Jardiance適糖達

Jardiance Adverse Reactions

empagliflozin

Manufacturer:

Boehringer Ingelheim

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Adverse Reactions
Type 2 diabetes mellitus: A total of 15,582 patients with T2DM were treated in clinical studies to evaluate the safety of empagliflozin, of which 10,004 patients were treated with empagliflozin, either alone or in combination with metformin, a sulfonylurea, a PPARγ agonist, DPP4 inhibitors, or insulin. This pool includes the EMPA-REG OUTCOME study involving 7020 patients at high cardiovascular risk (mean age 63.1 years, 9.3% patients at least 75 years old, 28.5% women) treated with JARDIANCE 10 mg/day (n=2345), JARDIANCE 25 mg/day (n=2342), or placebo (n=2333) up to 4.5 years. The overall safety profile of empagliflozin in this study was comparable to the previously known safety profile.
In the previously described trials, the frequency of adverse effects leading to discontinuation was similar by treatment groups for placebo (5.6%), JARDIANCE 10 mg (5.0%) and JARDIANCE 25 mg (5.3%).
Placebo controlled double-blinded trials of 18 to 24 weeks of exposure included 3534 patients, of which 1183 were treated with placebo, 1185 were treated with JARDIANCE 10 mg and 1166 were treated with JARDIANCE 25 mg (Table 17).
The most frequent adverse drug reaction was hypoglycaemia, which depended on the type of background therapy used in the respective studies (Table 18).
Heart failure: The EMPEROR-Reduced study included 3730 patients with heart failure and reduced ejection fraction treated with empagliflozin 10 mg or placebo. Approximately half of the patients had type 2 diabetes mellitus. The most frequent adverse reaction was volume depletion (empagliflozin 10 mg: 10.6%. placebo: 9.9%). Major hypoglycaemia (events requiring assistance) was observed only in patients with diabetes mellitus.
The overall safety profile of empagliflozin was generally consistent across the studied indications. No new adverse reactions were identified in the EMPEROR-Reduced heart failure study. (See Table 17.)

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Hypoglycaemia: The frequency of hypoglycaemia depended on the background therapy in the respective studies and was similar for JARDIANCE and placebo as monotherapy, as add-on to metformin, add-on to pioglitazone +/- metformin, and as add-on with linagliptin + metformin. The frequency of patients with hypoglycaemia was increased in patients treated with JARDIANCE compared to placebo when given as add-on to metformin plus sulfonylurea, and as add-on to insulin +/- metformin and +/- sulfonylurea (Table 18).
In the EMPEROR-Reduced heart failure study, similar frequency of hypoglycaemia was noted when used add-on to sulphonylurea or insulin (empagliflozin 10 mg: 4.2%, placebo: 4.6%).
Major hypoglycaemia (events requiring assistance): The frequency of patients with major hypoglycaemic events was low (<1%) and similar for JARDIANCE and placebo as monotherapy, as add-on to metformin +/- sulfonylurea, as add-on to pioglitazone +/- metformin, and as add-on with linagliptin + metformin.
The frequency of patients with major hypoglycaemic events was increased in patients treated with JARDIANCE compared to placebo when given as add-on to insulin +/- metformin and +/- sulfonylurea.
In the EMPEROR-Reduced heart failure study, major hypoglycaemia was observed only in patients with diabetes mellitus when used as add-on to sulphonylurea or insulin (empagliflozin 10 mg: 1.2%, placebo: 1.5%). (See Table 18.)

