Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Hepatic impairment
There is limited experience in clinical studies 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 and/or hypotension
Due to its mechanism of action, dapagliflozin increases diuresis which may lead to the modest decrease in blood pressure observed in clinical studies (see section 5.1). It may be more pronounced in patients with very high blood glucose concentrations.

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

In case of intercurrent conditions that may lead to volume depletion (e.g. gastrointestinal illness), 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).

Ketoacidosis in Patients with Diabetes Mellitus

Reports of ketoacidosis, including life-threatening and fatal cases, have been identified in post marketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including FORXIGA. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. .
The reports were seen in patients treated with type 2 diabetes and type 1 diabetes. FORXIGA is not indicated for the treatment of patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

In a number of cases, the presentation of the condition was atypical with only moderately increased blood (Relative to expectations in diabetic ketoacidosis) glucose values, below 14 mmol/l (250 mg/dl), therefore the ketoacidosis wasn’t immediately identified, and treatment was delayed.

DKA risk factors includes: Insulin dose reduction, acute febrile illness, reduced caloric intake due to illness or surgery, dehydration, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse. The patients Risk factors should be assessed and taken into consideration before beginning treatment with FORXIGA.
You should monitor DKA and consider a temporary interruption of treatment in situation that raise the risk of developing DKA, such as: hospitalization for major surgical procedures or acute serious medical illnesses.

Patients should be alerted to symptoms and signs of DKA, including: nausea, vomiting, abdominal pain, fatigue, difficulty breathing, lack of appetite, confusion, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat.

Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level (even if their blood glucose levels are less than 250 mg/dL).

If ketoacidosis is suspected, FORXIGA should be discontinued, the patient should be evaluated and prompt treatment should be instituted.

Necrotising fasciitis of the perineum (Fournier’s gangrene)
Post-marketing cases of necrotising fasciitis of the perineum (also known as Fournier’s gangrene) have been reported in female and male patients taking SGLT2 inhibitors (see section 4.8). This is a rare but serious and potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment.

Patients should be advised to seek medical attention if they experience a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If Fournier’s gangrene is suspected, Forxiga should be discontinued and prompt treatment (including antibiotics and surgical debridement) should be instituted.

Urinary tract infections
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, urosepsis

Elderly (≥ 65 years)
Elderly patients may be at a greater risk for volume depletion and are more likely to be treated with diuretics.

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).

Cardiac failure
Experience with dapagliflozin in NYHA class IV is limited.

Chronic kidney disease
There is no experience with dapagliflozin for the treatment of chronic kidney disease in patients without diabetes who do not have albuminuria. Patients with albuminuria may benefit more from treatment with dapagliflozin.

Lower limb amputations
An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term, clinical studies in type 2 diabetes mellitus with SGLT2 inhibitors. It is unknown whether this constitutes a class effect. It is important to counsel patients with diabetes on routine preventative foot care.


Urine laboratory assessments
Due to its mechanism of action, patients taking Forxiga will test positive for glucose in their urine.

Lactose
The tablets contain lactose anhydrous. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Effects on Driving

4.7 Effects on ability to drive and use machines
Forxiga has no or negligible influence on the ability to drive and use machines. Patients should be alerted to the risk of hypoglycaemia when dapagliflozin is used in combination with a sulphonylurea or insulin.