Indication: NESINA (alogliptin), KAZANO (alogliptin and metformin HCl), and OSENI (alogliptin and pioglitazone) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. NESINA, KAZANO, and OSENI are not for treatment of type 1 diabetes or diabetic ketoacidosis.

Privacy policy

Takeda Website Privacy Policy

Thank you for visiting one of the websites (the "Websites") owned by Takeda Pharmaceuticals U.S.A., Inc., its affiliates or subsidiaries (collectively, “Takeda”).

This privacy policy (the “Privacy Policy”) applies to the personal information collected on Takeda Websites. It also applies to Social Security numbers obtained by oral, written or electronic means, as described below in the “Use of Personal Information” section of this Privacy Policy. The term "personal information" as used throughout this Privacy Policy, applies to any information that is used by or on behalf of Takeda to identify an individual.

We have provided this Privacy Policy to describe to you how we collect, use, share and protect the personal information you provide to us at this Website. This Privacy Policy only applies to personal information we collect at our Websites and via the electronic communications technologies that we use. It does not apply to personal information collected through other means, including personal information you provide in e-mail messages you send to us or personal information we may collect from you offline. This Privacy Policy is intended for all visitors of Takeda Websites including consumers, healthcare professionals and Takeda business partners.

At some of our Websites, we may use personal information in a manner not described in this Privacy Policy. In those instances, the different uses of personal information will be disclosed to you at the web page where your personal information is collected, prior to such collection.

From time to time, our internal processes may change, or we may offer new or altered features at our Websites. If appropriate, we will revise this Privacy Policy. We encourage you to return to this area to read the most recent version of our Privacy Policy. If we alter our practices in a manner that will affect the treatment of the personal information you have already provided, we will attempt to provide visitors who have registered on our Websites with notice of our new Privacy Policy via e-mail.

Table of Contents

Personal Information Collected

  • Information You Provide

In general, you may browse the Takeda Websites without providing any personal information. At our Websites, we may provide you with opportunities to sign up to receive information or services from us. As part of this process, we ask you to provide us with personal information about you (such as name, address, telephone number or e-mail address). For example, you may choose to register to receive e-mail updates about a Website, information about a particular health condition, or materials relating to products or services offered by Takeda and its product-related co-promotion partners, and you may provide us with your e-mail address to receive such communications. You may always choose not to provide us with your personal information, and we will disclose to you at the time we collect your personal information whether it is required for you to receive the information or services you have requested.

To better understand and address your interests, and to keep the personal information we have about you accurate, we may correct or add to the personal information you provide to us at our Websites with personal information we receive from you offline or from other sources.

  • Automatically Collected Information -- Cookies and Other Website Information

Like most other commercial websites, we use standard “cookie” and “web beacon” technology and web server logs to collect information about how our Website is used. Web beacons are transparent pixel images that are used in collecting information about Website visitor activities and e-mail response and tracking. For example, if we send you an e-mail message, we (or third parties providing services on our behalf) may collect information through web beacons to determine whether you have opened the e-mail message or clicked on links located within the e-mail message.

Cookies are pieces of data that a website transfers to a visitor's hard drive for record-keeping purposes. Cookies placed on our Websites may be set directly by our servers or by third parties providing technical services to us. To prevent cookies from tracking you as you navigate our Websites, you can reset your browser to refuse all cookies or to indicate when a cookie is being sent. Please note that some portions of our Websites may not work properly if you refuse cookies.

Information gathered through cookies and by our web server logs may include your IP address, your Internet browser (e.g., Netscape), your operating system (e.g., Windows 2000), the domain name of your internet service provider (e.g., AOL) the date and time of your visits, the pages viewed, the time spent at our Website, and the websites visited just before and just after our Website. This information may be associated with your personal information.

Your Choices

You have several choices regarding your use of our Websites. You could decide not to submit any personal information at all. Although certain Websites may ask for permission to use your personal information for certain purposes, you can agree or decline to provide your personal information. If you subscribe for particular communications or services such as e-mail updates, you will be able to unsubscribe at any time by: (i) following any opt-out instructions contained in communications you receive from Takeda, (ii) un-subscribing at specific areas of the Websites where you registered, if available, or (iii) sending a written request to the Takeda contact address, which appears at the end of this Privacy Policy.

