7/29/2016
`
`Adult Type 2 Diabetes Treatment | ONGLYZA® (saxagliptin)
`
`DPP-4 Inhibitors:
`
`ONGLYZA®
`(saxagliptin)
`
`KOMBIGLYZE® XR
`(saxagliptin and metformin
`HCl extended-release) tablets
`
`Our Type 2 Diabetes Portfolio »
`
`Prescribing Information |
`Prescribing Information
`
` |
`
`Important Safety Information
`Indication | Medication Guide |
`Indication & Limitations of Use | Medication Guide
`For US Health Care Professionals
`Go to Patient Site
`
`|
`
`Menu
`Share
`Register
`Important Safety Information for ONGLYZA® (saxagliptin)
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA ...Read More(eg, anaphylaxis, angioedema, or
`exfoliative skin conditions)...Read More...Read More
`
`Search
`
`ONGLYZA IS A DIPEPTIDYL PEPTIDASE-4 (DPP4) INHIBITOR INDICATED AS AN ADJUNCT TREATMENT TO DIET AND
`EXERCISE TO
`IMPROVE GLYCEMIC CONTROL IN ADULTS WITH TYPE 2 DIABETES MELLITUS. ONGLYZA IS NOT INDICATED FOR
`THE TREATMENT OF TYPE 1 DIABETES MELLITUS OR DIABETIC KETOACIDOSIS.
`
`Add an ONGLYZA
`
`A1C reductions that can help your patients get where they need to be
`
`VIEW DATA
`
`PATIENT
`SAVINGS
`
`LEARN MORE »
`
`https://www.onglyza­hcp.com/
`
`1/5
`
`AstraZeneca Exhibit 2128
`Mylan v. AstraZeneca
`IPR2015-01340
`
`Page 1 of 23
`
`

`
`7/29/2016
`
`Adult Type 2 Diabetes Treatment | ONGLYZA® (saxagliptin)
`
`DOSING
`INFORMATION
`
`LEARN MORE »
`
`MECHANISM
`OF ACTION
`Learn how ONGLYZA prolongs the activity of incretin gut hormones
`1
`
` 
`
`FORMULARY COVERAGE »
`
`Important Safety Information for ONGLYZA® (saxagliptin)
`
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA (eg, anaphylaxis, angioedema, or exfoliative
`skin conditions)
`
`Warnings and Precautions
`Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking
`ONGLYZA, and in the SAVOR cardiovascular outcomes trial a匜䓜er initiating ONGLYZA. A匜䓜er initiating
`ONGLYZA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is
`suspected, promptly discontinue ONGLYZA and initiate appropriate management. It is unknown
`whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while
`
`https://www.onglyza­hcp.com/
`
`2/5
`
`Page 2 of 23
`
`

