Prescription Required
Manufacturer
ASTRAZENECA
SKU
00310612560

brand kombiglyze xr 2.5-1,000 mg tab

Brand
$7.03 / Tablet
First Order Ships Free Free 1-5 Day Shipping
+ -
In Stock
Total Price:

Uses

Diabetes Mellitus

Saxagliptin is used as monotherapy as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Saxagliptin also is used as initial therapy in combination with metformin hydrochloride (given separately or as the fixed combination of saxagliptin and extended-release metformin hydrochloride) as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus when treatment with both saxagliptin and metformin is appropriate. Saxagliptin also is used in combination with other oral antidiabetic agents (e.g., metformin, a sulfonylurea, a thiazolidinedione [peroxisome proliferator-activated receptorγ] agonist) or insulin as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control with one or more oral antidiabetic agents and/or insulin.

While metformin generally is the preferred antidiabetic agent for initial therapy in patients with type 2 diabetes mellitus, the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) suggests a dipeptidyl peptidase-4 (DPP-4) inhibitor as one of several alternative antidiabetic agents for initial monotherapy in patients with a contraindication to metformin (e.g., renal disease, hepatic disease, GI intolerance, risk of lactic acidosis). DPP-4 inhibitors also are recommended by AACE/ACE as part of combination therapy, particularly when both postprandial and fasting plasma glucose concentrations are elevated.

In pivotal clinical trials, glycemic efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus was evaluated at dosages of 2.5, 5, and 10 mg once daily as monotherapy or in combination with other antidiabetic agents. In these trials, the 10-mg daily dosage (currently not an FDA-labeled dosage) of saxagliptin did not demonstrate greater efficacy than the 5-mg daily dosage.

Saxagliptin should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Saxagliptin Monotherapy

Efficacy of saxagliptin as monotherapy in treatment-naive patients with type 2 diabetes mellitus is supported by results of 2 double-blind, placebo-controlled trials of 24 weeks' duration. In these trials, saxagliptin (2.5 or 5 mg once daily) improved glycemic control as evidenced by mean reductions in glycosylated hemoglobin (hemoglobin A1c; HbA1c) of about 0.4-0.7% (from a mean baseline HbA1c of 7.9%) compared with a mean increase in HbA1c of about 0.2-0.3% with placebo.

Combination Therapy

Clinical trials evaluating the efficacy and safety of the fixed combination of saxagliptin and extended-release metformin hydrochloride (Kombiglyze XR) in reducing HbA1c have not been conducted; unless otherwise specified, clinical trials of saxagliptin in combination with metformin discussed in this monograph were conducted using concomitantly administered saxagliptin and immediate-release metformin. Bioequivalence between the fixed combination of saxagliptin and extended-release metformin hydrochloride (Kombiglyze XR) and each agent (saxagliptin and extended-release metformin hydrochloride) given concurrently as separate tablets has been demonstrated.(See Description.)

Efficacy of the combination of saxagliptin and metformin as initial therapy in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise is supported by results of a 24-week randomized, active-controlled trial. In this trial, concurrent therapy with saxagliptin (5 or 10 mg once daily) and metformin hydrochloride (500 mg daily initially, titrated up to a maximum of 2 g daily given in 2 divided doses with meals) improved HbA1c, fasting plasma glucose, and 2-hour postprandial glucose values compared with saxagliptin or metformin monotherapy. Mean reductions in HbA1c from baseline were 2.5% in patients receiving saxagliptin 5 mg daily plus metformin, 2.5% in patients receiving saxagliptin 10 mg daily plus metformin, 2% with metformin plus placebo, and 1.7% with saxagliptin 10 mg daily plus placebo. The proportion of patients achieving an HbA1c less than 7% at week 24 was approximately 60% in patients receiving saxagliptin 5 or 10 mg daily plus metformin, 32% in patients receiving saxagliptin 10 mg daily plus placebo, and 41% in patients receiving metformin plus placebo.

