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Saxagliptin: Drug information

Copyright 1978-2019 Lexicomp, Inc. All rights reserved.

(For additional information see "Saxagliptin: Patient drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)

Brand Names: US
Onglyza

Brand Names: Canada

Onglyza

Pharmacologic Category
Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor

Dosing: Adult

Diabetes mellitus, type 2: Oral: 2.5 to 5 mg once daily

Concomitant use with strong CYP3A4/5 inhibitors (eg, atazanavir, clarithromycin, indinavir,
itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin): 2.5
mg once daily

Concomitant use with insulin or insulin secretagogues: Reduced dose of insulin or insulin
secretagogues (eg, sulfonylureas) may be needed

Dosing: Renal Impairment: Adult

eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary.

eGFR <45 mL/minute/1.73 m2: 2.5 mg once daily.

ESRD requiring hemodialysis: 2.5 mg once daily; administer postdialysis

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Peritoneal dialysis: There are no dosage adjustments provided in the manufacturer's

labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild to severe impairment: No dosage adjustment necessary.

Dosing: Geriatric
Refer to adult dosing.

Dosage Forms: US
Excipient information presented when available (limited, particularly for generics); consult
specific product labeling.

Tablet, Oral:

Onglyza: 2.5 mg, 5 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult
specific product labeling.

Tablet, Oral:

Onglyza: 2.5 mg, 5 mg [contains FD&C BLUE #2 (INDIGOTINE)]

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and
at http://www.azpicentral.com/onglyza/onglyza_med.pdf#page=1, must be dispensed with this
medication.

Administration: Adult
Oral: May be administered without regard to meals. Swallow whole; do not split or cut tablets.

Use: Labeled Indications

Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in
adults with type 2 diabetes mellitus as monotherapy or in combination therapy.

Medication Safety Issues

Sound-alike/look-alike issues:

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SAXagliptin may be confused with SITagliptin, SUMAtriptan

Adverse Reactions
Frequencies and adverse reactions reported with monotherapy unless otherwise noted.

1% to 10%:

Cardiovascular: Peripheral edema (4%; combination therapy with thiazolidinediones:

8%)

Central nervous system: Headache (7%)

Endocrine & metabolic: Hypoglycemia (6%; combination therapy with glyburide: 13%
to 15%; with metformin: 6% to 8%; with insulin: 5%)

Genitourinary: Urinary tract infection (7%)

Hematologic & oncologic: Lymphocytopenia (2%)

Hypersensitivity: Hypersensitivity reaction (2%; including facial edema and urticaria)

<1%, postmarketing, and/or case reports: Acute pancreatitis, anaphylaxis, angioedema,

exfoliative dermatitis, immune thrombocytopenia, increased creatine phosphokinase,
increased serum creatinine

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions) to saxagliptin or

any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to

another DPP-4 inhibitor; diabetic ketoacidosis, diabetic coma/precoma, type 1 diabetes
mellitus

Warnings/Precautions

Concerns related to adverse effects:

• Arthralgia: Severe and disabling arthralgia has been reported with DPP-IV inhibitor
use; onset may occur within one day to years after treatment initiation and may
resolve with discontinuation of therapy. Some patients may experience a recurrence of
symptoms if DPP-IV inhibitor therapy resumed.

• Bullous pemphigoid: DPP-4 inhibitor use has been associated with development of
bullous pemphigoid; cases have typically resolved with topical or systemic

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immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise

patients to report development of blisters or erosions. Discontinue therapy if bullous
pemphigoid is suspected and consider referral to a dermatologist.

• Hematologic: Dose-related decrease in lymphocyte count has been observed; clinical

significance is not known. Monitoring of lymphocyte counts may be warranted in
patients with unusual or persistent infection.

• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis,

angioedema, and exfoliative dermatologic reactions have been reported; discontinue if
signs/symptoms of severe hypersensitivity reaction occur. Events have generally
occurred within the first 3 months of therapy, and may occur after the initial dose. Use
with caution if patient has experienced angioedema with other DPP-IV inhibitor use.