`
`7/29/2016
`
`Adult Type 2 Diabetes Treatment | ONGLYZA® (saxagliptin)
`
`using ONGLYZA
`Heart Failure: In SAVOR, a cardiovascular outcomes trial enrolling participants with established or
`multiple risk factors for atherosclerotic cardiovascular disease (ASCVD), more patients treated with
`ONGLYZA were hospitalized for heart failure compared to placebo. Patients with a prior history of
`heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the
`risks and benefits of ONGLYZA in patients who have known risk factors for heart failure. Monitor for
`signs and symptoms. If heart failure develops, initiate appropriate management and consider
`discontinuation of ONGLYZA
`Hypoglycemia with Concomitant Use of Sulfonylurea or Insulin: When ONGLYZA was used in
`combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the
`incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a
`sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be
`required to minimize the risk of hypoglycemia when used in combination with ONGLYZA
`Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity
`reactions in patients treated with ONGLYZA, including anaphylaxis, angioedema, and exfoliative skin
`conditions. Onset of these reactions occurred within the first 3 months a匜䓜er initiation of treatment
`with ONGLYZA, with some reports occurring a匜䓜er the first dose. If a serious hypersensitivity reaction is
`suspected, discontinue ONGLYZA, assess for other potential causes for the event, and institute
`alternative treatment for diabetes. Use caution in patients with a history of angioedema to another
`DPP-4 inhibitor as it is unknown whether they will be predisposed to angioedema with ONGLYZA
`
`Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling
`arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of
`drug therapy varied from one day to years. Patients experienced relief of symptoms upon
`discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when
`restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause
`for severe joint pain and discontinue drug if appropriate
`Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of
`macrovascular risk reduction with ONGLYZA or any other antidiabetic drug
`
`Most Common Adverse Reactions
`Most common adverse reactions reported in ≥5% of patients treated with ONGLYZA and more
`commonly than in patients treated with control were upper respiratory tract infection (7.7%, 7.6%),
`urinary tract infection (6.8%, 6.1%), and headache (6.5%, 5.9%)
`
`When used as add-on combination therapy with a thiazolidinedione, the incidence of peripheral
`edema for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1%, 8.1% and 4.3%, respectively
`
`Confirmed hypoglycemia was reported more commonly in patients treated with ONGLYZA 2.5 mg and
`ONGLYZA 5 mg compared to placebo in the add-on to glyburide trial (2.4%, 0.8% and 0.7%,
`respectively), with ONGLYZA 5 mg compared to placebo in the add-on to insulin (with or without
`metformin) trial (5.3% and 3.3%, respectively),with ONGLYZA 2.5 mg compared to placebo in the
`renal impairment trial (4.7% and 3.5%, respectively), and with ONGLYZA 5 mg compared to placebo in
`the add-on to metformin plus sulfonylurea trial (1.6% and 0.0%, respectively)
`
`Drug Interactions
`Because ketoconazole, a strong CYP3A4/5 inhibitor, increased saxagliptin exposure, the dose of
`ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor (eg,
`
`https://www.onglyza­hcp.com/
`
`3/5
`
`Page 3 of 23
`
`

`
`7/29/2016
`
`Adult Type 2 Diabetes Treatment | ONGLYZA® (saxagliptin)
`atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir,
`saquinavir, and telithromycin)
`
`Use in Specific Populations
`Patients with Renal Impairment: The dose of ONGLYZA is 2.5 mg once daily for patients with
`moderate or severe renal impairment, or with end-stage renal disease requiring hemodialysis
`(creatinine clearance [CrCl] ≤50 mL/min). ONGLYZA should be administered following hemodialysis.
`ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal
`function is recommended prior to initiation of ONGLYZA and periodically therea匜䓜er
`Pregnant and Nursing Women: There are no adequate and well-controlled studies in pregnant
`women. ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if
`clearly needed. It is not known whether saxagliptin is secreted in human milk. Because many drugs
`are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing
`woman
`Pediatric Patients: Safety and effectiveness of ONGLYZA in pediatric patients have not been
`established
`
`Indication and Limitations of Use for ONGLYZA® (saxagliptin)
`ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2
`diabetes mellitus.
`ONGLYZA is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
`
`Please see accompanying US Full Prescribing Information
`
` and Medication Guide
`
` for ONGLYZA.
`
`You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
`www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.
`
`Reference:
`
`1. ONGLYZA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016.
`
`Contact Us
`AstraZeneca US Corporate Site
`Privacy Notice
`Legal Statement
`Site Map
`Prescribing Information
`This product information is intended for US Health Care Professionals only.
`ONGLYZA is a registered trademark and AZ&Me is a trademark of the AstraZeneca group of companies.
`
`https://www.onglyza­hcp.com/
`
`4/5
`
`Page 4 of 23
`
`

`
`7/29/2016
`Adult Type 2 Diabetes Treatment | ONGLYZA® (saxagliptin)
`©2016 AstraZeneca. All rights reserved. 1946703-3179624 Last Updated 4/16
`
`https://www.onglyza­hcp.com/
`
`5/5
`
`Page 5 of 23
`
`