Efficacy of saxagliptin in combination with metformin, a sulfonylurea (glyburide), or a thiazolidinedione (pioglitazone or rosiglitazone) in patients with type 2 diabetes mellitus inadequately controlled on monotherapy with these drugs is supported by results of several long-term (24-52 weeks' duration), randomized, placebo- or active-controlled trials demonstrating improvements in HbA1c and fasting and/or 2-hour postprandial plasma glucose concentrations. In a trial in patients already receiving metformin hydrochloride (1.5-2.55 g daily), add-on therapy with saxagliptin (2.5 or 5 mg daily) resulted in a mean HbA1c decrease of about 0.6 or 0.7%, respectively, (from a mean baseline HbA1c of 8.1%) compared with a mean HbA1c increase of about 0.1% with add-on placebo. In patients receiving either pioglitazone (30-45 mg daily) or rosiglitazone (4-8 mg daily) therapy, addition of saxagliptin (2.5 or 5 mg daily) resulted in a mean HbA1c reduction of 0.7 or 0.9%, respectively, (from a mean baseline HbA1c of 8.3 or 8.4%, respectively) compared with a mean reduction of 0.3% (from a mean baseline HbA1c of 8.2%) with add-on placebo. In patients receiving a submaximal dosage of glyburide (7.5 mg daily as a fixed dosage), addition of saxagliptin (2.5 or 5 mg daily) resulted in a mean HbA1c reduction of 0.5 or 0.6%, respectively, (from a mean baseline HbA1c of 8.4 or 8.5%, respectively) compared with a mean increase of 0.1% with placebo added to glyburide 10 mg daily and titrated up to a maximum dosage of 15 mg daily (about 92% of patients had glyburide dosage titrated up to 15 mg daily within the initial 4 weeks of the trial).

In a 24-week trial in patients already receiving metformin and a sulfonylurea, addition of saxagliptin (5 mg once daily) resulted in a mean HbA1c reduction of 0.7% (from a mean baseline HbA1c of 8.4%) compared with a mean reduction of 0.1% with placebo (from a mean baseline HbA1c of 8.2%).

In another trial comparing add-on therapy with saxagliptin versus add-on therapy with glipizide in patients already receiving metformin hydrochloride (1.5-3 g daily), addition of saxagliptin (5 mg daily) resulted in a mean HbA1c reduction of 0.6% (from a mean baseline HbA1c of 7.7%) versus a reduction of 0.7% (from a mean baseline HbA1c of 7.6%) with add-on glipizide therapy (initial glipizide dosage of 5 mg daily, titrated up to a mean final dosage of 15 mg daily).

Efficacy of saxagliptin in combination with insulin in patients with type 2 diabetes mellitus inadequately controlled with insulin (with or without metformin) is supported by results of a 24-week, randomized, placebo-controlled trial. In this trial, addition of saxagliptin (5 mg once daily) to existing stable therapy with premixed insulin or intermediate- or long-acting insulin (insulin given in combination with metformin in some patients) resulted in improvements in HbA1c and 2-hour postprandial glucose concentrations at week 24 compared with addition of placebo. Mean reductions in HbA1c were similar for patients receiving saxagliptin as add-on therapy with insulin alone or insulin with metformin (0.4% in both groups). The mean reduction from baseline in 2-hour postprandial glucose at week 24 was 27 mg/dL with add-on saxagliptin and 4 mg/dL with add-on placebo. The mean change from baseline in daily insulin dosage at the end of the study was 2 or 5 units with saxagliptin or placebo, respectively.

Dosage and Administration

Administration

When saxagliptin is administered as monotherapy, the drug should be administered orally once daily without regard to meals. If a dose is missed, the missed dose should be taken as soon as it is remembered followed by resumption of the regular schedule. If the missed dose is not remembered until the time of the next dose, the missed dose should be skipped and the regular schedule resumed; the dose should not be doubled to replace a missed dose.

When saxagliptin is administered in fixed combination with extended-release metformin hydrochloride, the combination should be administered orally once daily with the evening meal; dosage should be titrated gradually to minimize adverse GI effects of the metformin component. The fixed-combination tablets with extended-release metformin hydrochloride should be swallowed whole and should not be cut, chewed, or crushed. If a dose is missed, the next dose should be taken as prescribed unless a healthcare provider instructs otherwise; an extra dose should not be taken the next day.

Dosage

Dosage of saxagliptin hydrochloride (anhydrous) is expressed in terms of saxagliptin.

Saxagliptin Monotherapy

The recommended dosage of saxagliptin for the management of type 2 diabetes mellitus in adults is 2.5 or 5 mg once daily. In clinical trials, higher dosages (e.g., 10 mg once daily) did not provide additional benefit and are not recommended by the manufacturer.

When saxagliptin is used concomitantly with a potent inhibitor of cytochrome P-450 (CYP) isoenzymes 3A4/5 (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin), dosage of saxagliptin should be limited to 2.5 mg once daily.