As described above, if you wish to prevent cookies from tracking you as you navigate our Websites, you can reset your browser to refuse all cookies or to indicate when a cookie is being sent. Please note, however, that some portions of our Websites may not work properly if you refuse cookies.

Use of Personal Information

Takeda and its service providers will use your personal information to provide information and services to you, including information and services you have requested, or as otherwise disclosed to you in this Privacy Policy or on the web page where you submit your personal information to us. We may also use that information to provide you with materials about products and services offered by Takeda and its product-related co-promotion partners, including new content or services on our Websites. We may provide you with these materials by phone, mail, facsimile or e-mail. We do not share any of your personal information with third parties for their own direct marketing purposes unless we have your consent.

We may use aggregate information collected from visitors of our Websites to help us better understand visitors’ needs and how they use the Websites. Aggregate information about Website visitors that does not contain personal information may be shared with third parties.

  • Policy on Use of Social Security Numbers

Takeda has a policy which provides for the proper use and protection of Social Security numbers obtained in the course of doing business by Takeda. Such policy protects the confidentiality of Social Security numbers, prohibits unlawful disclosure of Social Security numbers, and limits access to Social Security numbers. This policy applies to all methods of collection of Social Security numbers, including Social Security numbers obtained by oral, written and electronic means.

  • E-mail a Friend or Colleague

On some of the Takeda Websites, you can send a link or e-mail message to a friend or colleague. E-mail addresses you may provide for a friend or colleague will be used to send your friend or colleague information on your behalf and will not be collected or used by Takeda or other third parties for any other purpose.

  • Note to Healthcare Professionals and Business Partners

If you have a business or professional relationship with Takeda, we may use your personal information, including personal information we may collect about you from other sources, to develop our business relationship with you and your organization.

Sharing of Personal Information

Takeda may share personal information about you with: (i) various third-party companies or agents working on our behalf to help us engage in the activities described in the “Use of Personal Information” section of this Privacy Policy, including fulfilling business transactions, providing services or information you requested, providing other customer services, sending marketing communications about our products, services and offers, and conducting technological maintenance, and (ii) our parent company, subsidiaries, affiliates and product-related co-promotion partners.

We may also share your personal information with third parties under the following circumstances:

  • if you request or authorize such a disclosure;
  • in connection with the sale, assignment, license or other transfer of our company or our parent company, subsidiaries, affiliates, product-related co-promotion partners or products;
  • to protect our rights, property or safety, or the rights, property or safety of our employees or others;
  • to enforce an agreement we have with you;
  • to comply with the terms of an agreement with a product-related co-promotion partner;
  • to respond to appropriate requests of legitimate government agencies or where required by applicable laws, court orders or government regulations; or
  • where needed for corporate audits or to investigate or respond to a complaint or security threat.

As a company with global operations, Takeda may share your personal information with parties described in this section who are (1) located in other countries, and (2) subject to other applicable laws, rules and regulations relating to your personal information, that do not offer the same protections as the country in which your personal information was collected. In particular, your personal information may be processed in the United States and subject to applicable US laws, rules and regulations. For more information about how Takeda is committed to protecting your personal information, see the “How We Protect Your Personal Information” section of this Privacy Policy.

Note: We do not share any of your personal information with third parties for their own direct marketing purposes unless you explicitly give us permission to do so.

Personal Information of Children

Our Websites are not intended or designed to attract children under the age of 18, and we do not believe that our Websites are appealing to children. Therefore, we do not knowingly collect any personal information from anyone under the age of 18 at our Websites.

Links to Other Websites

Our Websites may provide links to other websites as a service to you. The third-party websites are operated by companies that are outside of our control, and your activities at those websites will be governed by the policies and privacy practices of those third parties. We do not recommend or endorse the content of these websites. We encourage you to review the policies and privacy practices of those third parties before disclosing any of your personal information, as we are not responsible for their policies and privacy practices.

