predict [60:<15 mL/minute or requiring hemodialysis): 6.25 mg once daily without regard to timing of hemodialysis. 1 Alogliptin/Metformin Hydrochloride Fixed Combination Fixed combination of alogliptin and metformin hydrochloride is contraindicated in patients with renal impairment. 2 Alogliptin/Pioglitazone Fixed Combination Mild renal impairment (Cl cr 60 mL/minute): No dosage adjustment necessary. 3 Moderate renal impairment (Cl cr 30 to> <60 mL/minute): Alogliptin 12.5 mg and pioglitazone 15, 30, or 45 mg once daily. 3 Severe renal impairment or end-stage renal disease: Not recommended. 3 Geriatric Patients Dosage adjustment not necessary. 1 Patients with CHF NYHA class III or IV: Do not initiate fixed combination of alogliptin and pioglitazone. 3 NYHA class I or II: 25 mg of alogliptin and 15 mg of pioglitazone once daily in fixed combination. 3 Cautions for Alogliptin Benzoate Contraindications Known serious hypersensitivity (e.g., anaphylaxis, angioedema, severe adverse cutaneous reactions) to alogliptin. 1 Warnings/Precautions Pancreatitis and Pancreatic Precancerous Changes Acute pancreatitis reported during postmarketing experience. 1 FDA has been evaluating unpublished findings suggesting an increased risk of pancreatitis and precancerous pancreatic cell changes in patients with type 2 diabetes mellitus receiving incretin mimetics. 17 18 FDA will notify healthcare professionals of its conclusions and recommendations when the review is complete, or when FDA has additional information to report. 17 FDA has recommended that clinicians continue to follow the recommendations in the prescribing information for incretin mimetics. 17 Manufacturer states that patients should be observed carefully for signs and symptoms of pancreatitis. 1 If pancreatitis is suspected, promptly discontinue alogliptin and institute appropriate management. 1 Not known if history of pancreatitis increases risk for pancreatitis with alogliptin. 1 Severe Arthralgia Severe, disabling joint pain reported in patients receiving DPP-4 inhibitors (e.g., alogliptin, linagliptin, saxagliptin, sitagliptin). 1 41 Onset of such symptoms has ranged from 1 day to years following initiation of therapy. 1 41 Symptoms resolved upon discontinuance of the DPP-4 inhibitor; symptoms recurred in some patients when the same or another DPP-4 inhibitor was restarted. 1 41 Consider DPP-4 inhibitors as a possible cause of severe joint pain and discontinue if appropriate. 1 41 (See Advice to Patients.) Sensitivity Reactions Hypersensitivity reactions (e.g., anaphylaxis, angioedema, severe adverse cutaneous reactions including Stevens-Johnson syndrome) reported. 1 Promptly discontinue alogliptin if a serious hypersensitivity reaction is suspected, investigate other potential causes, and institute alternative antidiabetic therapy. 1 (See Advice to Patients.) Use with caution in patients with a history of angioedema to other DDP-4 inhibitors; unknown whether such patients will be predisposed to angioedema with alogliptin. 1 Hepatic Effects Fatal and nonfatal hepatic failure reported. 1 Assess hepatic function prior to alogliptin initiation; use with caution in patients with abnormal liver function test results. 1 Promptly assess liver function in patients with signs or symptoms indicating liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice). 1 Interrupt alogliptin treatment if clinically important liver enzyme elevations and if liver function test abnormalities persist or worsen. 1 Do not restart the drug in these patients without another explanation for the test abnormalities. 1 Concomitant Therapy with Hypoglycemic Agents When used in combination with an insulin secretagogue (e.g., a sulfonylurea) or insulin, consider reducing the dosage of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. 1 Cardiovascular Effects Macrovascular Outcomes Manufacturer states that evidence of macrovascular risk reduction with alogliptin or any other antidiabetic agent not conclusively demonstrated in clinical trials. 