Combination Therapy with Metformin Hydrochloride

Dosage of saxagliptin hydrochloride in fixed combination with extended-release metformin hydrochloride should be individualized based on the patient's current antidiabetic regimen, clinical response, and tolerability. Any change in therapy should be undertaken with care and appropriate monitoring because changes in glycemic control can occur.

When the fixed-combination preparation containing saxagliptin and extended-release metformin hydrochloride is used in patients inadequately controlled on monotherapy with saxagliptin 5 mg daily, the recommended initial dosage is 5 mg of saxagliptin and 500 mg of extended-release metformin hydrochloride once daily; dosage should be increased gradually to reduce adverse GI effects of metformin.

When the fixed-combination preparation containing saxagliptin and extended-release metformin hydrochloride is used in patients inadequately controlled on monotherapy with extended-release metformin hydrochloride, dosage of the fixed combination should provide metformin hydrochloride at the patient's current dosage, or the nearest therapeutically appropriate dosage. Following a switch from immediate-release to extended-release metformin, glycemic control should be closely monitored and dosage adjustments made accordingly.

In patients inadequately controlled on monotherapy with saxagliptin 2.5 mg daily, the recommended initial dosage of saxagliptin in fixed combination with extended-release metformin hydrochloride is 2.5 mg of saxagliptin and 1 g of extended-release metformin hydrochloride daily. Patients who require 2.5 mg of saxagliptin and who are either metformin naive or require a dose of metformin hydrochloride exceeding 1 g should use the individual components.

The maximum recommended dosage of saxagliptin in fixed combination with extended-release metformin hydrochloride is 5 mg of saxagliptin and 2 g of extended-release metformin hydrochloride daily. When the fixed combination preparation is used concomitantly with a potent CYP3A4/5 inhibitor (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin), dosage of saxagliptin should be limited to 2.5 mg once daily.

Special Populations

No dosage adjustment is recommended in patients with mild renal impairment (creatinine clearance exceeding 50 mL/minute). In patients with moderate or severe renal impairment (creatinine clearance of 50 mL/minute or less) or with end-stage renal disease requiring hemodialysis, the recommended dosage of saxagliptin is 2.5 mg once daily. In patients undergoing hemodialysis, saxagliptin should be administered following the dialysis procedure. Saxagliptin has not been studied in patients undergoing peritoneal dialysis.

No dosage adjustment is recommended in patients with hepatic impairment.

No dosage adjustment is recommended for geriatric patients based solely on age; however, because of the greater frequency of decreased renal function in geriatric patients, dosage in geriatric patients should be selected with caution.

Cautions

Contraindications

Saxagliptin is contraindicated in patients with known serious hypersensitivity (e.g., anaphylaxis, angioedema, exfoliative skin reaction) to saxagliptin or any ingredient in the formulation.

Warnings/Precautions

Pancreatitis and Pancreatic Precancerous Changes

Acute pancreatitis has been reported during postmarketing experience in patients receiving saxagliptin therapy. In a randomized, double-blind study (SAVOR) in 16,492 patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease or at high risk for the disease, acute pancreatitis was confirmed in 0.2 or 0.1% of patients receiving saxagliptin or placebo, respectively, in addition to standard care. Preexisting risk factors for pancreatitis were present in 88% of patients who developed pancreatitis while receiving saxagliptin and in 100% of those who developed pancreatitis while receiving placebo. FDA has been evaluating unpublished findings suggesting an increased risk of pancreatitis and precancerous pancreatic cell changes (pancreatic duct metaplasia) in patients with type 2 diabetes mellitus receiving incretin mimetics (exenatide, liraglutide, sitagliptin, saxagliptin, alogliptin, or linagliptin). These findings are based on examination of a small number of pancreatic tissue specimens taken from patients who died from unspecified causes while receiving an incretin mimetic. FDA will notify healthcare professionals of its conclusions and recommendations when the review is complete or when the agency has additional information to report.

FDA has recommended that clinicians continue to follow the recommendations in the prescribing information for incretin mimetics. The manufacturer states that patients receiving saxagliptin-containing therapy should be monitored for manifestations of pancreatitis.(See Advice to Patients.) If pancreatitis is suspected, saxagliptin should be promptly discontinued and appropriate management instituted. Safety and efficacy of saxagliptin have not been established in patients with a history of pancreatitis and it is not known whether such patients are at increased risk for pancreatitis with saxagliptin therapy.

