Thirst
Urinary tract infections
Urticaria
Vaginal candidiasis

Effects on Laboratory Tests

Due to its mechanism of action, patients taking canagliflozin will test positive for glucose in their urine.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2018

Reference Sources

Summary of Product Characteristics: Invokana 100 mg and 300 mg film-coated tablets. Napp Pharmaceuticals Limited. Revised November 2021.

MHRA Drug Safety Update April 2016
Available at:https://www.mhra.gov.uk
Last accessed: 03 July 2018

HPRA Safety Notice May 2016
Available at: https://www.hpra.ie
Last accessed: 03 July 2018

MHRA Drug Safety Update February 2019
Available at:https://www.mhra.gov.uk
Last accessed: 22 February 2019

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Canagliflozin. Last revised: 02 April 2018
Last accessed: 03 July 2018

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 September 2022