Januet XR 50/500mg

Sitagliptin (Januet XR 50/500mg) PHOSPHATE + Metformin (Januet XR 50/500mg) HCl (Januet XR 50/500mg) are indicated as initial therapy in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise do not provide adequate glycemic control.

Sitagliptin (Januet XR 50/500mg) PHOSPHATE + Metformin (Januet XR 50/500mg) HCl (Januet XR 50/500mg) are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus inadequately controlled on Metformin (Januet XR 50/500mg) or Sitagliptin (Januet XR 50/500mg) alone or in patients already being treated with the combination of Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg).

Sitagliptin (Januet XR 50/500mg) PHOSPHATE + Metformin (Januet XR 50/500mg) HCl (Januet XR 50/500mg) are indicated as part of triple combination therapy with a sulfonylurea as an adjunct to diet and exercise in patients with type 2 diabetes mellitus inadequately controlled with any two of the three agents: Metformin (Januet XR 50/500mg), Sitagliptin (Januet XR 50/500mg), or a sulfonylurea.

Sitagliptin (Januet XR 50/500mg) PHOSPHATE + Metformin (Januet XR 50/500mg) HCl (Januet XR 50/500mg) are indicated as part of triple combination therapy with a PPARγ agonist (i.e., thiazolidinediones) as an adjunct to diet and exercise in patients with type 2 diabetes mellitus inadequately controlled with any two of the three agents: Metformin (Januet XR 50/500mg), Sitagliptin (Januet XR 50/500mg), or a PPARγ agonist.

Sitagliptin (Januet XR 50/500mg) PHOSPHATE + Metformin (Januet XR 50/500mg) HCl (Januet XR 50/500mg) are indicated in patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in combination with insulin.

Januet XR 50/500mg are oral diabetes medicines that help control blood sugar levels.

Metformin (Januet XR 50/500mg) works by decreasing glucose (sugar) production in the liver and decreasing absorption of glucose by the intestines. Sitagliptin (Januet XR 50/500mg) works by regulating the levels of insulin your body produces after eating.

Januet XR 50/500mg is a combination medicine used to treat type 2 diabetes. This medication is not for treating type 1 diabetes.

Januet XR 50/500mg may also be used for purposes not listed in this medication guide.

Recommended Dosing

The dose of Januet XR 50/500mg 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 (Januet XR 50/500mg) and 2000 mg Metformin (Januet XR 50/500mg). Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the healthcare provider.

• In patients not currently treated with Metformin (Januet XR 50/500mg), the recommended total daily starting dose of Januet XR 50/500mg is 100 mg Sitagliptin (Januet XR 50/500mg) and 1000 mg Metformin (Januet XR 50/500mg) hydrochloride (HCl) extended-release. Patients with inadequate glycemic control on this dose of Metformin (Januet XR 50/500mg) can be titrated gradually, to reduce gastrointestinal side effects associated with Metformin (Januet XR 50/500mg), up to the maximum recommended daily dose.
• In patients already treated with Metformin (Januet XR 50/500mg), the recommended total daily starting dose of Januet XR 50/500mg is 100 mg Sitagliptin (Januet XR 50/500mg) and the previously prescribed dose of Metformin (Januet XR 50/500mg).
• For patients taking Metformin (Januet XR 50/500mg) immediate-release 850 mg twice daily or 1000 mg twice daily, the recommended starting dose of Januet XR 50/500mg is two 50 mg Sitagliptin (Januet XR 50/500mg)/1000 mg Metformin (Januet XR 50/500mg) hydrochloride extended-release tablets taken together once daily.
• Maintain the same total daily dose of Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) when changing between Januet XR 50/500mg (Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) HCl immediate-release) and Januet XR 50/500mg. Patients with inadequate glycemic control on this dose of Metformin (Januet XR 50/500mg) can be titrated gradually, to reduce gastrointestinal side effects associated with Metformin (Januet XR 50/500mg), up to the maximum recommended daily dose.

