Empagliflozin with linagliptin oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of empagliflozin with linagliptin.
Drugs List
Therapeutic Indications
Uses
Oral combination treatment of type 2 diabetes
Indicated in adults with type 2 diabetes mellitus:
- To achieve better glycaemic control when the combination treatment with metformin and/or sulfonylurea and either empagliflozin or linagliptin does not adequately control blood glucose level.
- When the treatment with combination of empagliflozin and linagliptin in separate dosage forms has been initiated.
Dosage
Adults
Initial dose: 1 tablet (10mg/5mg) once a day.
Increase if necessary to 1 tablet (25mg/5mg) once a day.
Patients with Renal Impairment
Creatinine clearance equal to or greater than 60ml/minute
No dose adjustment required.
Creatinine clearance below 60ml/minute
Treatment should not be initiated.
Creatinine clearance falls persistently below 60ml/minute
The dose should be adjusted to or maintained at a maximum daily dose of 10mg empagliflozin and 5mg linagliptin.
Creatinine clearance of less than 45ml/minute
Treatment should be discontinued.
Additional Dosage Information
Missed doses
If a dose is missed and it is 12 hours or more until the next dose, it should be taken as soon as possible. The next dose should be taken at the usual time.
If a dose is missed with less than 12 hours until the next dose, the dose should be skipped and the next dose taken at the usual time.
Combination with sulfonylurea or insulin
A lower dose of the sulfonylurea or insulin may be necessary to reduce the risk of hypoglycaemia.
Contraindications
Children under 18 years
Patients over 75 years at initiation
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute at baseline
Severe hepatic impairment
Precautions and Warnings
Acute illness
Major surgery
Predisposition to hypotension
Cardiovascular disorder
Dehydration
History of alcohol abuse
History of pancreatitis
Hypotension
Hypovolaemia
Renal impairment - creatinine clearance 45 - 60ml/minute
Urinary tract infection
Reduce dose in patients with creatinine clearance below 60ml/min
Advise ability to drive/operate machinery may be affected by side effects
Exclude volume depletion before commencing treatment
Contains mannitol
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 annually in patients with normal renal function
Advise patient to report genital/perineal symptoms with fever or malaise
Advise patient to report symptoms of diabetic ketoacidosis immediately
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue SGLT2 inhibitor if Fournier's gangrene is suspected
Interrupt treatment temporarily in complicated urinary tract infections
Test results for urinary glucose will be positive
Discontinue if creatinine clearance below 45ml/minute
Discontinue if pancreatitis is suspected
Do not restart treatment following confirmation of pancreatitis
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 not to take St John's wort concurrently
Advise patient on the need for adequate foot hygiene
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk
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.
Clinical trials suggest there is an increased risk of lower limb amputation in patients treated with another SGLT2 inhibitor. 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 with linagliptin.
Cases of necrotising fasciitis of the perineum (Fournier's gangrene) have been reported in patients taking SGLT2 inhibitors. Urgent surgical intervention and antibiotics may be necessary. Patients should seek medical attention if symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise arise.
If bullous pemphigoid is suspected, empagliflozin with linagliptin should be discontinued.
Pregnancy and Lactation
Pregnancy
Empagliflozin with linagliptin is contraindicated in pregnancy.
The manufacturer advises avoiding empagliflozin with linagliptin during pregnancy.
Animal studies have indicated empagliflozin with linagliptin crosses the placenta during late gestation but does not indicate harmful effects regarding early embryonic development. Studies with empagliflozin in animals 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
Lactation
Empagliflozin with linagliptin is contraindicated in breastfeeding.
The manufacturer does not recommend breastfeeding whilst taking empagliflozin with linagliptin.
There is limited data regarding the excretion of empagliflozin with linagliptin into breast milk. Animal studies have shown excretion of empagliflozin and linagliptin into milk. A risk to newborns cannot be excluded.
Counselling
Advise patients to report symptoms of diabetic ketoacidosis immediately.
Advise patients to report genital/perineal symptoms with fever or malaise.
Advise patient to report symptoms of pancreatitis.
Advise patients on the need for adequate foot hygiene.
Advise ability to drive/operate machinery may be affected by side effects.
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
Bullous pemphigoid
Cough
Decrease in glomerular filtration rate
Diabetic ketoacidosis
Dysuria
Elevated serum lipase
Fournier's gangrene
Genital infections
Genital moniliasis
Hypersensitivity reactions
Hypoglycaemia
Increase in haematocrit
Increased amylase secretion
Increased urination
Mouth ulcers
Nasopharyngitis
Pancreatitis
Pruritus
Rash
Rise in blood lipids
Serum creatinine increased
Thirst
Urinary tract infections
Urticaria
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: February 2022
Reference Sources
Summary of Product Characteristics: Glyxambi 10mg/5mg and 25mg/5mg film-coated tablets. Boehringer Ingelheim Ltd. Revised July 2021.
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