Xelevia 100mg

Monotherapy: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Combination with Metformin: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin as initial therapy or when the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Combination with a Sulfonylurea: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with a sulfonylurea when treatment with the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Combination with a PPARγ Agonist: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with a PPARγ agonist (i.e., thiazolidinediones) as initial therapy or when the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Combination with Metformin and a Sulfonylurea: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and a sulfonylurea when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.

Combination with Metformin and a PPARγ agonist: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and a PPARγ agonist (i.e., thiazolidinediones) when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.

Combination with Insulin: Xelevia 100mg PHOSPHATE (Xelevia 100mg) is indicated in patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in combination with insulin (with or without metformin).

Xelevia 100mg is used alone or together with other medicines (e.g., insulin, glimepiride, metformin, or pioglitazone) to treat high blood sugar levels caused by type 2 diabetes. Normally, after you eat, your pancreas releases insulin to help your body store excess sugar for later use. This process occurs during normal digestion of food. In patients with type 2 diabetes, your body does not work properly to store the excess sugar and the sugar remains in your blood. Chronic high blood sugar can lead to serious health problems in the future.

Many people can control type 2 diabetes with diet alone or diet and exercise. Following a specially planned diet and exercising will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of Xelevia 100mg you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet, your exercise, or both, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.

Xelevia 100mg does not help patients who have insulin-dependent or type 1 diabetes, because they cannot produce insulin from their pancreas. Their blood sugar is best controlled with insulin injections.

Xelevia 100mg is available only with your doctor's prescription.

The recommended dose of Xelevia 100mg PHOSPHATE (Xelevia 100mg) is 100 mg once daily as monotherapy or as combination therapy with metformin, a sulfonylurea, insulin (with or without metformin), a PPARγ agonist (e.g., thiazolidinediones), metformin plus a sulfonylurea, or metformin plus a PPARγ agonist.

When Xelevia 100mg PHOSPHATE (Xelevia 100mg) is used in combination with a sulfonylurea or with insulin, a lower dose of sulfonylurea or insulin may be considered to reduce the risk of sulfonylurea- or insulin-induced hypoglycemia. (Hypoglycemia in Combination with a Sulfonylurea or with Insulin under Precautions.)

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 for Xelevia 100mg PHOSPHATE (Xelevia 100mg) 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 Xelevia 100mg PHOSPHATE (Xelevia 100mg) 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 Xelevia 100mg PHOSPHATE (Xelevia 100mg) is 25 mg once daily. Xelevia 100mg PHOSPHATE (Xelevia 100mg) may be administered without regard to the timing of dialysis.

Because there is a dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of Xelevia 100mg PHOSPHATE (Xelevia 100mg) and periodically thereafter.

Administration: Xelevia 100mg PHOSPHATE (Xelevia 100mg) can be taken orally with or without food.

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What is the most important information I should know about Xelevia 100mg?

Do not use this medication if you are allergic to Xelevia 100mg or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

Before taking Xelevia 100mg, tell your doctor if you have kidney disease, if you are on dialysis, or if you have a history of pancreatitis.

You may take this medicine with or without food. Follow your doctor's instructions.

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are taking Xelevia 100mg.

Stop taking Xelevia 100mg and call your doctor at once if you have severe pain in your upper stomach spreading to your back, nausea and vomiting, loss of appetite, or fast heart rate.

Take care not to let your blood sugar get too low. Low blood sugar (hypoglycemia) can occur if you skip a meal, exercise too long, drink alcohol, or are under stress. Symptoms include headache, hunger, weakness, sweating, tremor, irritability, or trouble concentrating. Carry hard candy or glucose tablets with you in case you have low blood sugar. Other sugar sources include orange juice and milk. Be sure your family and close friends know how to help you in an emergency.

Xelevia 100mg is only part of a complete program of treatment that also includes diet, exercise, weight control, and possibly other medications. It is important to use this medicine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Use Xelevia 100mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Xelevia 100mg comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Xelevia 100mg refilled.
• Take Xelevia 100mg by mouth with or without food.
• Swallow Xelevia 100mg whole. Do not break, split, crush, or chew before swallowing. If you cannot swallow Xelevia 100mg whole, contact your doctor.
• Take Xelevia 100mg on a regular schedule to get the most benefit from it.
• Continue to take Xelevia 100mg even if you feel well. Do not miss any doses.
• If you miss a dose of Xelevia 100mg, take it 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 Xelevia 100mg.

Xelevia 100mg is used with a proper diet and exercise program and possibly with other medications to control high blood sugar. It is used 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.

Xelevia 100mg is an anti-diabetic drug that 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.

How to use Xelevia 100mg

Read the Medication Guide provided by your pharmacist before you start using Xelevia 100mg and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food, as directed by your doctor, usually once daily.

The dosage is based on your medical condition, kidney function, and response to treatment. 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.