How We Protect Your Personal Information

To help protect the privacy and security of personal information you transmit through the use of our Websites, we have implemented reasonable physical, technical and administrative safeguards to help protect your personal information against unauthorized access, disclosure, alteration or destruction.

Changing Your Preferences; Opt-Out of Receiving Communications

When you provide us with your personal information, you will be given some choices about how we use that personal information. You may change these preferences later. For example, if you sign up for an e-mail newsletter, you may opt out of receiving future e-mail newsletters at any time. Takeda will always provide you with one or more of the following ways to opt out: (i) by following any opt-out instructions contained in communications you receive from Takeda, (ii) by un-subscribing at specific areas of the Website(s) where you registered, if available, or (iii) by sending a written request to the Takeda contact address immediately below.

Questions; Updating Your Personal Information; Takeda Contact Address

If you have any questions about our privacy practices or if you need help accessing your personal information or changing your preferences, please send a written request to us at the following address:

Takeda Pharmaceuticals U.S.A., Inc.
Attn: Privacy Office/Legal Department – Website Communications
One Takeda Parkway
Deerfield, Illinois 60015

Note: Please make sure to provide the name of the Website(s) applicable to your request, and your name, address, telephone number and e-mail address (if any). If you do not provide us with this information, we may not be able to respond.

  • Note to Employment-Applicant Users of Our Websites

If you wish to modify or update your personal information submitted at one of our Websites in response to an employment opportunity at Takeda, you can do so on the appropriate web page of the Website where you applied.

Effective Date of Privacy Policy

This Privacy Policy is effective as of January 1, 2013.

Important Safety Information for NESINA, KAZANO, and OSENI

WARNING: CONGESTIVE HEART FAILURE—for OSENI

  • Thiazolidinediones, including pioglitazone, which is a component of OSENI, cause or exacerbate congestive heart failure in some patients.

  • After initiation of OSENI, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone in OSENI must be considered.

  • OSENI is not recommended in patients with symptomatic heart failure.

  • Initiation of OSENI in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated.

WARNING: LACTIC ACIDOSIS—for KAZANO

  • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

  • Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information.

  • If metformin-associated lactic acidosis is suspected, immediately discontinue KAZANO and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

  • NESINA, KAZANO, and OSENI are contraindicated in patients with a history of serious hypersensitivity reaction to any of the components of these products, such as anaphylaxis, angioedema, or severe cutaneous adverse reactions.

  • KAZANO is contraindicated in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m2).

  • KAZANO is contraindicated in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis.

  • Do not initiate OSENI in patients with established NYHA Class III or IV heart failure.

Warnings and Precautions—for KAZANO

  • Lactic acidosis: Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to immediately discontinue KAZANO and report these symptoms to their healthcare provider. Because metformin is substantially excreted by the kidney, obtain an eGFR before initiating KAZANO and at least annually thereafter; assess more frequently in patients at increased risk for the development of renal impairment (e.g., the elderly); KAZANO is not recommended in patients with an eGFR between 30-60 mL/min/1.73 m2. Discontinue KAZANO at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart KAZANO if renal function is stable. KAZANO should be temporarily discontinued while patients have restricted food and fluid intake. Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur, discontinue KAZANO. Avoid use of KAZANO in patients with clinical or laboratory evidence of hepatic disease.

  • Vitamin B12 deficiency: Metformin may lower Vitamin B12 levels. Monitor hematologic parameters annually.

Warnings and Precautions—for OSENI

  • Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Monitor patients for signs and symptoms.

  • Edema: Dose-related edema may occur. Use with caution in patients with edema.

  • Fractures: Increased incidence in female patients. Apply current standards of care for assessing and maintaining bone health.

  • Bladder cancer: May increase the risk of bladder cancer. Do not use OSENI in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer. Tell patients to promptly report any sign of hematuria or other symptoms such as dysuria or urinary urgency as these may be due to bladder cancer.

  • Macular edema: Macular edema has been reported in some patients taking pioglitazone. Recommend regular eye exams. Instruct patients to report any visual changes promptly.

  • Ovulation: Advise premenopausal females of the potential for an unintended pregnancy as therapy with pioglitazone may result in ovulation in some anovulatory women.

