Short version of the Summary of Product Characteristics (SPC)

Medicinal Product:

Trajenta 5 mg film-coated tablets. Each tablet contains 5 mg of linagliptin. For the full list of excipients, consult section 6.1. of the full SPC.

Therapeutic indications:

Trajenta is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control as: a) monotherapy: when metformin is inappropriate due to intolerance, or contraindicated due to renal impairment. b) combination therapy: in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control.

Posology and method of administration:

Posology: The dose of linagliptin is 5 mg once daily. When linagliptin is added to metformin, the dose of metformin should be maintained, and linagliptin administered concomitantly. When linagliptin 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. Renal impairment: For patients with renal impairment, no dose adjustment for linagliptin is required. Hepatic impairment: Pharmacokinetic studies suggest that no dose adjustment is required for patients with hepatic impairment but clinical experience in such patients is lacking. Elderly: No dose adjustment is necessary based on age. However, clinical experience in patients > 80 years of age is limited and caution should be exercised when treating this population. Paediatric population: The safety and efficacy of linagliptin in children and adolescents has not yet been established. No data are available. Method of administration: The tablets can be taken with or without a meal at any time of the day. If a dose is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day.

Contraindications:

Hypersensitivity to the active substance or to any of the excipients.

Special warnings and precautions for use:

Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Hypoglycaemia: Linagliptin alone showed a comparable incidence of hypoglycaemia to placebo. In clinical trials of linagliptin as part of combination therapy with medicinal products not known to cause hypoglycaemia (metformin), rates of hypoglycaemia reported with linagliptin were similar to rates in patients taking placebo. 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 linagliptin is used in combination with a sulphonylurea and/or insulin. A dose reduction of the sulphonylurea or insulin may be considered.
Acute pancreatitis: Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. In post marketing experience of linagliptin there have been spontaneously reported adverse reactions of acute pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Trajenta should be discontinued; if acute pancreatitis is confirmed, Trajenta should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Bullous pemphigoid: There have been post-marketing reports of bullous pemphigoid in patients taking linagliptin. If bullous pemphigoid is suspected, Trajenta should be discontinued.

Interaction with other medicinal products and other forms of interaction:

Linagliptin is considered unlikely to cause interactions with other P-gp substrates. Clinical data suggest that the risk for clinically meaningful interactions by co-administered medicinal products is low. For more detailed information on interactions with linagliptin, please consult the full version of the SPC.

Pregnancy and lactation:

Pregnancy: The use of linagliptin has not been studied in pregnant women. As a precautionary measure, it is preferable to avoid the use of linagliptin during pregnancy. Breast-feeding: A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from linagliptin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Effects on ability to drive and use machines:

Linagliptin has no or negligible influence on the ability to drive and use machines. However patients should be alerted to the risk of hypoglycaemia especially when combined with sulphonylurea and/or insulin.

Undesirable effects:

Linagliptin monotherapy: common (≥ 1/100 to <1/10) - Lipase increased; uncommon (≥ 1/1,000 to < 1/100) – Nasopharyngitis, Hypersensitivity (e.g. bronchial hyperreactivity), Cough, Rash; rare (≥ 1/10,000 to < 1/1,000) – Angioedema, Urticaria, Amylase increased; not known (cannot be estimated from the available data) – Pancreatitis, Bullous pemphigoid. Linagliptin + Metformin: common - Lipase increased; uncommon - Nasopharyngitis, Hypersensitivity (e.g. bronchial hyperreactivity), Cough, Rash, Amylase increased; rare - Angioedema, Urticaria; not known– Pancreatitis; Bullous pemphigoid. Linagliptin + Metformin + Sulphonylurea: very common (≥ 1/10) – Hypoglycaemia; common - Lipase increased; uncommon - Hypersensitivity (e.g. bronchial hyperreactivity), Rash, Amylase increased; rare - Angioedema, Urticaria; not known – Nasopharyngitis; Cough; Pancreatitis; Bullous pemphigoid. Linagliptin +
Insulin
: common - Lipase increased; uncommon - Nasopharyngitis, Hypersensitivity (e.g. bronchial hyperreactivity), Cough, Pancreatitis, Constipation; Rash; rare - Angioedema, Urticaria; not known – Amylase increased; Bullous pemphigoid.  Linagliptin + Metformin + Empagliflozin: common - Lipase increased; uncommon - Amylase increased; not known – Nasopharyngitis, Hypersensitivity (e.g. bronchial hyperreactivity), Cough, Pancreatitis.