Check your blood sugar regularly as directed by your doctor. Keep track of the results, and share them with your doctor. Tell your doctor if your blood sugar measurements are too high or too low. Your dosage/treatment may need to be changed.

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What other drugs will affect Xelevia 100mg?

In drug interaction studies, Xelevia 100mg did not have clinically meaningful effects on the pharmacokinetics of the following: Metformin, rosiglitazone, glyburide, simvastatin, warfarin, and oral contraceptives. Based on these data, Xelevia 100mg does not inhibit CYP isozymes CYP3A4, 2C8, or 2C9. Based on in vitro data, Xelevia 100mg is also not expected to inhibit CYP2D6, 1A2, 2C19 or 2B6 or to induce CYP3A4.

Co-administration of multiple twice-daily doses of metformin with Xelevia 100mg did not meaningfully alter the pharmacokinetics of Xelevia 100mg in patients with type 2 diabetes.

Population pharmacokinetic analyses have been conducted in patients with type 2 diabetes. Concomitant medications did not have a clinically meaningful effect on the pharmacokinetics of Xelevia 100mg. Medications assessed were those that are commonly administered to patients with type 2 diabetes including cholesterol-lowering agents (e.g., statins, fibrates, ezetimibe), anti-platelet agents (e.g., clopidogrel), antihypertensives (e.g., ACE inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, hydrochlorothiazide), analgesics and non-steroidal anti-inflammatory agents (e.g., naproxen, diclofenac, celecoxib), anti-depressants (e.g., bupropion, fluoxetine, sertraline), antihistamines (e.g., cetirizine), proton-pump inhibitors (e.g., omeprazole, lansoprazole), and medications for erectile dysfunction (e.g., sildenafil).

There was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (C_max, 18%) of digoxin with the co-administration of Xelevia 100mg. These increases are not considered to be clinically meaningful. Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or Xelevia 100mg PHOSPHATE (Xelevia 100mg) is recommended.

The AUC and C_max of Xelevia 100mg were increased approximately 29% and 68%, respectively, in subjects with co-administration of a single 100-mg oral dose of Xelevia 100mg PHOSPHATE (Xelevia 100mg) and a single 600-mg oral dose of cyclosporine, a potent probe inhibitor of p-glycoprotein. The observed changes in Xelevia 100mg pharmacokinetics are not considered to be clinically meaningful. No dosage adjustment for Xelevia 100mg PHOSPHATE (Xelevia 100mg) is recommended when co-administered with cyclosporine or other p-glycoprotein inhibitors (e.g., ketoconazole).

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What are the possible side effects of Xelevia 100mg?

Xelevia 100mg PHOSPHATE (Xelevia 100mg) was generally well tolerated in controlled clinical studies as both monotherapy and combination therapy, with discontinuation of therapy due to clinical adverse experiences similar to placebo.

In four placebo-controlled clinical studies as both monotherapy (one study of 18- and one of 24-week duration) and add-on combination therapy with metformin or pioglitazone (both of 24-week duration), there were 1082 patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg once daily and 778 patients given placebo. (Two of these studies also included 456 patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) 200 mg daily, two times the recommended daily dose.) There were no drug-related adverse reactions reported that occurred with an incidence of ≥1% in patients receiving Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg. Overall, the safety profile of the 200-mg daily dose was similar to that of the 100-mg daily dose.

In a prespecified pooled analysis of the above studies, the overall incidence of adverse experiences of hypoglycemia in patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg was similar to placebo (1.2% vs. 0.9%). The incidences of selected gastrointestinal adverse experiences in patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) or placebo were: Abdominal pain (Xelevia 100mg PHOSPHATE (Xelevia 100mg), 2.3%; placebo, 2.1%), nausea (1.4%, 0.6%), vomiting (0.8%, 0.9%), and diarrhea (3.0%, 2.3%).

In all studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required.

Add-on Combination with a Sulfonylurea: In a 24-week placebo-controlled study of Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg in combination with glimepiride or with glimepiride and metformin (Xelevia 100mg PHOSPHATE (Xelevia 100mg), N=222; placebo, N=219), the drug-related adverse reaction reported in ≥1% of patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) and more commonly than in patients treated with placebo was hypoglycemia [Xelevia 100mg PHOSPHATE (Xelevia 100mg), 9.5%; placebo, 0.9%].

Add-on Combination with Metformin and a PPARγ Agonist: In a placebo-controlled study of Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg in combination with metformin and rosiglitazone (Xelevia 100mg PHOSPHATE (Xelevia 100mg), N=170; placebo, N=92), the drug-related adverse reactions reported through the primary time point at Week 18 in ≥1% of patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) and more commonly than in patients treated with placebo were: Headache [Xelevia 100mg PHOSPHATE (Xelevia 100mg), 2.4%; placebo, 0.0%], diarrhea (1.8%, 1.1%), nausea (1.2%, 1.1%), hypoglycemia (1.2%, 0.0%), and vomiting (1.2%, 0.0%). Through Week 54, the drug-related adverse reactions reported in ≥1% of patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) and more commonly than in patients treated with placebo were: headache (2.4%, 0.0%), hypoglycemia (2.4%, 0.0%), upper respiratory tract infection (1.8%, 0.0%), nausea (1.2%, 1.1%), cough (1.2%, 0.0%), fungal skin infection (1.2%, 0.0%), peripheral edema (1.2%, 0.0%), and vomiting (1.2%, 0.0%).

