1. Name of the medicinal product
Forxiga 5 mg film-coated tablets

Forxiga 10 mg film-coated tablets

2. Qualitative and quantitative composition
5 mg:

Each tablet contains dapagliflozin propanediol monohydrate equivalent to 5 mg dapagliflozin.

Excipient with known effect:

Each tablet contains 25 mg of lactose anhydrous.

For the full list of excipients, see section 6.1.

10 mg:

Each tablet contains dapagliflozin propanediol monohydrate equivalent to 10 mg dapagliflozin.

Excipient with known effect:

Each tablet contains 50 mg of lactose anhydrous.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form
Film-coated tablet (tablet).

5 mg:

Yellow, biconvex, 0.7 cm diameter round, film-coated tablets with “5” engraved on one side and “1427” engraved on the other side.

10 mg:

Yellow, biconvex, approximately 1.1 x 0.8 cm diagonally diamond-shaped, film-coated tablets with “10” engraved on one side and “1428” engraved on the other side.

4. Clinical particulars
4.1 Therapeutic indications
Forxiga is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control as:

Monotherapy

When diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance.

Add-on combination therapy

In combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control (see sections 4.4, 4.5 and 5.1 for available data on different combinations).

4.2 Posology and method of administration
Posology

Monotherapy and add-on combination therapy

The recommended dose is 10 mg dapagliflozin once daily for monotherapy and add-on combination therapy with other glucose-lowering medicinal products including insulin. When dapagliflozin is used in combination with insulin or an insulin secretagogue, such as a sulphonylurea, a lower dose of insulin or insulin secretagogue may be considered to reduce the risk of hypoglycaemia (see sections 4.5 and 4.8).

Special populations

Renal impairment

The efficacy of dapagliflozin is dependent on renal function, and efficacy is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment. Forxiga is not recommended for use in patients with moderate to severe renal impairment (patients with creatinine clearance [CrCl] < 60 ml/min or estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2, see sections 4.4, 4.8, 5.1 and 5.2).

No dosage adjustment is indicated in patients with mild renal impairment.

Hepatic impairment

No dosage adjustment is necessary for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, a starting dose of 5 mg is recommended. If well tolerated, the dose may be increased to 10 mg (see sections 4.4 and 5.2).

Elderly (≥ 65 years)

In general, no dosage adjustment is recommended based on age. Renal function and risk of volume depletion should be taken into account (see sections 4.4 and 5.2). Due to the limited therapeutic experience in patients 75 years and older, initiation of dapagliflozin therapy is not recommended.

Paediatric population

The safety and efficacy of dapagliflozin in children aged 0 to < 18 years have not yet been established. No data are available.

Method of administration

Forxiga can be taken orally once daily at any time of day with or without food. Tablets are to be swallowed whole.

4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use
General

Forxiga should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Use in patients with renal impairment

The efficacy of dapagliflozin is dependent on renal function, and efficacy is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment (see section 4.2). In subjects with moderate renal impairment (patients with CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m2), a higher proportion of subjects treated with dapagliflozin had adverse reactions of increase in creatinine, phosphorus, parathyroid hormone (PTH) and hypotension, compared with placebo. Forxiga is not recommended for use in patients with moderate to severe renal impairment (patients with CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m2). Forxiga has not been studied in severe renal impairment (CrCl < 30 ml/min or eGFR < 30 ml/min/1.73 m2) or end-stage renal disease (ESRD).

Monitoring of renal function is recommended as follows:

• Prior to initiation of dapagliflozin and at least yearly, thereafter (see sections 4.2, 4.8, 5.1 and 5.2)

• Prior to initiation of concomitant medicinal products that may reduce renal function and periodically thereafter

• For renal function approaching moderate renal impairment, at least 2 to 4 times per year. If renal function falls below CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m2, dapagliflozin treatment should be discontinued.

Use in patients with hepatic impairment

There is limited experience in clinical trials in patients with hepatic impairment. Dapagliflozin exposure is increased in patients with severe hepatic impairment (see sections 4.2 and 5.2).

Use in patients at risk for volume depletion, hypotension and/or electrolyte imbalances

Due to its mechanism of action, dapagliflozin increases diuresis associated with a modest decrease in blood pressure (see section 5.1), which may be more pronounced in patients with very high blood glucose concentrations.

Dapagliflozin is not recommended for use in patients receiving loop diuretics (see section 4.5) or who are volume depleted, e.g. due to acute illness (such as gastrointestinal illness).

Caution should be exercised in patients for whom a dapagliflozin-induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or elderly patients.

For patients receiving dapagliflozin, in case of intercurrent conditions that may lead to volume depletion, careful monitoring of volume status (e.g. physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended. Temporary interruption of treatment with dapagliflozin is recommended for patients who develop volume depletion until the depletion is corrected (see section 4.8).

Urinary tract infections

Urinary tract infections were more frequently reported for dapagliflozin 10 mg compared to placebo in a pooled analysis up to 24 weeks (see section 4.8). Pyelonephritis was uncommon and occurred at a similar frequency to control. Urinary glucose excretion may be associated with an increased risk of urinary tract infection; therefore, temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis.

Elderly patients

Elderly patients are more likely to have impaired renal function, and/or to be treated with anti-hypertensive medicinal products that may cause changes in renal function such as angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB). The same recommendations for renal function apply to elderly patients as to all patients (see sections 4.2, 4.4, 4.8 and 5.1).

In subjects ≥ 65 years of age, a higher pro