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 via the national reporting systems.

Revision date: June 2017

Click here for full Prescribing Information, including Medication Guide.

Short version of the Summary of Product Characteristics (SPC)

Medicinal Product:

Jentadueto 2,5 mg / 850 mg and 2,5 mg / 1.000 mg film-coated tablets. Each tablet contains 2.5 mg of linagliptin and 850 mg of metformin hydrochloride or 2.5 mg of linagliptin and 1,000 mg of metformin hydrochloride.

Indications:

adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: 1) in patients inadequately controlled on their maximally tolerated dose of metformin alone. 2) in combination with other medicinal products for the treatment of diabetes, including insulin, in patients inadequately controlled with metformin and these medicinal products. 3) in patients already being treated with the combination of linagliptin and metformin as separate tablets.

Posology:

Adults with normal renal function (GFR ≥90 ml/min): The dose 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. Patients inadequately controlled on maximal tolerated dose of metformin monotherapy: 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. Patients switching from co-administration of linagliptin and metformin: Jentadueto should be initiated at the dose of linagliptin and metformin already being taken. 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 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. 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 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. Special populations: Elderly: Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis. Clinical experience with patients > 80 years of age is limited and caution should be exercised when treating this population. Renal impairment: GFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter. In patients at an increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months. Factors that may increase the risk of lactic acidosis should be reviewed before considering initiation of metformin in patients with GFR<60 ml/min. If no adequate strength of Jentadueto is available, individual monocomponents should be used instead of the fixed dose combination. Posology for renally impaired patients: GFR: 60-89 ml/min: Metformin - Maximum daily dose is 3000 mg. Dose reduction may be considered in relation to declining renal function. Linagliptin - No dose adjustment. / GFR: 45-59 ml/min: Metformin - Maximum daily dose is 2000 mg. The starting dose is at most half of the maximum dose. Linagliptin - No dose adjustment. / TFG: 30-44 ml/min: Metformin - Maximum daily dose is 1000 mg. The starting dose is at most half of the maximum dose. Linagliptin - No dose adjustment. / GFR: < 30 ml/min: Metformin - contraindicated. Linagliptin - No dose adjustment. Hepatic impairment: not recommended in patients with hepatic impairment due to the active substance metformin. Paediatric population: The safety and efficacy of Jentadueto in children and adolescents aged 0 to 18 years have not been established.

Method of administration:

jentadueto should be taken twice daily with meals to reduce the gastrointestinal adverse reactions associated with metformin. 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.

Contraindications:

Hypersensitivity to the active substances or to any of the excipients; any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis); diabetic pre-coma; Severe renal failure (GFR <30 ml/min); Acute conditions with the potential to alter renal function (e.g. dehydration, severe infection, shock); Disease which may cause tissue hypoxia (e.g. decompensated heart failure, respiratory failure, recent myocardial infarction, shock); Hepatic impairment, acute alcohol intoxication, alcoholism.

