Trajenta Duo Special Precautions

General: Trajenta Duo 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 Trajenta Duo is used in combination with a sulphonylurea and/or insulin. A dose reduction of the sulphonylurea or insulin may be considered (see Dosage & Administration).
Hypoglycaemia is not identified as adverse reaction for linagliptin, metformin, or linagliptin plus metformin. In clinical trials, the incidence rates of hypoglycaemia were comparably low in patients taking linagliptin in combination with metformin or metformin alone.
Lactic acidosis: Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. 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 and contact with a health care professional is recommended.
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 (see Contraindications and Interactions).
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. Diagnostic laboratory findings are decreased blood pH (<7.35), increased plasma lactate levels (>5 mmol/l), and an increased anion gap and lactate/pyruvate ratio.
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, see Dosage & Administration and Interactions.
Renal function: GFR should be assessed before treatment initiation and regularly thereafter, see Dosage & Administration. Trajenta Duo is contraindicated in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function, see Contraindications).
Cardiac function: Patients with heart failure are more at risk of hypoxia and renal impairment. In patients with stable chronic heart failure, Trajenta Duo may be used with a regular monitoring of cardiac and renal function.
For patients with acute and unstable heart failure, Trajenta Duo is contraindicated due to the metformin component (see Contraindications).
Surgery: Metformin must be discontinued at the time of surgery under general, spinal or epidural anaesthesia. 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.
Change in clinical status of patients with previously controlled type 2 diabetes: As Trajenta Duo contains metformin, a patient with previously well controlled type 2 diabetes on Trajenta Duo who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and metformin levels. If acidosis of either form occurs, Trajenta Duo must be stopped immediately and other appropriate corrective measures initiated.
Acute Pancreatitis: Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. Acute pancreatitis has been observed in patients taking linagliptin. In a cardiovascular and renal safety study (CARMELINA) with median observation period of 2.2 years, adjudicated acute pancreatitis was reported in 0.3% of patients treated with linagliptin and in 0.1% of patients treated with placebo. Patients should be informed of the characteristic symptom of acute pancreatitis. If pancreatitis is suspected, Trajenta Duo should be discontinued; if acute pancreatitis is confirmed, Trajenta Duo should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Bullous pemphigoid: Bullous pemphigoid has been observed in patients taking linagliptin. If bullous pemphigoid is suspected, Trajenta Duo should be discontinued.
Vitamin B12: The risk of low vitamin B12 levels increases with increasing metformin dose, treatment duration, and/or in patients with risk factors known to cause vitamin B12 deficiency. In case of suspicion of vitamin B12 deficiency (such as anaemia or neuropathy), vitamin B12 serum levels should be monitored. Periodic vitamin B12 monitoring could be necessary in patients with risk factors for vitamin B12 deficiency. Metformin therapy should be continued for as long as it is tolerated and not contra-indicated and appropriate corrective treatment for vitamin B12 deficiency provided in line with current clinical guidelines.
Effects on ability to drive and use machines: Trajenta Duo has no or negligible influence on the ability to drive and use machines. However, patients should be alerted to the risk of hypoglycaemia when Trajenta Duo is used in combination with other antidiabetic medicinal products known to cause hypoglycaemia (e.g. sulphonylureas).
Use in Elderly: Caution should be exercised when treating patients 80 years and older (see Dosage & Administration).