Luseogliflozin

Luseogliflozin should be administered with care in patients who consume alcohol excessively.

Patients using other antidiabetic drugs (in particular, sulfonylureas or, insulin preparations or GLP-1 receptor agonists).

Because these drugs may cause hypoglycemia, they should be administered while closely monitoring plasma glucose and other conditions of patients. In combined use with sulfonylureas, insulin preparations or GLP-1 receptor agonists, dose reduction of these drugs should be considered in order to reduce the risk of hypoglycemia associated with them. When hypoglycemic symptoms are observed, sucrose is usually administered. When α-glucosidase inhibitors are concomitantly used, glucose should be administered.

Adrenaline, corticosteroid, thyroid hormone, etc.

Because hypoglycemic action may be weakened due to hyperglycemic action of these drugs, they should be administered with luseogliflozin while closely monitoring plasma glucose and other conditions of patients.

β-blockers, salicylic acids, MAO inhibitors, fibrates, etc.

Because plasma glucose may be further decreased due to hypoglycemic action of these drugs, they should be administered with luseogliflozin while closely monitoring plasma glucose and other conditions of patients.

Patients who are likely to develop dehydration (patients whose plasma glucose is controlled extremely poorly, elderly patients, patients concomitantly using diuretics, etc.). Diuretic effect of luseogliflozin may lead to dehydration.

Because diuretic action can be enhanced in combined use with Luseogliflozin, caution should be exercised by, for example, adjusting the dose of diuretics as needed.

Luseogliflozin should be administered with care in patients with strenuous muscular exercise.

Luseogliflozin should be administered with care in patients with pituitary dysfunction or adrenal insufficiency.

Luseogliflozin should be administered with care in patients with poor nutritional status, starvation, irregular diet, insufficient dietary intake or debility.

Patients with urinary tract infection or genital infection. Appropriate treatment should be provided before the administration of luseogliflozin because it may exacerbate the symptoms.

In pregnant women or women who may possibly be pregnant, luseogliflozin should not be administered and other drugs including insulin preparations should be used.

Safety for use during pregnancy has not been established. In animal studies (rats) of luseogliflozin, skeletal variations, delayed ossification, or membranous ventricular septum defect which were considered to be caused by a decrease in body weight of dams were observed in the oral administration at a dose of 150 mg/kg/day (equivalent to approximately 47 times the exposure [AUC] at the maximum recommended clinical dose (once daily administration of 5 mg)) or higher doses to pregnant animals. In animal studies (rats) of similar drugs, exposure of juvenile animals in the period corresponding to the mid to late pregnancy in humans was reported to cause dilatation of renal pelvis and renal tubule. In addition, transfer to fetuses was reported in animal studies (rats) of luseogliflozin.

Nursing women should be recommended to avoid breastfeeding during the administration of this drug.

In animal studies (rats), secretion into breast milk was observed.

Because hypoglycemic symptoms may occur, caution should be exercised in the administration to patients who work in high places or drive.

Adverse drug reactions including abnormal investigation findings were observed in 236 out of 1,262 subjects (18.7%) in clinical studies administered at 2.5 mg dose (including at increased dose of 5 mg) of luseogliflozin, at the time of approval in Japan. Major adverse drug reactions (adverse drug reactions observed in more than 2% of subjects) were pollakiuria in 35 subjects (2.8%), hypoglycemia in 30 subjects (2.4%), and β2-microglobulin urine increased in 26 subjects (2.1%).

1. Clinically Significant Adverse Reactions

(1) Hypoglycemia (1.0%*): Hypoglycemia may occur in combined use with other antidiabetic drugs (in particular, sulfonylureas, insulin preparations or GLP-1 receptor agonists). In addition, hypoglycemia was reported without combined use of other antidiabetic drugs. When hypoglycemic symptoms are observed, appropriate measures such as eating food containing carbohydrates should be taken. However, when hypoglycemic symptoms are observed in combined use with α-glucosidase inhibitors, glucose should be administered.

^*: The incidence calculated from the results of clinical studies (monotherapy), at the time of approval in Japan

(2) Pyelonephritis (0.1%), sepsis (incidence unknown): Since pyelonephritis may occur and result in sepsis (including septic shock), patients should be closely monitored. If any abnormality is noted, administration should be discontinued and appropriate treatment should be provided.

(3) Necrotising fasciitis of the perineum (Fournier’s gangrene) (incidence unknown): 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. 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 necrotizing fasciitis. If Fournier’s gangrene is suspected, luseogliflozin should be discontinued and prompt treatment (including antibiotics and surgical debridement) should be instituted.

(4) Dehydration (0.1%): Dehydration may occur. Patients should be instructed to drink fluid appropriately and be monitored sufficiently. When symptoms including thirst, polyuria, pollakiuria and blood pressure decreased appear and dehydration is suspected, appropriate measures including interruption of administration and fluid replacement should be taken. Since onset of thromboembolism such as cerebral infarction following dehydration has been reported, sufficient attention should be paid.

(5) Ketoacidosis (incidence unknown): Since ketoacidosis (including diabetic ketoacidosis) may occur, patients should be closely monitored. If any abnormality is noted, administration should be discontinued and appropriate treatment should be provided.

2. Other Adverse Reactions

The following adverse reactions have been reported in all the clinical trials and from post-marketing experience with luseogliflozin. Adverse reactions listed below are classified according to frequency and system organ class (SOC). Frequency categories are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).