Class: Antidiabetic agent
- Tablets, oral 2.5 mg
- Tablets, oral 5 mg
Competitive dipeptidyl peptidase-4 (DPP4) inhibitor that slows the inactivation of incretin hormones, thereby reducing fasting and postprandial glucose concentrations.
Following a 5 mg oral dose, mean AUC was 78 ng•h/mL for saxagliptin and 214 ng•h/mL for its active metabolite. C max and T max were 24 ng/mL and 2 h for saxagliptin and 47 ng/mL and 4 h for the active metabolite, respectively. Administration with a high-fat meal increased T max by 20 min and AUC by 27%.
Protein binding is negligible.
Metabolized by CYP3A4/5. The major metabolite is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.
Terminal half-life is 2.5 h for saxagliptin and 3.1 h for its active metabolite. Average renal Cl is approximately 230 mL/min. Approximately 22% is excreted in feces with 24% and 36% excreted in urine as saxagliptin and its active metabolite, respectively.
Special PopulationsRenal 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. No dosage adjustment is required in patients with mild renal impairment.Hepatic Function Impairment
C max and AUC were 8% and 77% higher, respectively, in patients with hepatic impairment (Child-Pugh class A, B, and C). The corresponding C max and AUC of the active metabolite were 59% and 33% lower, respectively. No dosage is adjustment required.Elderly
Elderly patients had 23% and 59% higher C max and AUC values, respectively, compared with younger subjects. Dosage adjustment based on age alone is not required.Gender
Women had approximately 25% higher exposure values for the active metabolite compared with men.Race
No significant differences in pharmacokinetics of saxagliptin were seen among different races.
Indications and Usage
Adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
Hypersensitivity to saxagliptin, such as anaphylaxis, angioedema, or exfoliative skin conditions.
Dosage and AdministrationAdults
PO 2.5 or 5 mg once daily.Renal Function Impairment
POModerate to severe renal impairment (CrCl 50 mL/min or less)
Do not exceed 2.5 mg once daily.ESRD requiring hemodialysis
Do not exceed 2.5 mg once daily after hemodialysis.Strong CYP3A4/5 Inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)
PO 2.5 mg once daily.
- May be taken with or without food.
Store between 59° and 86°F.
Drug InteractionsAluminum hydroxide/magnesium hydroxide/simethicone, metformin
Saxagliptin plasma concentrations may be reduced slightly. No dosage adjustment is required.Antidiabetic agents (eg, sulfonylureas)
The risk of hypoglycemia may be increased when used with other antidiabetic agents. A lower dose of the antidiabetic agent may be needed.Digoxin
Digoxin concentrations may be elevated slightly. No dosage adjustment is required.Diltiazem, pioglitazone
Plasma concentrations of diltiazem, pioglitazone, and saxagliptin may be elevated slightly. No dosage adjustment is required.Ethinyl estradiol/norgestimate
Ethinyl estradiol, norelgestromin, and norgestrel concentrations may be elevated slightly. No dosage adjustment is required.Famotidine
Saxagliptin plasma concentrations may be elevated slightly. No dosage adjustment is required.Food
High-fat meals increase saxagliptin T max approximately 20 minutes compared with fasting. Compared with fasting, giving saxagliptin with a meal increases the AUC by 27%. Saxagliptin may be administered without regard to food.Glyburide
Glyburide and saxagliptin plasma concentrations may be elevated slightly. No dosage adjustment is required.Ketoconazole
Ketoconazole plasma concentrations may be decreased slightly by saxagliptin. No ketoconazole dosage adjustment is required. However, the saxagliptin dosage should be limited to 2.5 mg once daily. See Strong CY3A4/5 Inhibitors.Omeprazole
Saxagliptin AUC may be increased slightly. No dosage adjustment is required.Rifampin
Saxagliptin C max and AUC may be reduced; however, dosage adjustment is not recommended. Monitor the clinical response of the patient. If an interaction is suspected, adjust treatment as needed.Simvastatin
Saxagliptin plasma concentrations may be elevated slightly and simvastatin concentrations may be decreased slightly. No dosage adjustment is required.Strong CYP3A4/5 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)
Saxagliptin C max and AUC may be increased, increasing the pharmacologic effects and risk of adverse reactions. The dosage of saxagliptin should be limited to 2.5 mg once daily when administered with a strong CYP3A4/5 inhibitor. Monitor the clinical response of the patient.
Nasopharyngitis (7%); sinusitis (3%).
Abdominal pain, gastroenteritis, vomiting (2%); pancreatitis (postmarketing).
Decreased absolute lymphocyte count (2%); lymphopenia (1%).
Hypoglycemia (6%); peripheral edema (4%).
Upper respiratory tract infection (8%).
Hypersensitivity reactions (eg, urticaria, facial edema) (2%); other hypersensitivity reactions (eg, anaphylaxis, angioedema, exfoliative skin conditions) (postmarketing).
Assess renal function prior to initiation of therapy and periodically thereafter. Periodically measure blood glucose and HbA 1c . Measure lymphocyte count when clinically indicated (eg, unusual or prolonged infection).
Category B .
Safety and efficacy have not been established.
Take care in dose selection based on renal function.
Dosage adjustments are required in patients with moderate or severe renal impairment.
There have been postmarketing reports of acute pancreatitis. If suspected, promptly discontinue saxagliptin.
Type 1 diabetes mellitus/diabetic ketoacidosis
Do not use in these settings, as it would not be effective.
- Instruct patients that this drug is not a substitute for diet and exercise and to follow their prescribed regimen.
- Emphasize the importance of regular daily blood glucose monitoring and periodic glycosylated Hgb tests.
- Review symptoms and management of hypoglycemia and hyperglycemia.
- Instruct patients to report hypoglycemic or hyperglycemic episodes to their health care provider.
- Advise patients that during periods of stress (eg, fever, trauma, infection, surgery), medication requirements may change and to seek medical advice promptly.
- Inform patients of the potential need to adjust their dose based on changes in renal function tests over time.
- Inform patients that there have been reports of pancreatitis in patients taking saxagliptin and symptoms, such as persistent severe abdominal pain sometimes radiating to the back that may be accompanied by vomiting, can indicate pancreatitis. Instruct patients to stop taking saxagliptin and contact their health care provider immediately if these symptoms occur.
- Inform patients that serious allergic reactions have been reported. Instruct patients to immediately contact their health care provider if symptoms such as rash; skin flaking, peeling, or swelling; itching; or swelling of the face, lips tongue, and throat that may cause difficulty in breathing and swallowing occur. Instruct patients to stop taking saxagliptin and seek medical attention immediately if these symptoms occur.
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