Galvus Met Special Precautions

Galvus Met: General considerations: Galvus Met is not a substitute for insulin in patients requiring insulin. Galvus Met should not be used in patients with type 1 diabetes or in patients with ketoacidosis.
Hypoglycaemia: Patients receiving Galvus Met in combination with a sulphonylurea or insulin may be at increased risk of hypoglycaemia. A lower dose of sulphonylurea or insulin should therefore be considered in order to reduce the risk of hypoglycaemia.
Vildagliptin: Hepatic impairment: Vildagliptin is not recommended in patients with hepatic dysfunction, including patients with pre-treatment AST or ALT >2.5 × ULN.
Galvus Met is therefore not recommended in patients with hepatic impairment.
Liver enzyme monitoring: Cases of hepatic dysfunction (including rare cases of hepatitis) have been reported. In these cases, the patients were generally asymptomatic without clinical sequelae, and liver function test (LFT) results returned to normal after discontinuation of treatment. LFTs should be performed prior to the initiation of treatment with Galvus Met to determine the patient's baseline values. Hepatic function should be monitored during Galvus Met treatment at three-month intervals during the first year and periodically thereafter. In patients who develop increased transaminase levels, this test should be repeated. If the results are confirmed, the patient should be monitored at frequent intervals until test results return to normal. Withdrawal of Galvus Met is recommended in patients with elevated AST or ALT levels ≥3 x ULN.
Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue treatment with Galvus Met.
Following withdrawal of treatment with Galvus Met and normalization of LFT results, treatment with Galvus Met should not be reinitiated.
Pancreatitis: In post-marketing experience there have been spontaneously reported adverse reactions of acute pancreatitis. Patients should therefore be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain.
Resolution of pancreatitis has been observed after discontinuation of vildagliptin. If pancreatitis is suspected, vildagliptin and other potentially suspect medicinal products should be discontinued.
Heart failure: A clinical trial of vildagliptin in patients with New York Heart Association (NYHA) functional class I-III showed that treatment with vildagliptin was not associated with a change in left-ventricular function or worsening of pre-existing congestive heart failure (CHF) versus placebo. Clinical experience in patients with NYHA functional class III treated with vildagliptin is still limited and results are inconclusive.There is no experience of vildagliptin use in clinical trials in patients with NYHA functional class IV and therefore use is not recommended in these patients.
Skin disorders: Skin lesions on the extremities of monkeys, such as blistering and ulceration, have been reported in non-clinical toxicology studies in association with the use of vildagliptin (see Pharmacology: Toxicology: Preclinical data under Actions). Although no increased incidence of skin lesions was observed in clinical trials, there is only limited experience in patients with diabetic skin complications. Therefore, in keeping with routine care of diabetic patients, monitoring for skin disorders, such as blistering or ulceration, is recommended.
Metformin: Heart failure: Metformin is contraindicated in patients with heart failure, therefore Galvus Met is contraindicated in this patient population (see Contraindications).
Lactic acidosis: Lactic acidosis is a very rare (3 cases per 100 000 patient-years), but serious, metabolic complication associated that 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 (e.g. due to severe diarrhea or vomiting, fever or reduced fluid intake), the patient should stop taking metformin-containing products (such as Galvus Met) and seek immediate medical attention.
Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in patients treated with metformin-containing products (such as Galvus Met). 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).
Cases of lactic acidosis reported thus far in association with metformin have been in patients with marked renal impairment. The incidence of lactic acidosis can and should be reduced by regular monitoring even of risk factors not associated with metformin, such as poorly controlled diabetes, ketoacidosis, prolonged fasting, excessive alcohol consumption, hepatic impairment and any hypoxic conditions.
Prior signs and symptoms are non-specific and may present as muscle cramps accompanied by gastrointestinal disorders, abdominal pain, elevated respiratory rate and pronounced asthenia. The attending physician should take note of these symptoms. The physician should also inform patients of the risk of lactic acidosis.
Lactic acidosis is characterized by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. Signs and symptoms can be recognized by the following laboratory parameters: decreased blood pH (< 7.35), increased plasma lactate levels >5 mmol/litre, an increased anion gap and an elevated lactate/pyruvate ratio.
If lactic acidosis is suspected, treatment with metformin-containing products (such as Galvus Met) should be discontinued and the patient should be hospitalized immediately. It is most effective to eliminate both lactate and metformin by haemodialysis (see Overdosage).
Renal function (see Contraindications): GFR should be assessed before treatment initiation and regularly thereafter (see Dosage & Administration). Metformin-containing products (such as Galvus Met) are contraindicated in patients with GFR < 30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function (see Contraindications).
Metformin is excreted via the kidneys, and creatinine clearance should therefore be monitored before initiating treatment, and regularly thereafter: once a year in patients with normal renal function; according to the physician's judgment in patients with levels at the lower limit of the normal range, or in elderly patients because asymptomatic reductions in renal function often occur in elderly patients in particular.
Iodinated contrast media: Intravascular administration of iodinated contrast media for radiological tests (i.v. urography, angiography, etc.) may lead to contrast-induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. Metformin-containing products (such as Galvus Met) 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).
Surgical procedures: Metformin-containing products (such as Galvus Met) must be discontinued at the time of surgery under general, spinal and epidural anaesthesia (except minor procedures not associated with restricted intake of food and fluids) and may be restarted no earlier than 48 hours following surgery until the patients's oral nutrition has resumed and renal function has been re-evaluated and found to be stable.
Alcohol intake: Alcohol potentiates the effect of metformin on lactate metabolism. Patients should therefore be warned against excessive alcohol intake while receiving metformin-containing products (such as Galvus Met).
Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of fasting, malnutrition or hepatic impairment.
Vitamin B₁₂ levels: Metformin has been associated with a decrease in serum vitamin B₁₂ levels, without clinical manifestations, in approximately 7% of patients. Such a decrease is very rarely associated with anaemia and appears to be rapidly reversible by discontinuation of metformin and/or by vitamin B₁₂ supplementation. Measurement of haematological parameters on at least an annual basis is advised for patients receiving metformin-containing products (such as Galvus Met). Any disturbance that occurs should be appropriately investigated and managed.
Change in the clinical status of patients with previously controlled type 2 diabetes: Patients with type 2 diabetes previously well controlled on Galvus Met who develop laboratory abnormalities or clinical illness (especially vague or poorly defined illness) should promptly be evaluated for ketoacidosis and/or lactic acidosis. If acidosis occurs, Galvus Met must be stopped immediately and appropriate measures initiated.
Hypoglycaemia: Hypoglycaemia does not usually occur in patients receiving Galvus Met alone, but it may occur if caloric intake is deficient, if strenuous exercise is not compensated by caloric supplementation or if alcohol is consumed. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication, are susceptible to hypoglycaemic effects. Hypoglycaemia may be difficult to recognize in the elderly and in patients taking beta-blockers.
Sulphonylureas are known to cause hypoglycaemia. Patients taking Galvus Met in combination with a sulphonylurea may be at risk of hypoglycaemia. Therefore, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia when used in combination with Galvus Met.
Loss of control of blood glucose: When a patient on antidiabetic therapy is exposed to stress such as fever, trauma, infection, surgery, etc., a temporary loss of glycaemic control may occur. In such situations, it may be necessary to withhold Galvus Met and temporarily administer insulin. Galvus Met may be reinstituted after the acute episode resolves.
Effects on ability to drive and use machines: There have been no studies of the effects of this product on the ability to drive or use machines. Patients who experience dizziness should thus avoid driving vehicles or using machines.