Januvia Information
Januvia (Sitagliptin phosphate) Indications And Usage
Januvia (Sitagliptin phosphate) 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.
Januvia (Sitagliptin phosphate) has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Januvia (Sitagliptin phosphate) .
Januvia (Sitagliptin phosphate) Dosage And Administration
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 for Januvia (Sitagliptin phosphate) 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 of Januvia (Sitagliptin phosphate) 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 of Januvia (Sitagliptin phosphate) is 25 mg once daily. Januvia (Sitagliptin phosphate) 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 Januvia (Sitagliptin phosphate) and periodically thereafter. Creatinine clearance can be estimated from serum creatinine using the Cockcroft-Gault formula.
When Januvia (Sitagliptin phosphate) 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.
Januvia (Sitagliptin phosphate) Contraindications
History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.
Januvia (Sitagliptin phosphate) Warnings And Precautions
There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking Januvia (Sitagliptin phosphate) . After initiation of Januvia (Sitagliptin phosphate) , patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, Januvia (Sitagliptin phosphate) 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 Januvia (Sitagliptin phosphate) .
When Januvia (Sitagliptin phosphate) 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.
Januvia (Sitagliptin phosphate) Adverse Reactions
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 Januvia (Sitagliptin phosphate) were similar to placebo. In combination with glimepiride, with or without metformin, the overall incidence of clinical adverse reactions with Januvia (Sitagliptin phosphate) was higher than with placebo, in part related to a higher incidence of hypoglycemia (see Table 3); 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 Januvia (Sitagliptin phosphate) 100 mg daily, Januvia (Sitagliptin phosphate) 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 Januvia (Sitagliptin phosphate) 100 mg daily or placebo. The adverse reactions, excluding hypoglycemia, reported regardless of investigator assessment of causality in ≥5% of patients treated with Januvia (Sitagliptin phosphate) 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. Incidences of hypoglycemia are shown in Table 3.
In the 24-week study of patients receiving Januvia (Sitagliptin phosphate) as add-on combination therapy with metformin, there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo.
In the 24-week study of patients receiving Januvia (Sitagliptin phosphate) as add-on therapy to insulin (with or without metformin), there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo, except for hypoglycemia (see Table 3).
In the study of Januvia (Sitagliptin phosphate) as add-on combination therapy with metformin and rosiglitazone (Table 1), through Week 54 the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with Januvia (Sitagliptin phosphate) and more commonly than in patients treated with placebo were: upper respiratory tract infection (Januvia (Sitagliptin phosphate) , 15.5%; placebo, 6.2%), nasopharyngitis (11.0%, 9.3%), peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%).
In a pooled analysis of the two monotherapy studies, the add-on to metformin study, and the add-on to pioglitazone study, the incidence of selected gastrointestinal adverse reactions in patients treated with Januvia (Sitagliptin phosphate) was as follows: abdominal pain (Januvia (Sitagliptin phosphate) 100 mg, 2.3%; placebo, 2.1%), nausea (1.4%, 0.6%), and diarrhea (3.0%, 2.3%).
In an additional, 24-week, placebo-controlled factorial study of initial therapy with sitagliptin in combination with metformin, the adverse reactions reported (regardless of investigator assessment of causality) in ≥5% of patients are shown in Table 2.
In a 24-week study of initial therapy with Januvia (Sitagliptin phosphate) in combination with pioglitazone, there were no adverse reactions reported (regardless of investigator assessment of causality) in ≥5% of patients and more commonly than in patients given pioglitazone alone.
No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed in patients treated with Januvia (Sitagliptin phosphate) .
Hypoglycemia
In all (N=9) studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia. A concurrent blood glucose measurement was not required although most (74%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When Januvia (Sitagliptin phosphate) was co-administered with a sulfonylurea or with insulin, the percentage of patients with at least one adverse reaction of hypoglycemia was higher than in the corresponding placebo group (Table 3).
In a pooled analysis of the two monotherapy studies, the add-on to metformin study, and the add-on to pioglitazone study, the overall incidence of adverse reactions of hypoglycemia was 1.2% in patients treated with Januvia (Sitagliptin phosphate) 100 mg and 0.9% in patients treated with placebo.
In the study of Januvia (Sitagliptin phosphate) as add-on combination therapy with metformin and rosiglitazone, the overall incidence of hypoglycemia was 2.2% in patients given add-on Januvia (Sitagliptin phosphate) and 0.0% in patients given add-on placebo through Week 18. Through Week 54, the overall incidence of hypoglycemia was 3.9% in patients given add-on Januvia (Sitagliptin phosphate) and 1.0% in patients given add-on placebo.