`
`7/29/2016
`
`Clinical Trials Type 2 Diabetes Mellitus|A1C Levels
`
`DPP-4 Inhibitors:
`
`ONGLYZA®
`(saxagliptin)
`
`KOMBIGLYZE® XR
`(saxagliptin and metformin
`HCl extended-release) tablets
`
`Our Type 2 Diabetes Portfolio »
`
`Prescribing Information |
`Prescribing Information
`
` |
`
`Important Safety Information
`Indication | Medication Guide |
`Indication & Limitations of Use | Medication Guide
`For US Health Care Professionals
`Go to Patient Site
`
`|
`
`Menu
`Share
`Register
`Share
`Important Safety Information for ONGLYZA® (saxagliptin)
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA ...Read More(eg, anaphylaxis, angioedema, or
`exfoliative skin conditions)...Read More...Read More
`
`Search
`
`A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISE
`
`DEMONSTRATED REDUCTIONS IN A1C LEVELS WITH ONGLYZA
`
`CLINICAL TRIALS
`
`ONGLYZA AS ADD-ON THERAPY
`To metformin IR
`ONGLYZA led to significant reductions in A1C levels when added to metformin
`therapy in patients with inadequately controlled type 2 diabetes mellitus with
`metformin alone
`1,2
`
`INITIAL COMBINATION THERAPY WITH ONGLYZA
`5 mg + metformin IR
`
`ONGLYZA given in combination with metformin as initial therapy improved glycemic control in
`patients with type 2 diabetes mellitus compared with ONGLYZA or metformin as monotherapy
`1,3 
`
` 
`
`ONGLYZA HEAD-TO-HEAD VS A SULFONYLUREA
`5 mg vs up-titrated glipizide as add-on to metformin IR
`ONGLYZA demonstrated reductions in A1C levels comparable to glipizide with lower rates of
`
`https://www.onglyza­hcp.com/efficacy.html
`
`1,4
`
`1/4
`
`Page 6 of 23
`
`

`
`7/29/2016
`
` 
`
`Clinical Trials Type 2 Diabetes Mellitus|A1C Levels
`hypoglycemia
`1,4
`
`ONGLYZA IN RENALLY IMPAIRED PATIENTS
`2.5 mg vs placebo
`ONGLYZA demonstrated significant reductions in A1C levels with similar rates of hypoglycemia,
`in renally impaired patients
`1,5
`Important Safety Information for ONGLYZA® (saxagliptin)
`
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA (eg, anaphylaxis, angioedema, or exfoliative
`skin conditions)
`
`Warnings and Precautions
`Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking
`ONGLYZA, and in the SAVOR cardiovascular outcomes trial a￿￿er initiating ONGLYZA. A￿￿er initiating
`ONGLYZA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is
`suspected, promptly discontinue ONGLYZA and initiate appropriate management. It is unknown
`whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while
`using ONGLYZA
`Heart Failure: In SAVOR, a cardiovascular outcomes trial enrolling participants with established or
`multiple risk factors for atherosclerotic cardiovascular disease (ASCVD), more patients treated with
`ONGLYZA were hospitalized for heart failure compared to placebo. Patients with a prior history of
`heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the
`risks and benefits of ONGLYZA in patients who have known risk factors for heart failure. Monitor for
`signs and symptoms. If heart failure develops, initiate appropriate management and consider
`discontinuation of ONGLYZA
`Hypoglycemia with Concomitant Use of Sulfonylurea or Insulin: When ONGLYZA was used in
`combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the
`incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a
`sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be
`required to minimize the risk of hypoglycemia when used in combination with ONGLYZA
`
`Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity
`reactions in patients treated with ONGLYZA, including anaphylaxis, angioedema, and exfoliative skin
`conditions. Onset of these reactions occurred within the first 3 months a￿￿er initiation of treatment
`with ONGLYZA, with some reports occurring a￿￿er the first dose. If a serious hypersensitivity reaction is
`suspected, discontinue ONGLYZA, assess for other potential causes for the event, and institute
`alternative treatment for diabetes. Use caution in patients with a history of angioedema to another
`DPP-4 inhibitor as it is unknown whether they will be predisposed to angioedema with ONGLYZA
`Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling
`arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of
`drug therapy varied from one day to years. Patients experienced relief of symptoms upon
`discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when
`restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause
`
`https://www.onglyza­hcp.com/efficacy.html
`
`2/4
`
`Page 7 of 23
`
`