Warnings and Precautions—for NESINA, KAZANO, and OSENI

  • Acute pancreatitis: There have been reports of acute pancreatitis in both the postmarketing setting and randomized clinical trials. If pancreatitis is suspected, promptly discontinue NESINA, KAZANO, or OSENI.

  • Heart failure: Consider the risks and benefits of NESINA, KAZANO, or OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Patients should be advised of the characteristic symptoms of heart failure and should be instructed to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of NESINA, KAZANO, or OSENI.

  • Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin such as anaphylaxis, angioedema or severe cutaneous adverse reactions, including Stevens-Johnson syndrome. In such cases, promptly discontinue NESINA, KAZANO, or OSENI, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. Use caution in patients with a history of angioedema with another dipeptidyl peptidase-4 inhibitor (DPP-4i) because it is unknown whether such patients will be predisposed to angioedema.

  • Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. Baseline liver test panel is recommended for OSENI. If liver injury is detected, promptly interrupt NESINA, KAZANO, or OSENI and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart NESINA, KAZANO, or OSENI if liver injury is confirmed and no alternative etiology can be found. Use with caution in patients with hepatic impairment.

  • Hypoglycemia: Insulin and insulin secretagogues are known to cause hypoglycemia. A lower dose of the insulin or insulin secretagogue may be required to minimize the risk when used in combination with NESINA, KAZANO, or OSENI.

  • Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate.

  • Bullous pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue NESINA, KAZANO, or OSENI.

  • Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with NESINA, KAZANO, OSENI, or any other anti-diabetic drug.

Adverse Reactions

  • Most common adverse reactions (≥4% of patients treated with NESINA 25 mg and more frequently than in patients who received placebo) were nasopharyngitis (4.8%), upper respiratory tract infection (4.5%), and headache (4.3%).

  • Most common adverse reactions (≥4% of patients treated with co-administration of alogliptin and metformin) were upper respiratory tract infection (8.0%), nasopharyngitis (6.8%), diarrhea (5.5%), hypertension (5.5%), headache (5.3%), back pain (4.3%), and urinary tract infection (4.2%).

  • Most common adverse reactions (≥4% of patients treated with co-administration of alogliptin and pioglitazone) were nasopharyngitis (4.9%), back pain (4.2%), and upper respiratory tract infection (4.1%).

Drug Interactions

  • Use of OSENI with CYP2C8 strong inhibitors (e.g., gemfibrozil) will, or inducers (e.g., rifampin) may, require dose adjustment.

  • Use of KAZANO with carbonic anhydrase inhibitors may increase the risk of lactic acidosis. Consider more frequent monitoring.

  • Use of KAZANO with drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use.

  • Use of KAZANO with alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake.

Indication

NESINA (alogliptin), KAZANO (alogliptin and metformin HCl), and OSENI (alogliptin and pioglitazone) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. NESINA, KAZANO, and OSENI are not for treatment of type 1 diabetes or diabetic ketoacidosis.

Please see the Full Prescribing Information including Medication Guide, for NESINA.

Please see the Full Prescribing Information including Medication Guide, for KAZANO.

Please see the Full Prescribing Information including Medication Guide, for OSENI.

Logo NESINA (alogliptin) 25 mg tablets
Logo KAZANO (alogliptin and metformin HCl) 12.5 mg/500 mg and 12.5 mg/1000 mg tablets
Logo OSENI (alogliptin and pioglitazone) 25 mg/15 mg, 25 mg/30 mg, and 25 mg/45 mg tablets
Hide references
  1. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36:S11-S66.

  2. NESINA (alogliptin) Prescribing Information. Takeda Pharmaceuticals.

  3. Nauck MA, Ellis GC, Fleck PR, Wilson CA, Mekki Q; Alogliptin Study 008 Group. 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.

  4. DeFronzo RA, Burant CF, Fleck P, Wilson C, Mekki Q, Pratley RE. 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;97:1615-1622.

  5. Rosenstock J, Inzucchi SE, Seufert J, Fleck PR, Wilson CA, Mekki Q. Initial combination therapy with alogliptin and pioglitazone in drug-naïve patients with type 2 diabetes. Diabetes Care. 2010;33:2406-2408.

