Galvusmet Special Precautions

Vildagliptin/Metformin: Not a substitute for insulin in patients requiring insulin. It should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Vildagliptin: Patients with hepatic impairment: Vildagliptin is not recommended in patients with hepatic impairment, including patients with a pre-treatment ALT or AST >2.5X the ULN.
Hepatic 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. LFTs should be monitored 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 liver function tests until the abnormality/abnormalities return to normal. Should an increase in AST or ALT of 3x the ULN or greater persist, withdrawal of therapy is recommended. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue treatment and contact their physician immediately. Following withdrawal of treatment and LFT normalization, treatment should not be reinitiated.
Vildagliptin + metformin HCl (Galvus Met) is not recommended in patients with hepatic impairment.
Heart failure: A clinical study 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 (see PHARMACOLOGY: PHARMACODYNAMICS: CLINICAL STUDIES under ACTIONS).
There is no experience of vildagliptin use in clinical studies in patients with NYHA functional class IV and therefore use is not recommended in these patients.
Metformin Hydrochloride: Lactic acidosis: Lactic acidosis is a very rare but serious metabolic complication that 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 vildagliptin + metformin HCl (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 vildagliptin + metformin HCl (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).
Diagnosis of lactic acidosis: Patients and/or caregivers should be informed of the risk of lactic acidosis. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. If suspected symptoms occur, the patient should stop taking metformin-containing products (such as vildagliptin + metformin HCl (Galvus Met)) 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. If metabolic acidosis is suspected, treatment metformin-containing products (such as vildagliptin + metformin HCl (Galvus Met) should be discontinued and the patient should be immediately hospitalized (see OVERDOSAGE).
Monitoring of renal function: GFR should be assessed before treatment initiation and regularly thereafter (see DOSAGE & ADMINISTRATION). Metformin-containing products (such as vildagliptin + metformin HCl (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 hydrochloride is known to be substantially excreted by the kidneys, and the risk of metformin hydrochloride accumulation and lactic acidosis increases with the degree of renal function impairment. Since advancing age is associated with reduced renal function, careful dose titration in the elderly to establish the minimum dose for adequate glycemic effect, and renal function should be monitored regularly. (See DOSAGE & ADMINISTRATION and CONTRAINDICATIONS).
Interactions: Concomitant medications that may affect renal function or metformin hydrochloride disposition: Concomitant medications that may affect renal function, result in significant hemodynamic change or inhibit renal transport and increase metformin systemic exposure should be used with caution (see INTERACTIONS).
Administration of intravascular iodinated contrast materials: Intravascular administration of iodinated contrast agents may lead to contrast-induced nephropathy, resulting in metformin accumulation and increased risk of lactic acidosis. Metformin-containing products (such as vildagliptin + metformin HCl (Galvus Met) should be discontinued prior to or at the time of the imaging procedures and not restarted until 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be stable (see DOSAGE & ADMINISTRATION and INTERACTIONS).
Hypoxic states: Cardiovascular collapse (shock), acute congestive heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. If such events occur, the medication should be promptly discontinued.
Surgical procedures: Use must be discontinued at the time surgery under general, spinal or 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 or until the patient's oral nutrition has resumed and renal function has been re-evaluated as and found to be stable.
Alcohol intake: Alcohol is known to potentiate the effect of metformin hydrochloride on lactate metabolism. Patients should be warned against excessive alcohol intake while receiving metformin-containing products (such as vildagliptin + metformin HCl (Galvus Met)).
Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of fasting, malnutrition or hepatic impairment.
Patients with hepatic impairment: Since impaired hepatic function has been associated with some cases of lactic acidosis, a risk associated with metformin hydrochloride, metformin-containing products (such as vildagliptin + metformin HCl (Galvus Met)) should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
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 anemia and appears to be rapidly reversible with discontinuation of metformin hydrochloride and/or vitamin B₁₂ supplementation. Measurement of hematological parameters on at least an annual basis is advised for patients receiving metformin-containing products (such as vildagliptin + metformin HCl (Galvus Met)) and any apparent abnormalities should be appropriately investigated and managed. Certain individuals (e.g., those with inadequate vitamin B₁₂ or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B₁₂ levels. In these patients, routine serum vitamin B₁₂ measurements at minimally two-to-three-year intervals may be useful.
Change in clinical status of patients with previously controlled type 2 diabetes: A patient with type 2 diabetes previously well-controlled on vildagliptin + metformin HCl (Galvus Met) who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should promptly be evaluated for ketoacidosis and/or lactic acidosis. If acidosis of either form occurs, use must be stopped immediately and appropriate measures initiated.
Hypoglycemia: Hypoglycemia does not usually occur in patients receiving vildagliptin + metformin HCl (Galvus Met) alone, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or ethanol use. Elderly, debilitated or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly and in people taking beta-adrenergic blocking drugs.
Loss of control of blood glucose: When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, surgery, etc., a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold the product and temporarily administer insulin. Treatment may be reinstituted after the acute episode is resolved.