`
`7/29/2016
`
`Clinical Trials Type 2 Diabetes Mellitus|A1C Levels
`for severe joint pain and discontinue drug if appropriate
`Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of
`macrovascular risk reduction with ONGLYZA or any other antidiabetic drug
`
`Most Common Adverse Reactions
`Most common adverse reactions reported in ≥5% of patients treated with ONGLYZA and more
`commonly than in patients treated with control were upper respiratory tract infection (7.7%, 7.6%),
`urinary tract infection (6.8%, 6.1%), and headache (6.5%, 5.9%)
`
`When used as add-on combination therapy with a thiazolidinedione, the incidence of peripheral
`edema for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1%, 8.1% and 4.3%, respectively
`
`Confirmed hypoglycemia was reported more commonly in patients treated with ONGLYZA 2.5 mg and
`ONGLYZA 5 mg compared to placebo in the add-on to glyburide trial (2.4%, 0.8% and 0.7%,
`respectively), with ONGLYZA 5 mg compared to placebo in the add-on to insulin (with or without
`metformin) trial (5.3% and 3.3%, respectively),with ONGLYZA 2.5 mg compared to placebo in the
`renal impairment trial (4.7% and 3.5%, respectively), and with ONGLYZA 5 mg compared to placebo in
`the add-on to metformin plus sulfonylurea trial (1.6% and 0.0%, respectively)
`
`Drug Interactions
`Because ketoconazole, a strong CYP3A4/5 inhibitor, increased saxagliptin exposure, the dose of
`ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor (eg,
`atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir,
`saquinavir, and telithromycin)
`
`Use in Specific Populations
`Patients with Renal Impairment: The dose of ONGLYZA is 2.5 mg once daily for patients with
`moderate or severe renal impairment, or with end-stage renal disease requiring hemodialysis
`(creatinine clearance [CrCl] ≤50 mL/min). ONGLYZA should be administered following hemodialysis.
`ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal
`function is recommended prior to initiation of ONGLYZA and periodically therea￿￿er
`Pregnant and Nursing Women: There are no adequate and well-controlled studies in pregnant
`women. ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if
`clearly needed. It is not known whether saxagliptin is secreted in human milk. Because many drugs
`are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing
`woman
`
`Pediatric Patients: Safety and effectiveness of ONGLYZA in pediatric patients have not been
`established
`
`Indication and Limitations of Use for ONGLYZA® (saxagliptin)
`ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2
`diabetes mellitus.
`ONGLYZA is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
`Please see accompanying US Full Prescribing Information
` and Medication Guide
` for ONGLYZA.
`
`You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
`www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.
`
`https://www.onglyza­hcp.com/efficacy.html
`
`3/4
`
`Page 8 of 23
`
`