1 Heart Failure Risk Possible increased risk of heart failure, particularly in patients with history of heart failure or renal impairment. 42 In a randomized, placebo-controlled, double-blind study in which alogliptin was added to standard care in 5380 patients with type 2 diabetes mellitus and recent acute coronary syndrome, 3.9% of patients receiving alogliptin experienced at least one hospitalization for heart failure compared with 3.3% of patients receiving placebo. 1 39 40 42 Consider potential risks and benefits of alogliptin therapy prior to use in patients at higher risk for heart failure. 1 42 Monitor patients for manifestations of heart failure. 1 42 (See Advice to Patients.) If heart failure develops, institute appropriate treatment and consider discontinuance of alogliptin. 1 42 Use of Fixed Combinations When used in fixed combination with metformin hydrochloride or pioglitazone, consider the cautions, precautions, and contraindications associated with metformin or pioglitazone. 1 Specific Populations Pregnancy Category B. 1 Lactation Distributed into milk in rats; not known whether distributed into human milk. 1 Use caution. 1 Pediatric Use Safety and efficacy of alogliptin alone, in fixed combination with metformin, or in fixed combination with pioglitazone not established in pediatric patients 1 2 3> <18 years of age. 24 Geriatric Use No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out. 1 Hepatic Impairment Moderate hepatic impairment decreased alogliptin total exposure. 1 (See Absorption: Special Populations, under Pharmacokinetics.) Data lacking in severe hepatic impairment. 1 Fixed combination of alogliptin and metformin hydrochloride not recommended in patients with hepatic impairment. 2 Renal Impairment Renal impairment increases AUC. 1 (See Absorption: Special Populations, under Pharmacokinetics.) Dosage adjustment recommended for patients with moderate or severe renal impairment or end-stage renal disease. 1 (See Renal Impairment under Dosage and Administration.) Fixed combination of alogliptin and metformin hydrochloride contraindicated in patients with renal impairment. 2 Assess renal function prior to initiation of therapy and periodically thereafter. 1 Common Adverse Effects Alogliptin monotherapy: Nasopharyngitis, 1 headache, 1 upper respiratory tract infection. 1 Alogliptin/metformin hydrochloride fixed combination: Upper respiratory tract infection, 2 nasopharyngitis, 2 diarrhea, 2 hypertension, 2 headache, 2 back pain, 2 urinary tract infection. 2 Alogliptin/pioglitazone fixed combination: Nasopharyngitis, 3 back pain, 3 upper respiratory tract infection. 3 Interactions for Alogliptin Benzoate Mainly renally excreted; CYP-related metabolism is negligible. 1 Does not induce CYP1A2, 2B6, 2C9, 2C19, or 3A4 and does not inhibit CYP1A2, 2C8, 2C9, 2C19, 3A4, or 2D6. 1 Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes CYP2C8, 2C9, and 3A4 inhibitors: No clinically important interactions observed with the inhibitors tested. 1 CYP1A2, 2C8, 2C9, 2D6, and 3A4 substrates: No clinically important interactions observed with the substrates tested. 1 Substrates or Inhibitors of P-glycoprotein Transport Systems No clinically important interactions observed with the substrates or inhibitors tested. 1 Specific Drugs Drug Interaction Comments Atorvastatin Did not alter peak plasma concentrations or AUC of either drug 1 No dosage adjustment necessary 1 Caffeine Did not alter peak plasma concentrations or AUC of caffeine 1 No dosage adjustment necessary 1 Cimetidine Did not alter peak plasma concentrations or AUC of either drug 1 No dosage adjustment necessary 1 Contraceptives, hormonal Did not alter peak plasma concentrations or AUC of ethinyl estradiol or norethindrone 1 13 No dosage adjustment necessary 1 13 Cyclosporine Did not alter peak plasma concentrations or AUC of alogliptin 1 No dosage adjustment necessary 1 Dextromethorphan Did not alter peak plasma concentrations or AUC of dextromethorphan 1 No dosage adjustment