Januvia

/ MSD

Recommended Dosing The recommended dose  is 100 mg once daily. this product  can be taken with or without food.
Patients with Renal Insufficiency: For patients with mild renal insufficiency (creatinine clearance [CrCl] ≥50 mL/min, approximately corresponding to serum creatinine levels of ≤1.7 mg/dL in men and ≤1.5 mg/dL in women), no dosage adjustment is required. For patients with moderate renal insufficiency (CrCl ≥30 to <50 mL/min, approximately corresponding to serum creatinine levels of >1.7 to ≤3.0 mg/dL in men and >1.5 to ≤2.5 mg/dL in women), the dose is 50 mg once daily. For patients with severe renal insufficiency (CrCl <30 mL/min, approximately corresponding to serum creatinine levels of >3.0 mg/dL in men and >2.5 mg/dL in women) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose is 25 mg once daily. this product may be administered without regard to the timing of hemodialysis. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of this product and periodically thereafter. Creatinine clearance can be estimated from serum creatinine using the Cockcroft-Gault formula.
Concomitant Use with an insulin Secretagogue: (e.g., Sulfonylurea) or with Insulin When this product is used in combination with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.
For full details see prescribing information.

As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.Important limitations of use: Should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis as it would not be effective in these settings. Has not been studied in patients with a history of pancreatitis and it is unknown whether these patients are at increased risk for pancreatitis with using Januvia.

History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking this product . After initiation, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, this product should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using this product .
Use in Patients with Renal Insufficiency: A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD requiring hemodialysis or peritoneal dialysis.
Use with Medications Known to Cause Hypoglycemia: When this product was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin.  Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with this product . These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including StevensJohnson syndrome. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Onset of these reactions occurred within the first 3 months after initiation of treatment with this product , with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue this product , assess for other potential causes for the event, and institute alternative treatment for diabetes.
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with this product or any other antidiabetic drug.

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In controlled clinical studies as both monotherapy and combination therapy with metformin, pioglitazone, or rosiglitazone and metformin, the overall incidence of adverse reactions, hypoglycemia, and discontinuation of therapy due to clinical adverse reactions with this product were similar to placebo. In combination with glimepiride, with or without metformin, the overall incidence of clinical adverse reactions with this product was higher than with placebo, in part related to a higher incidence of hypoglycemia; the incidence of discontinuation due to clinical adverse reactions was similar to placebo. Two placebo-controlled monotherapy studies, one of 18- and one of 24-week duration, included patients treated with 100 mg daily,  200 mg daily, and placebo. Five placebo-controlled add-on combination therapy studies were also conducted: one with metformin; one with pioglitazone; one with metformin and rosiglitazone; one with glimepiride (with or without metformin); and one with insulin (with or without metformin). In these trials, patients with inadequate glycemic control on a stable dose of the background therapy were randomized to add-on therapy with 100 mg daily or placebo. The adverse reactions, excluding hypoglycemia, reported regardless of investigator assessment of causality in ≥5% of patients treated with 100 mg daily and more commonly than in patients treated with placebo, are shown in Table 1 for the clinical trials of at least 18 weeks duration.
For full details see prescribing information.

Digoxin: There was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (Cmax, 18%) of digoxin with the co-administration of 100 mg sitagliptin for 10 days. Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or this product is recommended.

Pregnancy Category B: Reproduction studies have been performed in rats and rabbits. Doses of sitagliptin up to 125 mg/kg (approximately 12 times the human exposure at the maximum recommended human dose) did not impair fertility or harm the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Sitagliptin administered to pregnant female rats and rabbits from gestation day 6 to 20 (organogenesis) was not teratogenic at oral doses up to 250 mg/kg (rats) and 125 mg/kg (rabbits), or approximately 30- and 20-times human exposure at the maximum recommended human dose (MRHD) of 100 mg/day based on AUC comparisons. Higher doses increased the incidence of rib malformations in offspring at 1000 mg/kg, or approximately 100 times human exposure at the MRHD. Sitagliptin administered to female rats from gestation day 6 to lactation day 21 decreased body weight in male and female offspring at 1000 mg/kg. No functional or behavioral toxicity was observed in offspring of rats. Placental transfer of sitagliptin administered to pregnant rats was approximately 45% at 2 hours and 80% at 24 hours postdose. Placental transfer of sitagliptin administered to pregnant rabbits was approximately 66% at 2 hours and 30% at 24 hours.
Nursing Mothers: Sitagliptin is secreted in the milk of lactating rats at a milk to plasma ratio of 4:1. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this product is administered to a nursing woman.

During controlled clinical trials in healthy subjects, single doses of up to 800 mg were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg, a mean effect that is not considered clinically important. There is no experience with doses above 800 mg in humans. In Phase I multiple-dose studies, there were no doserelated clinical adverse reactions observed with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for up to 28 days. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient’s clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.