`
`7/29/2016
`
`References:
`
`Clinical Trials Type 2 Diabetes Mellitus|A1C Levels
`
`1. ONGLYZA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016.
`
`2. DeFronzo RA, Hissa MN, Garber AJ, et al. The efficacy and safety of saxagliptin when added to
`metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone.
`Diabetes Care. 2009;32(9):1649-1655.
`
`3. Jadzinsky M, Pfützner A, Paz-Pacheco E, et al. Saxagliptin given in combination with metformin as
`initial therapy improves glycaemic control in patients with type 2 diabetes compared with either
`monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009;11(6):611-622.
`
`4. Göke B, Gallwitz B, Eriksson J, Hellqvist A, Gause-Nilsson I; D1680C00001 Investigators. Saxagliptin is
`non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on
`metformin alone: a 52-week randomised controlled trial. Int J Clin Pract. 2010;64(12):1619-1631.
`
`5. Nowicki M, Rychlik I, Haller H, et al. Saxagliptin improves glycaemic control and is well tolerated in
`patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab. 2011;13(6):523-
`532.
`
`Contact Us
`AstraZeneca US Corporate Site
`Privacy Notice
`Legal Statement
`Site Map
`Prescribing Information
`This product information is intended for US Health Care Professionals only.
`ONGLYZA is a registered trademark of the AstraZeneca group of companies.
`©2016 AstraZeneca. All rights reserved. 1946703-3179624 Last Updated 4/16
`
`https://www.onglyza­hcp.com/efficacy.html
`
`4/4
`
`Page 9 of 23
`
`

`
`7/29/2016
`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`
`DPP-4 Inhibitors:
`
`ONGLYZA®
`(saxagliptin)
`
`KOMBIGLYZE® XR
`(saxagliptin and metformin
`HCl extended-release) tablets
`
`Our Type 2 Diabetes Portfolio »
`
`Prescribing Information |
`Prescribing Information
`
` |
`
`Important Safety Information
`Indication | Medication Guide |
`Indication & Limitations of Use | Medication Guide
`For US Health Care Professionals
`Go to Patient Site
`
`|
`
`Menu
`Share
`Register
`Share
`Important Safety Information for ONGLYZA® (saxagliptin)
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA ...Read More(eg, anaphylaxis, angioedema, or
`exfoliative skin conditions)...Read More...Read More
`
`Search
`
`EXPLORE THE ONGLYZA MECHANISM OF ACTION
`
`Discover how ONGLYZA helps reduce blood glucose by prolonging GLP-1 (glucagon-like peptide-1) and GIP
`(glucose-dependent insulinotropic polypeptide) incretin activity in a glucose-dependent manner.
`
`1
`
`THE ROLE OF INCRETINS
`IN GLUCOSE HOMEOSTASIS
`Eating increases levels of glucose  
`
` in the body.
`
`In response to increased levels of glucose, the small intestine increases production
`and release of GLP-1 and GIP incretins  
`into the bloodstream. These hormones
`contribute to glucose homeostasis.
`
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`1/7
`
`Page 10 of 23
`
`

`
`7/29/2016
`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`
`2
`
`THE ROLE OF DPP-4
`IN THE LIFESPAN OF INCRETINS
`
`The enzyme dipeptidyl peptidase-4 (DPP-4) begins degrading the GLP-1 and GIP
` within minutes of their release. Consequently, GLP-1 and GIP are
`incretins  
`short-lived, disrupting glucose homeostasis.
`
`3
`
`HOW ONGLYZA WORKS
`TO INHIBIT DPP-4
`
`ONGLYZA is a DPP-4 inhibitor indicated as an adjunct to diet and exercise to
`
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`2/7
`
`Page 11 of 23
`
`

`
`7/29/2016
`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`improve glycemic control in adults with type 2 diabetes mellitus.
`ONGLYZA inhibits DPP-4 enzymes for a 24-hour period, thereby prolonging the
`body’s own action of naturally secreted incretins GLP-1 and GIP.
`
`HOW ONGLYZA MAY HELP TO LOWER A1C LEVELS
`
`4
`
`GLP-1 signals to the pancreas to decrease glucose secretion by pancreatic
`alpha cells, which decreases hepatic glucose productions.
`
`GLP-1 and GIP increase insulin release by signaling the pancreatic beta cells,
`which increase uptake of glucose by the muscle, fat, and peripheral tissues.
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`3/7
`
`Page 12 of 23
`
`

