General: Galvus Met is not a substitute for insulin in patients requiring insulin and should not be used in patients with type 1 diabetes.
Lactic acidosis: Lactic acidosis is a very rare but serious metabolic complication, most often occurs with acute worsening of renal function, or cardiorespiratory illness or sepsis. Metformin accumulation occurs with 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 insufficiency, 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 characterized by acidotic dyspnoea, 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 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 impairment: GFR should be assessed before treatment initiation and regularly thereafter (see DOSAGE & ADMINISTRATION). Metformin 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).
Hepatic impairment: Patients with hepatic impairment, including those with pre-treatment ALT or AST > 3x ULN, should not be treated with Galvus Met (see DOSAGE & ADMINISTRATION, CONTRAINDICATIONS and ADVERSE REACTIONS).
Liver enzyme monitoring: Rare cases of hepatic dysfunction (including hepatitis) have been reported with vildagliptin. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function tests (LFTs) returned to normal after discontinuation of treatment. LFTs should be performed prior to the initiation of treatment with Galvus Met in order to know the patient's baseline value. Liver function should be monitored during treatment with Galvus Met at three-month intervals during the first year and periodically thereafter. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed up thereafter with frequent LFTs until the abnormality/abnormalities return to normal. Should an increase in AST or in ALT of 3x ULN or greater persist, withdrawal of Galvus Met therapy is recommended. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Galvus Met.
Following withdrawal of treatment with Galvus Met and LFT normalization, treatment with Galvus Met should not be re-initiated.
Skin disorders: Skin lesions, including blistering and ulceration have been reported with vildagliptin in extremities of monkeys in non-clinical toxicology studies (see Pharmacology: Toxicology: PRECLINICAL SAFETY DATA under Actions). Although skin lesions were not observed at an increased incidence in clinical trials, there was limited experience in patients with diabetic skin complications. Furthermore, there have been post-marketing reports of bullous and exfoliative skin lesions. Therefore, in keeping with routine care of the diabetic patient, monitoring for skin disorders, such as blistering or ulceration, is recommended.
Acute pancreatitis: Use of vildagliptin has been associated with a risk of developing acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis.
If pancreatitis is suspected, vildagliptin should be discontinued; if acute pancreatitis is confirmed, vildagliptin should not be restarted. Caution should be exercised in patients with a history of acute pancreatitis.
Hypoglycaemia: Sulphonylureas are known to cause hypoglycaemia. Patients receiving vildagliptin in combination with a sulphonylurea may be at risk for hypoglycaemia. Therefore, a lower dose of sulphonylurea may be considered to reduce the risk of hypoglycaemia.
Surgery: As Galvus Met contains metformin, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not usually be resumed earlier than 48 hours afterwards.
Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. Patients who may experience dizziness as an undesirable effect should avoid driving vehicles or using machines.