Drug Action
Reversibly inhibits sodium-glucose co- transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
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Individual generic drug information
Extracted information for Dapagliflozin only.
Reversibly inhibits sodium-glucose co- transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
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Type 2 diabetes mellitus [as monotherapy if metformin inappropriate] | Type 2 diabetes mellitus [in combination with insulin or other antidiabetic drugs] ▶BY MOUTH ▶Adult: 10 mg once daily Type 1 diabetes mellitus [as an adjunct to insulin in patients with a BMI greater than or equal to 27 kg/m2, when insulin alone fails to achieve adequate glycaemic control] ▶BY MOUTH ▶Adult: 5 mg once daily
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DUE TO INTERACTIONS ▶Dose of concomitant insulin or drugs that stimulate insulin secretion may need to be reduced (risk of hypoglycaemia)—consult product literature.
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▶When used for type 1 diabetes mellitus High risk of diabetic ketoacidosis (consult product literature)
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Elderly (risk of volume depletion). hypotension . raised haematocrit. risk of volume depletion CAUTIONS, FURTHER INFORMATION ▶Volume depletion Correct hypovolaemia before starting treatment.
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NICE decisions ▶Dapagliflozin in combination therapy for treating type 2 diabetes (updated November 2016) NICE TA288 Dapagliflozin (Forxiga ®) in a dual therapy regimen in combination with metformin is recommended for the treatment of type 2 diabetes, only if the patient is at significant risk of hypoglycaemia or its consequences, or if a sulfonylurea is contra-indicated or not tolerated. Dapagliflozin in combination with insulin (alone or with other antidiabetic drugs) is an option for the treatment of type 2 diabetes. Patients currently receiving dapagliflozin in a dual therapy regimen that is not recommended according to the above criteria should have the option to continue treatment until they and their clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta288 ▶Canagliflozin, dapagliflozin and empagliflozin as monotherapies for treating type 2 diabetes (May 2016) NICE TA390 Dapagliflozin (Forxiga ®) as monotherapy is recommended as an option for treating type 2 diabetes in adults for whom metformin is contra-indicated or not tolerated, only if a dipeptidyl peptidase-4 (DPP-4) inhibitor would otherwise be prescribed, and a sulfonylurea or pioglitazone is not appropriate. Patients currently receiving dapagliflozin whose disease Endocrine system does not meet the above criteria should be able to continue treatment until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta390 ▶Dapagliflozin in triple therapy for treating type 2 diabetes (November 2016) NICE TA418 Dapagliflozin (Forxiga ®) in a triple therapy regimen is recommended as an option for treating type 2 diabetes in adults, only in combination with metformin and a sulfonylurea. Patients currently receiving dapagliflozin in other triple therapy regimens, whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta418 ▶Dapagliflozin with insulin for treating type 1 diabetes (updated February 2020) NICE TA597 Dapagliflozin (Forxiga ®) with insulin is recommended as an option for treating type 1 diabetes in adults with a body mass index (BMI) of at least 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy, only if: . they are on insulin doses of more than 0.5 units/kg of body weight per day, and . they have completed a structured education programme that is evidence based, quality assured, delivered by trained educators and includes information about diabetic ketoacidosis, such as: . how to recognise its risk factors, signs and symptoms . how and when to monitor blood ketone levels . what actions to take for elevated blood ketones, and . treatment is started and supervised by a consultant physician specialising in endocrinology and diabetes treatment, and haemoglobin A1c (HbA1c) levels are assessed after 6 months and regularly after this. Stop dapagliflozin if there has not been a sustained improvement in glycaemic control (that is, a fall in HbA1c level of about 0.3% or 3 mmol/mol). Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta597 Scottish Medicines Consortium (SMC) decisions SMC No. SMC2185 The Scottish Medicines Consortium has advised (September 2019) that dapagliflozin (Forxiga ®) is accepted for use within NHS Scotland for the treatment of type 1 diabetes as an adjunct to insulin, in adults with a body mass index (BMI) of at least 27 kg/m2, when insulin alone fails to achieve adequate glycaemic control.
Source page 765
Extracted information for Dapagliflozin only.