  6. DeFronzo RA, Fleck PR, Wilson CA, Mekki Q; Alogliptin Study 010 Group. Efficacy and safety of 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;31:2315-2317.

  7. KAZANO (alogliptin and metformin HCl) Prescribing Information. Takeda Pharmaceuticals.

  8. Pratley RE, Fleck P, Wilson C. Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab. 2014;16(7):613-621.

  9. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-1379.

  10. OSENI (alogliptin and pioglitazone) Prescribing Information. Takeda Pharmaceuticals.

  11. Defronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773-795.

  12. Bajaj M, Suraamornkul S, Pratipanawatr T, et al. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes. 2003;52:1364-1370.

  13. Bosi E, Ellis GC, Wilson CA, Fleck PR. 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;13:1088-1096.

  14. Pratley RE, Reusch JE, Fleck PR, Wilson CA, Mekki Q; Alogliptin Study 009 Group. 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;25:2361-2371.

  15. Puddu A, Sanguineti R, Durante A, Viviani GL. Pioglitazone attenuates the detrimental effects of advanced glycation end-products in the pancreatic beta cell line HIT-T15. Regul Pept. 2012;177:79-84.

  16. Gastaldelli A, Miyazaki Y, Mahankali A, et al. The effect of pioglitazone on the liver: role of adiponectin. Diabetes Care. 2006;29:2275-2281.

  17. Nam S, Chesla C, Stotts NA, Kroon L, Janson SL. Barriers to diabetes management: patient and provider factors. Diabetes Res Clin Pract. 2011;93(1):1-9.

Important Safety Information for NESINA, KAZANO, and OSENI

WARNING: CONGESTIVE HEART FAILURE—for OSENI

  • Thiazolidinediones, including pioglitazone, which is a component of OSENI, cause or exacerbate congestive heart failure in some patients.

  • After initiation of OSENI, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone in OSENI must be considered.

  • OSENI is not recommended in patients with symptomatic heart failure.

  • Initiation of OSENI in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated.

WARNING: LACTIC ACIDOSIS—for KAZANO

  • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

  • Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information.

  • If metformin-associated lactic acidosis is suspected, immediately discontinue KAZANO and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

  • NESINA, KAZANO, and OSENI are contraindicated in patients with a history of serious hypersensitivity reaction to any of the components of these products, such as anaphylaxis, angioedema, or severe cutaneous adverse reactions.

  • KAZANO is contraindicated in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m2).

  • KAZANO is contraindicated in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis.

  • Do not initiate OSENI in patients with established NYHA Class III or IV heart failure.

Warnings and Precautions—for KAZANO

  • Lactic acidosis: Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to immediately discontinue KAZANO and report these symptoms to their healthcare provider. Because metformin is substantially excreted by the kidney, obtain an eGFR before initiating KAZANO and at least annually thereafter; assess more frequently in patients at increased risk for the development of renal impairment (e.g., the elderly); KAZANO is not recommended in patients with an eGFR between 30-60 mL/min/1.73 m2. Discontinue KAZANO at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart KAZANO if renal function is stable. KAZANO should be temporarily discontinued while patients have restricted food and fluid intake. Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur, discontinue KAZANO. Avoid use of KAZANO in patients with clinical or laboratory evidence of hepatic disease.

  • Vitamin B12 deficiency: Metformin may lower Vitamin B12 levels. Monitor hematologic parameters annually.

Warnings and Precautions—for OSENI

  • Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Monitor patients for signs and symptoms.

  • Edema: Dose-related edema may occur. Use with caution in patients with edema.

  • Fractures: Increased incidence in female patients. Apply current standards of care for assessing and maintaining bone health.

  • Bladder cancer: May increase the risk of bladder cancer. Do not use OSENI in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer. Tell patients to promptly report any sign of hematuria or other symptoms such as dysuria or urinary urgency as these may be due to bladder cancer.

  • Macular edema: Macular edema has been reported in some patients taking pioglitazone. Recommend regular eye exams. Instruct patients to report any visual changes promptly.

