Drugs List

Therapeutic Indications

Uses

Chronic kidney disease
Symptomatic chronic cardiac failure
Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone

Type 2 diabetes mellitus:
a) As monotherapy when diet and exercise do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate.
b) In combination with other glucose lowering medication including insulin where the existing regimen with diet and exercise does not provide adequate glycaemic control.

Heart failure
Treatment of adults with symptomatic chronic heart failure.

Chronic kidney disease
Treatment of adults with chronic kidney disease.

Contraindications

Children under 10 years
Breastfeeding
Diabetic ketoacidosis
Galactosaemia
Pregnancy
Renal impairment - eGFR below 15ml/minute/1.73m sq

Precautions and Warnings

Children under 18 years
Major surgery
Patients over 65 years
Predisposition to hypotension
Dehydration
Glucose-galactose malabsorption syndrome
Hypotension
Hypovolaemia
Lactose intolerance
Polycythaemia
Renal impairment - eGFR below 60 ml/minute/1.73 m squared
Severe hepatic impairment
Urinary tract infection

Correct hypovolaemia prior to administration
Exclude volume depletion before commencing treatment
Not all available strengths are licensed for all indications
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 fluid and electrolyte status
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
Test for raised ketones in patients with symptoms of diabetic ketoacidosis
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
Interrupt treatment temporarily in complicated urinary tract infections
May affect results of some laboratory tests
Test results for urinary glucose will be positive
Interrupt therapy if acute serious illness requiring hospitalisation occurs
Interrupt treatment in patients undergoing major surgery
Pregnancy confirmed: Discontinue this medication
Discontinue if diabetic ketoacidosis is suspected
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 in patients treated with another sodium-glucose co-transporter 2 (SGLT2) inhibitor. An increased risk of amputation has not yet been seen in studies of dapagliflozin. However, the increased risk of amputation cannot be excluded and caution should be advised in patients receiving dapagliflozin.

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 perineal 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.

Cases of diabetic ketoacidosis (DKA) have been reported in patient 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. The 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.
Restarting treatment in patients with previous DKA while on SGLT2 inhibitor is not recommended, unless another precipitating factor has been identified and resolved.

Treatment for patient's with type 2 diabetes mellitus should consider additional glucose-lowering treatment if glomerular filtration rate falls persistently below 45 ml/minute.

Patients with glomerular filtration rate below 60 ml/minute has been observed to have adverse reactions of increased parathyroid hormone (PTH) and hypotension.

Pregnancy and Lactation

Pregnancy

Dapagliflozin is contraindicated during pregnancy.

Manufacturer states that dapagliflozin should be discontinued if pregnancy is detected. There are no data from the use of dapagliflozin in pregnant women. Studies in rats have shown toxicity to the developing kidney in the time period corresponding to the second and third trimesters for human pregnancy.

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.

Lactation

Dapagliflozin is contraindicated during breastfeeding.

Manufacturer recommends that dapagliflozin should not be used during breastfeeding. It is unknown whether dapagliflozin and/or its metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dapagliflozin and/or its metabolites in milk, as well as pharmacologically-mediated effects in nursing offspring. A risk to the newborns/infants cannot be excluded.

Side Effects

Angioedema
Back pain
Balanitis
Constipation
Dehydration
Dizziness
Dry mouth
Dyslipidaemia
Dysuria
Fournier's gangrene
Genital infections
Genital pruritus
Hepatitis
Hyperhidrosis
Hypoglycaemia
Hypotension
Hypovolaemia
Increase in blood urea or creatinine
Increase in haematocrit
Ketoacidosis
Nausea
Nocturia
Plasma volume depletion
Polyuria
Rash
Thirst
Urinary tract infections
Vulvovaginal infections
Vulvovaginal itching
Weight loss

Presentation

Tablets containing dapagliflozin.

Drugs List

Therapeutic Indications

Uses

Chronic kidney disease
Symptomatic chronic cardiac failure
Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone

Type 2 diabetes mellitus:
a) As monotherapy when diet and exercise do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate.
b) In combination with other glucose lowering medication including insulin where the existing regimen with diet and exercise does not provide adequate glycaemic control.