Special warnings and precautions for use:

Jentadueto should not be used in patients with type 1 diabetes. Hypoglycaemia: 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. Lactic acidosis: Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis. In case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), metformin should be temporarily discontinued.  Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic impairment, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis. Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention. Administration of iodinated contrast agent: Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. Metformin should be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable. Renal function: GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicated in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function. Cardiac function: Jentadueto may be used with a regular monitoring of cardiac and renal function. For patients with acute and unstable heart failure, Jentadueto is contraindicated. Surgery: Metformin must be discontinued at the time of surgery under general, spinal or epidural anesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable. Elderly: Caution should be exercised when treating patients 80 years and older. Change in clinical status of patients with previously controlled type 2 diabetes: a patient with previously well controlled type 2 diabetes on Jentadueto who develops laboratory abnormalities or clinical illness should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. If acidosis of either form occurs, Jentadueto must be stopped immediately and other appropriate corrective measures initiated. Acute pancreatitis: In post-marketing experience of linagliptin there have been spontaneously reported adverse reactions of acute pancreatitis. If pancreatitis is suspected, Jentadueto should be discontinued; if acute pancreatitis is confirmed, Jentadueto should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Bullous pemphigoid: There have been post-marketing reports of bullous pemphigoid in patients taking linagliptin. If bullous pemphigoid is suspected, Jentadueto should be discontinued.

Interactions:

Effects of other medicinal products on linagliptin: full efficacy of linagliptin in combination with strong P-gp inducers might not be achieved, particularly if these are administered long-term; Combination requiring precautions for use: Glucocorticoids (given by systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. If necessary, the dose of the anti-hyperglycaemic medicinal product should be adjusted during therapy with the other medicinal product and on its discontinuation. Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin, close monitoring of renal function is necessary. Organic cation transporters (OCT): Co-administration of metformin with: a) Inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin. b) Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of metformin. c) Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration. d) Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin. Caution is therefore advised, especially in patients with renal impairment, when these drugs are coadministered with metformin, as metformin plasma concentration may increase. If needed, dose adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efficacy of metformin. Concomitant use not recommended: Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of fasting, malnutrition or hepatic impairment. Iodinated contrast agentes:  Jentadueto must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable.

Pregnancy and lactation:

pregnancy: Jentadueto should not be used during pregnancy. If the patient plans to become pregnant, or if pregnancy occurs, treatment with Jentadueto should be discontinued and switched to insulin treatment as soon as possible in order to lower the risk of foetal malformations associated with abnormal blood glucose levels; Breast-feeding: Metformin is excreted in human milk in small amounts. It is not known whether linagliptin is excreted into human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Jentadueto therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility: The effect of Jentadueto on human fertility has not been studied.

Undesirable effects:

Linagliptin + metformin : common: diarrhoea, lipase increased; uncommon: nasopharyngitis; hypersensitivity, cough; decreased appetite; nausea; vomiting; rash; pruritus; blood amylase increased; rare: angioedema; urticaria; not known: pancreatitis; bullous pemphigoid. Linagliptin+metformin and sulphonylurea: very common: hypoglycaemia; common: lipase increased; uncommon: hypersensitivity; diarrhoea; nausea; vomiting; rash; pruritus; blood amylase increased; rare: angioedema; urticaria; not known: nasopharyngitis; cough; decreased appetite; pancreatitis; bullous pemphigoid. Linagliptin+metformin and insulin: common: nausea; lipase increased; uncommon: nasopharyngitis; hypersensitivity, cough; diarrhoea; pancreatitis; constipation; liver function disorders; rash; pruritus; rare: angioedema; urticaria; not known: decreased appetite; vomiting; bullous pemphigoid; blood amylase increased. Linagliptin+metformin and empagliflozin: common: lipase increased; uncommon: vomiting; rash; blood amylase increased; rare: angioedema; urticaria; not known: nasopharyngitis; hypersensitivity; cough; decreased appetite; diarrhoea; nausea; pancreatitis; pruritus; bullous pemphigoid;  Metformin in monotherapy: very common: abdominal pain; common: taste disturbance; very rare: Lactic acidosis; Vitamin B12 deficiency, hepatitis, skin reactions such as erythema, urticaria.

Revision date: June 2017

Click here for full Prescribing Information, including Medication Guide.