Sitaplus Special Precautions

Sitagliptin phosphate + Metformin HCl should not be used in patients with type 1 diabetes of for the treatment of diabetic ketoacidosis.
Pancreatitis: There have been reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin. Patients should be informed of the characteristics symptom of acute pancreatitis; persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin. If pancreatitis is suspected, Sitagliptin phosphate + Metformin HCl and other potentially suspect medicinal products should be discontinued.
Monitoring of renal function: Sitagliptin phosphate + Metformin HCl are known to be substantially excreted by the kidney. The risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Sitagliptin phosphate + Metformin HCl is contraindicated in severe renal impairment, patients with an eGFR, mL/min/1.73 m².
Before initiation of therapy with Sitagliptin phosphate + Metformin HCl and at least annually thereafter, renal function should be assessed. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and Sitagliptin phosphate + Metformin HCl discontinued if evidence of renal impairment is present.
Hypoglycemia in Combination with a Sulfonylurea or with Insulin: As is typical with other antihyperglycemic agents, hypoglycemia has been observed when Sitagliptin + Metformin were used in combination with insulin or a sulfonylurea. Therefore, to reduce the risk of sulfonylurea- or insulin-induced hypoglycemia, a lower dose of sulfonylurea or insulin may be considered.
Metformin hydrochloride: Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with Sitagliptin phosphate + Metformin HCl; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 μg/mL are generally found.
Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism.
In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure.
The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur. Metformin should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to acidosis or other serious disease.
Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling.
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.
Hypoglycemia: Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking β-adrenergic blocking drugs.
Use of concomitant medications that may affect renal function or metformin disposition: Concomitant medication(s) that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion should be used with caution.
Radiologic studies involving the use of intravascular iodinated materials (for example intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials): Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin. Therefore, in patients with an eGFR ≥30 <60 mL/min/1.73 m², in patients with a history of hepatic impairment, alcoholism, or heart failure, or in patients who will be administered intra-arterial iodinated contrast, Sitagliptin phosphate + Metformin HCl should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be acceptable.
Hypoxic states: Cardiovascular collapse (shock) from whatever cause, 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. When such events occur in patients on Sitagliptin phosphate + Metformin HCl therapy, the drug should be promptly discontinued.
Surgical procedures: Use of Sitagliptin phosphate + Metformin HCl should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as acceptable.
Alcohol intake: Alcohol is known to potentiate the effect of metformin on lactate. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving Sitagliptin phosphate + Metformin HCl.
Vitamin B12 levels: Certain individuals (those with adequate 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 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 Sitagliptin phosphate + Metformin HCl who develop 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, Sitagliptin phosphate + Metformin HCl must be stopped immediately and other appropriate corrective measures initiated.
Loss of control of blood glucose: When a patient stabilized on any diabetic regimen exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold Sitagliptin phosphate + Metformin HCl and temporarily administer insulin. Sitagliptin phosphate + Metformin HCl may be reinstituted after the acute episode is resolved.
Impaired hepatic function: Since impaired hepatic function has been associated with some cases of lactic acidosis, Sitagliptin phosphate + Metformin HCl should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
Use in Children: Safety and effectiveness of Sitagliptin phosphate + Metformin HCl in pediatric patients under 18 years have not been established.
Use in the Elderly: Sitagliptin Phosphate + Metformin HCl: Because Sitagliptin + Metformin is substantially excreted by the kidney and because aging can be associated with reduced renal function, Sitagliptin phosphate + Metformin HCl should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function.