`
`7/29/2016
`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`
`By inhibiting DPP-4, ONGLYZA helps to reduce fasting plasma glucose (FPG), and postprandial
`glucose (PPG) in a glucose-dependent manner, which helps to reduce blood glucose levels and
`A1C.
`
`CONSIDER ONGLYZA
`A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND
`EXERCISE
`
`Consider ONGLYZA as an add-on to commonly
`used oral agents such as metformin to help
`your patients get to where they need to be.
`
`EXPLORE A1C DATA »
`
`Important Safety Information for ONGLYZA® (saxagliptin)
`
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA (eg, anaphylaxis, angioedema, or exfoliative
`skin conditions)
`
`Warnings and Precautions
`
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`4/7
`
`Page 13 of 23
`
`

`
`7/29/2016
`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking
`ONGLYZA, and in the SAVOR cardiovascular outcomes trial a凲䢃er initiating ONGLYZA. A凲䢃er initiating
`ONGLYZA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is
`suspected, promptly discontinue ONGLYZA and initiate appropriate management. It is unknown
`whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while
`using ONGLYZA
`Heart Failure: In SAVOR, a cardiovascular outcomes trial enrolling participants with established or
`multiple risk factors for atherosclerotic cardiovascular disease (ASCVD), more patients treated with
`ONGLYZA were hospitalized for heart failure compared to placebo. Patients with a prior history of
`heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the
`risks and benefits of ONGLYZA in patients who have known risk factors for heart failure. Monitor for
`signs and symptoms. If heart failure develops, initiate appropriate management and consider
`discontinuation of ONGLYZA
`Hypoglycemia with Concomitant Use of Sulfonylurea or Insulin: When ONGLYZA was used in
`combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the
`incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a
`IMPORTANT SAFETY INFORMATION
`BACK TO TOP
`sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be
`required to minimize the risk of hypoglycemia when used in combination with ONGLYZA
`Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity
`reactions in patients treated with ONGLYZA, including anaphylaxis, angioedema, and exfoliative skin
`conditions. Onset of these reactions occurred within the first 3 months a凲䢃er initiation of treatment
`with ONGLYZA, with some reports occurring a凲䢃er the first dose. If a serious hypersensitivity reaction is
`suspected, discontinue ONGLYZA, assess for other potential causes for the event, and institute
`alternative treatment for diabetes. Use caution in patients with a history of angioedema to another
`DPP-4 inhibitor as it is unknown whether they will be predisposed to angioedema with ONGLYZA
`Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling
`arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of
`drug therapy varied from one day to years. Patients experienced relief of symptoms upon
`discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when
`restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause
`for severe joint pain and discontinue drug if appropriate
`
`Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of
`macrovascular risk reduction with ONGLYZA or any other antidiabetic drug
`
`Most Common Adverse Reactions
`Most common adverse reactions reported in ≥5% of patients treated with ONGLYZA and more
`commonly than in patients treated with control were upper respiratory tract infection (7.7%, 7.6%),
`urinary tract infection (6.8%, 6.1%), and headache (6.5%, 5.9%)
`
`When used as add-on combination therapy with a thiazolidinedione, the incidence of peripheral
`edema for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1%, 8.1% and 4.3%, respectively
`
`Confirmed hypoglycemia was reported more commonly in patients treated with ONGLYZA 2.5 mg and
`ONGLYZA 5 mg compared to placebo in the add-on to glyburide trial (2.4%, 0.8% and 0.7%,
`respectively), with ONGLYZA 5 mg compared to placebo in the add-on to insulin (with or without
`metformin) trial (5.3% and 3.3%, respectively),with ONGLYZA 2.5 mg compared to placebo in the
`
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`5/7
`
`Page 14 of 23
`
`