Initial Combination Therapy with Metformin: In a 24-week placebo-controlled factorial study of initial therapy with Xelevia 100mg 100 mg in combination with metformin at 1000 mg or 2000 mg per day (administered as Xelevia 100mg 50 mg/metformin 500 mg or 1000 mg twice daily), the drug-related adverse reactions reported in ≥1% of patients treated with Xelevia 100mg plus metformin (N=372) and more commonly than in patients treated with metformin alone (N=364) were: Diarrhea (Xelevia 100mg plus metformin, 3.5%; metformin, 3.3%), dyspepsia (1.3%; 1.1%), flatulence (1.3%; 0.5%), vomiting (1.1%; 0.3%), and headache (1.3%; 1.1%). The incidence of hypoglycemia was 1.1% in patients given Xelevia 100mg in combination with metformin and 0.5% in patients given metformin alone.

Initial Combination Therapy with a PPARγ Agonist: In a 24-week study of initial therapy with Xelevia 100mg PHOSPHATE (Xelevia 100mg) at 100 mg/day in combination with pioglitazone at 30 mg/day, the only drug-related adverse reaction reported in ≥1% of patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) with pioglitazone (N=261) and more commonly than in patients treated with pioglitazone alone (N=259) was (asymptomatic) decreased blood glucose [Xelevia 100mg PHOSPHATE (Xelevia 100mg) with pioglitazone, 1.1%; pioglitazone, 0.0%]. The incidence of (symptomatic) hypoglycemia was 0.4% in patients given Xelevia 100mg PHOSPHATE (Xelevia 100mg) in combination with pioglitazone and 0.8% in patients given pioglitazone.

Add-on Combination with Insulin: In a 24-week placebo-controlled study of Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg in combination with stable-dose insulin (with or without metformin), the drug-related adverse reactions reported in ≥1% of patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) (N=322) and more commonly than in patients treated with placebo (N=319) were: Hypoglycemia [Xelevia 100mg PHOSPHATE (Xelevia 100mg), 9.6%; placebo, 5.3%], influenza (1.2%, 0.3%), and headache (1.2%, 0.0%). In another 24-week study of patients receiving Xelevia 100mg PHOSPHATE (Xelevia 100mg) as add-on therapy while undergoing insulin intensification (with or without metformin), there were no drug-related adverse reactions reported that occurred with an incidence of ≥1% in patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg and more commonly than in patients treated with placebo.

Pancreatitis: In a pooled analysis of 19 double-blind clinical trials that included data from 10,246 patients randomized to receive Xelevia 100mg 100 mg/day (N=5429) or corresponding (active or placebo) control (N=4817), the incidence of acute pancreatitis was 0.1 per 100 patient-years in each group (4 patients with an event in 4708 patient-years for Xelevia 100mg and 4 patients with an event in 3942 patient-years for control)..

No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed in patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg).

Postmarketing Experience: Additional adverse reactions have been identified during postmarketing use of Xelevia 100mg PHOSPHATE (Xelevia 100mg) as monotherapy 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; acute pancreatitis, including fatal and non-fatal hemorrhagic and necrotizing pancreatitis; worsening renal function, including acute renal failure (sometimes requiring dialysis); upper respiratory tract infection; nasopharyngitis; constipation; vomiting; headache; arthralgia; myalgia; pain in extremity; back pain, pruritus.

Laboratory Test Findings: The incidence of laboratory adverse experiences was similar in patients treated with Xelevia 100mg PHOSPHATE (Xelevia 100mg) 100 mg compared to patients treated with placebo.

Across clinical studies, a small increase in white blood cell count (approximately 200 cells/microL difference in WBC vs placebo; mean baseline WBC approximately 6600 cells/microL) was observed due to an increase in neutrophils. This observation was seen in most but not all studies. This change in laboratory parameters is not considered to be clinically relevant.

Each film-coated tablet contains 32.13, 64.25, or 128.5 mg of Xelevia 100mg phosphate monohydrate, which is equivalent to 25, 50, or 100 mg, respectively, of free base.

Xelevia 100mg PHOSPHATE (Xelevia 100mg) tablets contain Xelevia 100mg phosphate, an orally-active, potent, and selective inhibitor of dipeptidyl peptidase 4 (DPP-4), which is described Xelevia 100mg PHOSPHATE chemically as: 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.

The empirical formula is C₁₆H₁₅F₆N₅O• H₃PO₄• H₂O and the molecular weight is 523.32.

Xelevia 100mg 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.