Severe Arthralgia

Severe, disabling joint pain has been reported during postmarketing experience in patients receiving DPP-4 inhibitors (e.g., alogliptin, linagliptin, saxagliptin, sitagliptin). Onset of such symptoms has ranged from 1 day to years following initiation of therapy. Fever, chills, rash, and swelling accompanied joint pain in some patients, suggesting an immunologic reaction; some patients have required hospitalization. Symptoms resolved upon discontinuance of the DPP-4 inhibitor, usually in less than a month. In some patients, symptoms recurred when the same or another DPP-4 inhibitor was restarted. DPP-4 inhibitors should be considered as a possible cause of severe joint pain and should be discontinued if appropriate.(See Advice to Patients.)

Concomitant Therapy with Hypoglycemic Agents

When saxagliptin is added to therapy with an insulin secretagogue (e.g., a sulfonylurea) or insulin, the incidence of hypoglycemia is increased compared with sulfonylurea or insulin monotherapy. Therefore, patients receiving saxagliptin may require a reduced dosage of a concomitant insulin secretagogue (e.g., a sulfonylurea) or insulin to reduce the risk of hypoglycemia.

Reduction in Lymphocyte Count

Dose-related mean decreases in absolute lymphocyte count have been reported with saxagliptin dosages of 5 and 10 mg daily in clinical trials; clinical importance is not known. In most patients, recurrence of this effect was not observed with repeated exposure; however, some patients had reductions in lymphocyte count upon rechallenge that led to discontinuance of saxagliptin. Reductions in lymphocyte count were not associated with clinically relevant adverse effects. When clinically indicated (i.e., settings of unusual or prolonged infection), lymphocyte count should be measured.

Sensitivity Reactions

In a pooled analysis of data from 5 studies, hypersensitivity reactions (e.g., urticaria, facial edema) were reported in 1.5% of patients receiving saxagliptin 2.5 or 5 mg daily. In addition, there have been postmarketing reports of serious allergic and hypersensitivity reactions (e.g., anaphylaxis, angioedema, exfoliative skin conditions). The onset of such reactions usually was within the first 3 months following treatment initiation; some reactions occurred after the first dose.(See Cautions: Contraindications.)

If a serious hypersensitivity reaction is suspected, saxagliptin should be promptly discontinued, other potential causes of the event should be investigated, appropriate treatment for the reaction should be provided, and alternative antidiabetic therapy should be instituted.(See Advice to Patients.) Saxagliptin should be used with caution in patients with a history of angioedema to other dipeptidyl peptidase-4 inhibitors because it is unknown whether such patients will be predisposed to angioedema with saxagliptin.

Cardiovascular Effects

Macrovascular Outcomes

In a pooled analysis of 8 randomized, phase 2 or 3 clinical trials (total of 4607 patients) designed to evaluate the relative risk of cardiovascular events (cardiovascular death, myocardial infarction, stroke) in patients receiving saxagliptin versus other antidiabetic agents (metformin, glyburide) or placebo, no increased cardiovascular risk was noted with saxagliptin therapy. The manufacturer states that evidence of macrovascular risk reduction with saxagliptin or any other antidiabetic agent has not been conclusively demonstrated in clinical trials.

Heart Failure Risk

Saxagliptin may increase the risk of heart failure, particularly in patients who have a history of heart failure or renal impairment. In a randomized, double-blind study (SAVOR) in which saxagliptin or placebo was added to standard care in 16,492 patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease or at high risk for the disease, more patients receiving saxagliptin were hospitalized for heart failure than patients receiving placebo (3.5 or 2.8%, respectively). After a median of 2 years of follow-up, treatment with saxagliptin was associated with a 27% increased risk of hospitalization for heart failure; however, therapy with the drug was not associated with increased or decreased rates of cardiovascular death or other ischemic events. Patients with a history of heart failure or renal impairment had a higher risk of hospitalization for heart failure in this study regardless of treatment (saxagliptin or placebo).

The potential risks and benefits of saxagliptin therapy should be considered prior to use in patients at higher risk for heart failure. Patients receiving saxagliptin-containing therapy should be monitored for manifestations of heart failure.(See Advice to Patients.) If heart failure develops, appropriate evaluation and management should be instituted and consideration given to discontinuing saxagliptin.

