OSENI (alogliptin and pioglitazone) tablet, film coated
[Takeda Pharmaceuticals America, Inc.]
HIGHLIGHTS OF PRESCRIBING INFORMATION
 
These highlights do not include all the information needed to use OSENI safely and effectively. See full prescribing information for OSENI.
 
OSENI (alogliptin and pioglitazone) tablets
Initial U.S. Approval: 2013
 
WARNING: CONGESTIVE HEART FAILURE

See full prescribing information for complete boxed warning
• Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients. (5.1) • 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. (4, 5.1)

INDICATIONS AND USAGE

OSENI is a dipeptidyl peptidase-4 inhibitor and thiazolidinedione combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1.1)

Limitation of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1.2)

DOSAGE AND ADMINISTRATION

• Individualize the starting dose of OSENI based on the patient’s current regimen and concurrent medical condition but do not exceed a daily dose of alogliptin 25 mg and pioglitazone 45 mg. • Can be taken with or without food. (2.1) • Limit initial dose of pioglitazone to 15 mg once daily in patients with NYHA Class I or II heart failure. (2.1) • Adjust dose if moderate renal impairment. (2.2)

Degree of Renal Impairment
 

Creatinine Clearance (mL/min)
 

Recommended Dosing

Moderate

≥30 to <60

12.5 mg/15 mg, 12.5 mg/30 mg or 12.5 mg/45 mg once daily

• OSENI is not recommended for patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis. (2.2) • The maximum recommended dose of pioglitazone is 15 mg once daily in patients taking strong CYP2C8 inhibitors (e.g., gemfibrozil). (2.3, 7.1)

DOSAGE FORMS AND STRENGTHS

Tablets:

25 mg alogliptin and 15 mg pioglitazone, 25 mg alogliptin and 30 mg pioglitazone, 25 mg alogliptin and 45 mg pioglitazone. (3)

12.5 mg alogliptin and 15 mg pioglitazone, 12.5 mg alogliptin and 30 mg pioglitazone, 12.5 mg alogliptin and 45 mg pioglitazone. (3)

CONTRAINDICATIONS

• History of a serious hypersensitivity reaction to alogliptin or pioglitazone, components of OSENI, such as anaphylaxis, angioedema or severe cutaneous adverse reactions. (4) • Do not initiate OSENI in patients with established NYHA Class III or IV heart failure. (4)

WARNINGS AND PRECAUTIONS
• 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. (5.1) • Acute pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue OSENI. (5.2) • Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin such as anaphylaxis, angioedema and severe cutaneous adverse reactions. In such cases, promptly discontinue OSENI, assess for other potential causes, institute appropriate monitoring and treatment and initiate alternative treatment for diabetes. (5.3) • Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt OSENI and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart OSENI if liver injury is confirmed and no alternative etiology can be found. Use with caution in patients with liver disease. (5.4) • Edema: Dose-related edema may occur. (5.5) • Fractures: Increased incidence in female patients. Apply current standards of care for assessing and maintaining bone health. (5.6) • Bladder cancer: Preclinical and clinical trial data, and results from an observational study suggest an increased risk of bladder cancer in pioglitazone users. The observational data further suggest that the risk increases with duration of use. Do not use in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer. (5.7) • Hypoglycemia: When an insulin secretagogue (e.g., sulfonylurea) or insulin is used in combination with OSENI, a lower dose of insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia. (5.8) • Macular edema: Postmarketing reports. Recommend regular eye exams in all patients with diabetes according to current standards of care with prompt eva luation for acute visual changes. (5.9) • Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with OSENI or any other antidiabetic drug. (5.11)

ADVERSE REACTIONS

Common adverse reactions reported in ≥4% of patients treated with coadministration of alogliptin 25 mg and pioglitazone 15 mg, 30 mg or 45 mg were nasopharyngitis, back pain and upper respiratory tract infection. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
 
DRUG INTERACTIONS

• Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. Limit the pioglitazone dose to 15 mg daily. (2.3, 7.1) • CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations. (7.2)

USE IN SPECIFIC POPULATIONS

• Nursing mothers: Discontinue drug or nursing, taking into consideration the importance of the drug to the mother. (8.3)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
 
Revised: 07/2013

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: CONGESTIVE HEART FAILURE

1 INDICATIONS AND USAGE

1.1 Monotherapy and Combination Therapy

1.2 Limitation of Use

2 DOSAGE AND ADMINISTRATION

2.1 Recommendations for All Patients

2.2 Patients with Renal Impairment

2.3 Coadministration with Strong CYP2C8 Inhibitors

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Congestive Heart Failure

5.2 Pancreatitis

5.3 Hypersensitivity Reactions

5.4 Hepatic Effects

5.5 Edema

5.6 Fractures

5.7 Urinary Bladder Tumors

5.8 Use with Medications Known to Cause Hypoglycemia

5.9 Macular Edema

5.10 Ovulation

5.11 Macrovascular Outcomes

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

6.2 Laboratory Abnormalities

6.3 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Strong CYP2C8 Inhibitors

