Drugs List

Therapeutic Indications

Uses

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

Treatment of adult patients with 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.

Contraindications

Children under 18 years
Patients over 85 years at initiation
Breastfeeding
Diabetic ketoacidosis
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute at baseline
Severe hepatic impairment

Precautions and Warnings

Acute illness
Major surgery
Patients over 75 years
Predisposition to hypotension
Cardiovascular disorder
Dehydration
Glucose-galactose malabsorption syndrome
History of alcohol abuse
Hypotension
Hypovolaemia
Lactose intolerance
Renal impairment - creatinine clearance 45 - 60ml/minute
Urinary tract infection

Advise ability to drive/operate machinery may be affected by side effects
Correct hypovolaemia prior to administration
Exclude volume depletion before commencing treatment
Contains lactose
Monitor renal function before treatment and regularly during 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 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 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
Discontinue if creatinine clearance below 45ml/minute
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 canagliflozin. An increased risk of amputation has not yet been seen in studies of empagliflozin. However, the increased risk of amputation cannot be excluded and caution should be advised in patients receiving empagliflozin.

Cases of diabetic ketoacidosis (DKA) have been reported in patient taking sodium-glucose co-transporter-2 (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.

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.

Pregnancy and Lactation

Pregnancy

Empagliflozin is contraindicated in pregnancy.

There are no data from the use of empagliflozin in pregnant women. Animal studies show that empagliflozin crosses the placenta during the late gestation to a very limited extent, but do not indicate direct or indirect harmful effects with respect to early embryonic development. However, animal studies have shown adverse effects on postnatal development.

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

Empagliflozin is contraindicated in breastfeeding.

It is not known whether empagliflozin is excreted into human breast milk. Animal studies have shown excretion of empagliflozin into milk, therefore a risk to the newborn/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

Angioedema
Balanitis
Blood lipid changes
Decrease in blood pressure
Decrease in glomerular filtration rate
Dehydration
Dysuria
Fournier's gangrene
Genital infections
Hypoglycaemia
Hypotension
Hypovolaemia
Increase in haematocrit
Ketoacidosis
Nocturia
Orthostatic hypotension
Pollakiuria
Polyuria
Pruritus
Pyelonephritis
Rash
Serum creatinine increased
Syncope
Thirst
Urinary tract infections
Urosepsis
Urticaria
Vaginal candidiasis
Vulvovaginal irritation

Presentation

Tablets containing empagliflozin.

Drugs List

Therapeutic Indications

Uses

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

Treatment of adult patients with 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.

Dosage

Adults

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Patients over 85 years at initiation
Breastfeeding
Diabetic ketoacidosis
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute at baseline
Severe hepatic impairment

Precautions and Warnings

Acute illness
Major surgery
Patients over 75 years
Predisposition to hypotension
Cardiovascular disorder
Dehydration
Glucose-galactose malabsorption syndrome
History of alcohol abuse
Hypotension
Hypovolaemia
Lactose intolerance
Renal impairment - creatinine clearance 45 - 60ml/minute
Urinary tract infection

Advise ability to drive/operate machinery may be affected by side effects
Correct hypovolaemia prior to administration
Exclude volume depletion before commencing treatment
Contains lactose
Monitor renal function before treatment and regularly during 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 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 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
Discontinue if creatinine clearance below 45ml/minute
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 canagliflozin. An increased risk of amputation has not yet been seen in studies of empagliflozin. However, the increased risk of amputation cannot be excluded and caution should be advised in patients receiving empagliflozin.

Cases of diabetic ketoacidosis (DKA) have been reported in patient taking sodium-glucose co-transporter-2 (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.

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.

Pregnancy and Lactation

Pregnancy

Empagliflozin is contraindicated in pregnancy.

There are no data from the use of empagliflozin in pregnant women. Animal studies show that empagliflozin crosses the placenta during the late gestation to a very limited extent, but do not indicate direct or indirect harmful effects with respect to early embryonic development. However, animal studies have shown adverse effects on postnatal development.

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

Empagliflozin is contraindicated in breastfeeding.

It is not known whether empagliflozin is excreted into human breast milk. Animal studies have shown excretion of empagliflozin into milk, therefore a risk to the newborn/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.

Advise patients of the warning signs of hypoglycaemia.

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 their GP if pregnancy is 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
Balanitis
Blood lipid changes
Decrease in blood pressure
Decrease in glomerular filtration rate
Dehydration
Dysuria
Fournier's gangrene
Genital infections
Hypoglycaemia
Hypotension
Hypovolaemia
Increase in haematocrit
Ketoacidosis
Nocturia
Orthostatic hypotension
Pollakiuria
Polyuria
Pruritus
Pyelonephritis
Rash
Serum creatinine increased
Syncope
Thirst
Urinary tract infections
Urosepsis
Urticaria
Vaginal candidiasis
Vulvovaginal irritation

Effects on Laboratory Tests

Patients will test positive for glucose in their urine due to the mechanism of action.

Interference with 1,5-anhydroglucitol (1,5-AG) assay
Monitoring glycaemic control with 1,5-AG assay is not recommended due to unreliable measurements of 1,5-AG in patients taking SGLT2 inhibitors. Alternative methods to monitor glycaemic control is advised.

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: December 2018.

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Jardiance 10 mg and 25 mg film-coated tablets. Boehringer Ingelheim Ltd. Revised June 2020.

MHRA Drug Safety Update April 2016
Available at:https://www.mhra.gov.uk
Last accessed: 21 November 2018

MHRA Drug Safety Update March 2017
Available at:https://www.mhra.gov.uk
Last accessed: 21 November 2018

HPRA Safety Notice May 2016
Available at: https://www.hpra.ie
Last accessed: 21 November 2018

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 21 November 2018