Jardiance Duo Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions in clinical trials were hypoglycaemia in combination with insulin and/or sulphonylurea and gastrointestinal symptoms (nausea, vomiting, diarrhoea, abdominal pain and loss of appetite). No additional adverse reactions were identified in clinical trials with empagliflozin as add-on to metformin compared to the side effects of the single components.
Tabulated list of adverse reactions: The adverse reactions are listed by absolute frequency. Frequencies are defined as 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), or very rare (<1/10,000), and not known (cannot be estimated from the available data). (See Table 10.)

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Description of selected adverse reactions: Hypoglycaemia: The frequency of hypoglycaemia depended on the background therapy in the respective studies and was similar for empagliflozin and placebo as add-on to metformin, as add-on to linagliptin and metformin, for the combination of empagliflozin with metformin in drug-naïve patients compared to those treated with empagliflozin and metformin as individual components, and as adjunct to standard care therapy. An increased frequency was noted when empagliflozin given as add-on to metformin and a sulfonylurea (empagliflozin 10 mg: 16.1%, empagliflozin 25 mg: 11.5% and placebo: 8.4%), or as add-on to metformin and insulin (empagliflozin 10 mg: 31.3%, empagliflozin 25 mg: 36.2% and placebo: 34.7%).
Major hypoglycaemia (events requiring assistance): The overall frequency of patients with major hypoglycaemic events was low (<1%) and similar for empagliflozin and placebo as add-on to metformin, and for the combination of empagliflozin with metformin in drug-naïve patients compared to those treated with empagliflozin and metformin as individual components, and as adjunct to standard care therapy. Major hypoglycaemic events occurred in 0.5%, 0% and 0.5% of patients treated with empagliflozin 10 mg, empagliflozin 25 mg and placebo when added on to metformin and insulin, respectively. No patient had a major hypoglycaemic event in the combination with metformin and a sulphonylurea and as add-on to linagliptin and metformin.
Urinary tract infection: The overall frequency of urinary tract infection adverse events was higher in metformin-treated patients who received empagliflozin 10 mg (8.8%) compared to empagliflozin 25 mg (6.6%) or placebo (7.8%). Similar to placebo, urinary tract infection was reported more frequently for empagliflozin in patients with a history of chronic or recurrent urinary tract infections. The intensity of urinary tract infections (i.e. mild/moderate/severe) was similar to placebo. Urinary tract infection events were reported more frequently for empagliflozin 10 mg compared with placebo in female patients, but not for empagliflozin 25 mg. The frequencies of urinary tract infections were low for male patients and were balanced across treatment groups.
Vaginal moniliasis, vulvovaginitis, balanitis and other genital infection: Vaginal moniliasis, vulvovaginitis, balanitis and other genital infections were reported more frequently in metformin-treated patients who received empagliflozin 10 mg (4.0%) and empagliflozin 25 mg (3.9%) compared to placebo (1.3%), and were reported more frequently for empagliflozin compared to placebo in female patients. The difference in frequency was less pronounced in male patients. Genital tract infections were mild and moderate in intensity, none was severe in intensity.
Increased urination: As expected from the mechanism of action, increased urination (as assessed by PT search including pollakiuria, polyuria, nocturia) was observed at higher frequencies in metformin-treated patients who received empagliflozin 10 mg (3.0%) and empagliflozin 25 mg (2.9%) compared to placebo (1.4%) as add-on to metformin therapy. Increased urination was mostly mild or moderate in intensity. The frequency of reported nocturia was comparable between placebo and empagliflozin (<1%).
Volume depletion: The overall frequency of volume depletion (including the predefined terms blood pressure (ambulatory) decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolaemia, orthostatic hypotension, and syncope) in metformin-treated patients who received empagliflozin was low: 0.6% for empagliflozin 10 mg, 0.3% for empagliflozin 25 mg and 0.1% for placebo. The effect of empagliflozin on urinary glucose excretion is associated with osmotic diuresis, which could affect hydration status of patients age 75 years and older. In patients ≥75 years of age volume depletion events have been reported in a single patient treated with empagliflozin 25 mg as add-on to metformin therapy.
Blood creatinine increased/Glomerular filtration rate decreased: The overall frequency of patients with increased blood creatinine and decreased glomerular filtration rate were similar between empagliflozin and placebo as add-on to metformin (blood creatinine increased: empagliflozin 10 mg 0.5%, empagliflozin 25 mg 0.1%, placebo 0.4%; glomerular filtration rate decreased: empagliflozin 10 mg 0.1%, empagliflozin 25 mg 0%, placebo 0.2%).
Initial increases in creatinine and initial decreases in estimated glomerular filtration rates in patients treated with empagliflozin as add-on to metformin therapy were generally transient during continuous treatment or reversible after drug discontinuation of treatment.
Consistently, in the EMPA-REG OUTCOME study, patients treated with empagliflozin experienced an initial fall in eGFR (mean: 3 ml/min/1.73 m²). Thereafter, eGFR was maintained during continued treatment. Mean eGFR returned to baseline after treatment discontinuation suggesting acute haemodynamic changes may play a role in these renal function changes.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.