In the 24-week, placebo-controlled factorial study of initial therapy with Januvia (Sitagliptin phosphate) in combination with metformin, the incidence of hypoglycemia was 0.6% in patients given placebo, 0.6% in patients given Januvia (Sitagliptin phosphate) alone, 0.8% in patients given metformin alone, and 1.6% in patients given Januvia (Sitagliptin phosphate) in combination with metformin.
In the study of Januvia (Sitagliptin phosphate) as initial therapy with pioglitazone, one patient taking Januvia (Sitagliptin phosphate) experienced a severe episode of hypoglycemia. There were no severe hypoglycemia episodes reported in other studies except in the study involving co-administration with insulin.
Laboratory Tests
Across clinical studies, the incidence of laboratory adverse reactions was similar in patients treated with Januvia (Sitagliptin phosphate) 100 mg compared to patients treated with placebo. A small increase in white blood cell count (WBC) was observed due to an increase in neutrophils. This increase in WBC (of approximately 200 cells/microL vs placebo, in four pooled placebo-controlled clinical studies, with a mean baseline WBC count of approximately 6600 cells/microL) is not considered to be clinically relevant. In a 12-week study of 91 patients with chronic renal insufficiency, 37 patients with moderate renal insufficiency were randomized to Januvia (Sitagliptin phosphate) 50 mg daily, while 14 patients with the same magnitude of renal impairment were randomized to placebo. Mean (SE) increases in serum creatinine were observed in patients treated with Januvia (Sitagliptin phosphate) [0.12 mg/dL (0.04)] and in patients treated with placebo [0.07 mg/dL (0.07)]. The clinical significance of this added increase in serum creatinine relative to placebo is not known.
The following additional adverse reactions have been identified during postapproval use of Januvia (Sitagliptin phosphate) . 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.
Hypersensitivity reactions include anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, and exfoliative skin conditions including Stevens-Johnson syndrome ; hepatic enzyme elevations; acute pancreatitis, including fatal and non-fatal hemorrhagic and necrotizing pancreatitis
.
Januvia (Sitagliptin phosphate) Use In Specific Populations
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. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., maintains a registry to monitor the pregnancy outcomes of women exposed to Januvia (Sitagliptin phosphate) while pregnant. Health care providers are encouraged to report any prenatal exposure to Januvia (Sitagliptin phosphate) by calling the Pregnancy Registry at (800) 986-8999.
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.
Of the total number of subjects (N=3884) in pre-approval clinical safety and efficacy studies of Januvia (Sitagliptin phosphate) , 725 patients were 65 years and over, while 61 patients were 75 years and over. No overall differences in safety or effectiveness were observed between subjects 65 years and over and younger subjects. While this and other reported clinical experience have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly, and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter .
Januvia (Sitagliptin phosphate) Overdosage
During controlled clinical trials in healthy subjects, single doses of up to 800 mg Januvia (Sitagliptin phosphate) were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg Januvia (Sitagliptin phosphate) , 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 dose-related clinical adverse reactions observed with Januvia (Sitagliptin phosphate) 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.
Januvia (Sitagliptin phosphate) Description
Januvia (Sitagliptin phosphate) Tablets contain sitagliptin phosphate, an orally-active inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme.
Sitagliptin phosphate monohydrate is described chemically as 7-[(3)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-]pyrazine phosphate (1:1) monohydrate.
The empirical formula is CHFNO•HPO•HO and the molecular weight is 523.32. The structural formula is:
Sitagliptin phosphate monohydrate is a white to off-white, crystalline, non-hygroscopic powder. It is soluble in water and N,N-dimethyl formamide; slightly soluble in methanol; very slightly soluble in ethanol, acetone, and acetonitrile; and insoluble in isopropanol and isopropyl acetate.
Each film-coated tablet of Januvia (Sitagliptin phosphate) contains 32.13, 64.25, or 128.5 mg of sitagliptin phosphate monohydrate, which is equivalent to 25, 50, or 100 mg, respectively, of free base and the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, and sodium stearyl fumarate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide, red iron oxide, and yellow iron oxide.
Januvia (Sitagliptin phosphate) Clinical Pharmacology
General
In patients with type 2 diabetes, administration of Januvia (Sitagliptin phosphate) led to inhibition of DPP-4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP-4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased responsiveness of insulin release to glucose, resulting in higher C-peptide and insulin concentrations. The rise in insulin with the decrease in glucagon was associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.
In a two-day study in healthy subjects, sitagliptin alone increased active GLP-1 concentrations, whereas metformin alone increased active and total GLP-1 concentrations to similar extents. Co-administration of sitagliptin and metformin had an additive effect on active GLP-1 concentrations. Sitagliptin, but not metformin, increased active GIP concentrations. It is unclear how these findings relate to changes in glycemic control in patients with type 2 diabetes.