`
`7/29/2016
`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`renal impairment trial (4.7% and 3.5%, respectively), and with ONGLYZA 5 mg compared to placebo in
`the add-on to metformin plus sulfonylurea trial (1.6% and 0.0%, respectively)
`
`Drug Interactions
`Because ketoconazole, a strong CYP3A4/5 inhibitor, increased saxagliptin exposure, the dose of
`ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor (eg,
`atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir,
`saquinavir, and telithromycin)
`
`Use in Specific Populations
`Patients with Renal Impairment: The dose of ONGLYZA is 2.5 mg once daily for patients with
`moderate or severe renal impairment, or with end-stage renal disease requiring hemodialysis
`(creatinine clearance [CrCl] ≤50 mL/min). ONGLYZA should be administered following hemodialysis.
`ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal
`function is recommended prior to initiation of ONGLYZA and periodically therea凲䢃er
`Pregnant and Nursing Women: There are no adequate and well-controlled studies in pregnant
`women. ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if
`IMPORTANT SAFETY INFORMATION
`BACK TO TOP
`clearly needed. It is not known whether saxagliptin is secreted in human milk. Because many drugs
`are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing
`woman
`Pediatric Patients: Safety and effectiveness of ONGLYZA in pediatric patients have not been
`established
`
`Indication and Limitations of Use for ONGLYZA® (saxagliptin)
`ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2
`diabetes mellitus.
`ONGLYZA is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
`Please see accompanying US Full Prescribing Information
` and Medication Guide
` for ONGLYZA.
`
`You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
`www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.
`
`Reference:
`
`1. ONGLYZA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016.
`
`Contact Us
`AstraZeneca US Corporate Site
`Privacy Notice
`Legal Statement
`Site Map
`
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`6/7
`
`Page 15 of 23
`
`

`
`ONGLYZA® (saxagliptin) | Mechanism of Action | Onglyza­HCP.com
`
`7/29/2016
`Prescribing Information
`This product information is intended for US Health Care Professionals only.
`ONGLYZA is a registered trademark of the AstraZeneca group of companies.
`©2016 AstraZeneca. All rights reserved. 1946703-3179624 Last Updated 4/16
`
`BACK TO TOP
`
`IMPORTANT SAFETY INFORMATION
`
`https://www.onglyza­hcp.com/mechanism­of­action.html
`
`7/7
`
`Page 16 of 23
`
`

`
`7/29/2016
`
`Safety Information | Onglyza­HCP.com
`
`DPP-4 Inhibitors:
`
`ONGLYZA®
`(saxagliptin)
`
`KOMBIGLYZE® XR
`(saxagliptin and metformin
`HCl extended-release) tablets
`
`Our Type 2 Diabetes Portfolio »
`
`Prescribing Information |
`Prescribing Information
`
` |
`
`Important Safety Information
`Indication | Medication Guide |
`Indication & Limitations of Use | Medication Guide
`For US Health Care Professionals
`Go to Patient Site
`
`|
`
`Share
`Menu
`Register
`Share
`Important Safety Information for ONGLYZA® (saxagliptin)
`Contraindications
`History of a serious hypersensitivity reaction to ONGLYZA ...Read More(eg, anaphylaxis, angioedema, or
`exfoliative skin conditions)...Read More...Read More
`
`Search
`
`A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISE
`
`SAFETY PROFILE
`
`Select a category below or scroll > to learn more.
`
`ONGLYZA Side Effects
`
`Discontinuation
`
`Hypoglycemic Events
`
`Renally Impaired Patients
`
`DEMONSTRATED SAFETY PROFILE ACROSS MULTIPLE STUDIES
`AND DIVERSE POPULATIONS
`1
`1,a
`Adverse reactions in placebo-controlled trials reported in ≥5% of patients
`IN MONOTHERAPY AND ADD-ON THERAPY STUDIES
`a
`
`IN MONOTHERAPY AND ADD-ON
`THERAPY STUDIES
`a
`
`Upper Respiratory Tract Infection
`
`Urinary Tract Infection
`
`Headache
`
`PERCENTAGE OF PATIENTS
`
`ONGLYZA 5 mg
`
`Placebo
`
`7.7%
`
`6.8%
`
`6.5%
`
`7.6%
`
`6.1%
`
`5.9%
`
`https://www.onglyza­hcp.com/safety­and­tolerability.html
`
`1/7
`
`Page 17 of 23
`
`