  • Ovulation: Advise premenopausal females of the potential for an unintended pregnancy as therapy with pioglitazone may result in ovulation in some anovulatory women.

Warnings and Precautions—for NESINA, KAZANO, and OSENI

  • Acute pancreatitis: There have been reports of acute pancreatitis in both the postmarketing setting and randomized clinical trials. If pancreatitis is suspected, promptly discontinue NESINA, KAZANO, or OSENI.

  • Heart failure: Consider the risks and benefits of NESINA, KAZANO, or OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Patients should be advised of the characteristic symptoms of heart failure and should be instructed to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of NESINA, KAZANO, or OSENI.

  • Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin such as anaphylaxis, angioedema or severe cutaneous adverse reactions, including Stevens-Johnson syndrome. In such cases, promptly discontinue NESINA, KAZANO, or OSENI, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. Use caution in patients with a history of angioedema with another dipeptidyl peptidase-4 inhibitor (DPP-4i) because it is unknown whether such patients will be predisposed to angioedema.

  • Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. Baseline liver test panel is recommended for OSENI. If liver injury is detected, promptly interrupt NESINA, KAZANO, or OSENI and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart NESINA, KAZANO, or OSENI if liver injury is confirmed and no alternative etiology can be found. Use with caution in patients with hepatic impairment.

  • Hypoglycemia: Insulin and insulin secretagogues are known to cause hypoglycemia. A lower dose of the insulin or insulin secretagogue may be required to minimize the risk when used in combination with NESINA, KAZANO, or OSENI.

  • Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate.

  • Bullous pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue NESINA, KAZANO, or OSENI.

  • Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with NESINA, KAZANO, OSENI, or any other anti-diabetic drug.

Adverse Reactions

  • Most common adverse reactions (≥4% of patients treated with NESINA 25 mg and more frequently than in patients who received placebo) were nasopharyngitis (4.8%), upper respiratory tract infection (4.5%), and headache (4.3%).

  • Most common adverse reactions (≥4% of patients treated with co-administration of alogliptin and metformin) were upper respiratory tract infection (8.0%), nasopharyngitis (6.8%), diarrhea (5.5%), hypertension (5.5%), headache (5.3%), back pain (4.3%), and urinary tract infection (4.2%).

  • Most common adverse reactions (≥4% of patients treated with co-administration of alogliptin and pioglitazone) were nasopharyngitis (4.9%), back pain (4.2%), and upper respiratory tract infection (4.1%).

Drug Interactions

  • Use of OSENI with CYP2C8 strong inhibitors (e.g., gemfibrozil) will, or inducers (e.g., rifampin) may, require dose adjustment.

  • Use of KAZANO with carbonic anhydrase inhibitors may increase the risk of lactic acidosis. Consider more frequent monitoring.

  • Use of KAZANO with drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use.

  • Use of KAZANO with alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake.

Indication

NESINA (alogliptin), KAZANO (alogliptin and metformin HCl), and OSENI (alogliptin and pioglitazone) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. NESINA, KAZANO, and OSENI are not for treatment of type 1 diabetes or diabetic ketoacidosis.

Please see the Full Prescribing Information including Medication Guide, for NESINA.

Please see the Full Prescribing Information including Medication Guide, for KAZANO.

Please see the Full Prescribing Information including Medication Guide, for OSENI.

Logo NESINA (alogliptin) 25 mg tablets
Logo KAZANO (alogliptin and metformin HCl) 12.5 mg/500 mg and 12.5 mg/1000 mg tablets
Logo OSENI (alogliptin and pioglitazone) 25 mg/15 mg, 25 mg/30 mg, and 25 mg/45 mg tablets
Hide references
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  2. NESINA (alogliptin) Prescribing Information. Takeda Pharmaceuticals.

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  4. DeFronzo RA, Burant CF, Fleck P, Wilson C, Mekki Q, Pratley RE. 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;97:1615-1622.

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  7. KAZANO (alogliptin and metformin HCl) Prescribing Information. Takeda Pharmaceuticals.

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  10. OSENI (alogliptin and pioglitazone) Prescribing Information. Takeda Pharmaceuticals.

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