In studies with healthy subjects, Januvia (Sitagliptin phosphate) did not lower blood glucose or cause hypoglycemia.
Cardiac Electrophysiology
In a randomized, placebo-controlled crossover study, 79 healthy subjects were administered a single oral dose of Januvia (Sitagliptin phosphate) 100 mg, Januvia (Sitagliptin phosphate) 800 mg (8 times the recommended dose), and placebo. At the recommended dose of 100 mg, there was no effect on the QTc interval obtained at the peak plasma concentration, or at any other time during the study. Following the 800 mg dose, the maximum increase in the placebo-corrected mean change in QTc from baseline was observed at 3 hours postdose and was 8.0 msec. This increase is not considered to be clinically significant. At the 800 mg dose, peak sitagliptin plasma concentrations were approximately 11 times higher than the peak concentrations following a 100 mg dose.
In patients with type 2 diabetes administered Januvia (Sitagliptin phosphate) 100 mg (N=81) or Januvia (Sitagliptin phosphate) 200 mg (N=63) daily, there were no meaningful changes in QTc interval based on ECG data obtained at the time of expected peak plasma concentration.
The pharmacokinetics of sitagliptin has been extensively characterized in healthy subjects and patients with type 2 diabetes. After oral administration of a 100 mg dose to healthy subjects, sitagliptin was rapidly absorbed, with peak plasma concentrations (median T) occurring 1 to 4 hours postdose. Plasma AUC of sitagliptin increased in a dose-proportional manner. Following a single oral 100 mg dose to healthy volunteers, mean plasma AUC of sitagliptin was 8.52 μM•hr, C was 950 nM, and apparent terminal half-life (t) was 12.4 hours. Plasma AUC of sitagliptin increased approximately 14% following 100 mg doses at steady-state compared to the first dose. The intra-subject and inter-subject coefficients of variation for sitagliptin AUC were small (5.8% and 15.1%). The pharmacokinetics of sitagliptin was generally similar in healthy subjects and in patients with type 2 diabetes.
Absorption
The absolute bioavailability of sitagliptin is approximately 87%. Because coadministration of a high-fat meal with Januvia (Sitagliptin phosphate) had no effect on the pharmacokinetics, Januvia (Sitagliptin phosphate) may be administered with or without food.
Distribution
The mean volume of distribution at steady state following a single 100 mg intravenous dose of sitagliptin to healthy subjects is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Metabolism
Approximately 79% of sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination.
Following a [C]sitagliptin oral dose, approximately 16% of the radioactivity was excreted as metabolites of sitagliptin. Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin. studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
Excretion
Following administration of an oral [C]sitagliptin dose to healthy subjects, approximately 100% of the administered radioactivity was eliminated in feces (13%) or urine (87%) within one week of dosing. The apparent terminal tfollowing a 100 mg oral dose of sitagliptin was approximately 12.4 hours and renal clearance was approximately 350 mL/min.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion. Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal elimination of sitagliptin. The clinical relevance of hOAT-3 in sitagliptin transport has not been established. Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin. However, cyclosporine, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin.
Special Populations
Renal Insufficiency
A single-dose, open-label study was conducted to evaluate the pharmacokinetics of Januvia (Sitagliptin phosphate) (50 mg dose) in patients with varying degrees of chronic renal insufficiency compared to normal healthy control subjects. The study included patients with renal insufficiency classified on the basis of creatinine clearance as mild (50 to <80 mL/min), moderate (30 to <50 mL/min), and severe (<30 mL/min), as well as patients with ESRD on hemodialysis. In addition, the effects of renal insufficiency on sitagliptin pharmacokinetics in patients with type 2 diabetes and mild or moderate renal insufficiency were assessed using population pharmacokinetic analyses. Creatinine clearance was measured by 24‑hour urinary creatinine clearance measurements or estimated from serum creatinine based on the Cockcroft-Gault formula:
CrCl = {x 0.85 for female patients} [72 x serum creatinine (mg/dL)]
Compared to normal healthy control subjects, an approximate 1.1- to 1.6-fold increase in plasma AUC of sitagliptin was observed in patients with mild renal insufficiency. Because increases of this magnitude are not clinically relevant, dosage adjustment in patients with mild renal insufficiency is not necessary. Plasma AUC levels of sitagliptin were increased approximately 2-fold and 4-fold in patients with moderate renal insufficiency and in patients with severe renal insufficiency, including patients with ESRD on hemodialysis, respectively. Sitagliptin was modestly removed by hemodialysis (13.5% over a 3- to 4-hour hemodialysis session starting 4 hours postdose). To achieve plasma concentrations of sitagliptin similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency, as well as in ESRD patients requiring hemodialysis.