Januet XR 50/500mg should be administered with food to reduce the gastrointestinal side effects associated with the Metformin (Januet XR 50/500mg) component. Januet XR 50/500mg should be given once daily with a meal preferably in the evening. Januet XR 50/500mg should be swallowed whole. The tablets must not be split, crushed, or chewed before swallowing. There have been reports of incompletely dissolved Januet XR 50/500mg tablets being eliminated in the feces. It is not known whether this material seen in feces contains active drug. If a patient reports repeatedly seeing tablets in feces, the healthcare provider should assess adequacy of glycemic control.

The 100 mg Sitagliptin (Januet XR 50/500mg)/1000 mg Metformin (Januet XR 50/500mg) hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using two Januet XR 50/500mg tablets (such as two 50 mg Sitagliptin (Januet XR 50/500mg)/500 mg Metformin (Januet XR 50/500mg) hydrochloride extended-release tablets or two 50 mg Sitagliptin (Januet XR 50/500mg)/1000 mg Metformin (Januet XR 50/500mg) hydrochloride extended-release tablets) should take the two tablets together once daily.

Patients treated with an insulin secretagogue or insulin

Coadministration of Januet XR 50/500mg 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 of Januet XR 50/500mg in patients previously treated with other oral antihyperglycemic agents and switched to Januet XR 50/500mg. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

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What is the most important information I should know about Januet XR 50/500mg?

Known hypersensitivity to Sitagliptin (Januet XR 50/500mg) phosphate, Metformin (Januet XR 50/500mg) HCl or any other component of Januet XR 50/500mg.

Renal disease or renal dysfunction, eg, as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females], or abnormal creatinine clearance, which may also result from conditions eg, cardiovascular collapse (shock), acute myocardial infarction, and septicemia.

Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Januet XR 50/500mg should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because the use of such products may result in acute alteration of renal function.

Use in lactation: No studies in lactating animals have been conducted with the combined components of Januet XR 50/500mg. In studies performed with the individual components, both Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) are secreted in the milk of lactating rats. It is not known whether Sitagliptin (Januet XR 50/500mg) is excreted in human milk. Therefore, Januet XR 50/500mg should not be used by a woman who is nursing.

Use Januet XR 50/500mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Januet XR 50/500mg comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Januet XR 50/500mg refilled.
• Take Januet XR 50/500mg by mouth with your evening meal, unless your doctor tells you otherwise.
• Swallow Januet XR 50/500mg whole. Do not break, crush, split, or chew before swallowing. If you have difficulty swallowing tablets whole, talk with your doctor.
• Taking Januet XR 50/500mg at the same times each day will help you remember to take it.
• Take Januet XR 50/500mg on a regular schedule to get the most benefit from it.
• Continue to take Januet XR 50/500mg even if you feel well. Do not miss any doses.
• If you miss a dose of Januet XR 50/500mg, take it with food as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Januet XR 50/500mg.

Sitagliptin (Januet XR 50/500mg)/Metformin (Januet XR 50/500mg) is used with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.

This product contains 2 medications: Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg). Sitagliptin (Januet XR 50/500mg) works by increasing levels of natural substances called incretins. Incretins help to control blood sugar by increasing insulin release, especially after a meal. They also decrease the amount of sugar your liver makes. Metformin (Januet XR 50/500mg) works by helping to restore your body's proper response to the insulin you naturally produce. It also decreases the amount of sugar that your liver makes and that your stomach/intestines absorb.

How to use Januet XR 50/500mg

Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using Sitagliptin (Januet XR 50/500mg)/Metformin (Januet XR 50/500mg) and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily with a meal, preferably in the evening. Do not crush or chew extended-release tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing. Drink plenty of fluids while taking this medication unless otherwise directed by your doctor.

The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects (such as upset stomach), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. Carefully follow the medication treatment plan, meal plan, and exercise program your doctor has recommended.

