Jentadueto 2.5 mg/850 mg film-coated tablets
Each tablet contains 2.5 mg of linagliptin and 850 mg of metformin hydrochloride.
For the full list of excipients, see section 6.1.
Film-coated tablet (tablet).
Oval, biconvex, light orange, film-coated tablet of 19.2 mm x 9.4 mm debossed with "D2/850" on one side and the company logo on the other.
Treatment of adult patients with type 2 diabetes mellitus:
Jentadueto is indicated as an adjunct to diet and exercise to improve glycaemic control in adult patients inadequately controlled on their maximal tolerated dose of metformin alone, or those already being treated with the combination of linagliptin and metformin.
Jentadueto is indicated in combination with a sulphonylurea (i.e. triple combination therapy) as an adjunct to diet and exercise in adult patients inadequately controlled on their maximal tolerated dose of metformin and a sulphonylurea.
Jentadueto is indicated in combination with insulin (i.e. triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in adult patients when insulin and metformin alone do not provide adequate glycaemic control.
Posology
The dose of antihyperglycaemic therapy with Jentadueto should be individualised on the basis of the patient's current regimen, effectiveness, and tolerability, while not exceeding the maximum recommended daily dose of 5 mg linagliptin plus 2,000 mg of metformin hydrochloride.
For patients inadequately controlled on maximal tolerated dose of metformin monotherapy
For patients not adequately controlled on metformin alone, the usual starting dose of Jentadueto should provide linagliptin dosed as 2.5 mg twice daily (5 mg total daily dose) plus the dose of metformin already being taken.
For patients switching from co-administration of linagliptin and metformin
For patients switching from co-administration of linagliptin and metformin, Jentadueto should be initiated at the dose of linagliptin and metformin already being taken.
For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a sulphonylurea
The dose of Jentadueto should provide linagliptin dosed as 2.5 mg twice daily (5 mg total daily dose) and a dose of metformin similar to the dose already being taken. When linagliptin plus metformin hydrochloride is used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be required to reduce the risk of hypoglycaemia (see section 4.4).
For patients inadequately controlled on dual combination therapy with insulin and the maximal tolerated dose of metformin
The dose of Jentadueto should provide linagliptin dosed as 2.5 mg twice daily (5 mg total daily dose) and a dose of metformin similar to the dose already being taken. When linagliptin plus metformin hydrochloride is used in combination with insulin, a lower dose of insulin may be required to reduce the risk of hypoglycaemia (see section 4.4).
For the different doses of metformin, Jentadueto is available in strengths of 2.5 mg linagliptin plus 850 mg metformin hydrochloride and 2.5 mg linagliptin plus 1,000 mg metformin hydrochloride.
Special populations
Older people
As metformin is excreted by the kidney, Jentadueto should be used with caution as age increases. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the older people (see sections 4.3 and 4.4). Clinical experience with patients > 80 years of age is limited and caution should be exercised when treating this population.
Renal impairment
Jentadueto must not be used in patients with moderate or severe renal impairment (creatinine clearance < 60 ml/min) due to the active substance metformin (see sections 4.3 and 4.4).
Hepatic impairment
Jentadueto is not recommended in patients with hepatic impairment due to the active substance metformin (see sections 4.3 and 5.2). Clinical experience with Jentadueto in patients with hepatic impairment is lacking.
Paediatric population
The safety and efficacy of Jentadueto in children and adolescents aged 0 to 18 years have not been established. No data are available.
Method of administration
Jentadueto should be taken twice daily with meals to reduce the gastrointestinal adverse reactions associated with metformin.
All patients should continue their diet with an adequate distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.
If a dose is missed, it should be taken as soon as the patient remembers. However, a double dose should not be taken at the same time. In that case, the missed dose should be skipped.
• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
• Diabetic ketoacidosis, diabetic pre-coma.
• Renal failure or renal dysfunction (creatinine clearance < 60 ml/min).
• Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock.
• Acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction, shock.
• Hepatic impairment, acute alcohol intoxication, alcoholism (see section 4.5).
General
Jentadueto should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Hypoglycaemia
When linagliptin was added to a sulphonylurea on a background of metformin, the incidence of hypoglycaemia was increased over that of placebo.
Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, caution is advised when Jentadueto is used in combination with a sulphonylurea and/or insulin. A dose reduction of the sulphonylurea or insulin may be considered (see section 4.2).
Hypoglycaemia is not identified as adverse reaction for linagliptin, metformin, or linagliptin plus metformin. In clinical trials, the incidence rates of hypoglycemia were comparably low in patients taking linagliptin in combination with metformin or metformin alone.
Lactic acidosis
Lactic acidosis is a very rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin hydrochloride accumulation. Reported cases of lactic acidosis in patients on metformin hydrochloride have occurred primarily in diabetic patients with significant renal failure. The incidence of lactic acidosis can and should be reduced by also assessing other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic impairment and any condition associated with hypoxia.
Diagnosis
The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps with digestive disorders such as abdominal pain and severe asthenia.
Lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/l, and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, metformin hydrochloride should be discontinued and the patient should be hospitalised immediately (see section 4.9).
Renal function
As metformin hydrochloride is excreted by the kidney, serum creatinine levels should be determined before initiating treatment and regularly thereafter:
• at least annually in patients with normal renal function,
• at least two to four times a year in patients with serum creatinine levels at or above the upper limit of normal and in older subjects.
Decreased renal function in older subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy or when starting therapy with a non-steroidal anti-inflammatory substance.
Surgery
As Jentadueto contains metformin hydrochloride the treatment must be discontinued 48 hours before elective surgery with general, spinal or epidural anaesthesia. Therapy with J