Use of Fixed Combinations

When saxagliptin is used in fixed combination with metformin hydrochloride, the cautions, precautions, and contraindications associated with metformin hydrochloride should be considered.

Specific Populations

Pregnancy

Category B.

Lactation

Saxagliptin is distributed into milk in rats at a milk-to-plasma ratio of approximately 1:1; it is not known whether saxagliptin is distributed into human milk. Caution is advised if the drug is administered in nursing women.

Pediatric Use

Safety and efficacy of saxagliptin have not been established in patients younger than 18 years of age.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults have been observed, but increased sensitivity cannot be ruled out.

Saxagliptin and its active metabolite are eliminated in part by the kidneys; renal function should be assessed periodically since geriatric patients are more likely to have decreased renal function.

Hepatic Impairment

In patients with hepatic impairment (Child-Pugh class A, B, and C), mean peak concentrations and area under the plasma concentration-time curve (AUC) of saxagliptin were increased by up to 8 and 77%, respectively, compared with healthy individuals following a single 10-mg dose of the drug; peak concentrations and AUC of the active metabolite were increased by up to 59 and 33%, respectively. These differences were not considered clinically important.

Renal Impairment

No dosage adjustment of saxagliptin is recommended in patients with mild renal impairment (creatinine clearance exceeding 50 mL/minute). However, dosage adjustment is recommended when the drug is used in patients with moderate or severe renal impairment (creatinine clearance of 50 mL/minute or less) or end-stage renal disease requiring hemodialysis.(See Dosage and Administration: Special Populations.) Renal function should be assessed prior to initiation of therapy and periodically thereafter. The fixed combination of saxagliptin and extended-release metformin hydrochloride is contraindicated in patients with renal impairment.

Common Adverse Effects

In clinical trials, the incidence of hypoglycemic adverse reactions in patients receiving saxagliptin was based on all reports of hypoglycemia, although a concurrent glucose measurement was not required or was normal in some patients with reported hypoglycemic reactions; therefore, it is not possible to determine conclusively whether all these reports represent true hypoglycemic events. In the clinical trial in which saxagliptin or placebo was added to insulin therapy (with or without metformin), (see Uses: Diabetes Mellitus) the incidence of adverse effects (except for confirmed hypoglycemia) was similar with add-on saxagliptin and add-on placebo. However, the incidence of confirmed hypoglycemia (as determined by fingerstick blood glucose of 50 mg/dL or less) in this trial was higher with saxagliptin 5 mg daily (5.3%) than with placebo (3.3%).

Adverse effects reported in at least 5% of patients in clinical trials receiving saxagliptin 5 mg daily as monotherapy or in combination with metformin, a thiazolidinedione (pioglitazone or rosiglitazone), or glyburide and more frequently than with placebo include upper respiratory tract infection, urinary tract infection, and headache.

Adverse effects reported in at least 5% of patients in clinical trials receiving saxagliptin in combination with immediate-release metformin and more frequently than with metformin alone include headache and nasopharyngitis.

Drug Interactions

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Saxagliptin and its active metabolite do not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4 and do not induce CYP1A2, 2B6, 2C9, or 3A4 in vitro. Pharmacokinetic interactions with drugs metabolized by these isoenzymes are unlikely.

Saxagliptin is metabolized principally via CYP3A4 and CYP3A5. Administration of a single dose of saxagliptin (100 mg) to healthy individuals receiving ketoconazole (200 mg every 12 hours for 9 days) decreased the peak steady-state plasma concentration and area under the plasma concentration-time curve (AUC) of ketoconazole by 16 and 13%, respectively, and increased the peak plasma concentration and AUC of saxagliptin by 62 and 145% (2.5-fold), respectively. Similar increases in saxagliptin plasma concentrations and AUC are anticipated with concomitant use of saxagliptin and other potent CYP3A4/5 inhibitors (e.g. atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Saxagliptin dosage should be limited to 2.5 mg daily when the drug is used concomitantly with a potent CYP3A4/5 inhibitor.

Inhibitors of P-glycoprotein Transport System

Saxagliptin is a substrate of the P-glycoprotein transport system but does not appreciably induce or inhibit P-glycoprotein.

Antacids

Concurrent administration of a single dose of saxagliptin (10 mg) and a single dose of liquid antacid containing aluminum hydroxide (2.4 g), magnesium hydroxide (2.4 g), and simethicone (240 mg) decreased peak plasma concentrations of saxagliptin by 26% and AUC by 3%. The manufacturer states that no dosage adjustments are required with concurrent use.