`
`7/29/2016
`
`Safety Information | Onglyza­HCP.com
`
` 
`
` 
`
`(n=799)
`(n=882)
`The 5 placebo-controlled trials include 2 monotherapy trials and 1 add-on combination therapy trial with each of the
`a
`following: metformin, thiazolidinedione, or glyburide. Table shows 24-week data regardless of glycemic rescue.
`In patients treated with ONGLYZA 2.5 mg, headache (6.5%) was the only adverse reaction reported at a
`rate ≥5% and more commonly than in patients treated with placebo
`1
`The overall proportion of patients who discontinued due to an adverse event was 2.2% with ONGLYZA
`2.5 mg, 3.3% with ONGLYZA 5 mg, and 1.8% with placebo
`1 
`There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA
`1
`
` 
`
`DISCONTINUATION OF THERAPY DUE TO ADVERSE REACTIONS
`1
`Most common adverse events associated with discontinuation of
`therapy
`1,b,c
`
`PERCENTAGE OF PATIENTS
`
`ONGLYZA 5 mg
`
`ONGLYZA 2.5 mg
`
`Placebo
`
`Lymphopenia
`
`Rash
`
`Blood Creatinine Increase
`
`Blood Creatine Phosphokinase Increase
`
`0.5%
`
`0.3%
`
`0.0%
`
`0.2%
`
`0.1%
`
`0.2%
`
`0.3%
`
`0.1%
`
`0.0%
`
`0.3%
`
`0.0%
`
`0.0%
`
` 
`
` 
`
` 
`
` 
`
`Prespecified pooled analysis of 2 monotherapy studies, add-on to metformin IR (vs metformin IR + placebo) study, the
`b
`add-on to the SU glyburide (vs glyburide + placebo) study, and the add-on to a TZD (vs TZD + placebo) study; 24-week data
`regardless of glycemic rescue.
`Reported in at least 2 patients treated with ONGLYZA.
`c
`Hypersensitivity-related events (eg, urticaria, facial edema) were reported in 1.5%, 1.5%, and 0.4% of
`patients who received ONGLYZA 5 mg, ONGLYZA 2.5 mg, and placebo, respectively *
`1,
`In the clinical trial database for saxagliptin to date, there have been 6 reports (0.12%) of tuberculosis
`among the patients treated with saxagliptin compared with no reports among the patients treated with
`the comparator. Causality has not been established. In addition, 1 patient treated with saxagliptin
`1
`developed suspected foodborne fatal salmonella sepsis. There have been no spontaneous reports of
`tuberculosis or opportunistic infections associated with saxagliptin use
`1
`There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA *
`1,
`*Prespecified pooled analysis of 3 monotherapy studies, the add-on to metformin IR (vs metformin IR + placebo) study, the
`add-on to the SU glyburide (vs glyburide + placebo) study, and the add-on to a TZD (vs TZD + placebo) study; 24-week data
`1
`regardless of glycemic rescue.
`
` 
`LOW RATES OF HYPOGLYCEMIA OVER 24 WEEKS WHEN ADDED
`
`https://www.onglyza­hcp.com/safety­and­tolerability.html
`
`2/7
`
`Page 18 of 23
`
`

`
`7/29/2016
`
`Safety Information | Onglyza­HCP.com
`
`LOW RATES OF HYPOGLYCEMIA OVER 24 WEEKS WHEN ADDED
`TO METFORMIN
`1,2
`The confirmed incidence of hypoglycemia with ONGLYZA 2.5 mg and ONGLYZA 5 mg vs placebo were
`0.5% and 0.5% vs 0.6%, respectively
`The reported incidence of hypoglycemia with ONGLYZA 2.5 mg and ONGLYZA 5 mg vs placebo was 7.8%
`and 5.8% vs 5%, respectively
`Confirmed hypoglycemia is defined by symptoms of hypoglycemia in the setting of a fingerstick blood glucose value <50
`mg/dL. Reported hypo