• Pancreatitis: Cases of acute pancreatitis have been reported with use. Monitor for
signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is
suspected and initiate appropriate management. Use with caution in patients with a
history of pancreatitis as it is not known if this population is at greater risk.

Disease-related concerns:

• Heart failure: Heart failure (HF) that may require hospitalization has been reported in
a multi-center, randomized, double-blind, placebo-controlled trial in patients with type 2
diabetes with a history of, or at risk for, cardiovascular events; risk was increased in
patients with preexisting heart failure or renal impairment and during the first 12
months of therapy (Scirica 2013; Scirica 2014). A population-based retrospective
study in an ambulatory setting with relatively lower baseline cardiovascular risk factors
failed to demonstrate increased risk in patients on saxagliptin compared to other
agents (eg, sitagliptin, pioglitazone, sulfonylureas, insulin) (Toh 2016). Monitor for
signs and symptoms of heart failure during therapy and consider discontinuation if
condition develops. In a scientific statement from the American Heart Association,
saxagliptin has been determined to be an agent that may exacerbate underlying
myocardial dysfunction (magnitude: major) (AHA [Page 2016]). The ADA recommends
avoiding use of saxagliptin in patients with HF (ADA 2019).

• Renal impairment: Use with caution in patients with moderate to severe renal
dysfunction (eGFR <45 mL/minute/1.73 m2) including end-stage renal disease (ESRD)
requiring hemodialysis; dosing adjustment required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose

or frequency adjustment, additional monitoring, and/or selection of alternative therapy.

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Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus or with
diabetic ketoacidosis (DKA).

• Patient education: Diabetes self-management education (DSME) is essential to

maximize the effectiveness of therapy.

Metabolism/Transport Effects
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1; Note: Assignment of Major/Minor
substrate status based on clinically relevant drug interaction potential

Drug Interactions
(For additional information: Launch drug interactions program)

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C:
Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Exceptions: Danazol. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Dipeptidyl Peptidase-IV Inhibitors may enhance

the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk
of angioedema may be increased. Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of SAXagliptin. Risk C:
Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of SAXagliptin. Risk
C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of SAXagliptin.

Management: Saxagliptin U.S. product labeling recommends limiting saxagliptin adult dose
to 2.5 mg/day when used with a strong CYP3A4 inhibitor. Monitor for increased saxagliptin

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levels/effects. A similar recommendation is not made in the Canadian product labeling.

Risk D: Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic
Agents. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk
with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk
with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates
(High risk with Inhibitors). Risk X: Avoid combination

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C:

Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic

Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic

effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk X: Avoid combination

Insulins: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of

Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a
dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider
therapy modification

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates.

Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C:
Monitor therapy

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MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk
with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for
increased concentrations/toxicity, during and 2 weeks following treatment with
mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide,
quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose
Lowering Agents. Risk C: Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of

P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the
distribution of p-glycoprotein substrates to specific cells/tissues/organs where
p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C:
Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of

P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the
distribution of p-glycoprotein substrates to specific cells/tissues/organs where
p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C:
Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents.
Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may
occur with quinolone use. Risk C: Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor
therapy

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Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk
C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood
Glucose Lowering Agents. Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to
have a narrow therapeutic index should be avoided due to the increased risk for adverse
effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Risk D: Consider therapy modification

Sulfonylureas: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of

Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating
therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk
D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic
Agents. Risk C: Monitor therapy

Pregnancy Implications
In women with diabetes, maternal hyperglycemia can be associated with congenital
malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 201
2018; ADA 2019; Metzger 2007). To prevent adverse outcomes prior to conception and
throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target
goals as possible but without causing significant hypoglycemia (ADA 2019; Blumer 2013).
Agents other than saxagliptin are currently recommended to treat diabetes in pregnant women
(ADA 2019).