Tell your doctor if your condition does not improve or if it worsens (your blood sugar levels are too high or too low).

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What other drugs will affect Januet XR 50/500mg?

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 50/500mg, 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 (Januet XR 50/500mg) 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 50/500mg 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 (Januet XR 50/500mg) 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 50/500mg the patient should be closely observed to maintain adequate glycemic control.

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What are the possible side effects of Januet XR 50/500mg?

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.

Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) Co-Administration in Patients with Type 2 Diabetes Inadequately Controlled on Diet and Exercise: Table 6 summarizes 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 (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) were co-administered to patients with type 2 diabetes inadequately controlled on diet and exercise.

Sitagliptin (Januet XR 50/500mg) Add-On Therapy in Patients with Type 2 Diabetes Inadequately Controlled on Metformin (Januet XR 50/500mg) Alone: In a 24-week placebo-controlled trial of Sitagliptin (Januet XR 50/500mg) 100 mg administered once daily added to a twice daily Metformin (Januet XR 50/500mg) regimen, there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo. Discontinuation of therapy due to clinical adverse reactions was similar to the placebo treatment group (Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg), 1.9%; placebo and Metformin (Januet XR 50/500mg), 2.5%).

Gastrointestinal Adverse Reactions: The incidences of pre-selected gastrointestinal adverse experiences in patients treated with Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) were similar to those reported for patients treated with Metformin (Januet XR 50/500mg) alone.

Sitagliptin (Januet XR 50/500mg) in Combination with Metformin (Januet XR 50/500mg) and Glimepiride: In a 24-week placebo-controlled study of Sitagliptin (Januet XR 50/500mg) 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on Metformin (Januet XR 50/500mg) and glimepiride (Sitagliptin (Januet XR 50/500mg), n=116; placebo, n=113), the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with Sitagliptin (Januet XR 50/500mg) and more commonly than in patients treated with placebo were: Hypoglycemia and headache (6.9%, 2.7%).

Sitagliptin (Januet XR 50/500mg) in Combination with Metformin (Januet XR 50/500mg) and Insulin: In a 24-week placebo-controlled study of Sitagliptin (Januet XR 50/500mg) 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on Metformin (Januet XR 50/500mg) and insulin (Sitagliptin (Januet XR 50/500mg), N=229; placebo, N=233), the only adverse reaction reported regardless of investigator assessment of causality in ≥5% of patients treated with Sitagliptin (Januet XR 50/500mg) and more commonly than in patients treated with placebo was hypoglycemia (Table 8).

Hypoglycemia: In all (N=5) studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required although most (77%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When the combination of Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) was co-administered with a sulfonylurea or with insulin, the percentage of patients reporting at least 1 adverse reaction of hypoglycemia was higher than that observed with placebo and Metformin (Januet XR 50/500mg) co-administered with a sulfonylurea or with insulin (Table 8).

The overall incidence of reported adverse reactions of hypoglycemia in patients with type 2 diabetes inadequately controlled on diet and exercise was 0.6% in patients given placebo, 0.6% in patients given Sitagliptin (Januet XR 50/500mg) alone, 0.8% in patients given Metformin (Januet XR 50/500mg) alone, and 1.6% in patients given Sitagliptin (Januet XR 50/500mg) in combination with Metformin (Januet XR 50/500mg). In patients with type 2 diabetes inadequately controlled on Metformin (Januet XR 50/500mg) alone, the overall incidence of adverse reactions of hypoglycemia was 1.3% in patients given add-on Sitagliptin (Januet XR 50/500mg) and 2.1% in patients given add-on placebo.

With the combination of Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg), no clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed.

The most common adverse experience in Sitagliptin (Januet XR 50/500mg) monotherapy reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo was nasopharyngitis.

The most common (>5%) established adverse reactions due to initiation of Metformin (Januet XR 50/500mg) therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia and headache.