Digoxin

Concurrent administration of saxagliptin (10 mg once daily for 7 days) and digoxin (0.25 mg every 6 hours the first day, then 0.25 mg every 12 hours the second day, then 0.25 mg once daily for 5 days), a P-glycoprotein substrate, increased the AUC and peak plasma concentration of digoxin by 6 and 9%, respectively; the AUC of saxagliptin was increased by 5% and peak plasma saxagliptin concentrations decreased by 1%. The manufacturer states that no dosage adjustments are required with concurrent use.

Diltiazem

Concurrent administration of saxagliptin (10-mg single dose) and a long-acting formulation of diltiazem (360 mg daily for 9 days) increased the peak steady-state plasma concentration of diltiazem by 16% and the AUC by 10%; in addition, peak plasma saxagliptin concentrations increased by 63% and saxagliptin AUC was increased by 2.1-fold. The manufacturer states that no dosage adjustments are required with concurrent use.

Famotidine

Administration of a single dose of saxagliptin (10 mg) concurrently with a single dose of famotidine (40 mg) increased the peak plasma concentration of saxagliptin by 14% and AUC by 3%. The manufacturer states that no dosage adjustments are required with concurrent use.

Hormonal Contraceptives

Concurrent administration of saxagliptin (5 mg once daily for 21 days) and an estrogen-progestin combination contraceptive (ethinyl estradiol 35 mcg in fixed combination with norgestimate 0.25 mg once daily for 21 days) did not appreciably alter the steady-state pharmacokinetics of ethinyl estradiol or the primary active progestin component, norelgestromin. The mean AUC and peak plasma concentration of norgestrel, an active metabolite of norelgestromin, were increased by 13 and 17%, respectively, which is not considered clinically important. The manufacturer states that no dosage adjustments are required with concurrent use.

Metformin

Concomitant administration of a single dose of saxagliptin (100 mg) and metformin hydrochloride (1 g) decreased the peak plasma concentration of saxagliptin by 21% and the AUC by 2%; metformin AUC and peak plasma concentration were increased by 20 and 9%, respectively. The manufacturer states that no dosage adjustments are required with concurrent use.

Omeprazole

Concurrent administration of saxagliptin (10 mg daily) and omeprazole (40 mg daily for 5 days) increased saxagliptin AUC by 13% and decreased peak plasma concentrations of the drug by 2%. The manufacturer states that no dosage adjustments are required with concurrent use.

Pioglitazone

Concurrent administration of saxagliptin (10 mg once daily for 5 days) and pioglitazone (45 mg daily for 10 days) increased the peak plasma concentration of pioglitazone by 14% and the AUC by 8%. In addition, the AUC and peak plasma concentration of saxagliptin were each increased by 11%. The manufacturer states that no dosage adjustments are required with concurrent use.

Rifampin

Concomitant administration of a single dose of saxagliptin (5 mg) with rifampin (600 mg daily for 6 days) decreased peak steady-state plasma concentrations and AUC of saxagliptin by 53 and 76%, respectively, while peak plasma concentration of the active metabolite was increased by 39%; there was no appreciable change in the AUC of the active metabolite of saxagliptin. The manufacturer states that no dosage adjustments are required with concurrent use.

Simvastatin

Concomitant administration of saxagliptin (10 mg once daily for 4 days) and simvastatin (40 mg once daily for 8 days) increased the peak plasma concentration and AUC of saxagliptin by 21 and 12%, respectively, while simvastatin peak plasma concentrations were reduced by 12% and AUC was increased by 4%. The manufacturer states that no dosage adjustments are required with concurrent use.

Sulfonylureas

Concomitant administration of single doses of saxagliptin (10 mg) and glyburide (5 mg) increased peak plasma concentrations of glyburide and saxagliptin by 16 and 8%, respectively; the AUC of glyburide was increased by 6% and that of saxagliptin was decreased by 2%. The manufacturer states that no dosage adjustments are required because of changes in systemic exposures when saxagliptin and glyburide are given concomitantly. However, in patients receiving saxagliptin concomitantly with a sulfonylurea antidiabetic agent, a reduced dosage of the sulfonylurea may be required to reduce the risk of hypoglycemia.

Write Your Own Review
You're reviewing:KOMBIGLYZE XR 2.5-1,000 MG TAB
Your Rating

How to save on your prescriptions!