7.2 CYP2C8 Inducers

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

17.1 Instructions
* Sections or subsections omitted from the full prescribing information are not listed.

2012年1月25日美国食品和药品监督管理局(FDA)批准三个新相关产品为与饮食和远动一起使用改善2型糖尿病成年血糖控制：Nesina (alogliptin)片，Kazano (alogliptin和盐酸二甲双胍[metformin hydrochloride])片和Oseni (alogliptin和吡格列酮[pioglitazone])片.
Alogliptin是一种新活性成分，而盐酸二甲双胍和吡格列酮早已被FDA-批准处理2型糖尿病。因疾病最常见型，2型糖尿病影响约2400万人和占美国被诊断糖尿病90%以上。

有2型糖尿病人们或对胰岛素抗力或生成不足胰岛素，导致高血糖水平。随着时间，高血糖水平可增加严重并发症风险，包括心衰，盲，和神经和肾损伤。

FDA药物评价和研究中心代谢和内分泌部主任Mary Parks，M.D.说：“在糖尿病的总体治疗和护理中控制血糖水平非常重要，”“Alogliptin有助于刺激餐后释放胰岛素，导致更佳控制血糖。”

作为独立治疗(单药治疗)和与其他2型糖尿病治疗，包括磺脲类药物[sulfonylureas]和胰岛素联用研究Nesina，Kazano，和Osen。它们不应用于治疗1型糖尿病人们或血液或尿有酮体人们 (糖尿病酮症酸中毒)。

在14项临床试验涉及约8,500例2型糖尿病患者证实Nesina是安全和有效。

● Nesina使用26周后与安慰剂比较导致糖化血红蛋白(HbA1c)，一种测量血糖控制，减低0.4%至0.6%。

● FDA正在要求对Nesina5项上市后研究：一项心血管结局试验；一项增强药物监察程序监视肝异常，胰腺炎严重病例，和严重高血压反应；和在儿童研究公平法案(PREA)下三项儿童研究，包括一项剂量发现研究和两项安全性和疗效研究，一项用Nesina单药治疗和一项用 Nesina和二甲双胍。

● Nesina的最常见副作用是鼻塞和流鼻涕，头痛，和上呼吸道感染。

在四项临床试验涉及2,500例以上2型糖尿病患者证实Kazano的安全性和疗效。

● Kazano使用26周后导致HbA1c超过Nesina另外减低1.1%和超过二甲双胍减低0.5%。

● FDA对Kazano正在要求两项上市后研究：一项增强药物监察程序监视肝脏异常，胰腺炎严重病例，和严重超敏性反应；和在PREA下一项儿童安全性和疗效研究。

● Kazano对伴二甲双胍在血液中的乳酸的积聚，乳酸性酸中毒有黑框警告。.

● Kazano的最常见副作用是上呼吸道感染，鼻塞和流鼻涕和喉痛，腹泻，头痛，高血压，背痛，和尿道感染。

再四项临床试验涉及1,500例2型糖尿病患者证实Oseni是安全和有效。

● Oseni导致HbA1c另外减低超过吡格列酮单药治疗 0.4%至 0.6% 和超过alogliptin单药治疗0.4%至0.9%。

● FDA对 Oseni正在要求一项增强药物监察程序。监视肝脏异常，胰腺炎严重病例，和严重超敏性反应。

● Oseni对伴吡格列酮试验心衰的黑框警告。

● Oseni的最常见副作用是鼻塞或流鼻涕和喉痛，背痛，和上呼吸道感染。

Nesina， Kazano，和Oseni由伊利诺伊州迪尔菲尔德，美国Takeda Pharmaceuticals发配。

阿格列汀介绍

Name:
ALOGLIPTIN(ALOGLIPTINE, ALOGLIPTINA) (Related Reference)
Molecular Formula:
C18H21N5O2
CAS Registry Number:
850649-61-5
Synonyms:
ALOGLIPTIN(ALOGLIPTINE, ALOGLIPTINA);Alogliptin;Unii-jhc049lo86
Molecular Structure:

This structure is also available as a 2d Mol file Chemical Properties
Molecular Weight:
339.397
Density:
1.342 g/cm3
Boiling Point:
519.238 °C at 760 mmHg
Flash Point:
267.826 °C
Usage:
Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Antidiabetic agent.