Start with once-daily JANUMET XR for convenient dosing - Januvia

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Start with once-daily JANUMET XR for convenient dosing - Januvia

As an adjunct to diet and exercise for appropriate patients with type 2 diabetesJANUMET XRCONVENIENT ONCE-DAILY DOSINGFor patients not currently treated with metforminAdminister once-daily with a meal preferably in the eveningStarting doseFor patients already treated with metforminMetformin 500 mg bid Metformin 850 mg bid to 1000 mg bidDosage and administration100/1000 mgTablet not shownat actual size.• The recommended total daily starting dose in patients not currently treated withmetformin is 100 mg sitagliptin/1000 mg metformin hydrochloride extendedreleaseonce daily• For patients with inadequate glycemic control, adjust the metformin dose asneeded, which should be individualized on the basis of the patient’s current regimen,effectiveness, and tolerability while not exceeding the maximum recommended dailydose of 100 mg sitagliptin/2000 mg metformin extended-release• JANUMET XR should generally be given once daily with meals, with gradual doseescalation, to reduce the gastrointestinal side effects due to metformin• Coadministration of JANUMET XR with an insulin secretagogue (eg, sulfonylurea) orinsulin may require lower doses of the insulin secretagogue or insulin to reduce therisk of hypoglycemiaImportant InformationJANUMET XR is indicated, as an adjunct to diet and exercise, to improveglycemic control in adults with type 2 diabetes mellitus when treatment withboth sitagliptin and metformin extended-release is appropriate.JANUMET XR should not be used in patients with type 1 diabetes or for thetreatment of diabetic ketoacidosis.JANUMET XR has not been studied in patients with a history of pancreatitis.It is unknown whether patients with a history of pancreatitis are at increasedrisk of developing pancreatitis while taking JANUMET XR.100/1000 mgJANUMET XR also is available as 50/500 mg, two tablets once daily.• The starting dose in patients already treated with metformin should providesitagliptin as a 100-mg total daily dose and the dose of metformin alreadybeing taken• For patients taking metformin 850 mg twice daily, the recommended startingdose of JANUMET XR is two tablets of 50 mg sitagliptin/1000 mg metforminhydrochloride extended-release once daily• For patients with inadequate glycemic control, adjust the metformin dose asneeded, which should be individualized on the basis of the patient’s current regimen,effectiveness, and tolerability while not exceeding the maximum recommended dailydose of 100 mg sitagliptin/2000 mg metformin extended-release• JANUMET XR should generally be given once daily with meals, with gradual doseescalation, to reduce the gastrointestinal side effects due to metformin• Coadministration of JANUMET XR with an insulin secretagogue (eg, sulfonylurea) orinsulin may require lower doses of the insulin secretagogue or insulin to reduce therisk of hypoglycemiaSelected Important Risk Information50/1000 mg50/1000 mgTablets not shownat actual size.WARNING: LACTIC ACIDOSISLactic acidosis is a rare, but serious complication that can occur dueto metformin accumulation. The risk increases with conditions such assepsis, dehydration, excess alcohol intake, hepatic impairment, renalimpairment, and acute congestive heart failure.The onset of lactic acidosis is often subtle, accompanied only bynonspecific symptoms such as malaise, myalgias, respiratory distress,increasing somnolence, and nonspecific abdominal distress.Laboratory abnormalities include low pH, increased anion gap, andelevated blood lactate.If acidosis is suspected, JANUMET XR should be discontinued and thepatient hospitalized immediately [see Warnings and Precautions].(Selected Important Risk Information continues on the next page.)Before prescribing JANUMET XR, please read the Prescribing Information,including the Boxed Warning about lactic acidosis.Page 1 of 3


As an adjunct to diet and exercise for appropriate patients with type 2 diabetesJANUMET XROFFERS POWERFUL A1C REDUCTIONS 1,2Mean change in A1C, %0–1–2–3–49.8%Metformin 2000 mg daily(n=564)–1.8%In a clinical trial including sitagliptin + metformin immediate-release (IR) FDCGreater A1C reductions vsmetformin IR alone at week 18 aPrimary end pointMean baseline A1C:P Median (9.7%)Mean baseline A1C: 8.4%11.4%Metformin 2000 mg daily Sitagliptin + metformin Metformin 2000 mg daily Sitagliptin + metformin(n=291)100/2000 mg daily(n=273)100/2000 mg daily–1.1%(n=288)(n=271)P