Breast-Feeding Considerations
It is not known if saxagliptin is present in breast milk. According to the manufacturer, the
decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of
breastfeeding to the infant, and benefits of treatment to the mother.

Dietary Considerations
Individualized medical nutrition therapy (MNT) is an integral part of therapy (ADA 2013).

Monitoring Parameters
Plasma glucose, HbA1c (at least twice yearly in patients who have stable glycemic control and

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are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy
change [ADA 2019]), renal function (prior to initiation of therapy and periodically thereafter);
lymphocyte counts (if unusual or persistent infection); signs/symptoms of pancreatitis and/or
heart failure

Reference Range

Recommendations for glycemic control in nonpregnant adults with diabetes (ADA 2019):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be
targeted based on patient-specific characteristics)

Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals
may be appropriate based on patient-specific characteristics)

Peak postprandial capillary blood glucose: <180 mg/dL (more or less stringent goals
may be appropriate based on patient-specific characteristics)

Recommendations for glycemic control in older adults (≥65 years) with diabetes (ADA
2019):

HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very

complex/poor health) (individualization may be appropriate based on patient and
caregiver preferences)

Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL

(complex/intermediate health); 100 to 180 mg/dL (very complex/poor health)

Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL
(complex/intermediate health); 110 to 200 mg/dL (very complex/poor health)

Mechanism of Action
Saxagliptin inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in prolonged active
incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent
insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis
and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic
alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production.
Under normal physiologic circumstances, incretin hormones are released by the intestine
throughout the day and levels are increased in response to a meal; incretin hormones are
rapidly inactivated by the DPP-IV enzyme.

Pharmacodynamics and Pharmacokinetics

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Duration: 24 hours

Protein binding: Negligible

Metabolism: Hepatic via CYP3A4/5 to 5-hydroxy saxagliptin (active; ~50% potency of the
parent compound)

Half-life elimination: Saxagliptin: 2.5 hours; 5-hydroxy saxagliptin: 3.1 hours

Time to peak, plasma: Saxagliptin: 2 hours; 5-hydroxy saxagliptin: 4 hours

Excretion: Urine (75%, 24% of the total dose as saxagliptin, 36% of the total dose as
5-hydroxy saxagliptin); feces (22%)

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: AUC was up to 2.1- and 4.5-fold higher in patients with
moderate or severe renal impairment. Dosage adjustment is required. In patients with mild
renal impairment, AUC for saxagliptin and its active metabolite were 20% and 70% higher,
respectively, which is not considered significant.

Hepatic function impairment: Cmax and AUC were 8% and 77% higher, respectively, in
patients with hepatic impairment (Child-Pugh class A, B, and C). The corresponding Cmax
and AUC of the active metabolite were 59% and 33% lower, respectively.

Pricing: US

Tablets (Onglyza Oral)

2.5 mg (per each): $16.82

5 mg (per each): $16.82

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided
as reference price only. A range is provided when more than one manufacturer's AWP price is
available and uses the low and high price reported by the manufacturers to determine the
range. The pricing data should be used for benchmarking purposes only, and as such should
not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or
considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly
disclaims all warranties of any kind or nature, whether express or implied, and assumes no
liability with respect to accuracy of price or price range data published in its solutions. In no
event shall Medi-Span be liable for special, indirect, incidental, or consequential damages
arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International

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Formigliptin (EG); Glipitrose (EG); Glyza (BD); Ongliza (UA); Onglyza (AE, AR, AT, AU, BB, BE,
BH, BR, CH, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EE, EG, ES, ET, FR, GB, GR, GT, HK,
HN, HR, ID, IE, IL, IN, IT, JO, JP, KR, KW, LB, LK, LT, LU, LV, MT, MY, NI, NL, NO, NZ, PA, PH,
PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, TW, VN); Sixtin (BD)

For country abbreviations used in Lexicomp (show table)

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Topic 9534 Version 188.0

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