Januet XR

/ MSD

The dose should be individualized on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider.
In patients not currently treated with metformin, the recommended total daily starting dose is 100 mg sitagliptin and 1000 mg metformin hydrochloride (HCl) extended-release. Patients with inadequate glycemic control on this dose of metformin can be titrated gradually, to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily dose.
In patients already treated with metformin, the recommended total daily starting dose is 100 mg sitagliptin and the previously prescribed dose of metformin.
For patients taking metformin immediate-release 850 mg twice daily or 1000 mg twice daily, the recommended starting dose is two 50 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablets taken together once daily.
Maintain the same total daily dose of sitagliptin and metformin when changing between JANUET (sitagliptin and metformin HCl immediate-release) and JANUET XR. Patients with inadequate glycemic control on this dose of metformin can be titrated gradually, to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily dose.
This product should be administered with food to reduce the gastrointestinal side effects associated with the metformin component. It should be given once daily with a meal preferably in the evening. It should be swallowed whole. The tablets must not be split, crushed, or chewed before swallowing.
The 100 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using two XR tablets (such as two 50 mg sitagliptin/500 mg metformin hydrochloride extended-release tablets or two 50 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablets) should take the two tablets together once daily.
Patients treated with an insulin secretagogue or insulin: Co-administration of this drug with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. No studies have been performed specifically examining the safety and efficacy in patients previously treated with other oral antihyperglycemic agents and switched to this product. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

JANUET® XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin extended-release is appropriate.
Important Limitations of Use: JANUET XR should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
JANUET XR 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 JANUET XR.

Renal impairment, which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
Hypersensitivity to metformin hydrochloride.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin.
History of a serious hypersensitivity reaction to JANUET XR or sitagliptin, such as anaphylaxis or angioedema.

Lactic acidosis: Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure.
The onset of lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress.
Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.
If acidosis is suspected, JANUET XR (sitagliptin and metformin HCl extended-release) tablets should be discontinued and the patient hospitalized immediately.
Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin with or without metformin. After initiation of JANUET XR, patients should be observed carefully for signs and symptoms of pancreatitis. If
pancreatitis is suspected, JANUET XR 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 JANUET XR.
Impaired Hepatic Function: Since impaired hepatic function has been associated with some cases of lactic acidosis, JANUET XR should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
Assessment of Renal Function: Metformin and sitagliptin are substantially excreted by the kidney.
Metformin hydrochloride: The risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Therefore, JANUET XR is contraindicated in patients with renal impairment.
Before initiation of JANUET XR and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated (e.g., elderly), renal function should be assessed more frequently and JANUET XR discontinued if evidence of renal impairment is present.
Sitagliptin: There have been postmarketing reports of worsening renal function in patients taking sitagliptin with or without metformin, including acute renal failure, sometimes requiring dialysis. Before initiation of therapy with JANUET XR and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, particularly in elderly patients, renal function should be assessed more frequently and JANUET XR discontinued if evidence of renal impairment is present.
Vitamin B12 Levels: In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on JANUET XR and any apparent abnormalities should be appropriately investigated and managed.
Certain individuals (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 two- to three-year intervals may be useful.
Alcohol Intake: Alcohol potentiates the effect of metformin on lactate metabolism. Patients should be warned against excessive alcohol intake while receiving JANUET XR.
Surgical Procedures: Use of JANUET XR 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 normal.
Change in Clinical Status of Patients with Previously Controlled Type 2 Diabetes: A patient with type 2 diabetes previously well controlled on JANUET XR who develops 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, JANUET XR must be stopped immediately and other appropriate corrective measures initiated.
See prescribing information for full details.

The most common (≥5% of patients) adverse reactions reported (regardless of
investigator assessment of causality) in a 24-week placebo-controlled factorial study in which sitagliptin and metformin immediate-release were coadministered to patients with type 2 diabetes inadequately controlled on diet and exercise: Diarrhea, Upper Respiratory Tract Infection, Headache.
See prescribing information for full details.

Carbonic Anhydrase Inhibitors: Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs may induce metabolic acidosis. Use these drugs with caution in patients treated with JANUET XR, as the risk of lactic acidosis may increase.
Cationic Drugs: Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems.
Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of JANUET XR and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
The Use of Metformin with Other Drugs: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving JANUET XR the patient should be closely observed to maintain adequate glycemic control.

Pregnancy: Category B. There are no adequate and well-controlled studies in pregnant women with JANUET XR or its individual components; therefore, the safety of JANUET XR in pregnant women is not known. JANUET XR should be used during pregnancy only if clearly needed.
Lactation: No studies in lactating animals have been conducted with the combined components of JANUET XR. In studies performed with the individual components, both sitagliptin and metformin are secreted in the milk of lactating rats. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when JANUET XR is administered to a nursing woman.
See prescribing information for full details.

Sitagliptin: During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg sitagliptin, a mean effect that is not considered clinically important. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with sitagliptin with doses of up to 400 mg per day for periods of 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 indicated 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.
Metformin Hydrochloride: Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdose is suspected.

Storage: Do not store above 25°C. Store in a dry place with cap tightly closed.
Shelf life after first opening: Up to 13 weeks