necessary 1 Digoxin Did not alter peak plasma concentrations or AUC of either drug 1 No dosage adjustment necessary 1 Fexofenadine Did not alter peak plasma concentrations or AUC of fexofenadine 1 No dosage adjustment necessary 1 Fluconazole Did not alter peak plasma concentrations or AUC of alogliptin 1 13 No dosage adjustment necessary 1 Gemfibrozil Did not alter peak plasma concentrations or AUC of alogliptin 1 13 No dosage adjustment necessary 1 Glyburide Did not alter peak plasma concentrations or AUC of glyburide 1 14 No dosage adjustment necessary 1 14 Ketoconazole Did not alter peak plasma concentrations or AUC of alogliptin 1 13 No dosage adjustment necessary 1 Metformin Did not alter peak plasma concentrations or AUC of either drug 1 No dosage adjustment necessary 1 Midazolam Did not alter peak plasma concentrations or AUC of midazolam 1 No dosage adjustment necessary 1 Pioglitazone Did not alter peak plasma concentrations or AUC of either drug 1 14 No dosage adjustment necessary 1 14 Tolbutamide Did not alter peak plasma concentrations or AUC of 1 tolbutamide No dosage adjustment necessary 1 Warfarin No change in peak plasma concentrations or AUC of warfarin; no change in PT or INR 1 13 No dosage adjustment necessary 1 Alogliptin Benzoate Pharmacokinetics Absorption Bioavailability Approximately 100%. 1 Onset Median time to peak plasma concentration was 1 2 hours following single oral dose. 1 13 16 Food Food does not appear to affect absorption. 1 13 Special Populations Total alogliptin exposure in patients with moderate hepatic impairment (Child-Pugh class B) is about 10% lower than in healthy individuals. 1 In patients with renal impairment, AUC increased 1.2-fold in those with Cl cr 60 to> <90 mL/minute, twofold in those with Cl cr 30 to> <60 mL/minute, threefold in those with Cl cr 15 to> <30 mL/minute, and fourfold in those with end-stage renal disease (Cl cr> <15 mL/minute or requiring dialysis). 1 Age does not substantially affect alogliptin pharmacokinetics. 1 Distribution Extent Distributed into milk in rats; not known whether distributed into human milk. 1 Plasma Protein Binding 20%. 1 Elimination Metabolism Does not undergo extensive metabolism. 1 Elimination Route Excreted in urine (76%) mainly as unchanged drug and in the feces (13%). 1 Half-life Approximately 21 hours. 1 Special Populations Hemodialysis (3-hour session) removes about 7% of the drug. 1 Stability Storage Oral Tablets 25 C (may be exposed to 15 30 C). 1 2 3 Keep alogliptin/pioglitazone fixed-combination tablets in tightly closed container and protect from moisture and humidity. 3 Keep alogliptin/metformin hydrochloride fixed-combination tablets in tightly closed container. 2 Actions Inhibits DPP-4, an enzyme that inactivates incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). 1 13 Increases circulating concentrations of GLP-1 and GIP in a glucose-dependent manner. 1 GLP-1 and GIP stimulate insulin secretion from pancreatic β-cells in a glucose-dependent manner (i.e., when glucose concentrations are elevated). 1 GLP-1 also decreases glucagon secretion from pancreatic α-cells, leading to reduced hepatic glucose production. 1 Selectively inhibits DPP-4 with no effect on DPP-8 or DPP-9 in vitro at concentrations approximating those from therapeutic exposures. 1 Advice to Patients Importance of patient reading medication guide before initiating therapy and each time the drug is dispensed. 1 24 Importance of informing patients of the potential risks and benefits of alogliptin. 1 24 Importance of not using alogliptin in patients with type 1 diabetes mellitus or diabetic ketoacidosis. 1 24 Risk of acute pancreatitis; may be severe or fatal. 1 24 Importance of patient informing clinicians about a history of pancreatitis, gallstones, alcoholism, or kidney or liver problems. 1 24 Importance of patient discontinuing alogliptin and promptly notifying clinician if signs and symptoms of pancreatitis, including persistent severe abdominal pain that may radiate to the back and may or may not be accompanied by vomiting, occur. 