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Urinary tract infection: The overall frequency of urinary tract infection adverse events was similar in patients treated with JARDIANCE 25 mg and placebo (7.0% and 7.2%), and higher in patients treated with JARDIANCE 10 mg (8.8%). Similar to placebo, urinary tract infection was reported more frequently for JARDIANCE in patients with a history of chronic or recurrent urinary tract infections. The intensity of urinary tract infections was similar to placebo for mild, moderate, and severe intensity reports. Urinary tract infection events were reported more frequently for empagliflozin compared to placebo in female patients, but not in male patients.
Vaginal moniliasis, vulvovaginitis, balanitis and other genital infection: Vaginal moniliasis, vulvovaginitis, balanitis and other genital infections were reported more frequently for JARDIANCE 10 mg (4.0%) and JARDIANCE 25 mg (3.9%) compared to placebo (1.0%). These adverse events were reported more frequently for empagliflozin compared to placebo in female patients, and the difference in frequency was less pronounced in male patients. The genital tract infections were mild and moderate in intensity, none was severe in intensity.
In the EMPEROR-Reduced heart failure study, the frequency of these infections was more pronounced in patients with diabetes mellitus (empagliflozin 10 mg: 1.9%; placebo: 0.4%) than in patients without diabetes mellitus (empagliflozin 10 mg: 1.4%; placebo: 0.9%) when treated with empagliflozin compared to placebo.
Increased urination: As expected via its mechanism of action, increased urination (as assessed by preferred term search including pollakiuria, polyuria, nocturia) was observed at higher frequencies in patients treated with JARDIANCE 10 mg (3.5%) and JARDIANCE 25 mg (3.3%) compared to placebo (1.4%). Increased urination was mostly mild or moderate in intensity. The frequency of reported nocturia was comparable between placebo and JARDIANCE (<1%).
In the EMPEROR-Reduced heart failure study, increased urination was observed at similar frequencies in patients treated with empagliflozin and placebo (empagliflozin 10 mg: 0.7%, placebo 0.4%).
Volume depletion: The overall frequency of volume depletion (including the predefined terms BP (ambulatory) decreased, SBP decreased, dehydration, hypotension, hypovolaemia, orthostatic hypotension and syncope) was similar to placebo (0.6% for JARDIANCE 10 mg, 0.4% for JARDIANCE 25 mg and 0.3% for placebo). The effect of empagliflozin on urinary glucose excretion is associated with osmotic diuresis, which could affect hydration status of patients aged 75 years and older. In patients ≥75 years of age (pooling of all patients with diabetes, n=13,402) the frequency of volume depletion events was similar for JARDIANCE 10 mg (2.3%) compared to placebo (2.1%), but it increased with JARDIANCE 25 mg (4.3%).
Blood creatinine increased and glomerular filtration rate decreased: Use of empagliflozin was associated with increases in serum creatinine and decreases in eGFR. These changes were observed to reverse after treatment discontinuation, suggesting acute haemodynamic changes play a role in the renal function abnormalities observed with empagliflozin.
Renal-related adverse reactions (e.g. acute kidney injury, renal impairment, acute prerenal failure) may occur in patients treated with empagliflozin.
The overall frequency of patients with increased blood creatinine and decreased glomerular filtration rate was similar between empagliflozin and placebo (blood creatinine increased: JARDIANCE 10 mg 0.6%, JARDIANCE 25 mg 0.1%, placebo 0.5%; glomerular filtration rate decreased: empagliflozin 10 mg 0.1%, empagliflozin 25 mg 0%, placebo 0.3%).
In placebo-controlled, double-blind studies up to 76 weeks, initial transient increases in creatinine (mean change from baseline after 12 weeks: JARDIANCE 10 mg 0.0011 mmol/L, JARDIANCE 25 mg 0.0006 mmol/L) and initial transient decreases in estimated glomerular filtration rates (mean change from baseline after 12 weeks: JARDIANCE 10 mg -1.34 mL/min/1.73m2, JARDIANCE 25 mg -1.37 mL/min/1.73m2) have been observed. These changes were generally reversible during continuous treatment or after drug discontinuation (see Pharmacology: Pharmacodynamics: Clinical Trials: Cardiovascular outcome (Figure 4) under Actions for the eGFR course in the EMPA-REG OUTCOME study).
Laboratory parameters: Haematocrit increased: In a pooled safety analysis (pooling of all patients with diabetes, n=13,402), mean changes from baseline in haematocrit were 3.4% and 3.6% for empagliflozin 10 mg and 25 mg, respectively, compared to -0.1% for placebo. In the EMPA-REG OUTCOME study, haematocrit values returned towards baseline values after a follow-up period of 30 days after treatment stop.
Serum lipids increased: In a pooled safety analysis (pooling of all patients with diabetes, n=13,402), mean percent increases from baseline for empagliflozin 10 mg and 25 mg versus placebo, respectively, were total cholesterol 4.9% and 5.7% versus 3.5%; HDL-cholesterol 3.3% and 3.6% versus 0.4%; LDL-cholesterol 9.5% and 10.0% versus 7.5%; triglycerides 9.2% and 9.9% versus 10.5%.
Postmarketing experience: The following postmarketing case reports have been reported during post-approval use of JARDIANCE. Because these cases are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency.
Metabolism and nutrition disorders: Ketoacidosis.
Infections and infestations: Pyelonephritis, urosepsis, necrotising fasciitis of the perineum (Fournier's gangrene).
Immune system disorders: Allergic skin reactions (e.g. rash, urticaria), angioedema.
Reproductive system and breast disorders: Phimosis.
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