Hepatic Insufficiency
In patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), mean AUC and C of sitagliptin increased approximately 21% and 13%, respectively, compared to healthy matched controls following administration of a single 100 mg dose of Januvia (Sitagliptin phosphate) . These differences are not considered to be clinically meaningful. No dosage adjustment for Januvia (Sitagliptin phosphate) is necessary for patients with mild or moderate hepatic insufficiency.
There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9).
Body Mass Index (BMI)
No dosage adjustment is necessary based on BMI. Body mass index had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.
Gender
No dosage adjustment is necessary based on gender. Gender had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.
Geriatric
No dosage adjustment is required based solely on age. When the effects of age on renal function are taken into account, age alone did not have a clinically meaningful impact on the pharmacokinetics of sitagliptin based on a population pharmacokinetic analysis. Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of sitagliptin compared to younger subjects.
Pediatric
Studies characterizing the pharmacokinetics of sitagliptin in pediatric patients have not been performed.
Race
No dosage adjustment is necessary based on race. Race had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of available pharmacokinetic data, including subjects of white, Hispanic, black, Asian, and other racial groups.
Drug Interactions
In Vitro Assessment of Drug Interactions
Sitagliptin is not an inhibitor of CYP isozymes CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 or 2B6, and is not an inducer of CYP3A4. Sitagliptin is a p-glycoprotein substrate, but does not inhibit p‑glycoprotein mediated transport of digoxin. Based on these results, sitagliptin is considered unlikely to cause interactions with other drugs that utilize these pathways.
Sitagliptin is not extensively bound to plasma proteins. Therefore, the propensity of sitagliptin to be involved in clinically meaningful drug‑drug interactions mediated by plasma protein binding displacement is very low.
In Vivo Assessment of Drug Interactions
Effects of Sitagliptin on Other Drugs
In clinical studies, as described below, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives, providing evidence of a low propensity for causing drug interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT).
Digoxin:
max
Metformin:
Sulfonylureas:
Simvastatin:
Thiazolidinediones:
Warfarin:
Oral Contraceptives:
Effects of Other Drugs on Sitagliptin
Clinical data described below suggest that sitagliptin is not susceptible to clinically meaningful interactions by co-administered medications.
Metformin:
Cyclosporine:
max
Januvia (Sitagliptin phosphate) Clinical Studies
There were approximately 5200 patients with type 2 diabetes randomized in nine double-blind, placebo-controlled clinical safety and efficacy studies conducted to evaluate the effects of sitagliptin on glycemic control. In a pooled analysis of seven of these studies, the ethnic/racial distribution was approximately 59% white, 20% Hispanic, 10% Asian, 6% black, and 6% other groups. Patients had an overall mean age of approximately 55 years (range 18 to 87 years). In addition, an active (glipizide)-controlled study of 52-weeks duration was conducted in 1172 patients with type 2 diabetes who had inadequate glycemic control on metformin.
In patients with type 2 diabetes, treatment with Januvia (Sitagliptin phosphate) produced clinically significant improvements in hemoglobin A1C, fasting plasma glucose (FPG) and 2-hour post-prandial glucose (PPG) compared to placebo.
Januvia (Sitagliptin phosphate) How Supplied/storage And Handling
Januvia (Sitagliptin phosphate) Patient Counseling Information
See FDA-approved .
Patients should be informed of the potential risks and benefits of Januvia (Sitagliptin phosphate) and of alternative modes of therapy. Patients should also be informed about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1C testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change and patients should be advised to seek medical advice promptly.
Patients should be informed that acute pancreatitis has been reported during postmarketing use of Januvia (Sitagliptin phosphate) . Patients should be informed that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue Januvia (Sitagliptin phosphate) and contact their physician if persistent severe abdominal pain occurs
Patients should be informed that the incidence of hypoglycemia is increased when Januvia (Sitagliptin phosphate) is added to a sulfonylurea or insulin and that a lower dose of the sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.
Patients should be informed that allergic reactions have been reported during postmarketing use of Januvia (Sitagliptin phosphate) . If symptoms of allergic reactions (including rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking Januvia (Sitagliptin phosphate) and seek medical advice promptly.
Physicians should instruct their patients to read the Medication Guide before starting Januvia (Sitagliptin phosphate) therapy and to reread each time the prescription is renewed. Patients should be instructed to inform their doctor or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.
Januvia (Sitagliptin phosphate)
Januvia (Sitagliptin phosphate)
Januvia (Sitagliptin phosphate)
