Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Boehringer Ingelheim International GmbH, Binger Str. 173, 55216 Ingelheim am Rhein, Germany
Glyxambi, fixed dose combination of empagliflozin and linagliptin, is indicated in adults aged 18 years and older with type 2 diabetes mellitus:
(See sections 4.2, 4.4, 4.5 and 5.1 for available data on combinations studied)
The recommended starting dose is one film-coated tablet of Glyxambi 10 mg/5 mg (10 mg empagliflozin plus 5 mg linagliptin) once daily.
In patients who tolerate this starting dose and require additional glycaemic control, the dose can be increased to one film-coated tablet of Glyxambi 25 mg/5 mg (25 mg empagliflozin plus 5 mg linagliptin) once daily.
When Glyxambi is used in combination with metformin, the metformin dose should be continued.
When Glyxambi is used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia (see sections 4.4, 4.5 and 4.8).
Patients switching from empagliflozin (either 10 mg or 25 mg daily dose) and linagliptin (5 mg daily dose) to Glyxambi should receive the same daily dose of empagliflozin and linagliptin in the fixed dose combination as in separate tablets.
If a dose is missed, and it is 12 hours or more until the next dose, the dose should be taken as soon as the patient remembers. The next dose should be taken at the usual time. If a dose is missed, and it is less than 12 hours until the next dose, the dose should be skipped and the next dose should be taken at the usual time. A double dose should not be taken to compensate for a forgotten dose.
The glycaemic efficacy of empagliflozin is dependent on renal function. For cardiovascular risk reduction as add on to standard of care, a dose of 10 mg empagliflozin once daily should be used in patients with an eGFR below 60 ml/min/1.73 m² (see Table 1). Because the glycaemic lowering efficacy of empagliflozin is reduced in patients with moderate renal impairment and likely absent in patients with severe renal impairment, if further glycaemic control is needed, the addition of other anti-hyperglycaemic agents should be considered. For dose adjustment recommendations according to eGFR or CrCL refer to Table 1.
Table 1. Dose adjustment recommendationsa:
| eGFR [ml/min/1.73 m²] or CrCL [ml/min] | Empagliflozin | Linagliptin |
|---|---|---|
| ≥60 | Initiate with 10 mg. In patients tolerating 10 mg and requiring additional glycaemic control, the dose can be increased to 25 mg. | 5 mg No dose adjustment for linagliptin is required. |
| 45 to <60 | Initiate with 10 mg.b Continue with 10 mg in patients already taking empagliflozin. | |
| 30 to <45 | Initiate with 10 mg.b Continue with 10 mg in patients already taking empagliflozin.b | |
| <30 | Empagliflozin is not recommended. |
a See sections 4.4, 4.8, 5.1 and 5.2
b patients with type 2 diabetes mellitus and established cardiovascular disease
Glyxambi should not be used in patients with end stage renal disease (ESRD) or in patients on dialysis, as there are insufficient data on empagliflozin to support use in these patients (see sections 4.4, 5.1 and 5.2).
No dose adjustment is required in patients with mild to moderate hepatic impairment.
Empagliflozin exposure is increased in patients with severe hepatic impairment and therapeutic experience in such patients is limited (see section 5.2). Therefore, Glyxambi is not recommended for use in this population.
No dose adjustment based on age is required. However, renal function and risk of volume depletion should be taken into account in elderly patients (see sections 4.4 and 4.8). Based on very limited experience in patients 75 years and older, initiation of Glyxambi therapy is not recommended in this population (see sections 4.4 and 5.2).
Safety and efficacy of Glyxambi in paediatric patients below 18 years of age have not been established. No data are available.
Glyxambi tablets are for oral use and can be taken with or without a meal at any time of the day at regular intervals. The tablets should be swallowed whole with water.
In controlled clinical trials single doses of up to 800 mg empagliflozin (equivalent to 32 times the highest recommended daily dose) in healthy volunteers and multiple daily doses of up to 100 mg empagliflozin (equivalent to 4 times the highest recommended daily dose) in patients with type 2 diabetes did not show any toxicity. Empagliflozin increased urine glucose excretion leading to an increase in urine volume. The observed increase in urine volume was not dose-dependent. There is no experience with doses above 800 mg in humans.
During controlled clinical trials in healthy subjects, single doses of up to 600 mg linagliptin (equivalent to 120 times the recommended dose) were generally well tolerated. There is no experience with doses above 600 mg in humans.
In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring and institute clinical measures as required.
The removal of empagliflozin by haemodialysis has not been studied. Linagliptin is not expected to be eliminated to a therapeutically significant degree by haemodialysis or peritoneal dialysis.
3 years.
This medicinal product does not require any special storage conditions.
PVC/PVDC/aluminium perforated unit dose blisters.
Pack sizes of 7 × 1, 10 × 1, 14 × 1, 28 × 1, 30 × 1, 60 × 1, 70 × 1, 90 × 1 and 100 × 1 film-coated tablets.
Not all pack sizes may be marketed.
No special requirements for disposal.
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