Laboratory Tests: Sitagliptin (Januet XR 50/500mg): The incidence of laboratory adverse reactions was similar in patients treated with Sitagliptin (Januet XR 50/500mg) and Metformin (Januet XR 50/500mg) (7.6%) compared to patients treated with placebo and Metformin (Januet XR 50/500mg) (8.7%). In most but not all studies, a small increase in white blood cell count (approximately 200 cells/microliter difference in WBC vs placebo, mean baseline WBC approximately 6600 cells/microliter) was observed due to a small increase in neutrophils. This change in laboratory parameters is not considered to be clinically relevant.

Metformin (Januet XR 50/500mg) HCl: In controlled clinical trials of Metformin (Januet XR 50/500mg) 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 vitamin 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 (Januet XR 50/500mg) or vitamin B12 supplementation.

Post-Marketing Experience: Additional adverse reactions have been identified during post-approval of Januet XR 50/500mg or Sitagliptin (Januet XR 50/500mg), 1 of the components of Januet XR 50/500mg. These reactions have been reported when Januet XR 50/500mg or Sitagliptin (Januet XR 50/500mg) have been used alone and/or in combination with other antihyperglycemic agents. 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, including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis and exfoliative skin conditions, including Stevens-Johnson syndrome, upper respiratory tract infection; hepatic enzyme elevations; acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis; worsening renal function, including acute renal failure (sometimes requiring dialysis); constipation; vomiting; headache; arthralgia; myalgia; pain in extremity; back pain.

Each film-coated tablet contains Sitagliptin (Januet XR 50/500mg) phosphate monohydrate 64.25 mg and Metformin (Januet XR 50/500mg) HCl equivalent to: Sitagliptin (Januet XR 50/500mg) 50 mg as free base and Metformin (Januet XR 50/500mg) HCl 500 mg (Januet XR 50/500mg 50/500 mg), Metformin (Januet XR 50/500mg) HCl 850 mg (Januet XR 50/500mg 50/850 mg) or Metformin (Januet XR 50/500mg) HCl 1000 mg (Januet XR 50/500mg 50/1000 mg).

It also contains the following inactive ingredients: Microcrystalline cellulose, polyvinylpyrrolidone, sodium lauryl sulfate 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 black iron oxide.

Januet XR 50/500mg contains 2 oral antihyperglycemic drugs used in the management of type 2 diabetes: Sitagliptin (Januet XR 50/500mg) phosphate and Metformin (Januet XR 50/500mg) HCl.

Sitagliptin (Januet XR 50/500mg) phosphate is an orally-active inhibitor of the dipeptidyl peptidase-4 (DDP-4) enzyme. Sitagliptin (Januet XR 50/500mg) is present in Januet XR 50/500mg in the form of Sitagliptin (Januet XR 50/500mg) phosphate monohydrate. Sitagliptin (Januet XR 50/500mg) phosphate monohydrate is 7-[(3R)-3-amino-1-oxo-4-(2, 4, 5-trifluorophenyl)butyl]-5, 6, 7, 8-tetrahydro-3-(trifluoromethyl)-1, 2, 4-triazolo[4, 3-a]pyrazine phosphate (1:1) monohydrate with an empirical formula of C₁₆H₁₅F₆N₅O·H₃PO₄·H₂O and a molecular weight of 523.32.

Sitagliptin (Januet XR 50/500mg) phosphate monohydrate is a white to off-white, crystalline, nonhygroscopic 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.

Metformin (Januet XR 50/500mg) HCl (N, N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. Metformin (Januet XR 50/500mg) HCl is a white to off-white crystalline compound with a molecular formula of C₄H₁₁N₅·HCl and a molecular weight of 165.63. Metformin (Januet XR 50/500mg) HCl is freely soluble in water and is practically insoluble in acetone, ether and chloroform. The pKa of Metformin (Januet XR 50/500mg) is 12.4. The pH of a 1% aqueous solution of Metformin (Januet XR 50/500mg) HCl is 6.68.