MHRA/CHM ADVICE (UPDATED APRIL 2016): RISK OF DIABETIC KETOACIDOSIS WITH SODIUM-GLUCOSE CO-TRANSPORTER 2 (SGLT2) INHIBITORS (CANAGLIFLOZIN, DAPAGLIFLOZIN OR EMPAGLIFLOZIN) A review by the European Medicines Agency has concluded that serious, life-threatening, and fatal cases of diabetic ketoacidosis (DKA) have been reported rarely in patients taking an SGLT2 inhibitor. In several cases, the presentation of DKA was atypical with patients having only moderately elevated blood glucose levels, and some of them occurred during off-label use. To minimise the risk of such effects when treating patients with a SGLT2 inhibitor, the European Medicines Agency has issued the following advice: . inform patients of the signs and symptoms of DKA, (including rapid weight loss, nausea or vomiting, abdominal 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), and advise them to seek immediate medical advice if they develop any of these . test for raised ketones in patients with signs and symptoms of DKA, even if plasma glucose levels are near-normal . use dapagliflozin with caution in patients with risk factors for DKA, (including a low beta cell reserve, conditions leading to restricted food intake or severe dehydration, sudden reduction in insulin, increased insulin requirements due to acute illness, surgery or alcohol abuse), and discuss these risk factors with patients . discontinue treatment if DKA is suspected or diagnosed . do not restart treatment with any SGLT2 inhibitor in patients who experienced DKA during use, unless another cause for DKA was identified and resolved . interrupt SGLT2 inhibitor treatment in patients who are hospitalised for major surgery or acute serious illnesses; treatment may be restarted once the patient’s condition has stabilised MHRA/CHM ADVICE: SGLT2 INHIBITORS: MONITOR KETONES IN BLOOD DURING TREATMENT INTERRUPTION FOR SURGICAL PROCEDURES OR ACUTE SERIOUS MEDICAL ILLNESS (MARCH 2020) New recommendations have been issued following a European review of peri-operative diabetic ketoacidosis in patients taking SGLT2 inhibitors. Healthcare professionals are advised to monitor ketone levels during SGLT2 inhibitor treatment interruption in patients who have been hospitalised for major surgery or acute serious illness—measurement of blood ketone levels is preferred to urine. Treatment may be restarted once ketone levels are normal and the patient’s condition has stabilised. MHRA/CHM ADVICE: SGLT2 INHIBITORS: REPORTS OF FOURNIER’S GANGRENE (NECROTISING FASCIITIS OF THE GENITALIA OR PERINEUM) (FEBRUARY 2019) Fournier’s gangrene, a rare but serious and potentially life-threatening infection, has been associated with the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors. If Fournier’s gangrene is suspected, stop the SGLT2 inhibitor and urgently start treatment (including antibiotics and surgical debridement). Patients should be advised to seek urgent medical attention if they experience severe pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise—urogenital infection or perineal abscess may precede necrotising fasciitis.
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→Appendix 1: dapagliflozin
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▶Common or very common Back pain. balanoposthitis. diabetic ketoacidosis (discontinue immediately). dizziness . dyslipidaemia. hypoglycaemia (in combination with insulin or sulfonylurea). increased risk of infection. rash. urinary disorders ▶Uncommon Constipation. dry mouth. genital pruritus. hypovolaemia. thirst. vulvovaginal pruritus. weight decreased ▶Rare or very rare Angioedema. Fournier’s gangrene (discontinue and initiate treatment promptly) SIDE-EFFECTS, FURTHER INFORMATION Interrupt treatment if volume depletion occurs.
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Avoid—toxicity in animal studies.
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Avoid—present in milk in animal studies.
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Manufacturer advises caution in severe impairment (risk of increased exposure, limited information available). Dose adjustments ▶When used for Type 2 diabetes mellitus Manufacturer advises initially 5 mg daily in severe impairment, increased if tolerated to 10 mg daily.
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Manufacturer advises avoid initiation if eGFR less than 60 mL/minute/1.73 m2 (reduced efficacy). Manufacturer advises avoid if eGFR persistently less than 45 mL/minute/1.73 m2 (reduced efficacy). If eGFR less than 60 mL/minute/1.73 m2 manufacturer advises monitor renal function at least 2–4 times per year.
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▶Manufacturer advises monitor renal function before treatment, and at least annually thereafter. ▶When used for Type 1 diabetes mellitus Manufacturer advises patients should monitor ketone levels before starting and during treatment (blood ketone levels are preferred to urine)—consult product literature.
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Extracted information for Dapagliflozin only.
There can be variation in the licensing of different medicines containing the same drug. Tablet ▶Forxiga (AstraZeneca UK Ltd) Dapagliflozin (as Dapagliflozin propanediol monohydrate) 5 mg Forxiga 5mg tablets | 28 tablet P £36.59 DT = £36.59 Dapagliflozin (as Dapagliflozin propanediol monohydrate) 10 mg Forxiga 10mg tablets | 28 tablet P £36.59 DT = £36.59 Combinations available: Saxagliptin with dapagliflozin, p. 733
Source pages 765, 766
Extracted information for Dapagliflozin only.
Patients should be informed of the signs and symptoms of diabetic ketoacidosis, see MHRA advice.
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Filter the extracted dose blocks for this individual drug.
First line only; read the complete Indications and dose section above.
10 mg once daily
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 764
First line only; read the complete Indications and dose section above.
5 mg once daily
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 764