1 24 Importance of informing patients of the possibility of severe and disabling joint pain. 1 24 41 Advise patients to contact a clinician promptly if severe and persistent joint pain occurs; patients should not discontinue therapy without consulting their clinician. 1 24 41 Importance of informing patients about possibility of heart failure with alogliptin therapy. 1 24 42 Importance of patients informing clinicians about a history of heart failure or renal impairment. 1 24 42 Importance of informing patients about signs and symptoms of heart failure (e.g., shortness of breath, weight gain, edema); importance of patients immediately contacting a clinician if manifestations of heart failure occur. 1 24 42 Risk of hypoglycemia, particularly if concomitant therapy with a sulfonylurea (i.e., insulin secretagogue) or insulin is used. 1 24 Risk of serious allergic (hypersensitivity) reaction. 1 24 If signs or symptoms of such reactions occur (e.g., rash, hives, swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing), importance of discontinuing alogliptin and informing clinician promptly. 1 24 Possibility of liver injury, sometimes fatal. 1 24 If signs or symptoms of liver injury (e.g., nausea, vomiting, abdominal pain, unusual/unexplained fatigue, anorexia, dark urine, jaundice) occur, importance of discontinuing alogliptin and informing clinician promptly. 1 24 Importance of taking alogliptin exactly as directed by clinician. 1 24 (See Administration under Dosage and Administration.) Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed. 1 24 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. 1 24 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Alogliptin Benzoate Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablets, film-coated 6.25 mg (of alogliptin) Nesina Takeda 12.5 mg (of alogliptin) Nesina Takeda 25 mg (of alogliptin) Nesina Takeda Alogliptin Benzoate Combinations Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablets, film-coated 12.5 mg (of alogliptin) with Metformin Hydrochloride 500 mg Kazano Takeda 12.5 mg (of alogliptin) with Metformin Hydrochloride 1 g Kazano Takeda 12.5 mg (of alogliptin) with Pioglitazone Hydrochloride 15 mg (of pioglitazone) Oseni Takeda 12.5 mg (of alogliptin) with Pioglitazone Hydrochloride 30 mg (of pioglitazone) Oseni Takeda 12.5 mg (of alogliptin) with Pioglitazone Hydrochloride 45 mg (of pioglitazone) Oseni Takeda 25 mg (of alogliptin) with Pioglitazone Hydrochloride 15 mg (of pioglitazone) Oseni Takeda 25 mg (of alogliptin) with Pioglitazone Hydrochloride 30 mg (of pioglitazone) Oseni Takeda 25 mg (of alogliptin) with Pioglitazone Hydrochloride 45 mg (of pioglitazone) Oseni Takeda AHFS DI Essentials. Copyright 2017, Selected Revisions April 13, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Takeda Pharmaceuticals America, Inc. Nesina (alogliptin) tablets prescribing information. Deerfield, IL; 2016 Apr. 2. Takeda Pharmaceuticals America, Inc. Kazano (alogliptin/metformin hydrochloride) tablets prescribing information. Deerfield, IL; 2015 Aug. 3. Takeda Pharmaceuticals America, Inc. Oseni (alogliptin/pioglitazone) tablets prescribing information. Deerfield, IL; 2015 Aug. 4. DeFronzo RA, Fleck PR, Wilson CA et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diabetes Care . 2008; 31:2315-7. [PubMed 18809631] 5. Rosenstock J, Inzucchi SE, Seufert J et al. Initial combination therapy with alogliptin and pioglitazone in drug-naïve patients with type 2 diabetes. Diabetes Care . 2010; 33:2406-8. [PubMed 20724648] 6. Nauck MA, Ellis GC, Fleck PR et al. Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study. Int J Clin Pract . 2009; 63:46-55. [PubMed 19125992] 7. DeFronzo RA, Burant CF, Fleck P et al. Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes. J Clin Endocrinol Metab . 2012; 97:1615-22. [PubMed 22419732] 8. Pratley RE, Reusch JE, Fleck PR et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin . 2009; 25:2361-71. [PubMed 19650752] 9. Bosi E, Ellis GC, Wilson CA et al. Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study. Diabetes Obes Metab . 2011; 13:1088-96. [PubMed 21733058] 10. Pratley RE, Kipnes MS, Fleck PR et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes Obes Metab . 2009; 11:167-76. [PubMed 19125778] 11. Rosenstock J, Rendell MS, Gross JL et al. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab . 2009; 11:1145-52. [PubMed 19758359] 12. Rosenstock J, Wilson C, Fleck P. Alogliptin versus glipizide monotherapy in elderly type 2 diabetes mellitus patients with mild hyperglycaemia: a prospective, double-blind, randomized, 1-year study. Diabetes Obes Metab . 2013; :15:906-14. 13. Christopher R, Karim A. Clinical pharmacology of alogliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of Type 2 diabetes. Expert Rev Clin Pharmacol . 2009; 2:589-600. [PubMed 22112254] 14. Karim A, Laurent A, Munsaka M et al. Coadministration of pioglitazone or glyburide and alogliptin: pharmacokinetic drug interaction assessment in healthy participants. J Clin Pharmacol . 2009; 49:1210-9. [PubMed 19622714] 15. Berhan A, Berhan Y. Efficacy of alogliptin in type 2 diabetes treatment: a meta-analysis of randomized double-blind controlled studies. BMC Endocr Disord . 2013; 13:9. [PubMed 23452780] 16. Covington P, Christopher R, Davenport M et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther . 2008; 30:499-512. [PubMed 18405788] 17. Food and Drug Administration. Early communication: reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas. Silver Spring, MD; 2013 Mar 14. From FDA website. Accessed 31 July 2013. 18. Singh S, Chang HY, Richards TM et al. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med . 2013; 173:534-9. [PubMed 23440284] 19. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet . 2006; 368:1696-705. [PubMed 17098089] 20. Garber AJ, Abrahamson MJ, Barzilay JI et al. AACE comprehensive diabetes management algorithm 2013. Endocr Pract . 2013 Mar-Apr; 19:327-36. 21. Rodbard HW, Jellinger PS, Davidson JA et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract . 2009 Sep-Oct; 15:540-59. 22. Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care . 2009; 32:193-203. [PubMed 18945920] 23. Bolen S, Feldman L, Vassy J et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med . 2007; 147:386-99. [PubMed 17638715] 24. Takeda Pharmaceuticals America, Inc. Nesina (alogliptin) tablets medication guide. Deerfield, IL; 2016 Apr. 39. White WB, Cannon CP, Heller SR et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med . 2013; 369:1327-35. [PubMed 23992602] 40. Zannad F, Cannon CP, Cushman WC et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet . 2015; 385:2067-76. [PubMed 25765696] 41. Food and Drug Administration. FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. Rockville, MD; 2015 Aug 28. From FDA website. 42. Food and Drug Administration. FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. Silver Spring, MD; 2016 April 5. From FDA website. Next Interactions Print this page Add to My Med List More about alogliptin Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 4 Reviews Add your own review/rating Drug class: dipeptidyl peptidase 4 inhibitors Consumer resources Alogliptin Alogliptin (Advanced Reading) Professional resources Alogliptin (FDA) Alogliptin (Wolters Kluwer) Other brands: Nesina Related treatment guides Diabetes, Type 2> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only B Pregnancy Category No proven risk in humans N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer Perrigo Company Drug Class Dipeptidyl peptidase 4 inhibitors Related Drugs Diabetes, Type 2 metformin , insulin aspart , glipizide , glimepiride , Januvia , pioglitazone , Victoza , Actos , Tradjenta , Glucophage , glyburide , Janumet , Invokana , Amaryl , Welchol , Onglyza , sitagliptin , Trulicity , Jardiance , Lantus , Farxiga , Levemir , Tresiba , Glucotrol , Bydureon , More... 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