IN THIS STUDY, SIMILAR WEIGHT CHANGE,RATES OF HYPOGLYCEMIA, AND GI EVENTSVS METFORMIN IR ALONE 1• Weight loss for sitagliptin + metformin IR FDC similar to metformin IR alone at week 18 (LS mean change from baseline: –3.5 lb for both groups)• Incidence of hypoglycemia for sitagliptin + metformin IR FDC similar to metformin IR alone over 18 weeks (2.1% [n/N=13/625] vs 1.8% [n/N=11/621], respectively)• Similar rate of GI adverse events vs metformin IR alone over 18 weeksWhen added to a sulfonylurea (glimepiride) or insulin, patients treated with sitagliptin + metformin IR experiencedincreased weight and incidence of hypoglycemia• Weight gain: +0.9 lb for patients treated with sitagliptin + metformin IR + glimepiride vs –1.5 lb for placebo + metformin IR + glimepiride• Hypoglycemia: 16% for patients treated with sitagliptin + metformin IR + glimepiride vs 1% for placebo + metformin IR + glimepiride and 15% for patients treated withsitagliptin + metformin IR + insulin vs 8% for placebo + metformin IR + insulin. A lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemiaGI = gastrointestinal.Please see Study Design on page 2 for more information.Selected Important Risk Information (continued)Intravascular contrast studies with iodinated materials can lead to acutealteration of renal function and have been associated with lactic acidosis inpatients receiving metformin. Therefore, in patients in whom any such studyis planned, JANUMET XR should be temporarily discontinued at the time of orbefore the procedure, withheld for 48 hours subsequent to the procedure, andreinstituted only after renal function has been re-evaluated and found tobe normal.There have been no clinical studies establishing conclusive evidence ofUse With Medications Known to Cause HypoglycemiaSitagliptinWhen sitagliptin was used in combination with a sulfonylurea or insulin,medications known to cause hypoglycemia, the incidence of hypoglycemiawas increased over that of placebo used in combination with a sulfonylurea orinsulin. Therefore, patients also receiving insulin or an insulin secretagogue (eg,sulfonylurea) may require a lower dose of insulin or the insulin secretagogue toreduce the risk of hypoglycemia.The incidence (and rate) of hypoglycemia based on all reports of symptomatichypoglycemia were: 16.4% (0.82 episodes/patient-year) for sitagliptin 100 mg incombination with metformin and glimepiride, 0.9% (0.02 episodes/patient-year)for placebo in combination with metformin and glimepiride, 8.2% (0.61 episodes/patient-year) for placebo in combination with metformin and insulin, and 15.3%(0.98 episodes/patient-year) for sitagliptin in combination with metforminand insulin.Adverse reactions with sitagliptin in combination with metformin and rosiglitazonethrough Week 18 were: upper respiratory tract infection (sitagliptin, 5.5%; placebo,5.2%) and nasopharyngitis (6.1%, 4.1%). Through Week 54 they were: upperrespiratory tract infection (sitagliptin, 15.5%; placebo, 6.2%), nasopharyngitis(11.0%, 9.3%), peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%).Metformin hydrochlorideHypoglycemia does not occur in patients receiving metformin alone under usualcircumstances of use but could occur when caloric intake is deficient, whenstrenuous exercise is not compensated by caloric supplementation, or duringCopyright © 2013 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved.DIAB-1079801-0001 07/13JanumetXR.comconcomitant use with other glucose-lowering agents (such as sulfonylureas andinsulin) or ethanol. Elderly, debilitated, or malnourished patients and those withadrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible tohypoglycemic effects.There have been postmarketing reports of serious hypersensitivity reactions inpatients treated with sitagliptin, one of the components of JANUMET XR, such asanaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnsonsyndrome. Onset of these reactions occurred within the first 3 months after initiationof treatment with sitagliptin, with some reports occurring after the first dose. If ahypersensitivity reaction is suspected, discontinue JANUMET XR, assess for otherpotential causes for the event, and institute alternative treatment for diabetes.Use caution in a patient with a history of angioedema to another dipeptidylpeptidase-4 (DPP-4) inhibitor because it is unknown whether such patients will bepredisposed to angioedema with JANUMET XR.In clinical studies, the most common adverse reactions reported, regardless ofinvestigator assessment of causality, in ≥5% of patients treated with eithersitagliptin in combination with metformin or placebo were as follows: diarrhea(7.5% vs 4.0%), upper respiratory tract infection (6.2% vs 5.1%), and headache(5.9% vs 2.8%). In patients treated with sitagliptin in combination with metforminand sulfonylurea or placebo in combination with metformin and sulfonylurea:hypoglycemia (16.4% vs 0.9%) and headache (6.9% vs 2.7%). In patients treatedwith sitagliptin in combination with metformin and insulin or placebo in combinationwith metformin and insulin: hypoglycemia (15.3% vs 8.2%). Other adverse eventswith an incidence of ≥5% included nasopharyngitis for sitagliptin monotherapy andhypoglycemia (13.7% vs 4.9%), diarrhea (12.5% vs 5.6%), and nausea (6.7% vs4.2%) for extended-release metformin vs placebo when added to glyburide.The incidence of selected gastrointestinal adverse reactions in patients treated withsitagliptin and metformin was similar to those of placebo and metformin: nausea(1.3%, 0.8%), vomiting (1.1%, 0.8%), abdominal pain (2.2%, 3.8%), and diarrhea(2.4%, 2.5%).Before prescribing JANUMET XR, please read the Prescribing Information,including the Boxed Warning about lactic acidosis.For additional copies of the Prescribing Information, please call 800-672-6372,visit JanumetXR.com, or contact your Merck representative.References: 1. Reasner C, Olansky L, Seck TL, et al. The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus. Diabetes ObesMetab. 2011;13(7):644–652. 2. Data available on request from Merck, Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package DIAB-1038791-0005. 3. Olansky L, Reasner C, Seck TL,et al. A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycaemic control versus metformin monotherapy due to a low rate of addition of antihyperglycaemic agents. Diabetes ObesMetab. 2011;13(9):841–849.Page 3 of 3

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