Heart failure
Treatment of adults with symptomatic chronic heart failure.

Chronic kidney disease
Treatment of adults with chronic kidney disease.

Dosage

Adults

Children

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 10 years
Breastfeeding
Diabetic ketoacidosis
Galactosaemia
Pregnancy
Renal impairment - eGFR below 15ml/minute/1.73m sq

Precautions and Warnings

Children under 18 years
Major surgery
Patients over 65 years
Predisposition to hypotension
Dehydration
Glucose-galactose malabsorption syndrome
Hypotension
Hypovolaemia
Lactose intolerance
Polycythaemia
Renal impairment - eGFR below 60 ml/minute/1.73 m squared
Severe hepatic impairment
Urinary tract infection

Correct hypovolaemia prior to administration
Exclude volume depletion before commencing treatment
Not all available strengths are licensed for all indications
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 fluid and electrolyte status
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
Test for raised ketones in patients with symptoms of diabetic ketoacidosis
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
Interrupt treatment temporarily in complicated urinary tract infections
May affect results of some laboratory tests
Test results for urinary glucose will be positive
Interrupt therapy if acute serious illness requiring hospitalisation occurs
Interrupt treatment in patients undergoing major surgery
Pregnancy confirmed: Discontinue this medication
Discontinue if diabetic ketoacidosis is suspected
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 in patients treated with another sodium-glucose co-transporter 2 (SGLT2) inhibitor. An increased risk of amputation has not yet been seen in studies of dapagliflozin. However, the increased risk of amputation cannot be excluded and caution should be advised in patients receiving dapagliflozin.

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 perineal 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.

Cases of diabetic ketoacidosis (DKA) have been reported in patient 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. The 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.
Restarting treatment in patients with previous DKA while on SGLT2 inhibitor is not recommended, unless another precipitating factor has been identified and resolved.

Treatment for patient's with type 2 diabetes mellitus should consider additional glucose-lowering treatment if glomerular filtration rate falls persistently below 45 ml/minute.

Patients with glomerular filtration rate below 60 ml/minute has been observed to have adverse reactions of increased parathyroid hormone (PTH) and hypotension.

Pregnancy and Lactation

Pregnancy

Dapagliflozin is contraindicated during pregnancy.

Manufacturer states that dapagliflozin should be discontinued if pregnancy is detected. There are no data from the use of dapagliflozin in pregnant women. Studies in rats have shown toxicity to the developing kidney in the time period corresponding to the second and third trimesters for human pregnancy.

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.

Lactation

Dapagliflozin is contraindicated during breastfeeding.

Manufacturer recommends that dapagliflozin should not be used during breastfeeding. It is unknown whether dapagliflozin and/or its metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dapagliflozin and/or its metabolites in milk, as well as pharmacologically-mediated effects in nursing offspring. A risk to the newborns/infants cannot be excluded.

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.

Advise patient on how to monitor for ketone levels and what action to take if levels are elevated.

When dapagliflozin is used in combination with other antidiabetics, patients should be advised of the potential risk of hypoglycaemia.

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.

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

Advise female patients to consult GP if pregnancy suspected or planned.

Advise patients 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

Angioedema
Back pain
Balanitis
Constipation
Dehydration
Dizziness
Dry mouth
Dyslipidaemia
Dysuria
Fournier's gangrene
Genital infections
Genital pruritus
Hepatitis
Hyperhidrosis
Hypoglycaemia
Hypotension
Hypovolaemia
Increase in blood urea or creatinine
Increase in haematocrit
Ketoacidosis
Nausea
Nocturia
Plasma volume depletion
Polyuria
Rash
Thirst
Urinary tract infections
Vulvovaginal infections
Vulvovaginal itching
Weight loss

Effects on Laboratory Tests

In diabetic patients taking dapagliflozin, it is advisable not to use the 1,5-anhydroglucitol (1,5 AG) assay to monitor glycaemic control. This is because measurements of 1,5 AG are unreliable in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycaemic control.

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: January 2019

Reference Sources

Summary of Product Characteristics: Forxiga 5mg & 10mg film coated tablets. AstraZeneca UK Ltd. Revised December 2022.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 August 2022